Sample records for alpha-glucosidases

  1. Production of {alpha}-glucosidases by Bacillus sp. strains

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    Castro, G.R. [Univ. Nacional de Tucuman, Facultad de Bioquimica, Quimica y Farmacia, Catedra de Microbiologia Superior, PROIMI-MIRCEN, Tucuman (Argentina); Baigori, M.D. [Univ. Nacional de Tucuman, Facultad de Bioquimica, Quimica y Farmacia, Catedra de Microbiologia Superior, PROIMI-MIRCEN, Tucuman (Argentina); Sineriz, F. [Univ. Nacional de Tucuman, Facultad de Bioquimica, Quimica y Farmacia, Catedra de Microbiologia Superior, PROIMI-MIRCEN, Tucuman (Argentina)


    {alpha}-Glucosidase was detected in four wild-type amylolytic production strains belonging to the Bacillus genus. The strains showed {alpha}-glucosidase activity in extracellular and membrane-bound fractions. Kinetic studies of the {alpha}-glucosidase synthesis in the batch cultures of four strains of the Bacillus genus showed two profiles: partially and totally growth-linked synthesis. The presence of different activities and production profiles of {alpha}-glucosidase in the strains at high or low glucose concentrations in the medium would indicate that {alpha}-glucosidase may have a role in the regulation of the metabolism of {alpha}-polysaccharides. (orig.)

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

    DEFF Research Database (Denmark)

    Stanley, Duncan; Rejzek, Martin; Næsted, Henrik


    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 complementary...... chemical-genetic and reverse-genetic approaches. We identified iminosugar inhibitors of a recombinant form of an alpha-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...

  3. Alpha-Glucosidase Inhibitory and Antioxidant Activity of Solvent ...

    African Journals Online (AJOL)

    Alpha-Glucosidase Inhibitory and Antioxidant Activity of Solvent Extracts and Fractions of Typha domingensis (Typhaceae) Fruit. Tsun-Thai Chai, Mei-Jee Chiam, Chi-Hou Lau, Nor Ismaliza Mohd Ismail, Hean-Chooi Ong, Fazilah Abd Manan, Fai-Chu Wong ...

  4. Alpha-glucosidase promotes hemozoin formation in a blood-sucking bug: an evolutionary history.

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    Flávia Borges Mury

    Full Text Available BACKGROUND: Hematophagous insects digest large amounts of host hemoglobin and release heme inside their guts. In Rhodnius prolixus, hemoglobin-derived heme is detoxified by biomineralization, forming hemozoin (Hz. Recently, the involvement of the R. prolixus perimicrovillar membranes in Hz formation was demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: Hz formation activity of an alpha-glucosidase was investigated. Hz formation was inhibited by specific alpha-glucosidase inhibitors. Moreover, Hz formation was sensitive to inhibition by Diethypyrocarbonate, suggesting a critical role of histidine residues in enzyme activity. Additionally, a polyclonal antibody raised against a phytophagous insect alpha-glucosidase was able to inhibit Hz formation. The alpha-glucosidase inhibitors have had no effects when used 10 h after the start of reaction, suggesting that alpha-glucosidase should act in the nucleation step of Hz formation. Hz formation was seen to be dependent on the substrate-binding site of enzyme, in a way that maltose, an enzyme substrate, blocks such activity. dsRNA, constructed using the sequence of alpha-glucosidase gene, was injected into R. prolixus females' hemocoel. Gene silencing was accomplished by reduction of both alpha-glucosidase and Hz formation activities. Insects were fed on plasma or hemin-enriched plasma and gene expression and activity of alpha-glucosidase were higher in the plasma plus hemin-fed insects. The deduced amino acid sequence of alpha-glucosidase shows a high similarity to the insect alpha-glucosidases, with critical histidine and aspartic residues conserved among the enzymes. CONCLUSIONS/SIGNIFICANCE: Herein the Hz formation is shown to be associated to an alpha-glucosidase, the biochemical marker from Hemipteran perimicrovillar membranes. Usually, these enzymes catalyze the hydrolysis of glycosidic bond. The results strongly suggest that alpha-glucosidase is responsible for Hz nucleation in the R. prolixus

  5. Cloning a cDNA for the lysosomal alpha-glucosidase

    NARCIS (Netherlands)

    KONINGS, A.; HUPKES, P.; Versteeg, R.; Grosveld, G.; Reuser, A.; Galjaard, H.


    Messenger RNA was isolated from monkey testes and size-fractionated on sucrose gradients. In vitro translation of these mRNA fractions resulted in nascent, labeled alpha-glucosidase that could be precipitated with anti human alpha-glucosidase antiserum. A cDNA library was constructed from the most

  6. Alpha-glucosidase inhibitory and antiplasmodial properties of terpenoids from the leaves of Buddleja saligna Willd

    Czech Academy of Sciences Publication Activity Database

    Chukwujekwu, J. C.; Rengasamy, K.R.R.; de Kock, C. A.; Smith, P. J.; Poštová Slavětínská, Lenka; van Staden, J.


    Roč. 31, č. 1 (2016), s. 63-66 ISSN 1475-6366 Institutional support: RVO:61388963 Keywords : alpha-glucosidase * antidiabetic * antiplasmodial * Buddleja saligna * terpenoids Subject RIV: CC - Organic Chemistry Impact factor: 4.293, year: 2016

  7. Enzyme therapy for pompe disease with recombinant human alpha-glucosidase from rabbit milk.

    NARCIS (Netherlands)

    Hout, J.M. van den; Reuser, A.J.J.; Klerk, J.B.C. de; Arts, W.F.M.; Smeitink, J.A.M.; Ploeg, A.T. van der


    Pompe disease is a metabolic myopathy caused by deficiency of lysosomal acid alpha-glucosidase. In this report we review the first 36 weeks of a clinical study on the safety and efficacy of enzyme therapy aimed at correcting the deficiency. Four patients with infantile Pompe disease were enrolled.

  8. Novel {alpha}-glucosidase from human gut microbiome : substrate specificities and their switch.

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    Tan, K.; Tesar, C.; Wilton, R.; Keigher, L.; Babnigg, G.; Joachimiak, A.; Biosciences Division


    The human intestine harbors a large number of microbes forming a complex microbial community that greatly affects the physiology and pathology of the host. In the human gut microbiome, the enrichment in certain protein gene families appears to be widespread. They include enzymes involved in carbohydrate metabolism such as glucoside hydrolases of dietary polysaccharides and glycoconjugates. We report the crystal structures (wild type, 2 mutants, and a mutant/substrate complex) and the enzymatic activity of a recombinant {alpha}-glucosidase from human gut bacterium Ruminococcus obeum. The first ever protein structures from this bacterium reveal a structural homologue to human intestinal maltase-glucoamylase with a highly conserved catalytic domain and reduced auxiliary domains. The {alpha}-glucosidase, a member of GH31 family, shows substrate preference for {alpha}(1-6) over {alpha}(1-4) glycosidic linkages and produces glucose from isomaltose as well as maltose. The preference can be switched by a single mutation at its active site, suggestive of widespread adaptation to utilization of a variety of polysaccharides by intestinal micro-organisms as energy resources. Novel {alpha}-glucosidase from human gut microbiome: substrate specificities and their switch.

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

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    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.

  10. Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico. (United States)

    Jhong, Chien-Hung; Riyaphan, Jirawat; Lin, Shih-Hung; Chia, Yi-Chen; Weng, Ching-Feng


    The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants. © 2015 International Union of Biochemistry and Molecular Biology.

  11. An alpha-glucosidase inhibitor from an endophytic Cladosporium sp. with potential as a biocontrol agent. (United States)

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


    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.

  12. Alpha-glucosidase inhibitors in the early treatment of type 2 diabetes

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    Floris Alexander van de Laar


    Full Text Available Floris Alexander van de LaarRadboud University Nijmegen Medical Centre, Department of General Practice, Nijmegen, The NetherlandsAbstract: Alpha-glucosidase inhibitors (AGIs are drugs that inhibit the absorption of carbohydrates from the gut and may be used in the treatment of patients with type 2 diabetes or impaired glucose tolerance. There is currently no evidence that AGIs are beneficial to prevent or delay mortality or micro- or macrovascular complications in type 2 diabetes. Its beneficial effects on glycated hemoglobin are comparable to metformin or thiazolidinediones, and probably slightly inferior to sulphonylurea. In view of the total body of evidence metformin seems to be superior to AGIs. More long-term studies are needed to study the effects of AGIs compared to other drugs. For patient with impaired glucose tolerance AGIs may prevent, delay or mask the occurrence of type 2 diabetes. A possible beneficial effect on cardiovascular events should be confirmed in new studies.Keywords: alpha-glucosidase inhibitors, type 2 diabetes mellitus, impaired glucose tolerance

  13. Biosynthesis and transport of lysosomal alpha-glucosidase in the human colon carcinoma cell-line Caco-2: secretion from the apical surface

    NARCIS (Netherlands)

    Klumperman, J.; Fransen, J.A.; Boekestijn, J.C.; Oude Elferink, R.P.; Matter, K.; Hauri, H.P.; Tager, J.M.; Ginsel, L.A.


    The human adenocarcinoma cell line Caco-2 was used for studies on the biosynthesis and transport of lysosomal acid alpha-glucosidase in polarized epithelial cells. Metabolic labelling revealed that in Caco-2 cells alpha-glucosidase is synthesized as a precursor form of 110 x 10(3) Mr. This form is

  14. Screening of endophytic fungi having ability for antioxidative and alpha-glucosidase inhibitor activities isolated from Taxus sumatrana. (United States)

    Artanti, N; Tachibana, S; Kardono, L B S; Sukiman, H


    Endophytic microbes are considered as an important source of natural products. They show antibiotic, anticancer, antioxidative and antidiabetic activities. Therefore, there are many reports on the isolation and bioactivity screening of endophytic fungi from various plants including Taxus species. Taxus sumatrana (Miq.) de Laub is found in Indonesia. The objective of this study is to conduct an in vitro screening of 14 endophytic fungi isolated from Taxus sumatrana having antioxidative and alpha-glucosidase inhibitor activities. Each endophytic fungus was cultured for 7 days and the fungal mycelium and medium were extracted with methanol and ethyl acetate, respectively, to produce each extract. The antioxidative activity of each extract was tested by DPPH free radical scavenging activity and beta-carotene bleaching assays, whereas antidiabetic activity was tested based on alpha-glucosidase inhibitor activity. The screening results showed that fungal mycelia of TSC 13 had the best alpha-glucosidase inhibitor activity and TSC 24 had the best antioxidative activity. Isolation of bioactive compounds from TSC 13 and TSC 24 is being conducted. This is the first report that endophytic fungi isolated from T. sumatrana exhibited anti alpha-glucosidase inhibitory and anti oxidative activities.

  15. alpha-Glucosidase inhibitory pentacyclic triterpenes from the stem bark of Fagara tessmannii (Rutaceae). (United States)

    Mbaze, Luc Meva'a; Poumale, Herve Martial P; Wansi, Jean Duplex; Lado, Jean Alexandre; Khan, Shamsun Nahar; Iqbal, Muhammad Choudhary; Ngadjui, Bonaventure Tchaleu; Laatsch, Hartmut


    In addition to fatty acids, a mixture of sterols (beta-sitosterol, stigmasterol, campesterol and stigmastanol), lupeol, arctigenin methylether, sesamin, vanillic acid (1), 2,6-dimethoxy-1,4-benzoquinone (2), betulinic acid and two pentacyclic triterpene acetates were isolated from Fagara tessmannii Engl. They were identified as 3beta-acetoxy-16beta-hydroxybetulinic acid (3a) and 3beta,16beta-diacetoxybetulinic acid (3b), and their structures were established using 1 and 2D NMR spectra and by comparison with published data. Two derivatives of the compounds were prepared. Some isolated compounds were evaluated for their antifungal and antibacterial activities. Compounds 1 and 3a showed significant inhibition of alpha-glucosidase.


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    Gunawan Pasaribu


    Full Text Available Raru (Shoreabalanocarpoides Sym signifies one of the tree species that grows widespread in Sumatra Island.  Its bark portion is commonly used by local villagers as additional ingredient mixed to nira (sugar palm juice.  This addition is intended to make the juice more durable and also to enrich its taste after the juice is previously fermented to become traditional toddy beverage or the so-call “tuak”.  Local villagers believe that raru bark can reduce the level of blood sugar. As the relevance, the research was conducted to confirm that the extract from raru bark could afford its biological activities to inhibit alpha-glucosidase enzyme through its characterization, quantification, and isolation of its boactive compound. The extraction was performed using two methods (i.e.reflux and maceration techniques. Result revealed that the bark extract obtained from both techniques contained polyphenol compounds: flavonoid, saponin and tannin. Further, raru-bark extract from the reflux and maceration techniques could inhibit the action of alpha glucosidase enzymes on carbohydrate substrate ( i.e. p -nitrophenil-α-D-glucopyranose, at respectively 90.67% and 97.33%. Meanwhile, the inhibition activities afforded by the patented drug as a control (i.e. glucobay equaled to 97.05%.  Assesment using UV-VIS spectroscopy, showed that the maximum spectrum of bioactive compound in the extract was at the wave length of 288.6 nm. Scrutiny using FTIR spectroscopy could identif y the presence of aromatic groups in the compound, containing -OH, C-H, C=C, C-O and C-H bond types. Analysis using GC-MS exhibited that the compound had molecular weight of 390 with molecular structure as C20H22O8. Ultimately, data analysis scrutiny with the aid of NMR judged the most plausible compound as bioactive was 4-Glucosyl-3, 4’, 5-trihydroxystilbene.

  17. Enzymatic profiles of Enterobacter sakazakii and related species with special reference to the alpha-glucosidase reaction and reproducibility of the test system. (United States)

    Muytjens, H L; van der Ros-van de Repe, J; van Druten, H A


    The enzymatic profiles of Enterobacter sakazakii, Enterobacter cloacae, Enterobacter aerogenes, and Enterobacter agglomerans were determined with the API ZYM system (API System S.A., La Balme Les Grottes, France). Each assay was performed three times. A simple formula was derived and applied to assess the reproducibility of the API ZYM tests. In addition, a separate alpha-glucosidase test was performed. All E. sakazakii isolates produced alpha-glucosidase, in contrast to the other Enterobacter isolates. No phosphoamidase activity was detected in any of the E. sakazakii isolates, whereas it was present in 72% of E. cloacae, 89% of E. agglomerans, and 100% of E. aerogenes isolates. It was concluded that detection of alpha-glucosidase permits rapid and reliable differentiation between E. sakazakii and other Enterobacter species. The reproducibilities of alpha-glucosidase and phosphoamidase reactions were estimated to be 89 and 81%, respectively. PMID:6386874

  18. Cloning and Molecular Characterization of an Alpha-Glucosidase (MalH from the Halophilic Archaeon Haloquadratum walsbyi

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    Mara F. Cuebas-Irizarry


    Full Text Available We report the heterologous expression and molecular characterization of the first extremely halophilic alpha-glucosidase (EC from the archaeon Haloquadratum walsbyi. A 2349 bp region (Hqrw_2071 from the Hqr. walsbyi C23 annotated genome was PCR-amplified and the resulting amplicon ligated into plasmid pET28b(+, expressed in E. coli Rosetta cells, and the resulting protein purified by Ni-NTA affinity chromatography. The recombinant protein showed an estimated molecular mass of 87 kDa, consistent with the expected value of the annotated protein, and an optimal activity for the hydrolysis of α-PNPG was detected at 40 °C, and at pH 6.0. Enzyme activity values were the highest in the presence of 3 M NaCl or 3–4 M KCl. However, specific activity values were two-fold higher in the presence of 3–4 M KCl when compared to NaCl suggesting a cytoplasmic localization. Phylogenetic analyses, with respect to other alpha-glucosidases from members of the class Halobacteria, showed that the Hqr. walsbyi MalH was most similar (up to 41% to alpha-glucosidases and alpha-xylosidases of Halorubrum. Moreover, computational analyses for the detection of functional domains, active and catalytic sites, as well as 3D structural predictions revealed a close relationship with an E. coli YicI-like alpha-xylosidase of the GH31 family. However, the purified enzyme did not show alpha-xylosidase activity. This narrower substrate range indicates a discrepancy with annotations from different databases and the possibility of specific substrate adaptations of halophilic glucosidases due to high salinity. To our knowledge, this is the first report on the characterization of an alpha-glucosidase from the halophilic Archaea, which could serve as a new model to gain insights into carbon metabolism in this understudied microbial group.

  19. Treatment with acarbose, an alpha-glucosidase inhibitor, reduces increased albumin excretion in streptozotocin-diabetic rats. (United States)

    Cohen, M P; Vasselli, J R; Neuman, R G; Witt, J


    1. We examined the effect of the alpha-glucosidase inhibitor acarbose on urinary albumin excretion (UAE) in streptozotocin diabetic rats. 2. Treatment with acarbose for 8 weeks after induction of diabetes prevented the significant increase in UAE observed in untreated diabetic rats relative to nondiabetic controls. 3. Acarbose significantly reduced integrated glycemia, which correlated with albumin excretion rates, and exerts a salutary effect on diabetic renal dysfunction.

  20. Alpha-glucosidase inhibitory and antiplasmodial properties of terpenoids from the leaves of Buddleja saligna Willd. (United States)

    Chukwujekwu, Jude C; Rengasamy, Kannan R R; de Kock, Carmen A; Smith, Peter J; Slavětínská, Lenka Poštová; van Staden, Johannes


    In our continuing search for biologically active natural product(s) of plant origin, Buddleja saligna, a South African medicinal plant, was screened in line with its traditional use for antidiabetic (yeast alpha glucosidase inhibitory) and antiplasmodial (against a chloroquine sensitive strain of Plasmodium falciparum (NF54)) activities. The hexane fraction showed the most promising activity with regards to its antidiabetic (IC(50) = 260 ± 0.112 µg/ml) and antiplasmodial (IC(50) = 8.5 ± 1.6 µg/ml) activities. Using activity guided fractionation three known terpenoids (betulonic acid, betulone and spinasterol) were isolated from this species for the first time. The compounds displayed varying levels of biological activities (antidiabetic: 27.31 µg/ml ≥ IC(50) ≥ 5.6 µg/ml; antiplasmodial: 14 µg/ml ≥ IC(50) ≥ 2 µg/ml) with very minimal toxicity.

  1. Expression of alpha subunit of alpha glucosidase II in adult mouse brain regions and selective organs (United States)

    Anji, Antje; Miller, Hayley; Raman, Chandrasekar; Phillips, Mathew; Ciment, Gary; Kumari, Meena


    Alpha glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in folding of nascent glycoproteins, is heterodimeric consisting of alpha (GIIα) and beta (GIIβ) subunits. The catalytic GIIα subunit with the help of mannose 6-phosphate receptor homology (MRH) domain of GIIβ sequentially hydrolyzes two α-1-3-linked glucose residues in the 2nd step of N-linked oligosaccharide-mediated protein folding. The soluble GIIα subunit is retained in the ER through its interaction with the HDEL-containing GIIβ subunit. N-glycosylation and correct protein folding is crucial for protein stability, trafficking, and cell surface expression of several proteins in the brain. Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies such as viral infection, cancer and diabetes. In spite of the widespread usage of GIIα inhibitory drugs and the role of GIIα in brain function little is known about its expression in brain and other tissues. Here, we report generation of a highly specific chicken antibody to GIIα subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. Using this antibody we show that the GIIα protein is highly expressed in testis, kidney, and lung, with the least amount in heart. GIIα polypeptide levels in whole brain were comparable to spleen. However, higher expression of GIIα protein was detected in cerebral cortex reflecting its continuous requirement in correct folding of cell surface proteins. PMID:25131991

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

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    Boonyadist Vongsak

    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.

  3. Effect of lipid extracts of Nigella sativa L. seeds on the liver ATP reduction and alpha-glucosidase inhibition. (United States)

    Sobhi, Widad; Stevigny, Caroline; Duez, Pierre; Calderon, Bedro Buc; Atmani, Djebbar; Benboubetra, Mustapha


    Various extracts from the seeds of Nigella sativa have been used in traditional folk medicine to treat inflammation, liver disorders and arthritis. These seeds have been experimentally shown to possess antioxidant and hepatoprotective properties. Beside the hypoglycaemic and hypolipidemic effects, this study was carried out to evaluate, in vitro, toxicological effect of lipid extracts from the Nigella sativa seeds. The tested fractions were: (i) defatted methanolic extract, (ii) total lipid extract obtained by hexane extraction from methanolic extract and (iii) neutral and polar lipid fractions. The fractions were assessed, in vitro, for their inhibitory activity potential on the enzyme alpha-glucosidase as suppressing the enzyme activity is one among the therapeutic approaches to attenuate postprandial hyperglycemia. High inhibition of alpha-glucosidase by the two polar lipid fractions (F6 and F7) was reflected by their IC50 (0.51±0.04mg/ml and 0.55±0.09mg/ml, respectively), compared to acarbose (0.53±0.06mg/ml) and thymoquinone (0.65±0.05mg/ml). The hypoglycaemic effect of the polar lipid fraction of Nigella sativa could be explained by the inhibition of alpha-glucosidase, which is one of early steps of carbohydrate metabolism. Toxicological evaluation was investigated on precision-cut rat liver slices (PCLS). On PCLS, lipid extracts reduced ATP levels by 27 to 35%. Results indicate suggest that Nigella sativa extracts don't show a hepatoprotective effect against acetaminophen, but don't exhibit a major hepatotoxicity when tested alone.

  4. Synergisms in Alpha-glucosidase Inhibition and Antioxidant Activity of Camellia sinensis L. Kuntze and Eugenia uniflora L. Ethanolic Extracts (United States)

    Vinholes, Juliana; Vizzotto, Márcia


    Background: Camellia sinensis, the most consumed and popular beverages worldwide, and Eugenia uniflora, a Brazilian native species, have been already confirmed to have beneficial effects in the treatment of diabetes mellitus. However, their potential acting together against an enzyme linked to this pathology has never been exploited. Objective: The aim of this study was to evaluate the inhibitory properties of individual and combined ethanolic extracts of the leaves of C. sinensis and E. uniflora over alpha-glucosidase, a key digestive enzyme used on the Type 2 diabetes mellitus (T2DM) control. In addition, their inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) and peroxyl radicals was also assayed. Materials and Methods: Enzyme inhibition and antioxidant potential were assessed based on in vitro assays. Total phenolic compounds, carotenoids, and chlorophylls A and B were achieved using spectrophotometric methods. Results: E. uniflora was almost 40 times more active on alpha-glucosidase than C. sinensis and combined extracts showed a significant synergistic effect with an obtained IC50 value almost 5 times lower than the theoretical value. C. sinensis extract was twice more active than E. uniflora concerning DPPH•, in contrast, E. uniflora was almost 10 times more effective than C. sinensis on inhibition of peroxyl radicals with a significant synergistic effect for combined extracts. The extracts activities may be related with their phytochemicals, mainly phenolic compounds, and chlorophylls. Conclusion: Combined C. sinensis and E. uniflora ethanolic extracts showed synergistic effect against alpha-glucosidase and lipid peroxidation. These herbal combinations can be used to control postprandial hyperglycemia and can also provide antioxidant defenses to patients with T2DM. SUMMARY Alfa-glucosidase and antioxidant Interaction between Camellia sinensis L. Kuntze and Eugenia uniflora L. ethanolic extracts was investigated.Extracts showed

  5. Nutrient Content, Phytonutrient Composition, Alpha Amylase, Alpha Glucosidase Inhibition Activity and Antioxidant Activity of the Stoechospermum Marginatum Collected in Pre Monsoon Season

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    Reka Palanivel


    Full Text Available The objective of this study was to investigate the nutrient content, phytonutrient composition, physicochemical properties, alpha amylase and alpha glucosidase inhibition activity and antioxidant activity of the brown algae Stoechospermum marginatum collected from Gulf of Mannar, Tamil Nadu, India in pre monsoon season (June- September, 2015. Six and eight hours of ethanol and aqueous extract of Stoechospermum marginatum were used for phytonutrient screening, alpha amylase, alpha glucosidase inhibition activity and antioxidant activity. From the results of the study it is understood that Stoechospermum marginatum contain a high amount of carbohydrate, protein, crude fiber and phytonutrients like tannin, flavonoid, saponin, alkaloid, terpenoids, steroid and total phenolic content. The physicochemical properties namely Water absorption and Swelling power were very promising. Alpha amylase and alpha glucosidase inhibition activity was recorded to be high in both aqueous and ethanol extracts of eight hour extraction than in extracts taken from six hours extraction. Antioxidant activity was detected using DPPH, FRAP, beta carotene scavenging and H2O2 assay and found to have a high radical scavenging activity. Stoechospermum marginatum possess a valuable amount of total phenolic content and other phytonutrients and physicochemical properties, it may the reason for the potential inhibition of alpha amylase, alpha glucosidase and antioxidant activity. It is concluded from the study that the brown algae may be incorporated into foods to enhance their nutritional and therapeutic value.

  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


    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 c......DNA 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 coding region. The four...

  7. Insulin secretagogue, alpha-glucosidase and antioxidant activity of some selected spices in streptozotocin-induced diabetic rats. (United States)

    Patil, Swapnil Balasaheb; Ghadyale, Varsha Adhikrao; Taklikar, Shreehari Subhash; Kulkarni, Chaitanya Ramesh; Arvindekar, Akalpita Umesh


    Spices are extensively used to enhance the taste and flavor of foods and are known to possess several medicinal properties. Myristica fragrans, Parmelia perlata, Illicium verum, Trachyspermum copticum and Myristica malabarica, the commonly used spices in India were assessed for antidiabetic activity in streptozotocin induced diabetic rats. In the in vitro insulin secretion studies on isolated islets of Langerhans, M. fragrans, T. copticum and M. malabarica showed dose dependent insulin secretion. At 1 mg/ml, P. perlata showed significant in vitro alpha-glucosidase inhibitory activity with IC(50) value of 0.14 mg/ml followed by M. malabarica (0.64 mg/ml), I. verum (0.67 mg/ml), M. fragrans (0.85 mg/ml) and T. copticum (0.92 mg/ml). The DPPH free radical scavenging activity of the extracts at a concentration of 1 mg/ml was as M. malabarica (90.45%), M. fragrans (89.89%), I. verum (87.22%), P. perlata (76.70%) and T. copticum (38.14%). P. perlata showed the highest phenolic content (i.e., 118.5 mg gallic acid equivalents/g) followed by M. malabarica (84.13 mg gallic acid equivalents/g). M. malabarica showed the highest flavonoid content (i.e., 38.35 mg quercetin equivalents/g). Regular use of these spices may prevent postprandial rise in glucose levels through inhibition of intestinal alpha-glucosidase and may maintain blood glucose level through insulin secretagogue action.

  8. Alpha-glucosidase inhibitory and antioxidant activities of Vietnamese edible plants and their relationships with polyphenol contents. (United States)

    Mai, Truong Tuyet; Thu, Nghiem Nguyet; Tien, Pham Gia; Van Chuyen, Nguyen


    The prevention and treatment of non-communicable diseases by using the beneficial biological effects of polyphenolic plants have attracted increasing interest from nutritional scientists. The a-glucosidase inhibitory and antioxidant activities of aqueous and methanolic extracts from 28 common Vietnamese edible plants, comprising 4 groups (plants used for making drinks, edible wild vegetables, herbs, and dark green vegetables), were investigated in vitro. The polyphenol contents of these extracts were determined by the Folin-Ciocalteu method and calculated as catechin equivalents. The extracts from plants used for making drinks showed the highest activities for both a-glucosidase inhibition and as antioxidants, followed by edible wild vegetables, herbs, and dark green vegetables. Positive relationships among alpha-glucosidase inhibitory activities, antioxidant activities and polyphenol contents of these 28 edible plants were found in both aqueous and methanolic extracts. Four new promising materials that are similar to or better than guava leaf extract, including Syzygium zeylanicum, Cleistocalyx operculatus, Horsfieldia amygdalina and Careya arborea demonstrated high alpha-glucosidase inhibitory activity (93, 76, 68 and 67%, respectively) at the final concentration of 0.8 mg lyophilized material/mL solution and antioxidant activity (85, 87, 78 and 80%, respectively) at the final concentration of 30 pg lyophilized material/mL solution. These four edible plants contained significantly high polyphenol contents (equivalent to 251.7, 146.6, 136.6 and 168.6 mg of catechin/g dry weight, respectively). Thus, these four materials might be possible new sources of a-glucosidase inhibition and antioxidants suitable for use as functional foods in the future.

  9. 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


    .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......High-isoelectric-point (pI) alpha-glucosidase was purified 7, 300-fold from an extract of barley (Hordeum vulgare) malt by ammonium sulfate fractionation, ion-exchange, and butyl-Sepharose chromatography. The enzyme had high activity toward maltose (k(cat) = 25 s(-1)), with an optimum at pH 4......DNA 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 coding region. The four...

  10. [In-vitro study of the drug interactions between Miglitol, an alpha-glucosidase inhibitor, and adsorbents]. (United States)

    Amioka, Katsuo; Wada, Ikuo; Furuta, Yoshiyuki


    The interactions between miglitol, an alpha-glucosidase inhibitor, and six adsorbents (carbon spheres, cholestyramine, colestimide, sevelamer hydrochloride, calcium polystyrene sulfonate, and sodium polystyrene sulfonate) were investigated in vitro. Miglitol corresponding to the minimum dose and adsorbents corresponding to the maximum dose were incubated at 37 degrees C for 180 min in solutions of pH 1.2 (gastric pH condition) and pH 6.8 (enteric pH condition), with and without the presence of carbohydrates, which were added to observe the effects on food adsorption. The adsorption ratio of miglitol to carbon spheres was 13.6% and 0% in pH 1.2 solution and 86.4% and 5.0% in pH 6.8 solution without and with the presence of carbohydrates, respectively. Thus, the adsorption ratio was higher in pH 6.8 solution. Adsorption of miglitol to calcium polystyrene sulfonate was nearly the same, 15.0-21.9%, at both pH. The adsorption ratio of miglitol to sodium polystyrene sulfonate was 43.4% and 45.5%, respectively, in pH 1.2 solution without and with carbohydrates. In the pH 6.8 solutions, however, the respective adsorption ratios were low (5.2% and 11.3%). Miglitol did not adsorb to cholestyramine, sevelamer hydrochloride or colestimide under any pH condition examined. The above results suggest that miglitol adsorbs to carbon spheres and polystyrene sulfonic acid cation exchange resins. However, considering that miglitol is taken just before eating and thus exists in gastointestinal fluids together with food, and that the site of its effect is the upper small intestine, the interactions between miglitol and these adsorbents will most likely not be a problem.

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

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    David Mizael Ortíz-Martinez


    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.

  12. Oral delivery of Acid Alpha Glucosidase epitopes expressed in plant chloroplasts suppresses antibody formation in treatment of Pompe mice. (United States)

    Su, Jin; Sherman, Alexandra; Doerfler, Phillip A; Byrne, Barry J; Herzog, Roland W; Daniell, Henry


    Deficiency of acid alpha glucosidase (GAA) causes Pompe disease in which the patients systemically accumulate lysosomal glycogen in muscles and nervous systems, often resulting in infant mortality. Although enzyme replacement therapy (ERT) is effective in treating patients with Pompe disease, formation of antibodies against rhGAA complicates treatment. In this report, we investigated induction of tolerance by oral administration of GAA expressed in chloroplasts. Because full-length GAA could not be expressed, N-terminal 410-amino acids of GAA (as determined by T-cell epitope mapping) were fused with the transmucosal carrier CTB. Tobacco transplastomic lines expressing CTB-GAA were generated through site-specific integration of transgenes into the chloroplast genome. Homoplasmic lines were confirmed by Southern blot analysis. Despite low-level expression of CTB-GAA in chloroplasts, yellow or albino phenotype of transplastomic lines was observed due to binding of GAA to a chloroplast protein that has homology to mannose-6 phosphate receptor. Oral administration of the plant-made CTB-GAA fusion protein even at 330-fold lower dose (1.5 μg) significantly suppressed immunoglobulin formation against GAA in Pompe mice injected with 500 μg rhGAA per dose, with several-fold lower titre of GAA-specific IgG1 and IgG2a. Lyophilization increased CTB-GAA concentration by 30-fold (up to 190 μg per g of freeze-dried leaf material), facilitating long-term storage at room temperature and higher dosage in future investigations. This study provides the first evidence that oral delivery of plant cells is effective in reducing antibody responses in ERT for lysosomal storage disorders facilitating further advances in clinical investigations using plant cell culture system or in vitro propagation. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  13. 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.


    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...

  14. 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*


    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.

  15. 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


    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.

  16. Effect of alpha-glucosidase inhibitor on exocrine and endocrine pancreatic function in rats fed a high-carbohydrate diet consisting of sucrose or glucose. (United States)

    Otsuki, M; Okabayashi, Y; Ohki, A; Suehiro, I; Baba, S


    The effect of the alpha-glucosidase inhibitor acarbose on pancreatic exocrine and endocrine function was studied using the isolated perfused pancreata prepared from rats fed a normal (control diet) or an acarbose-containing sucrose- (ACS diet) or glucose-supplemented diet (ACG diet) for 10 days. Pancreatic amylase and insulin contents in rats fed the ACS diet were significantly decreased compared with those in rats with the control diet. Rats fed the ACG diet, however, had normal enzyme and hormone contents. Basal and cerulein-stimulated flow rates of pancreatic juice in rats with the ACS or ACG diet were similar to those in rats fed the control diet, suggesting that the pancreata from rats treated with acarbose have normal sensitivity and responsiveness to cerulein. On the other hand, cerulein-stimulated amylase output was significantly decreased in rats with the ACS diet, but was normal in rats with the ACG diet. Insulin secretion to both glucose and cerulein stimulation in rats fed the ACS diet was reduced by approximately 55% compared with the control rats. On the other hand, rats fed the ACG diet showed normal insulin secretion to glucose stimulation, although the insulin response to cerulein stimulation was reduced by 30%. These results suggest that the addition of acarbose to the sucrose-rich diet decreases the secretory responsiveness of amylase to cerulein stimulation and that of insulin to both glucose and cerulein stimulation. All these alterations, except the sensitivity of B cells to cerulein, can be normalized by replacing sucrose with glucose.

  17. Properties and stabilization of an extracellular alpha-glucosidase from the extremely thermophilic archaebacteria Thermococcus strain AN1: enzyme activity at 130 degrees C. (United States)

    Piller, K; Daniel, R M; Petach, H H


    An extracellular alpha-glucosidase from the thermophilic archaebacterium Thermococcus strain AN1 was purified 875-fold in five steps (Hiload Q-Sepharose, phenyl Sepharose, HPHT-hydroxyapatite, gel filtration and Mono Q chromatography) with a yield of 4%. It is a monomer with a molecular mass of about 60 kDa and a pI around 5. At 98 degrees C, the purified enzyme in buffer has a half-life around 35 min, which is increased to around 215 min in presence of 1% (w/v) dithiothreitol and 1% (w/v) BSA. Dithiothreitol (1%, w/v) and BSA (0.4%, w/v) also substantially increase the enzyme activity. The Km at 75 degrees C is 0.41 mM with pNP-alpha-D-glucopyranoside as substrate. The substrate preference of the enzyme is: pNP-alpha-D-glucoside > nigerose > panose > palatinose > isomaltose > maltose and turanose. No activity was found against starch, pullulan, amylose, maltotriose, maltotetraose, isomaltotriose, cellobiose and beta-gentiobiose. A variety of techniques including immobolization (e.g., on epoxy and glass beads), chemical modification (cross- and cocross-linking) and the use of additives (including polyhydroxylic molecules, BSA, salts, etc.) were applied to enhance stability at temperatures above 100 degrees C. The half-life could be increased from about 4 min at 100 degrees C to 30-60 min at 130 degrees C in presence of 90% (w/v) sorbitol, 1% (w/v) dithiothreitol and 1% (w/v) BSA, and by cross-linking with BSA in the presence of 90% (w/v) sorbitol. The stabilized enzyme showed good activity at 130 degrees C.

  18. The loss of a polymorphic glycosylation site caused by Thr-927 [yields] Ile is linked to a second polymorphic Val-816 [yields] Ile substitution in lysosomal [alpha]-glucosidase of American blacks

    Energy Technology Data Exchange (ETDEWEB)

    Hermans, M.M.P.; Oostra, B.A.; Reuser, A.J.J. (Erasmus Univ., Rotterdam (Netherlands)); Svetkey, L.P.; Chen, Y.T. (Duke Univ., Durham, NC (United States))


    Inherited deficiency of the lysosomal hydrolase [alpha]-glucosidase (acid maltase) causes lysosomal accumulation of glycogen, a condition known as glycogen storage disease type II (GSD II). The clinical phenotype is heterogeneous, and heterogeneity also exists at the molecular level. Point mutations were recently identified in two cases of severe infantile and one case of adult GSD II. In addition to mutations with a deleterious effect on enzyme function, several polymorphisms have been documented. Of note are those polymorphisms that relate to racial differences, but they can pose a problem when mutant alleles are being analyzed. An example of this was an American black patient with an adult form of GSD II (GM1935). Mutation analysis revealed three amino acid substitutions that were not encountered in the Caucasian population. The three substitutions were Asp-645 [r arrow] Glu (exon 14), Val-816 [r arrow] Ile (exon 17), and Thr-927 [r arrow] Ile (exon 19), and they were linked to the same allele . The Thr-927 [r arrow] Ile substitution deleting the most carboxyl-terminal N-linked glycosylation site was found to have no effect on enzyme function, in agreement with the studies on the role of the individual glycosylation sites. There were different opinions, however, with respect to the effect of the other two substitutions. The Val-816 [r arrow] Ile substitution was reported by Martiniuk et al. to cause the lysosomal [alpha]-glucosidase deficiency, but the authors concluded on the basis of more extensive studies that the Asp-645[r arrow] Glu substitution was actually the deleterious mutation and the Val-816 [r arrow] Ile substitution a polymorphism. 8 refs., 1 fig.

  19. Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study. (United States)

    Chan, Cheng-Wei; Yu, Chu-Leng; Lin, Jiunn-Cherng; Hsieh, Yu-Cheng; Lin, Che-Chen; Hung, Chen-Ying; Li, Cheng-Hung; Liao, Ying-Chieh; Lo, Chu-Pin; Huang, Jin-Long; Lin, Ching-Heng; Wu, Tsu-Juey


    Metformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA) remains unclear. We investigated the cardiovascular risk of various ADAs used as add-on medication to metformin in T2DM patients from a nationwide cohort. T2DM patients using different add-on oral ADAs after an initial metformin therapy of > 90 days were identified from the Taiwan National Health Insurance Database. Five classes of ADAs, including sulphonylureas (SU), glinides, thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), and dipeptidyl peptidase-4 inhibitors (DPP-4I) were selected for analysis. The reference group was the SU added to metformin. Patients were excluded if aged cardiovascular event (MACE) including ACS, ischemic/hemorrhagic stroke, and death. A Cox regression model was used to estimate the hazard ratio (HR) for MACE. A total of 26,742 patients receiving their add-on drug to metformin of either SU (n = 24,277), glinides (n = 962), TZD (n = 581), AGI (n = 808), or DPP-4I (n = 114) were analyzed. After a mean follow-up duration of 6.6 ± 3.4 years, a total of 4775 MACEs occurred. Compared with the SU+metformin group (reference), the TZD+metformin (adjusted HR: 0.66; 95% CI 0.50-0.88, p = 0.004) and AGI+metformin (adjusted HR: 0.74; 95% CI 0.59-0.94, p = 0.01) groups showed a significantly lower risk of MACE. Both TZD and AGI, when used as an add-on drug to metformin were associated with lower MACE risk when compared with SU added to metformin in this retrospective cohort study. Trial registration CE13152B-3. Registered 7 Mar, 2013, retrospectively registered.

  20. 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


    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

  1. A cis-acting region in the N-methyl-D-aspartate R1 3′-untranslated region interacts with the novel RNA-binding proteins beta subunit of alpha glucosidase II and annexin A2: effect of chronic ethanol exposure in vivo (United States)

    Anji, Antje; Kumari, Meena


    A cis-acting region, Δ4, located in the 3′-untranslated region of N-methyl-D-aspartate R (NR) mRNA interacts with several trans-acting proteins present in polysomes purified from fetal cortical neurons. Chronic ethanol exposure of fetal cortical neurons increases Δ4 RNA–protein interactions. This increased interaction is due to an increase in one of the Δ4-binding trans-acting proteins identified as beta subunit of alpha glucosidase II (GIIβ). In this study, we examined whether ethanol-mediated regulation of NR1 mRNA in vivo is similar to that in vitro and whether Δ4–trans interactions are important for ethanol-mediated NR1 mRNA stability. Our data show that polysomal proteins from adult mouse cerebral cortex (CC) formed a complex with Δ4 RNA, suggesting the presence of NR1 mRNA-binding trans-acting proteins in CC polysomes. The intensity of the Δ4 RNA–protein complex was increased with polysomes from chronic ethanol-exposed CC. The Δ4 RNA–protein complex harbored GIIβ and a second trans-acting protein identified as annexin A2 (AnxA2). Ethanol-sensitive GIIβ was upregulated by 70% in ethanol-exposed CC. Heparin, a known binding partner of AnxA2, inhibited Δ4 RNA–protein complex formation. Transient transfection studies using chimeric constructs with and without the Δ4 region revealed that cis–trans interactions are important for ethanol-mediated stability of NR1 mRNA. Furthermore, our data highlight, for the first time, the presence of a binding site on the 3′-untranslated region of NR1 mRNA for AnxA2 and demonstrate the regulation of NR1 mRNA by AnxA2, GIIβ and a third NR1 mRNA-binding protein, which is yet to be identified. PMID:21995826

  2. An alpha-glucosidase inhibitory activity of thermostable lectin ...

    African Journals Online (AJOL)

    A novel GI lectin was enriched from the seeds of the Djenkol bean, A. jiringa, to apparent homogeneity by 90% saturation ammonium sulfate precipitation and Con A-Sepharose affinity column chromatography. This lectin had an IC50 value for GI activity of 0.031 „b 0.02 mg/ml, an estimated molecular mass of 35.7 kDa, ...

  3. Alpha-Glucosidase Inhibitory and Antioxidant Activity of Solvent ...

    African Journals Online (AJOL)

    50603 Kuala Lumpur, 5Department of Biosciences and Health Sciences, Faculty of Biosciences and Medical Engineering,. Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, ... fruit of Typha domingensis. Methods: Extracts were prepared using hexane, chloroform, ethyl acetate, acetone (AE), methanol, and water.

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

    NARCIS (Netherlands)

    Hout, J.M. van den; Kamphoven, J.H.; Winkel, L.P.; Arts, W.F.M.; Klerk, J.B.C. de; Loonen, M.C.B.; Vulto, A.G.; Cromme-Dijkhuis, A.H.; Weisglas-Kuperus, N.; Hop, W.C.J.; Hirtum, H. van; Diggelen, O.P. van; Boer, M. de; Kroos, M.A.; Doorn, P.A. van; Voort, E.I. van der; Sibbles, B.; Corven, E.J. van; Brakenhoff, J.P.; Hove, J.L. van; Smeitink, J.A.M.; Jong, G. de; Reuser, A.J.J.; Ploeg, A.T. van der


    OBJECTIVE: 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 obtained at relatively low costs,

  5. 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. van der 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)


    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

  6. Role of alpha-glucosidase in the fermentable sugar composition of sorghum malt mashes

    CSIR Research Space (South Africa)

    Taylor, JRN


    Full Text Available The cause of the high glucose to maltose ratio in sorghum malt worts was studied. Mashing temperature and pH strongly affected both the amount of glucose and the proportion of glucose relative to total fermentable sugars. The relative proportion...

  7. HPLC profile, in vitro alpha-amylase, alpha-glucosidase inhibitory ...

    African Journals Online (AJOL)

    High Performance Liquid Chromatography profile revealed Resorcinol/Catechol to be one of the phenolics detected and may be responsible for GSEALE's inhibition of α-amylase and α-glucosidase and antioxidant properties. This shows that GS can probably be used for antidiabetic purpose due to significant antioxidant ...

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

    Directory of Open Access Journals (Sweden)

    Malinee Wongnawa


    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.

  9. A New alpha-Glucosidase Inhibitor, 10-Hydroxy-8(E)-Octadecenoic Acid (United States)

    In our continuous effort to screen natural products for their anti-microbial and enzyme inhibitor activities, we found that 10-Hydroxy-8(E)-Octadecenoic acid (HOD) exhibited strong anti- a-glucosidase (EC activity. HOD is an intermediate in the bioconversion of oleic acid to 7,10-dihydrox...

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


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


    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...

  11. Cuparane sesquiterpenes from Laurencia natalensis Kylin as inhibitors of alpha-glucosidase, dipeptidyl peptidase IV and xanthine oxidase

    Czech Academy of Sciences Publication Activity Database

    Rengasamy, K.R.R.; Poštová Slavětínská, Lenka; Kulkarni, M. G.; Stirk, W. A.; Van Staden, J.


    Roč. 25, Jul (2017), s. 178-183 ISSN 2211-9264 Institutional support: RVO:61388963 Keywords : 1-deoxyalgoane * dipeptidyl peptidase IV * diabetes * gout * Laurencia natalensis Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 3.994, year: 2016

  12. Antioxidant rich grape pomace extract suppresses postprandial hyperglycemia in diabetic mice by specifically inhibiting alpha-glucosidase

    Directory of Open Access Journals (Sweden)

    Hogan Shelly


    Full Text Available Abstract Background Postprandial hyperglycemia is an early defect of type 2 diabetes and one of primary anti-diabetic targets. Treatment of postprandial hyperglycemia can be achieved by inhibiting intestinal α-glucosidase, the key enzyme for oligosaccharide digestion and further glucose absorption. Grape pomace is winemaking byproduct rich in bioactive food compounds such as phenolic antioxidants. This study evaluated the anti-diabetic potential of two specific grape pomace extracts by determining their antioxidant and anti-postprandial hyperglycemic activities in vitro and in vivo. Methods The extracts of red wine grape pomace (Cabernet Franc and white wine grape pomace (Chardonnay were prepared in 80% ethanol. An extract of red apple pomace was included as a comparison. The radical scavenging activities and phenolic profiles of the pomace extracts were determined through the measurement of oxygen radical absorbance capacity, DPPH radical scavenging activity, total phenolic content and flavonoids. The inhibitory effects of the pomace extracts on yeast and rat intestinal α-glucosidases were determined. Male 6-week old C57BLKS/6NCr mice were treated with streptozocin to induce diabetes. The diabetic mice were then treated with vehicle or the grape pomace extract to determine whether the oral intake of the extract can suppress postprandial hyperglycemia through the inhibition of intestinal α-glucosidases. Results The red grape pomace extract contained significantly higher amounts of flavonoids and phenolic compounds and exerted stronger oxygen radical absorbance capacity than the red apple pomace extract. Both the grape pomace extracts but not the apple pomace extract exerted significant inhibition on intestinal α-glucosidases and the inhibition appears to be specific. In the animal study, the oral intake of the grape pomace extract (400 mg/kg body weight significantly suppressed the postprandial hyperglycemia by 35% in streptozocin-induced diabetic mice following starch challenge. Conclusion This is the first report that the grape pomace extracts selectively and significantly inhibits intestinal α-glucosidase and suppresses postprandial hyperglycemia in diabetic mice. The antioxidant and anti-postprandial hyperglycemic activities demonstrated on the tested grape pomace extract therefore suggest a potential for utilizing grape pomace-derived bioactive compounds in management of diabetes.

  13. Orthosiphol A from the aerial parts of Orthosiphon aristatus is putatively responsible for hypoglycemic effect via alpha-glucosidase inhibition. (United States)

    Damsud, Thanakorn; Grace, Mary H; Adisakwattana, Sirichai; Phuwapraisirisan, Preecha


    An infusion of Orthosiphon aristatus has long been used for diabetes therapy; however, the active principles remained unknown. Herein, we report the identification of the putative agents responsible for this antidiabetic activity using an a-glucosidase-guided isolation. Four flavonoids named sinensetin (1), salvigenin (2), tetramethylscutellarein (3) and 3,7,4'-tri-O-methylkaempferol (4), together with a diterpenoid named orthosiphol A (5), were characterized, based on analysis of their spectroscopic data. Flavonoids 3 and 4 inhibited yeast a-glucosidase with IC,o values of 6.34 and 0.75 mM, respectively, whereas orthosiphol A (5) selectively inhibited intestinal maltase with an IC5o, value of 6.54 mM. A kinetic investigation of 5 indicated that it retarded maltase function in a noncompetitive manner.

  14. Increased glucose metabolism and alpha-glucosidase inhibition in Cordyceps militaris water extract-treated HepG2 cells (United States)

    Kim, Dae Jung; Kang, Yun Hwan; Kim, Kyoung Kon; Kim, Tae Woo; Park, Jae Bong


    BACKGROUND/OBJECTIVES Recent living condition improvements, changes in dietary habits, and reductions in physical activity are contributing to an increase in metabolic syndrome symptoms including diabetes and obesity. Through such societal developments, humankind is continuously exposed to metabolic diseases such as diabetes, and the number of the victims is increasing. This study investigated Cordyceps militaris water extract (CMW)-induced glucose uptake in HepG2 cells and the effect of CMW treatment on glucose metabolism. MATERIALS/METHODS Colorimetric assay kits were used to determine the glucokinase (GK) and pyruvate dehydrogenase (PDH) activities, glucose uptake, and glycogen content. Either RT-PCR or western blot analysis was performed for quantitation of glucose transporter 2 (GLUT2), hepatocyte nuclear factor 1 alpha (HNF-1α), phosphatidylinositol 3-kinase (PI3k), protein kinase B (Akt), phosphorylated AMP-activated protein kinase (pAMPK), phosphoenolpyruvate carboxykinase, GK, PDH, and glycogen synthase kinase 3 beta (GSK-3β) expression levels. The α-glucosidase inhibitory activities of acarbose and CMW were evaluated by absorbance measurement. RESULTS CMW induced glucose uptake in HepG2 cells by increasing GLUT2 through HNF-1α expression stimulation. Glucose in the cells increased the CMW-induced phosphorylation of AMPK. In turn, glycolysis was stimulated, and glyconeogenesis was inhibited. Furthermore, by studying the mechanism of action of PI3k, Akt, and GSK-3β, and measuring glycogen content, the study confirmed that the glucose was stored in the liver as glycogen. Finally, CMW resulted in a higher level of α-glucosidase inhibitory activity than that from acarbose. CONCLUSION CMW induced the uptake of glucose into HepG2 cells, as well, it induced metabolism of the absorbed glucose. It is concluded that CMW is a candidate or potential use in diabetes prevention and treatment. PMID:28584574

  15. Lactic Acid Bacteria Producing Inhibitor of Alpha Glucosidase Isolated from Ganyong (Canna Edulis) and Kimpul (Xanthosoma sagittifolium) (United States)

    Nurhayati, Rifa; Miftakhussolikhah; Frediansyah, Andri; Lailatul Rachmah, Desy


    Type 2 diabetes is a disease that caused by the failure of insulin secretion by the beta cells of the pancreas and insulin resistance in peripheral levels. One therapy for diabetics is by inhibiting the activity of α-glucosidase. Lactic acid bacteria have the ability to inhibit of α-glucosidase activity. The aims of this research was to isolation and screening of lactic acid bacteria from ganyong tuber (Canna Edulis) and kimpul tuber (Xanthosoma sagittifolium), which has the ability to inhibit the activity of α-glucosidase. Eightteen isolates were identified as lactic acid bacteria and all of them could inhibit the activity of α-glukosidase. The GN 8 isolate was perform the highest inhibition acivity.

  16. Antioxidant, anti-alpha-glucosidase and pancreatic beta-cell protective effects of methanolic extract of Ensete superbum Cheesm seeds

    Directory of Open Access Journals (Sweden)

    Solomon Habtemariam


    Conclusions: The reputed antidiabetic therapeutic uses of the seeds extract of E. superbum may be justified on the basis of inhibition of carbohydrate enzymes, antioxidant effects and pancreatic β-cell protection.

  17. Combination of alpha-glucosidase inhibitor and ribavirin for the treatment of Dengue virus infection in vitro and in vivo (United States)

    Chang, Jinhong; Schul, Wouter; Butters, Terry D.; Yip, Andy; Liu, Boping; Goh, Anne; Lakshminarayana, Suresh B.; Alonzi, Dominic; Reinkensmeier, Gabriele; Pan, Xiaoben; Qu, Xiaowang; Weidner, Jessica M.; Wang, Lijuan; Yu, Wenquan; Borune, Nigel; Kinch, Mark A.; Rayahin, Jamie E.; Moriarty, Robert; Xu, Xiaodong; Shi, Pei-Yong; Guo, Ju-Tao; Block, Timothy M.


    Cellular α-glucosidases I and II are enzymes that sequentially trim the three terminal glucoses in the N-linked oligosaccharides of viral envelope glycoproteins. This process is essential for the proper folding of viral glycoproteins and subsequent assembly of many enveloped viruses, including dengue virus (DENV). Imino sugars are substrate mimics of α-glucosidases I and II. In this report, we show that two oxygenated alkyl imino sugar derivatives, CM-9-78 and CM-10-18, are potent inhibitors of both α-glucosidases I and II in vitro and in treated animals, and efficiently inhibit DENV infection of cultured human cells. Pharmacokinetic studies reveal that both compounds are well tolerated at doses up to 100mg/kg in rats and have favorable pharmacokinetic properties and bioavailability in mice. Moreover, we showed that oral administration of either CM-9-78 or CM-10-18 reduces the peak viremia of DENV in mice. Interestingly, while treatment of DENV infected mice with ribavirin alone did not reduce the viremia, combination therapy of ribavirin with sub-effective dose of CM-10-18 demonstrated a significantly enhanced antiviral activity, as indicated by a profound reduction of the viremia. Our findings thus suggest that combination therapy of two broad-spectrum antiviral agents may provide a practically useful approach for the treatment of DENV infection. PMID:21073903

  18. Inhibitory effect of leaf extract of Newbouldia laevis on the metabolic activities of alpha-glucosidase and alpha-amylase

    Directory of Open Access Journals (Sweden)

    Oyetunji T. Kolawole


    Full Text Available In this study, the effect of ethanol extract of the leaves of Newbouldia laevis on the activity of α-amylase and α-glucosidase was investigated. Inhibitory effect of N. laevis extract on α-glucosidase was tested in vitro using baker’s yeast α-glucosidase and rat intestinal α-glucosidase while α-amylase inhibitory effect was assayed using rat pancreatic α-amylase. α-Glucosidase inhibitory effect of the extract was also tested in vivo in diabetic and non-diabetic rats. N. laevis extract exhibited good α-glucosidase inhibitory activity in vitro with IC50 values of 2.2 µg/mL and 43.5 µg/mL for baker’s yeast and rat intestinal α-glucosidase respectively. The extract also inhibited rat pancreatic α-amylase activity with IC50 value of 58.7 µg/mL. In both diabetic and non-diabetic rats, N. laevis extract caused a significant reduction in postprandial blood glucose level after oral sucrose load. The results of this study indicate that N. laevis extract exerts its glucose-lowering effect through inhibition of α-glucosidase and α-amylase.

  19. Preliminary phytochemical screening and alpha-glucosidase inhibitory activity of Philippine taro (Colocasia esculenta (L.) Schott var. PSB-VG #9) (United States)

    Lebosada, Richemae Grace R.; Librando, Ivy L.


    The study was conducted to determine the anti-hyperglycemic property in terms of α-glucosidase inhibitory activity of the various parts (corm, leaf and petiole) of Colocasia esculenta (L.) Schott var. PSB-VG #9. Each of the plant parts were extracted with 95% ethanol and concentrated using a rotary evaporator at 40 °C. The crude extracts were screened for the presence of alkaloids, flavonoids, glycosides and saponins using Thin Layer Chromatography. The α-glucosidase inhibitory activity of the crude extracts (50 mg/L) were assayed spectrophotometrically using a microplate reader. The results of the phytochemical screening revealed the presence of alkaloids, flavonoids, and saponins in the leaf part while flavonoids and saponins were detected in the petiole and only saponins were present in the corm. The assay showed that the percentage α-glucosidase inhibition of the 50 mg/L ethanolic crude extract of the corm, leaves and petiole of C. esculenta are 68.03, 71.64 and 71.39%, respectively. Statistical analysis shows significant differences in the α-glucosidase inhibition among the various plant parts. It can be concluded that the ethanolic crude extracts of the different parts of C. esculenta (L.) Schott var. PSB-VG #9 exhibited inhibitory activity against α-glucosidase and the presence of phytochemicals like alkaloids, flavonoids and saponins may have contributed greatly to the inhibitory activity of the plant extract and can be further subjected for isolation of the therapeutically active compounds with antidiabetes potency.

  20. In vitro anti-diabetic activity of flavonoids and pheophytins from Allophylus cominia Sw . on PTP1B, DPPIV, alpha-glucosidase and alpha-amylase enzymes. (United States)

    Semaan, D G; Igoli, J O; Young, L; Marrero, E; Gray, A I; Rowan, E G


    Ethno-botanical information from diabetic patients in Cuba led to the identification of Allophylus cominia as a possible source of new drugs for the treatment of type 2 diabetes mellitus (T2-DM). Chemical characterization of the extracts from A. cominia was carried out using chromatographic and spectroscopic methods. The extracts were tested for their activity on PTP1B, DPPIV, α-glucosidase enzymes and α-amylase. The flavonoid rich fractions from A. cominia inhibited DPPIV enzyme (75.3±2.33%) at 30µg/ml and produced a concentration-dependent inhibition against DPPIV with a Ki value of 2.6µg/ml. At 30µg/ml, flavonoids and pheophytins extracts significantly inhibited PTP1B enzyme (100±2.6% and 68±1% respectively). The flavonoids, pheophytin A and pheophytin B fractions showed significant concentration-dependent inhibition against PTP1B with Ki values of 3µg/ml, 0.64µg/ml and 0.88µg/ml respectively. At 30µg/ml, the flavonoid fraction significantly inhibited α-glucosidase enzyme (86±0.3%) in a concentration-dependent pattern with a Ki value of 2µg/ml. None of the fractions showed significant effects on α-amylase. Fatty acids, tannins, pheophytins A and B, and a mixture of flavonoids were detected in the methanolic extract from A. cominia. The identified flavonoids were mearnsitrin, quercitrin, quercetin-3-alloside, and naringenin-7-glucoside. The pharmacological effects of the extracts from A. cominia earlier observed in experimental diabetic models was confirmed in this study. Thus a new drug or formulation for the treatment of T2-DM could be developed from A. cominia. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  1. Differential effects of sugars and the alpha-glucosidase inhibitor acarbose (Bay g 5421) on satiety in the Zucker obese rat. (United States)

    Maggio, C A; Decarr, L B; Vasselli, J R


    To examine the satiety responses of Zucker obese and lean rats to simple sugars, adult male rats were given equicaloric intragastric infusions of fructose, glucose, and sucrose. All three sugars reduced the short-term intakes of both genotypes, although no reliable between-genotype differences in the satiety effects of the sugars were observed. Within each genotype, fructose had a larger satiety effect than sucrose. To examine a potential basis for the observed effects, rats were given sucrose infusions containing the intestinal glucosidase inhibitor acarbose (Bay g 5421). In obese rats, addition of a low dose of acarbose increased the satiety effect of sucrose infusion. Delaying carbohydrate absorption via acarbose administration may alter gastrointestinal and/or postabsorptive satiety processes, and may prove useful as a probe for investigating the nature of satiety signals.

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


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


    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...

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

    Directory of Open Access Journals (Sweden)

    Kamenan A.


    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.

  4. 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


    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...... to approximately 25 pmol/l, P = 0.37) and integrated responses of GLP-1 (P = 0.37) were not changed significantly by acarbose treatment. Postprandial plasma glucose concentrations (P concentrations of insulin and C...

  5. Drug: D09779 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09779 Drug Emiglitate (JAN/INN) ... C17H25NO7 D09779.gif ... Antidiabetic agent ... DG01...663 ... alpha-Glucosidase inhibitor ... DG01803 ... Antidiabetic, alpha-glucosidase inhibitor Unclassified ... DG02044 ... Hypoglycemics ... DG01803 ... Antidiabetic, alpha-glucosidase inhibitor ... GAA [HSA:2548] [KO:K12316]; GANC [HS

  6. Drug: D01665 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01665 Drug Voglibose (JP17/USAN/INN); Basen (TN) ... C10H21NO7 D01665.gif ... Antidiabetic... agent ... DG01663 ... alpha-Glucosidase inhibitor ... DG01803 ... Antidiabetic, alpha-glucosidase inhibitor Uncla...ssified ... DG02044 ... Hypoglycemics ... DG01803 ... Antidiabetic, alpha-glucosidase inhibitor Therapeutic category: 3

  7. Drug: D00625 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00625 Drug Miglitol (JP17/USAN/INN); Glyset (TN) ... C8H17NO5 D00625.gif ... Antidiabetic... agent ... DG01663 ... alpha-Glucosidase inhibitor ... DG01803 ... Antidiabetic, alpha-glucosidase inhibitor Unclas...sified ... DG02044 ... Hypoglycemics ... DG01803 ... Antidiabetic, alpha-glucosidase inhibitor Same as: C07708 Therapeu

  8. Drug: D03342 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03342 Drug Camiglibose (USAN) ... (C13H25NO9)2. 3H2O D03342.gif ... Antidiabetic agen...t ... DG01663 ... alpha-Glucosidase inhibitor ... DG01803 ... Antidiabetic, alpha-glucosidase inhibitor Unclassified ... D...G02044 ... Hypoglycemics ... DG01803 ... Antidiabetic, alpha-glucosidase inhibitor ... CAS: 132438-21-2 PubChem: 17397492 LigandBox: D03342 ...

  9. Gene : CBRC-CJAC-01-0177 [SEVENS

    Lifescience Database Archive (English)


  10. A Rare Case of Benign Pneumatosis Intestinalis with Portal Venous Gas and Pneumoperitoneum Induced by Acarbose. (United States)

    Rottenstreich, Amihai; Agmon, Yahel; Elazary, Ram


    Alpha glucosidase inhibitors have been shown to be associated with pneumatosis intestinalis (PI) in recent reports. We herein report the case of a 73-year old man who received treatment with an alpha glucosidase inhibitor (acarbose) and presented with acute abdomen. A computed tomography scan demonstrated PI in addition to intrahepatic portal air and pneumoperitoneum. During exploratory laparotomy, we found no evidence of hollow organ perforation or bowel necrosis. The patient recovered after conservative treatment with cessation of the alpha glucosidase inhibitor. This is the first report to describe the combination of PI with portal venous gas and pneumoperitoneum caused by an alpha-glucosidase inhibitor.

  11. Dgroup: DG01803 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG01803 DGroup Antidiabetic, alpha-glucosidase inhibitor -bose ... D00216 ... Acarbose (...e (USAN) D09779 ... Emiglitate (JAN/INN) Antidiabetic agent ... DG01663 ... alpha-Glucosidase inhibitor Unclassified ... DG02044 ... Hypoglycemics ATC code: A10BF Antidiabetics GAA [HSA:2548] [KO:K12316] GANC [HSA:2595] [KO:K12317] MGAM [HSA:8972] [KO:K12047] ...

  12. Drug: D00216 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available etic agent ... DG01663 ... alpha-Glucosidase inhibitor ... DG01803 ... Antidiabetic, alpha-glu...cosidase inhibitor Unclassified ... DG02044 ... Hypoglycemics ... DG01803 ... Antidiabetic, alpha-glucosidase inhibitor... D00216 Drug Acarbose (JAN/USAN/INN); Precose (TN) ... C25H43NO18 D00216.gif ... Actinoplanes [TAX:1865] Antidiab

  13. Dgroup: DG01663 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG01663 DGroup alpha-Glucosidase inhibitor -bose, -glustat ... DG01803 ... Antidiabetic, ... D09605 ... Duvoglustat (USAN/INN) ... D09606 ... Duvoglustat hydrochloride (USAN) Antidiabetic agent ... alpha-glucosidase [KO:K12316 K12317 K12047] ...

  14. Cloning and characterization of two a-glucosidases from Bifidobacterium adolescentis DSM20083.

    NARCIS (Netherlands)

    Broek, van den L.A.M.; Struijs, K.; Verdoes, J.C.; Beldman, G.; Voragen, A.G.J.


    Two alpha-glucosidase encoding genes (aglA and aglB) from Bifidobacterium adolescentis DSM 20083 were isolated and characterized. Both alpha-glucosidases belong to family 13 of the glycosyl hydrolases. Recombinant AglA (EC and AglB (EC, expressed in Escherichia coli, showed high

  15. ORF Alignment: NC_004307 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_004307 gi|23465117 >1g5aA 80 628 2 589 5e-59 ... gb|AAL05573.1| alpha-glucosidase [Bifidobacterium adolesce...ntis] ... Length = 588 ... Query: 1 ... MTANNLNDDWWKQAVVYQIYPRSFKDVNGDGLGDIAGVTEK

  16. Drug treatment of type 2 diabetes mellitus in patients for whom metformin is contraindicated [Corrigendum

    Directory of Open Access Journals (Sweden)

    Irons BK


    Full Text Available Irons BK, Minze MG. Drug treatment of type 2 diabetes mellitus in patients for whom metformin is contraindicated. Diabetes Metab Syndr Obes. 2014;7:15–24.There is an error in the text on page 19:“Alpha-glucosidase inhibitors are infrequently used in the treatment of T2DM.3 These agents competitively inhibit the absorption of alpha-glucosidase along the brush border of the small intestine, which slows gut absorption of carbohydrates and ultimately reduces post-prandial blood glucose.34–36” should read as “Alpha-glucosidase inhibitors are infrequently used in the treatment of T2DM.3 These agents competitively inhibit the degradation of complex carbohydrates along the brush border of the small intestine, which slows gut absorption of metabolized carbohydrates and ultimately reduces post-prandial blood glucose.34–36”Read the original article

  17. 72 - 80_Aminu_HPLC1

    African Journals Online (AJOL)


    Glucose itself, as well as its metabolites, is known to react with hydrogen peroxide in the presence of iron and copper ions to form hydroxyl radical and subsequent generation of MDA as observed in this study. The present study indicated that the plant extracts produced a better alpha-glucosidase enzyme inhibition. (IC50.

  18. Different sucrose-isomaltase response of Caco-2 cells to glucose and maltose suggests dietary maltose sensing (United States)

    Using the small intestine enterocyte Caco-2 cell model, sucrase-isomaltase (SI, the mucosal alpha-glucosidase complex) expression and modification were examined relative to exposure to different mono- and disaccharide glycemic carbohydrates. Caco-2/TC7 cells were grown on porous supports to post-con...

  19. Ionic liquids as cosolvents for glycosylation by sucrose phosphorylase: balancing acceptor solubility and enzyme stability

    Czech Academy of Sciences Publication Activity Database

    De Winter, K.; Verlinden, K.; Křen, Vladimír; Weignerová, Lenka; Soetaert, W.; Desmet, T.


    Roč. 15, č. 7 (2013), s. 1949-1955 ISSN 1463-9262 R&D Projects: GA MŠk(CZ) 7E11011 Institutional support: RVO:61388971 Keywords : DISACCHARIDE PHOSPHORYLASES * THERMAL-STABILITY * ALPHA-GLUCOSIDASE Subject RIV: CE - Biochemistry Impact factor: 6.852, year: 2013

  20. Author Details

    African Journals Online (AJOL)

    Effects of aqueous extract of Allium cepa (red onion) on ovalbumininduced allergic asthma in wistar rats. Abstract PDF · Vol 10, No 1 (2017) - Articles HPLC profile, in vitro alpha-amylase, alpha-glucosidase inhibitory and antioxidant activities of Gymnema sylvestre ethyl acetate leaf extract. Abstract PDF. ISSN: 2006-6996.

  1. Comparisons of modern United States and Canadian malting barley cultivars with those from pre-Prohibition: II. Amylolytic enzyme activities and thermostabilities (United States)

    United States and Canadian pre-Prohibition and modern elite malting barley cultivars were evaluated for activities of alpha-amylase, beta-amylase, alpha-glucosidase and limit dextrinase over the course of Congress mashing to determine the changes in activities and thermostabilities since the end of ...

  2. Author Details

    African Journals Online (AJOL)

    Aliero, AA. Vol 19, No 1 (2011) - Articles Evaluation of Nutrient and Anti-nutrient Contents of Parkia biglobosa (L.) Flower Abstract PDF · Vol 19, No 2 (2011) - Articles Phytochemical Screening, Polyphenolic Content and Alpha-Glucosidase Inhibitory Potential of Leptadenia hastata (Pers.) Decne Abstract PDF · Vol 19, No 2 ...

  3. Recent advances in the Management of Diabetes Mellitus | Sanusi ...

    African Journals Online (AJOL)

    Life style modi cation, oral hypoglycaemic agents, insulin therapy and islet cell transplantation are some of the approaches in the management of diabetes mellitus. Several classes of oral hypoglycemic agents like sulfonylureas, biguanides and alpha-glucosidase inhibitors are available for the treatment of type II diabetes ...

  4. Low-dose acarbose does not delay digestion of starch but reduces its bioavailability

    NARCIS (Netherlands)

    Wachters-Hagedoorn, R. E.; Priebe, M. G.; Heimweg, J. A. J.; Heiner, A. M.; Elzinga, H.; Stellaard, F.; Vonk, R. J.

    Aims Slowly digestible starch is associated with beneficial health effects. The glucose-lowering drug acarbose has the potential to retard starch digestion since it inhibits alpha-amylase and alpha-glucosidases. We tested the hypothesis that a low dose of acarbose delays the rate of digestion of

  5. Alpha-amylase Inhibition and Antioxidant Activity of Marine Green Algae and its Possible Role in Diabetes Management. (United States)

    Unnikrishnan, P S; Suthindhiran, K; Jayasri, M A


    In the continuing search for safe and efficient antidiabetic drug, marine algae become important source which provide several compounds of immense therapeutic potential. Alpha-amylase, alpha-glucosidase inhibitors, and antioxidant compounds are known to manage diabetes and have received much attention recently. In the present study, four green algae (Chaetomorpha aerea, Enteromorpha intestinalis, Chlorodesmis, and Cladophora rupestris) were chosen to evaluate alpha-amylase, alpha-glucosidase inhibitory, and antioxidant activity in vitro. The phytochemical constituents of all the extracts were qualitatively determined. Antidiabetic activity was evaluated by inhibitory potential of extracts against alpha-amylase and alpha-glucosidase by spectrophotometric assays. Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide (H2O2), and nitric oxide scavenging assay. Gas chromatography-mass spectrometry (GC-MS) analysis was carried out to determine the major compound responsible for its antidiabetic action. Among the various extracts screened, chloroform extract of C. aerea (IC50 - 408.9 μg/ml) and methanol extract of Chlorodesmis (IC50 - 147.6 μg/ml) showed effective inhibition against alpha-amylase. The extracts were also evaluated for alpha-glucosidase inhibition, and no observed activity was found. Methanol extract of C. rupestris showed notable free radical scavenging activity (IC50 - 666.3 μg/ml), followed by H2O2 (34%) and nitric oxide (49%). Further, chemical profiling by GC-MS revealed the presence of major bioactive compounds. Phenol, 2,4-bis (1,1-dimethylethyl) and z, z-6,28-heptatriactontadien-2-one were predominantly found in the methanol extract of C. rupestris and chloroform extract of C. aerea. Our results demonstrate that the selected algae exhibit notable alpha-amylase inhibition and antioxidant activity. Therefore, characterization of active compounds and its in vivo assays will be noteworthy. Four green algae were

  6. Epididymal and sex accessory gland secretions in transfusion-dependent beta-thalassemic patients: evidence of an impaired prostatic function. (United States)

    Carpino, A; De Sanctis, V; Siciliano, L; Maggiolini, M; Vivacqua, A; Pinamonti, A; Sisci, D; Andó, S


    Neutral alpha-glucosidase levels as epididymal marker, fructose levels as vesicular marker, zinc, citric acid and prostate specific antigen levels as prostatic markers were measured in the seminal plasma of eight transfusion-dependent beta-thalassemic patients in order to study epididymal and sex accessory gland secretions (eighteen subjects served as controls). FSH and LH as well as total and free testosterone were detected displaying unaltered serum values. Ejaculate of patients showed normal sperm count and low sperm motility, in the meantime seminal plasma exhibited unaltered both neutral alpha-glucosidase and fructose values but low levels of zinc, citric acid and prostate specific antigen were noticed as well. These data suggest an impaired prostatic secretion in the thalassemic patients studied. A local iron toxicity on the prostatic tissue could be supported by the decrease of its specific markers observed only in the subgroup of patients with high ferritin serum levels.

  7. Functionality of bioactive compounds in Brazilian strawberry (Fragaria x ananassa Duch.) cultivars: evaluation of hyperglycemia and hypertension potential using in vitro models. (United States)

    da Silva Pinto, Marcia; Kwon, Young-In; Apostolidis, Emmanouil; Lajolo, Franco Maria; Genovese, Maria Inés; Shetty, Kalidas


    Fruits of seven fully ripened strawberry cultivars grown in Brazil (Dover, Camp Dover, Camarosa, Sweet Charlie, Toyonoka, Oso Grande, and Piedade) were evaluated for total phenolics, antioxidant activity based on DPPH radical scavenging assay, and functionality such as inhibition of alpha-amylase, alpha-glucosidase, and angiotensin I-converting enzyme (ACE) relevant for potentially managing hyperglycemia and hypertension. The total phenolics content ranged from 966 to 1571 microg of gallic acid/g of fruit fresh weight for Toyonoka and Dover, respectively. No correlation was found between total phenolics and antioxidant activity. The major phenolic compounds in aqueous extracts of strawberries were ellagic acid, quercetin, and chlorogenic acid. Strawberries had high alpha-glucosidase inhibitory activity. However, alpha-amylase inhibitory activity was very low in all cultivars. This suggested that strawberries could be considered as a potential dietary source with anti-hyperglycemic potential. The evaluated cultivars had no significant ACE inhibitory activity, reflecting low anti-hypertensive potential.

  8. The biochemical mechanism of hypoxia-induced mobilization of glycogen in cultured cancer cell


    Mung, KL; Wong, NS


    BACKGROUND: Metabolic reprogramming is one of the strategies adopted by cancer cells to survive hypoxic conditions. Recent findings suggest that hypoxic cancer cells derive the energy that they need through glycolysis using glucose mobilized from intracellular glycogen reserve. Glycogen phosphorylase (GP) is the major rate-determining enzyme for glycogen mobilization in many normal cells under the condition of starvation or physical exercise. The lysosomal alpha-glucosidase (GAA) has also bee...

  9. 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


    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, 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.

  10. A TLC bioautographic method for the detection of alpha- and beta-glucosidase inhibitors in plant extracts. (United States)

    Simões-Pires, Claudia A; Hmicha, Bouchra; Marston, Andrew; Hostettmann, Kurt


    Bioautographic assays using TLC play an important role in the search for active compounds from plants. A TLC assay has previously been established for the detection of beta-glucosidase inhibitors but not for alpha-glucosidase. Nonetheless, alpha-glucosidase inhibition is an important target for therapeutic agents against of type 2 diabetes and anti-viral infections. To develop a TLC bioautographic method to detect alpha- and beta-glucosidase inhibitors in plant extracts. The enzymes alpha- and beta-d-glucosidase were dissolved in sodium acetate buffer. After migration of the samples, the TLC plate was sprayed with enzyme solution and incubated at room temperature for 60 min in the case of alpha-d-glucosidase, and 37 degrees C for 20 min in the case of beta-d-glucosidase. For detection of the active enzyme, solutions of 2-naphthyl-alpha-D-glucopyranoside or 2-naphthyl-beta-D-glucopyranoside and Fast Blue Salt were mixed at a ratio of 1 : 1 (for alpha-d-glucosidase) or 1 : 4 (for beta-d-glucosidase) and sprayed onto the plate to give a purple background colouration after 2-5 min. Enzyme inhibitors were visualised as white spots on the TLC plates. Conduritol B epoxide inhibited alpha-d-glucosidase and beta-d-glucosidase down to 0.1 microg. Methanol extracts of Tussilago farfara and Urtica dioica after migration on TLC gave enzymatic inhibition when applied in amounts of 100 microg for alpha-glucosidase and 50 microg for beta-glucosidase. The screening test was able to detect inhibition of alpha- and beta-glucosidases by pure reference substances and by compounds present in complex matrices, such as plant extracts.

  11. Enantiospecific synthesis of pseudoacarviosin as a potential antidiabetic agent. (United States)

    Shing, Tony K M; Cheng, Hau M; Wong, Wai F; Kwong, Connie S K; Li, Jianmei; Lau, Clara B S; Leung, Po Sing; Cheng, Christopher H K


    A pseudo-1,4'- N-linked disaccharide, pseudoacarviosin 5, was constructed via a key palladium-catalyzed coupling reaction of pseudoglycosyl chloride 8 (prepared from d-glucose via a novel direct intramolecular aldol addition in 12 steps) and pseudo-4-amino-4,6-dideoxy-alpha- d-glucose 9 (prepared from l-arabinose via an unusual trans-fused isoxazolidine-selective intramolecular nitrone-alkene cycloaddition in 11 steps). Pseudoacarviosin 5 has been shown to be a potent inhibitor of alpha-glucosidases, particularly the intestinal mucosal enzymes sucrase and glucoamylase of relevance to blood glucose control.

  12. 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)


    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.)

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

    International Nuclear Information System (INIS)

    Del Gaizo, Andrew; Banerjee, Sima; Terk, Michael


    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.)

  14. 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


    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....

  15. Genetic and phenotypic comparison of Nocardia seriolae isolated from fish in Japan. (United States)

    Shimahara, Y; Nakamura, A; Nomoto, R; Itami, T; Chen, S-C; Yoshida, T


    The phenotypic and genetic characterizations of 58 isolates of the fish pathogen Nocardia seriolae, from amberjack, Seriolae dumerili, yellowtail, Seriola quinqueradiata, Japanese flounder, Paralichthys olivaceus, and chub mackerel, Scomber japonicus, in Japan from 1970-2005, were examined to investigate the epidemiological relationship between isolates. The phenotypic and genetic characterizations were determined by alpha-glucosidase activity and biased sinusoidal field gel electrophoresis (BSFGE) analysis, respectively. There was no alpha-glucosidase activity in strains isolated from 2000-05 (n = 50) with a few exceptions (n = 3), while all strains isolated from 1970-90 (n = 8) were positive. In BSFGE analysis, digestions with restriction enzymes Xba I and Ase I produced 15 and 16 restriction patterns, respectively. All restriction patterns obtained from 50 strains isolated during 2000-05 were unrelated to those obtained from eight strains isolated during 1970-90, with the exception of two strains isolated during recent outbreaks. Based on the phenotypic and genetic characterizations, recent outbreaks of nocardiosis in Japan are suggested to be epidemiologically unrelated to earlier outbreaks in Japan. Although a low genetic relationship was observed in the restriction pattern between recent and earlier isolates, identity was confirmed between these groups of isolates because five representative strains showed 99.9% homology with N. seriolae ATCC43993(T) in the 16S rRNA sequence.

  16. Bioactive compounds and phenolic-linked functionality of powdered tropical fruit residues. (United States)

    Correia, Roberta T P; Borges, Kátia C; Medeiros, Maria F; Genovese, Maria I


    Tropical fruit residues consisting of seeds, peels and residual pulp generated as by-products of fruit processing industry were investigated for bioactive compounds, the in vitro antioxidant capacity as well as alpha-glucosidase and alpha-amylase inhibitory activities. Cyanidin, quercetin, ellagic acid (EA) and proanthocyanidins were found in acerola, jambolan, pitanga and cajá-umbu residue powders. Acerola powder had the highest phenolic content (8839.33 mg catechin equivalents (CE)/100 g) and also high-ascorbic acid (AA) concentration (2748.03 mg/100 g), followed by jambolan and pitanga. The greatest 1,1-Diphenyl-2-picrylhydrazyl (DPPH) inhibition was observed for jambolan (436.76 mmol Trolox eq/g) followed by pitanga (206.68 mmol Trolox eq/g) and acerola (192.60 mmol Trolox eq/g), while acerola had the highest ferric reducing antioxidant power (FRAP) assay result (7.87 mmol Trolox eq/g). All fruit powders exhibited enzymatic inhibition against alpha-amylase (IC50 ranging from 3.40 to 49.5 mg CE/mL) and alpha-glucosidase (IC50 ranging from 1.15 to 2.37 mg CE/mL). Therefore, acerola, jambolan and pitanga dried residues are promising natural ingredients for food and nutraceutical manufacturers, due to their rich bioactive compound content.

  17. BcGs1, a glycoprotein from Botrytis cinerea, elicits defence response and improves disease resistance in host plants. (United States)

    Zhang, Yi; Zhang, Yunhua; Qiu, Dewen; Zeng, Hongmei; Guo, Lihua; Yang, Xiufen


    In this study, a necrosis-inducing protein was purified from the culture filtrate of the necrotrophic fungus Botrytis cinerea BC-98 strain. Secreted proteins were collected and fractionated by liquid chromatography. The fraction with the highest necrosis-inducing activity was further purified. A glycoprotein named BcGs1 was identified by 2D electrophoresis and mass spectrometry. The BcGs1 protein consisted of 672 amino acids with a theoretical molecular weight of 70.487 kDa. Functional domain analysis indicated that BcGs1 was a glucan 1,4-alpha-glucosidase, a cell wall-degrading enzyme, with a Glyco_hydro_15 domain and a CBM20_glucoamylase domain. The BcGs1 protein caused necrotic lesions that mimicked a typical hypersensitive response and H2O2 production in tomato and tobacco leaves. BcGs1-treated plants exhibited resistance to B. cinerea, Pseudomonas syringae pv. tomato DC3000 and tobacco mosaic virus in systemic leaves. In addition, BcGs1 triggered elevation of the transcript levels of the defence-related genes PR-1a, TPK1b and Prosystemin. This is the first report of a Botrytis glucan 1,4-alpha-glucosidase triggering host plant immunity as an elicitor. These results lay a foundation for further study of the comprehensive interaction between plants and necrotrophic fungi. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. A New Mutation Causing Severe Infantile-Onset Pompe Disease Responsive to Enzyme Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Hossein Moravej


    Full Text Available Pompe disease (PD, also known as “glycogen storage disease type II (OMIM # 232300” is a rare autosomal recessive disorder characterized by progressive glycogen accumulation in cellular lysosomes. It ultimately leads to cellular damage. Infantile-onset Pompe disease (IOPD is the most severe type of this disease and is characterized by severe hypertrophic cardiomyopathy and generalized hypotonia. Mutations in the acid alpha-glucosidase (GAA gene, located at locus 17q25.3, are responsible for the disease leading to reduced activity of the acid alpha-glucosidase enzyme. To date, approximately 400 pathogenic mutations have been reported in the GAA gene. The aim of this study is to report a novel nonsense mutation in exon 4 of the GAA gene in an Iranian child suffering from IOPD. The patient was a female neonate with hypertrophic cardiomyopathy and a positive family history of IOPD. After definite diagnosis, enzyme-replacement therapy (ERT was started for the patient, who was 2 months old. Now at the age of 20 months, she has had good growth and development and her echocardiographic parameters are within the normal range. This report shows that IOPD patients with this mutation can be treated with ERT successfully.

  19. Pompe disease: clinical perspectives

    Directory of Open Access Journals (Sweden)

    Cabello JF


    Full Text Available Juan Francisco Cabello,1 Deborah Marsden21Genetics and Metabolic Disease Laboratory, Nutrition and Food Technology Institute (INTA, University of Chile, Santiago, Chile; 2Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA Abstract: Pompe disease (acid alpha-glucosidase deficiency, OMIM 232300 is a rare lysosomal storage disorder due to autosomal recessive mutations in the GAA gene. It has also been called acid maltase deficiency and glycogen storage disease type II. There is a broad clinical presentation: the most severe form that presents in the first few months of life with cardiomyopathy and generalized muscle weakness that rapidly progresses to death from cardio-respiratory failure in the first year of life (infant-onset Pompe disease. A more slowly progressive disease, with little or no cardiac involvement, presents with proximal myopathy and/or pulmonary insufficiency, from the second year of life to late adulthood (late-onset Pompe disease. The recent development and introduction of enzyme replacement therapy with intravenous infusion of recombinant human acid alpha-glucosidase have made a major improvement in the morbidity and mortality of this disease. New therapies are also in development. With the availability of treatment, diagnostic methods have also improved, allowing for earlier recognition and potential early therapeutic intervention. The advent of newborn screening for Pompe disease may identify patients who can be treated before significant irreversible disease has occurred. Keywords: Pompe disease, glycogen storage disease, lysosomal storage disease, enzyme replacement therapy, gene therapy, chaperone therapy, genotype/phenotype, newborn screening

  20. Evaluation of antihyperglycemia and antihypertension potential of native Peruvian fruits using in vitro models. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Mariasofia Cotelli


    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.

  2. Modification to AOAC official methods 2009.01 and 2011.25 to allow for minor overestimation of low molecular weight soluble dietary fiber in samples containing starch. (United States)

    Mccleary, Barry V


    AOAC Official Methods 2009.01 and 2011.25 have been modified to allow removal of resistant maltodextrins produced on hydrolysis of various starches by the combination of pancreatic alpha-amylase and amyloglucosidase (AMG) used in these assay procedures. The major resistant maltodextrin, 6(3),6(5)-di-alpha-D-glucosyl maltopentaose, is highly resistant to hydrolysis by microbial alpha-glucosidases, isoamylase, pullulanase, pancreatic, bacterial and fungal alpha-amylase and AMG. However, this oligosaccharide is hydrolyzed by the mucosal alpha-glucosidase complex of the pig small intestine (which is similar to the human small intestine), and thus must be removed in the analytical procedure. Hydrolysis of these oligosaccharides has been by incubation with a high concentration of a purified AMG at 60 degrees C. This incubation results in no hydrolysis or loss of other resistant oligosaccharides such as FOS, GOS, XOS, resistant maltodextrins (e.g., Fibersol 2) or polydextrose. The effect of this additional incubation with AMG on the measured level of low molecular weight soluble dietary fiber (SDFS) and of total dietary fiber in a broad range of samples is reported. Results from this study demonstrate that the proposed modification can be used with confidence in the measurement of dietary fiber.

  3. [Clinical sequelae of 17 cases with glycogen storage disease type II/Pompe disease]. (United States)

    Zhang, Han-bing; Zhang, Wei-min; Qiu, Jia-jing; Meng, Yan; Qiu, Zheng-qing


    To analyze and summarize the characteristics of glycogen storage disease type II (Pompe disease) patients according to the clinical description and prognosis. 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 reach the objective. Four of 17 patients diagnosed by acid alpha-glucosidase are infantile-onset, symptoms started between 2 to 6 months after birth with increased serum creatine kinase and cardiac problems, with or without respiratory concerns. Other 13 patients were later-onset cases, and their symptoms started between 2 to 22 years of age with increased serum creatine kinase. Eleven later-onset patients started with muscle weakness, 2 patients developed respiratory insufficiency, 2 patients showed scoliosis, and 1 patient expressed increased serum creatine kinase with abnormal liver function. Just 3 of the later-onset patients were treated with mechanical ventilator and adjuvant therapy, others were not. All patients' acid alpha-glucosidase (GAA) enzyme activity analysis showed lower than 10% of normal. Fourteen patients were tested by muscle biopsy pathology, and 9 of them progressed to glycogen storage disease type II; 10 patients received genetic analysis, and 6 of them had two mutations which cause the disorder. Twelve of the 17 patients were interviewed successfully. In 3 of the infant-onset patients the disease resulted in death from respiratory failure, and 1 is still alive at the age of 1 year and 7 months. In 4 of 8 later-onset patients the disease resulted in death from respiratory failure between 3 to 5 years after onset of symptoms. Three of 4 survivors had increased muscle weakness, and 1 patient kept alive with ventilator without any changes. Seven of 12 interviewed patients died, the mortality rate was 58.3%. Glycogen storage disease type II (Pompe disease) present differently in the

  4. Hypolipidemic and hypoglycemic effects of Centella asiatica (L.) extract in vitro and in vivo. (United States)

    Supkamonseni, Nattapon; Thinkratok, Aree; Meksuriyen, Duangdeun; Srisawat, Rungrudee


    In vitro study revealed that pancreatic lipase inhibitory activity of C. asiatica extract was significantly higher than rutin but lower than orlistat, an anti-obesity drug. alpha-Amylase inhibitory activities of C. asiatica extract and rutin were significantly lower than acarbose, an anti-diabetic drug. Inhibition of alpha-glucosidase activity by C. asiatica extract, rutin, and acarbose was not different. The in vivo study substantiated the in vitro results. C. asiatica extract (1000 and 2000 mg/4 mL/kg), rutin (1000 mg/4 mL/kg), and orlistat (45 mg/4 mL/kg) significantly decreased plasma glucose, triglyceride and total cholesterol levels in lipid emulsion-induced hyperlipidemic rats at 3 h. However, plasma aspartate aminotransferase and alanine aminotransferase levels did not show significant change. The present work further supports that the C. asiatica extract and its bioactive rutin may help managing hypolipidemic and hypoglycemic effects.

  5. Identification of phenolic antioxidants and bioactives of pomegranate seeds following juice extraction using HPLC-DAD-ESI-MSn. (United States)

    Ambigaipalan, Priyatharini; de Camargo, Adriano Costa; Shahidi, Fereidoon


    Phenolics from free and hydrolyzed fractions of pomegranate juice (PJ) and seeds (PS) were evaluated. In general, total phenolic contents and scavenging of ABTS + , DPPH and hydroxyl radicals, as well as metal chelation of the soluble fraction from PS, were higher than those for PJ. Insoluble-bound phenolics from PS accounted for up to 27% of total scavenging capacity (free+esterified+insoluble-bound). Phenolic acids (13), monomeric flavonoids (8), hydrolysable tannins (12), proanthocyanidin (1) and anthocyanins (12) were tentatively characterized using HPLC-DAD-ESI-MS n . Several compounds were identified for the first time in PJ or PS. The inhibition of DNA damage (induced by hydroxyl and peroxyl radicals), copper-induced LDL-cholesterol peroxidation, as well as alpha-glucosidase and lipase activities were demonstrated, therefore supporting the potential exploitation of PJ and PS as sources of bioactive compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Diet and the Role of Altered Carbohydrate Absorption in the Treatment of Noninsulin-Dependent Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Thomas MS Wolever


    Full Text Available The gastrointestinal tract has no clear role in the pathophysiology of noninsulin-dependent diabetes mellitus (NIDDM, but it may be an appropriate site for therapeutic intervention, specifically changes in diet, meal frequency and medications. Studies suggest that for patients with NIDDM, a calorie-restricted, high carbohydrate diet low in fat and rich in fibre may improve glycemic control, mitigate the risk of atherosclerosis and retard such diabetic complications as nephropathy and retinopathy. Increased meal frequency slows the rate of carbohydrate absorption, flattens blood insulin responses and reduces serum cholesterol. New therapeutic interventions, such as soluble fibre, low glycemic index foods or alpha glucosidase inhibitors, can further slow carbohydrate absorption and thus reduce secondary risks from hyperglycemia and hyperinsulinemia.

  7. Drug treatment in elderly diabetic. (United States)

    Parikh, A O


    Diabetes causes greater decline in physical and functional status in elderly diabetic than in a younger one. Also the rise of MI, stroke and hypertension is also higher. In elderly diabetics management is always on challenging task due to atypical disease presentation, classical symptoms often absent, presence of other coexisting conditions delays the diagnosis, dietary advice not followed properly and due to non-compliance of drug therapy. The antidiabetic drugs which are often used are: sulfonylureas, metformin, thiazolidinediones, meglitinides, alpha-glucosidase inhibitors, insulin. Advantages and disadvantages of these drugs are discussed in a nutshell. Moreover control of hypertension, CAD risk reduction and practice pearls eg, lifestyle changes and goals setting for HbA(1c) are important.

  8. Balanced trafficking between the ER and the Golgi apparatus increases protein secretion in yeast

    DEFF Research Database (Denmark)

    Bao, Jichen; Huang, Mingtao; Petranovic, Dina


    of ADP-ribosylation factor GTP activating proteins, Gcs1p and Glo3p, which are involved in the process of COPI-coated vesicle formation. Engineering the retrograde trafficking increased the secretion of alpha-amylase but did not induce production of reactive oxygen species. An expanded ER membrane......The yeast Saccharomyces cerevisiae is widely used as a cell factory to produce recombinant proteins. However, S. cerevisiae naturally secretes only a few proteins, such as invertase and the mating alpha factor, and its secretory capacity is limited. It has been reported that engineering protein...... recombinant proteins, endoglucanase I from Trichoderma reesei and glucan-1,4-alpha-glucosidase from Rhizopus oryzae, indicating overexpression of GLO3 in a SEC16 moderate overexpression strain might be a general strategy for improving production of secreted proteins by yeast....

  9. Change of Oral to Topical Corticosteroid Therapy Exacerbated Glucose Tolerance in a Patient with Plaque Psoriasis. (United States)

    Hongo, Yui; Ashida, Kenji; Ohe, Kenji; Enjoji, Munechika; Yamaguchi, Miyuki; Kurata, Tsuyoshi; Emoto, Akiko; Yamanouchi, Hiroko; Takagi, Satoko; Mori, Hitoe; Kawata, Nozomi; Hisata, Yoshio; Sakanishi, Yuta; Izumi, Kenichi; Sugioka, Takashi; Anzai, Keizo


    BACKGROUND Psoriasis is known as the most frequent disease treated by long-term topical steroids. It is also known that patients with thick, chronic plaques require the highest potency topical steroids. However, the treatment is limited to up to four weeks due to risk of systemic absorption. CASE REPORT An 80-year-old man was diagnosed with type 2 diabetes 16 years before, and was being administered insulin combined with alpha glucosidase inhibitor. He was diagnosed with plaque psoriasis and his oral steroid treatment was switched to topical steroid treatment due to lack of improvement and poorly controlled blood glucose level. The hypoglycemic events improved after the psoriatic lesions improved. CONCLUSIONS Control of blood glucose level is difficult at the very beginning of topical steroid treatment for psoriasis especially if a patient is receiving insulin treatment. Intense monitoring of blood glucose level during initiation of topical steroid treatment is necessary to prevent unfavorable complications.

  10. An exopolysaccharide (EPS) from a Lactobacillus plantarum BR2 with potential benefits for making functional foods. (United States)

    Sasikumar, Keerthi; Kozhummal Vaikkath, Deepti; Devendra, Leena; Nampoothiri, K Madhavan


    A high molecular weight EPS of glucomannan nature was recovered and purified to get an yield of 2.8±0.5g/L from Lb. plantarum BR2 and it displayed potent antioxidant activity with 29.8% radical scavenging activity and 19% total antioxidant capacity. At 100µg/ml concentration, it is capable of inhibiting the alpha amylase activity by 10% and at 300µg/ml, it drastically inhibited the alpha-glucosidase activity by 67% which indicates its antidiabetic potential. More interestingly, at a concentration level of 0.1%, it reduced the cholesterol level by a margin of 45% in an in vitro assay. The sample didn't reveal any cytotoxicity against H9C2 normal cells indicating its potential for safe use as a food additive. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Two cases of Pompe's disease: case report and review of literature

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    A. Jegadeeswari


    We are presenting two cases of infantile form of Pompe's disease with secondary hypertrophic cardiomyopathy (CMP. The first case was a 1-year-old female child who presented with Ross Class III heart failure (HF of 3 months duration. Echocardiography (ECHO showed concentric left ventricular (LV hypertrophy, with the posterobasal segment more hypertrophic than the inter-ventricular septum and moderate pericardial effusion. The second case was a 2-month-old male child who presented with Ross Class II HF. His ECHO showed eccentric hypertrophy of the posterobasal left ventricle, with thickening of the mitral valve leaflets and the chordae with Grade I mitral regurgitation (MR. Both children were diagnosed to have Pompe's disease by blood alpha-glucosidase assay.

  12. Pomegranate extract mouth rinsing effects on saliva measures relevant to gingivitis risk. (United States)

    DiSilvestro, Robert A; DiSilvestro, Daniel J; DiSilvestro, David J


    Pomegranate components have properties that could promote oral health, including reducing the risk of gingivitis. The present study examined young adults (n = 32, split evenly among both genders), for the effects of 4 weeks of thrice daily mouth rinsing with the pomegranate (Punica granatum L.) extract PomElla dissolved in water. This treatment changed salivary measures relevant to oral health including gingivitis. The changes were: reduced total protein (which can correlate with plaque forming bacteria readings), reduced activities of aspartate aminotransferase (an indicator of cell injury), reduced alpha-glucosidase activity (a sucrose degrading enzyme), increased activities of the antioxidant enzyme ceruloplasmin (which could give better protection against oral oxidant stress) and increased radical scavenging capacity (though this increase was significant only by nonparametric statistical analysis). A placebo of cornstarch in water did not affect these measures. These data raise the possibility of using pomegranate extracts in oral health products such as toothpaste and mouthwashes. Copyright 2009 John Wiley & Sons, Ltd.

  13. Skeletal muscle metabolism during prolonged exercise in Pompe disease

    DEFF Research Database (Denmark)

    Preisler, Nicolai; Laforêt, Pascal; Madsen, Karen Lindhardt


    OBJECTIVE: Pompe disease (glycogenosis type II) is caused by lysosomal alpha-glucosidase deficiency, which leads to a block in intra-lysosomal glycogen breakdown. In spite of enzyme replacement therapy, Pompe disease continues to be a progressive metabolic myopathy. Considering the health benefits...... of exercise, it is important in Pompe disease to acquire more information about muscle substrate use during exercise. METHODS: Seven adults with Pompe disease were matched to a healthy control group (1:1). We determined (1) peak oxidative capacity (VO2peak) and (2) carbohydrate and fatty acid metabolism...... during submaximal exercise (33 W) for 1 h, using cycle-ergometer exercise, indirect calorimetry and stable isotopes. RESULTS: In the patients, VO2peak was less than half of average control values; mean difference -1659 mL/min (CI: -2450 to -867, P = 0.001). However, the respiratory exchange ratio...

  14. New Enzyme-Inhibitory Triterpenoid from Marine Macro Brown Alga Padina boergesenii Allender & Kraft

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    Liaqat Ali


    Full Text Available In continuation to our study of the chemical and biological potential of the secondary metabolites isolated from Omani seaweeds, we investigated a marine brown alga, Padina boergesenii. The phytochemical investigation resulted in the isolation of a new secondary metabolite, padinolic acid (1, along with some other semi-pure fractions and sub-fractions. The planar structure was confirmed through MS and NMR (1D and 2D spectral data. The NOESY experiments coupled with the biogenetic consideration were helpful in assigning the stereochemistry in the molecule. Compound 1 was subjected to enzyme inhibition studies using urease, lipid peroxidase, and alpha-glucosidase enzymes. Compound 1 showed low to moderate α-glucosidase and urease enzyme inhibition, respectively, and moderate anti-lipid peroxidation activities. The current study indicates the potential of this seaweed and provides the basis for further investigation.

  15. Computational and Pharmacological Evaluation of Ferrocene-Based Acyl Ureas and Homoleptic Cadmium Carboxylate Derivatives for Anti-diabetic Potential

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    Shahar Bano


    Full Text Available We investigated possible anti-diabetic effect of ferrocene-based acyl ureas: 4-ferrocenyl aniline (PFA, 1-(4-chlorobenzoyl-3-(4-ferrocenylphenyl urea (DPC1, 1-(3-chlorobenzoyl-3-(4-ferrocenylphenyl urea (DMC1, 1-(2-chlorobenzoyl-3-(4-ferrocenylphenyl urea (DOC1 and homoleptic cadmium carboxylates: bis (diphenylacetato cadmium (II (DPAA, bis (4-chlorophenylacetato cadmium (II (CPAA, using in silico and in vivo techniques. PFA, DPC1, DMC1, DOC1, DPAA and CPAA exhibited high binding affinities (ACE ≥ −350 Kcal/mol against targets: aldose reductase, peroxisome proliferator-activated receptor γ, 11β-hydroxysteroid dehydrogenase-1, C-alpha glucosidase and glucokinase, while showed moderate affinities (ACE ≥ −250 Kcal/mol against N-alpha glucosidase, dipeptidyl peptidase-IV, phosphorylated-Akt, glycogen synthase kinase-3β, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase, whereas revealed lower affinities (ACE < −250 Kcal/mol vs. alpha amylase, protein tyrosine phosphatases 1B, glycogen phosphorylase and phosphatidylinositol 3 kinase. In alloxan (300 mg/Kg-induced diabetic mice, DPAA and DPC1 (1–10 mg/Kg at day 1, 5, 10, 15, and 20th decreased blood glucose levels, compared to diabetic control group and improved the treated animals body weight. DPAA (10 mg/Kg and DPC1 (5 mg/Kg in time-dependent manner (30–120 min. enhanced tolerance of oral glucose overload in mice. DPAA and DPCI dose-dependently at 1, 5, and 10 mg/Kg decreased glycosylated hemoglobin levels in diabetic animals, as caused by metformin. These results indicate that aforementioned derivatives of ferrocene and cadmium possess anti-diabetic potential.

  16. Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II. (United States)

    Bembi, Bruno; Pisa, Federica Edith; Confalonieri, Marco; Ciana, Giovanni; Fiumara, Agata; Parini, Rossella; Rigoldi, Miriam; Moglia, Arrigo; Costa, Alfredo; Carlucci, Annalisa; Danesino, Cesare; Pittis, Maria Gabriela; Dardis, Andrea; Ravaglia, Sabrina


    Type II glycogenosis (GSDII) is a lysosomal storage disorder due to acid alpha-glucosidase (GAA) deficiency. Enzyme replacement therapy (ERT) with human recombinant alpha-glucosidase (rhGAA) has been demonstrated to be effective in the treatment of infantile forms of GSDII, but little information is available concerning late-onset phenotypes. Long-term follow-up studies are not available at present. The aim of this study was to evaluate the ERT long-term effects in late-onset GSDII. Twenty-four patients, including 7 juveniles and 17 adults, received bi-weekly infusion of rhGAA (20 mg/kg) for at least 36 months. Clinical conditions, muscular function (6-min walking test, 6MWT; Walton scale, WS), respiratory function (vital capacity, VC; forced expiratory volume, FEV1; arterial pCO(2)), and muscle enzymes were assessed every 6 months. The 6MWT improved in both juvenile and adult patients (p = 0.01, p = 0.0002, respectively), as well as in patients with moderate to severe muscle function impairment (WS >3.5; p = 0.002). An overall improvement in WS was also observed (p = 0.0003). VC and FEV1 remained unchanged, while pCO(2) decreased (p = 0.017). Muscle enzymes decreased significantly (p < 0.0001). Two patients (8%) showed transient secondary events during ERT. Long-term ERT with rhGAA was shown to be safe, well tolerated, and effective in improving motor function and in stabilizing respiratory function in late-onset GSDII. The response pattern showed a progressive clinical improvement during the follow-up period in juvenile patients, while in adults it reached and maintained a plateau after the first year of treatment.

  17. Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study. (United States)

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul


    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.

  18. Digestive enzymes of leaf-cutting ants, Acromyrmex subterraneus (Hymenoptera: Formicidae: Attini): distribution in the gut of adult workers and partial characterization. (United States)

    Erthal, Milton; Peres Silva, Carlos; Samuels, Richard Ian


    Enzyme activities associated with the labial glands, midgut and rectum of adult Acromyrmex subterraneus were investigated in order to understand their role in digestion of plant and fungal material. High chitinolytic activity was detected in the labial glands, indicating a possible role in the degradation of fungus ingested by the ants. Chitinolytic activity seen in other compartments of the alimentary canal probably originated in the labial glands. The highest activity detected in the midgut was for alpha-glucosidase, which was considered to be of insect origin due to its association with midgut epithelium and it is probably involved in glucose assimilation from nutrient sources such as maltose and sucrose present in plant material. A large range of enzyme activities were detected in the rectal lumen contents, and as in the midgut the highest values were for alpha-glucosidase activity. The absence of activity associated with the epithelium, in the particulate fraction, indicates that the rectal epithelium does not have a secretory function. The detection of enzymes in the rectal lumen contents, which were not detected in the midgut lumen contents, indicates that the rectum acts as a reservoir, accumulating enzymes. The major digestive enzymes were partially characterized using hydrophobic interaction chromatography, gel filtration and SDS-PAGE. The pH of the adult intestinal tract and flow rate of dye through the tract was investigated. A gradual acidification of the intestinal tract was noted commencing with the crop (pH 6-8.2) and terminating with the rectum (pH 3-5). The flow of dye through the different compartments of the tract showed a rapid fill time for all the gut compartments and a short residence time in the crop. In all other compartments, the dye remained detectable for 10 days or longer.

  19. Species identification of members of the Streptococcus milleri group isolated from the vagina by ID 32 Strep system and differential phenotypic characteristics. (United States)

    Ahmet, Z; Warren, M; Houang, E T


    The importance of bacterial vaginosis as a risk factor in obstetric and gynecological infections has recently been recognized. The bacterial vaginosis group of organisms includes members of the Streptococcus milleri group, the identification of which has caused much confusion. We prospectively surveyed the rates of carriage of S. milleri group organisms in 397 high vaginal swabs received in our laboratory. For the identification of 99 clinical isolates and 23 control strains, we compared the results obtained by the rapid ID 32 Strep system (Analytab Products) and by a scheme utilizing six differential phenotypic characteristics (presence of beta-N-acetylglucosaminidase, alpha-glucosidase, beta-D-fucosidase, beta-galactosidase, beta-N-acetylgalactosaminidase, and beta-glucosidase) as described by Whiley et al. (R. A. Whiley, H. Fraser, J. M. Hardie, and D. Beighton, J. Clin. Microbiol. 28:1497-1501, 1990). We identified Streptococcus anginosus in 18% and Streptococcus constellatus in 0.05% of the specimens examined. Of the isolates of S. anginosus that reacted with grouping antisera, 20 of 25 belonged to Lancefield group F. The incubation conditions for bacterial cultures and for reaction mixtures affected the results of phenotypic characterization in the production of alpha-glucosidase, beta-galactosidase, and beta-glucosidase. However, by using bacterial cultures grown under hypercapnic conditions and incubating the reaction mixtures aerobically, consistent phenotypic characteristics were obtained, allowing identification similar to that obtained by the ID 32 Strep system. We therefore recommend the phenotypic scheme as an inexpensive, reliable, and convenient method for the initial identification of species of the S. milleri group.

  20. Effect to the Glycolit which the absorption to the solution of sacarose marked with a 14C

    International Nuclear Information System (INIS)

    Fleitas Estevez, Andres; Simon Carballo, Rafael; Perez Perez, Luisa; Derivet Zarzabal, Milagros


    Previous studies conducted in vitro and in experimental animals have served as the basis for a working hypothesis about the antihyperglycemic effect of a product derived from a natural zeolite (Fz), called glicolit. The objective of this paper was to demonstrate by the use of a radioisotopic method the effect of the joint administration of this product and a source of glucose (sacarose) on the blood levels of this monosaccharide. The study group was composed of 10 rats; 5 were administered glicolit and the other 5 were used as controls. Measurements of glucose in plasma were made at different times by a radioisotopic method after the oral administration of a solution of sacarose marked with a 14 C. The results showed a decrease of the levels of blood glucose in those rats that received glicolit. A graphic of absorption kinetics was made (specific activities against time) and it was obtained an area under the curve that was 16,2% lower in the group of animals that received glicolit. The radioisotopic method proved to be useful for studying the absorption kinetics of glucose when it is administered in the form of sacarose together with glicolit, which showed that it is effective in the reduction of the postprandial glycemic peaks in the studied rats. It seems that glicolit catches the glucose released by the intestinal alpha glucosidases enzymes. The radioisotopic method was also used to verify the hypothesis on the usefulness of glicolit to reduce the levels of glycemic after the ingestion of carbohydrates

  1. Anti-hyperglycemic and anti-hyperlipidemic effects of guava leaf extract (United States)


    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

  2. Improved glycemic control in patients with advanced type 2 diabetes mellitus taking Urtica dioica leaf extract: a randomized double-blind placebo-controlled clinical trial. (United States)

    Kianbakht, Saeed; Khalighi-Sigaroodi, Farahnaz; Dabaghian, Fataneh Hashem


    Advanced type 2 diabetes mellitus (T2DM) needing insulin therapy is common. Most conventional anti-hyperglycemic drugs have limited efficacies and significant side effects, so that better anti-hyperglycemic agents are needed. Urtica dioica L. (nettle) leaves have insulin secretagogue, PPARgamma agonistic, and alpha-glucosidase inhibitory effects. Moreover, nettle leaves are used in traditional medicine as an anti-hyperglycemic agent to treat diabetes mellitus. Thus, efficacy and safety of nettle in the treatment of patients with advanced type 2 diabetes mellitus needing insulin were studied. In this randomized double-blind placebo-controlled clinical trial, we evaluated the effects of taking nettle leaf extract (one 500 mg capsule every 8 hours for 3 months) combined with the conventional oral anti-hyperglycemic drugs on the blood levels of fasting glucose, postprandial glucose, glycosylated hemoglobin (HbA1c), creatinine and liver enzymes SGOT and SGPT, and systolic and diastolic blood pressures in 46 patients and compared with the placebo group (n = 46). At the endpoint, the extract lowered the blood levels of fasting glucose, 2 hours postprandial glucose, and HbA1c significantly (p 0.05) compared with placebo. Nettle may safely improve glycemic control in type 2 diabetic patients needing insulin therapy.

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

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    M. Marconi


    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.

  4. Prevalence of adult Pompe disease in patients with proximal myopathic syndrome and undiagnosed muscle biopsy. (United States)

    Golsari, Amir; Nasimzadah, Arzoo; Thomalla, Götz; Keller, Sarah; Gerloff, Christian; Magnus, Tim


    We examined patients with limb-girdle muscle weakness and/or hyper-CKaemia and undiagnosed muscle biopsy for late onset Pompe disease (LOPD). Patients with an inconclusive limb-girdle muscle weakness who presented at our neuromuscular centre between 2005 and 2015 with undiagnosed muscle biopsies were examined by dry blood spot testing (DBS) including determination of the enzyme activity of acid alpha-glucosidase (GAA). In the case of depressed enzyme activity, additional gene testing of the GAA gene was carried out. Of the 340 evaluated muscle biopsies, 69 patients fulfilled the inclusion criteria and were examined with DBS. Among those patients, 76% showed a limb-girdle muscle weakness and 14% showed a hyper-CKaemia. A diagnosis of LOPD could be established in the case of two patients (2.9%) with reduced GAA enzyme activity and proof of mutations in the GAA gene. One of the two patients presents in the muscle biopsy suggestive features of Pompe disease including vacuoles with positive acid phosphatase reaction. In summary, our results show that a muscle biopsy can be helpful in identifying LOPD patients, but vacuolation with glycogen storage can also be absent. An inconspicuous muscle biopsy does not rule out Pompe disease. Consequently, all patients with limb-girdle muscle weakness should be examined by DBS before conducting a muscle biopsy. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. In vitro antidiabetic activity of various crude extracts of Boletus variipes (United States)

    Muniandy, Sutha; Fazry, Shazrul; Daud, Fauzi; Senafi, Sahidan


    Diabetes mellitus is a complex metabolic disease that progressively spread worldwide and difficult to treat due to various physical and metabolic complications. Current treatment using synthetic drugs has lead to various undesirable side effects. Here we determined the effect of Boletus variipes extracts on diabetes related enzymes. In this study, hot water, cold water and methanol extracts of B. variipes were utilized in order to assess their in vitro antidiabetic activity by measuring the effect on α-amylase and α-glucosidase enzyme. Hot water extract possessed the highest inhibition activity of α-amylase and α-glucosidase in a concentration dependent manner with the IC50 value 87 mg/mL and 89 mg/mL respectively. The methanol extract also showed inhibition activity of α-amylase and α-glucosidase but significantly lower than the hot water extract. Whereas cold water extract did not show any inhibition activity towards both the enzymes. Therefore, it is hypothesized that the hot water extract of Boletus variipes contains bioactive compound that can inhibit alpha-amylase and alpha-glucosidase enzyme activity. At the request of all authors of the paper an updated version was published on 11 May 2016. The original version identified the species of mushroom as Boletus variipes, but new findings have proved the species of mushroom to be Boletus qriseipurpureus. The species name has been updated throughout the revised version of this paper.

  6. Acarbose improved severe postprandial hypotension in a patient with diabetes mellitus. (United States)

    Sasaki, E; Goda, K; Nagata, K; Kitaoka, H; Ohsawa, N; Hanafusa, T


    Postprandial hypotension (PPH) is defined as a decrease of systolic blood pressure by more than 20 mmHg after meals. Severe PPH is a troublesome diabetic complication, which has no established means of treatment. We encountered a patient who had diabetes mellitus complicated by severe PPH and attempted to treat this problem using several medications (octreotide, midodrine hydrochloride, and acarbose). A 58-year-old male with diabetic triopathy complained of orthostatic dizziness and vertigo after meals. The blood pressure was monitored for 24 h with an ambulatory blood pressure monitor, revealing that the systolic blood pressure decreased markedly after breakfast and dinner by 45 and 50 mmHg, respectively. PPH was not improved by a subcutaneous injection of octreotide. Administration of midodrine hydrochloride reduced the frequency of hypotensive episodes from twice to once daily, but the magnitude of the postprandial fall in blood pressure was still around 30 mmHg. After the patient started to receive acarbose therapy, the postprandial fall in blood pressure was diminished to 18 mmHg and his symptoms largely disappeared. For the treatment of PPH in diabetic patients, our experience suggests that it may be appropriate to try first on alpha-glucosidase inhibitor like acarbose.

  7. Acute Hypoglycemic and Antidiabetic Effect of Teuhetenone A Isolated from Turnera diffusa

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    Aída Parra-Naranjo


    Full Text Available Diabetes mellitus is a chronic degenerative disease that causes long-term complications and represents a serious public health problem. Turnera diffusa (damiana is a shrub that grows throughout Mexico and is traditionally used for many illnesses including diabetes. Although a large number of plant metabolites are known, there are no reports indicating which of these are responsible for this activity, and this identification was the objective of the present work. Through bioassay-guided fractionation of a methanolic extract obtained from the aerial part of T. diffusa, teuhetenone A was isolated and identified as the main metabolite responsible for the plant’s hypoglycemic activity. Alpha-glucosidase inhibitory activity and cytotoxicity of this metabolite were determined. Hypoglycemic and antidiabetic activities were evaluated in a murine model of diabetes in vivo, by monitoring glucose levels for six hours and comparing them with levels after administering various controls. Teuhetenone A was not cytotoxic at the tested concentrations, and did not show inhibitory activity in the glucosidase test, and the in vivo assays showed a gradual reduction in glucose levels in normoglycemic and diabetic mice. Considering these results, we suggest that teuhetenone A has potential as an antidiabetic compound, which could be further submitted to preclinical assays.

  8. A Review on the Medicinal Plant Dalbergia odorifera Species: Phytochemistry and Biological Activity

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    Son Ninh The


    Full Text Available The crucial medicinal plant Dalbergia odorifera T. Chen species belongs to genus Dalbergia, with interesting secondary metabolites, consisting of main classes of flavonoid, phenol, and sesquiterpene derivatives, as well as several arylbenzofurans, quinones, and fatty acids. Biological studies were carried out on extracts, fractions, and compounds from this species involved in cytotoxic assays; antibacterial, antioxidative, anti-inflammatory, antithrombotic, antiplatelet, antiosteosarcoma, antiosteoporosis, antiangiogenesis, and prostaglandin biosynthetic enzyme inhibition activities; vasorelaxant activities; alpha-glucosidase inhibitory activities; and many other effects. In terms of the valuable resources for natural new drugs development, D. odorifera species are widely used as medicinal drugs in many countries for treatment of cardiovascular diseases, cancer, diabetes, blood disorders, ischemia, swelling, necrosis, or rheumatic pain. Although natural products from this plant have been increasingly playing an important role in drug discovery programs, there is no supportive evidence to provide a general insight into phytochemical studies on D. odorifera species and biological activities of extracts, fractions, and isolated compounds. To a certain extent, this review deals with an overview of almost naturally occurring compounds from this species, along with extensive coverage of their biological evaluations.

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

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    Liaqat Ali


    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.

  10. RNA Interference based Approach to Down Regulate Osmoregulators of Whitefly (Bemisia tabaci): Potential Technology for the Control of Whitefly (United States)

    Raza, Amir; Malik, Hassan Jamil; Shafiq, Muhammad; Amin, Imran; Scheffler, Jodi A.; Scheffler, Brian E.; Mansoor, Shahid


    Over the past decade RNA interference (RNAi) technology has emerged as a successful tool not only for functional genomics, but in planta expression of short interfering RNAs (siRNAs) that could offer great potential for insect pest management. The diet of insects feeding exclusively on phloem sieves contains water and sugars as main components, and the uptake of the liquid food greatly depends on the osmotic pressure within the insect body. Based on this physiological mechanism, transgenic plants of Nicotiana tabacum were generated expressing double stranded RNA (dsRNA) against both aquaporin (AQP) and a sucrase gene, alpha glucosidase (AGLU). These two genes are involved in osmotic pressure maintenance particularly in sap sucking insects, and the aim was to disrupt osmoregulation within the insect ultimately leading to mortality. Real time quantitative PCR (RT-qPCR) was performed to assess the suppression of gene expression in Bemisia tabaci (B. tabaci) and mortality was recorded during transgenic tobacco feeding bioassays. Feeding of insects on plants expressing dsRNA significantly reduced the transcript level of the target genes in B. tabaci after six days of feeding and more than 70% mortality was observed in B. tabaci fed on transgenic plants compared to the control plants. Our data shows that down-regulation of genes related to osmoregulation may find practical applications for the control of this important pest in cotton and other crops. PMID:27105353

  11. RNA Interference based Approach to Down Regulate Osmoregulators of Whitefly (Bemisia tabaci: Potential Technology for the Control of Whitefly.

    Directory of Open Access Journals (Sweden)

    Amir Raza

    Full Text Available Over the past decade RNA interference (RNAi technology has emerged as a successful tool not only for functional genomics, but in planta expression of short interfering RNAs (siRNAs that could offer great potential for insect pest management. The diet of insects feeding exclusively on phloem sieves contains water and sugars as main components, and the uptake of the liquid food greatly depends on the osmotic pressure within the insect body. Based on this physiological mechanism, transgenic plants of Nicotiana tabacum were generated expressing double stranded RNA (dsRNA against both aquaporin (AQP and a sucrase gene, alpha glucosidase (AGLU. These two genes are involved in osmotic pressure maintenance particularly in sap sucking insects, and the aim was to disrupt osmoregulation within the insect ultimately leading to mortality. Real time quantitative PCR (RT-qPCR was performed to assess the suppression of gene expression in Bemisia tabaci (B. tabaci and mortality was recorded during transgenic tobacco feeding bioassays. Feeding of insects on plants expressing dsRNA significantly reduced the transcript level of the target genes in B. tabaci after six days of feeding and more than 70% mortality was observed in B. tabaci fed on transgenic plants compared to the control plants. Our data shows that down-regulation of genes related to osmoregulation may find practical applications for the control of this important pest in cotton and other crops.

  12. Reappraisal and perspectives of clinical drug-drug interaction potential of α-glucosidase inhibitors such as acarbose, voglibose and miglitol in the treatment of type 2 diabetes mellitus. (United States)

    Dash, Ranjeet Prasad; Babu, R Jayachandra; Srinivas, Nuggehally R


    1. Amidst the new strategies being developed for the management of type 2 diabetes mellitus (T2DM) with both established and newer therapies, alpha glucosidase inhibitors (AGIs) have found a place in several treatment protocols. 2. The objectives of the review were: (a) to compile and evaluate the various clinical pharmacokinetic drug interaction data for AGIs such as acarbose, miglitol and voglibose; (b) provide perspectives on the drug interaction data since it encompasses coadministered drugs in several key areas of comorbidity with T2DM. 3. Critical evaluation of the interaction data suggested that the absorption and bioavailability of many coadministered drugs were not meaningfully affected from a clinical perspective. Therefore, on the basis of the current appraisal, none of the AGIs showed an alarming and/or overwhelming trend of interaction potential with several coadministered drugs. Hence, dosage adjustment is not warranted in the use of AGIs in T2DM patients in situations of comorbidity. 4. The newly evolving fixed dose combination strategies with AGIs need to be carefully evaluated to ensure that the absorption and bioavailability of the added drug are not impaired due to concomitant food ingestion.

  13. Phenolic compounds, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension of commonly used medicinal plants, herbs and spices in Latin America. (United States)

    Ranilla, Lena Galvez; Kwon, Young-In; Apostolidis, Emmanouil; Shetty, Kalidas


    Traditionally used medicinal plants, herbs and spices in Latin America were investigated to determine their phenolic profiles, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension. High phenolic and antioxidant activity-containing medicinal plants and spices such as Chancapiedra (Phyllantus niruri L.), Zarzaparrilla (Smilax officinalis), Yerba Mate (Ilex paraguayensis St-Hil), and Huacatay (Tagetes minuta) had the highest anti-hyperglycemia relevant in vitro alpha-glucosidase inhibitory activities with no effect on alpha-amylase. Molle (Schinus molle), Maca (Lepidium meyenii Walp), Caigua (Cyclanthera pedata) and ginger (Zingiber officinale) inhibited significantly the hypertension relevant angiotensin I-converting enzyme (ACE). All evaluated pepper (Capsicum) genus exhibited both anti-hyperglycemia and anti-hypertension potential. Major phenolic compounds in Matico (Piper angustifolium R.), Guascas (Galinsoga parviflora) and Huacatay were chlorogenic acid and hydroxycinnamic acid derivatives. Therefore, specific medicinal plants, herbs and spices from Latin America have potential for hyperglycemia and hypertension prevention associated with Type 2 diabetes. (c) 2010 Elsevier Ltd. All rights reserved.

  14. 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


    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.)

  15. Kytococcus schroeteri sp. nov., a novel Gram-positive actinobacterium isolated from a human clinical source. (United States)

    Becker, Karsten; Schumann, Peter; Wüllenweber, Jörg; Schulte, Martina; Weil, Hans-Peter; Stackebrandt, Erko; Peters, Georg; von Eiff, Christof


    A strain of a gram-positive, coccoid, yellow-pigmented bacterium was isolated from human blood. The bacterium was aerobic, non-encapsulated and non-motile. Phenotypically, the bacterium closely resembled Kytococcus sedentarius, but could be distinguished from this species by physiological tests and chemotaxonomic investigations. The peptidoglycan type is L-Lys-Glu2, variation A4alpha. The predominant menaquinones are MK-8 and MK-7. The major cellular fatty acids are iso-C17:1, iso-C17:0, iso-C15:0 and anteiso-C17:0. The strain contains catalase and does not produce acid from carbohydrates. The ability to hydrolyse Tween 80 and the lack of alpha-glucosidase activity are the most characteristic features. The results of comparative 16S rDNA analysis revealed that the strain represents a novel species within the genus Kytococcus, for which the name Kytococcus schroeteri sp. nov. is proposed. The type strain is strain Muenster 2000T (= DSM 13884T = CCM 4918T).

  16. Involvement of Kytococcus schroeteri in a case of prosthetic valve endocarditis

    Directory of Open Access Journals (Sweden)

    Antonella D’Andria


    Full Text Available We report a fourth case of prosthetic valve endocarditis caused by the newly described micrococcal species: Kytococcus schroeteri. A 38-year old male was admitted to our hospital with suspected prosthetic valve endocarditis. In three blood cultures and in the prosthetic heart valve culture grew the same type of microrganism, initially identified as Micrococcus luteus. Presuntive assignment to the genus Kytococcus was suggested by the arginina dihydrolase activity and by the resistence to penicillin, oxacillin and methicillin, characteristics which are not shared by other micrococci. Further biochemical tests confirmed that the isolates belonged to the genus Kytococcus (negative reaction for oxydase, esculin and urease, positive for catalase and arginine dihydrolase species schroeteri (alpha-glucosidase positive. The patient was treated with vancomycin, gentamicin and rifampicin. After the valve replacement, on the 20th day of hospitalization, the patient’s biological parameters returned to normal values, and after one mounth the resolution of the disease was completed. The diagnosis of four cases by K. schroeteri endocarditis, described within a short period of time (2003-2006, might indicate a specific pathogenicity of this new species. In case of endocarditis diagnosis, the suspect of the genus Kytococcus involvement should be considered each time the aerobic Gram positive cocci, with arginina dihidrolase activiy and the resistence to penicillin, oxacillin and methicillin, are isolated by significative biological samples.

  17. Effects of culture medium compositions on antidiabetic activity and anticancer activity of marine endophitic bacteria isolated from sponge (United States)

    Maryani, Faiza; Mulyani, Hani; Artanti, Nina; Udin, Linar Zalinar; Dewi, Rizna Triana; Hanafi, Muhammad; Murniasih, Tutik


    High diversity of Indonesia marine spesies and their ability in producing secondary metabolite that can be used as a drug candidate cause this fascinating topic need to explore. Most of marine organisms explored to discover drug is macroorganism whereas microorganism (such as Indonesia marine bacteria) is very limited. Therefore, in this report, antidiabetic and anticancer activity of Indonesia marine bacteria isolated from Sponges's extract have been studied. Bacteria strain 8.9 which are collection of Research Center for Oseanography, Indonesian Institute of Sciences were from Barrang Lompo Island, Makasar, Indonesia. Bacteria were cultured in different culture medium compositions (such as: different pH, source of glucose and water) for 48 hours on a shaker, then they were extracted with ethyl asetate. Extracts of bacteria were tested by DPPH method (antioxidant activity), alpha glucosidase inhibitory activity method (antidiabetic activity), and Alamar Blue assay (anticancer activity) at 200 ppm. According to result, extract of bacteria in pH 8.0 exhibited the greatest antioxidant (19.27% inhibition), antidiabetic (63.95% inhibition) and anticancer activity of T47D cell line (44.62% cell viability) compared to other extracts. However, effect of addition of sugar sources (such as: glucose, sucrose, and soluble starch) and effect of addition of water/sea water exhibited less influence on their bioactivities. In conclusion, Indonesia marine bacteria isolated from sponge have potential a source of bioactive compound in drug discovery field.

  18. Functional flexibility of the honey bee hypopharyngeal gland in a dequeened colony. (United States)

    Ohashi, K; Sasaki, M; Sasagawa, H; Nakamura, J; Natori, S; Kubo, T


    The role of the worker honey bee Apis mellifera L. changes depending on age after eclosion (age polyethism): young workers (nurse bees) take care of their brood by synthesizing and secreting brood food (royal jelly), while older workers (foragers) forage for nectar and process it into honey. Previously, we showed that the major proteins synthesized in the hypopharyngeal gland of the worker change from brood food proteins to alpha-glucosidase at the single secretory cell level in parallel with this age polyethism [Kubo et al., J. Biochem. 119, 291-295 (1996); Ohashi et al., Eur. J. Biochem. 249, 797-802 (1997)]. Here, we examined whether the function of the hypopharyngeal gland has flexibility depending on the colony conditions, by creating a dequeened colony in which the older workers were compelled to feed the drone larvae. It was found that most of the older workers in the dequeened colony synthesized brood food proteins as did nurse bees. Furthermore, the percentage of workers that synthesized brood food proteins was maintained at 80-90% of the total workers for at least two months, as in a normal colony. These results indicate that the function of the hypopharyngeal gland cells of the worker has flexibility and can, if necessary, be maintained as that of the nurse bee, depending on the condition of the colony.

  19. Production of a functional human acid maltase in tobacco seeds: biochemical analysis, uptake by human GSDII cells, and in vivo studies in GAA knockout mice. (United States)

    Martiniuk, Frank; Reggi, Serena; Tchou-Wong, Kam-Meng; Rom, William N; Busconi, Matteo; Fogher, Corrado


    Genetic deficiency of acid alpha glucosidase (GAA) results in glycogen storage disease type II (GSDII) or Pompe's disease. To investigate whether we could generate a functional recombinant human GAA enzyme (tobrhGAA) in tobacco seeds for future enzyme replacement therapy, we subcloned the human GAA cDNA into the plant expression plasmid-pBI101 under the control of the soybean β-conglycinin seed-specific promoter and biochemically analyzed the tobrhGAA. Tobacco seeds contain the metabolic machinery that is more compatible with mammalian glycosylation-phosphorylation and processing. We found the tobrhGAA to be enzymatically active was readily taken up by GSDII fibroblasts and in white blood cells from whole blood to reverse the defect. The tobrhGAA corrected the enzyme defect in tissues at 7 days after a single dose following intraperitoneal (IP) administration in GAA knockout (GAA(-/-)) mice. Additionally, we could purify the tobrhGAA since it bound tightly to the matrix of Sephadex G100 and can be eluted by competition with maltose. These data demonstrate indirectly that the tobrhGAA is fully functional, predominantly proteolytically cleaved and contains the minimal phosphorylation and mannose-6-phosphate residues essential for biological activity.

  20. The active role of leguminous plant components in type 2 diabetes. (United States)

    Gętek, Monika; Czech, Natalia; Muc-Wierzgoń, Małgorzata; Grochowska-Niedworok, Elżbieta; Kokot, Teresa; Nowakowska-Zajdel, Ewa


    Diabetes appears to be one of the most frequent noncommunicable diseases in the world. A permanent growth in the incidence of diabetes can be observed and according to the International Diabetes Federation (IDF) the year 2030 will mark the increase in the number of diabetics to 439 mln worldwide. Type 2 diabetes accounts for about 90% of all diabetes incidence. Nutrition model modification not only features the basic element in type 2 diabetes treatment but also constitutes the fundamental factor influencing a morbidity rate decrease. Leguminous plants are a key factor in the diabetic diet; plants such as pulses or soybeans are nutritious products valued highly in nutrition. These legumes are high in the content of wholesome protein and contain large amounts of soluble alimentary fiber fractions, polyunsaturated fatty acids, vitamins and minerals, and bioactive substances with antioxidant, anti-inflammatory, and anticancer activity. They are distinguished by the high amount of bioactive compounds that may interfere with the metabolism of glucose. The most significant bioactive compounds displaying antidiabetic activity in leguminous plants are as follows: genistein and daidzein, alpha-amylase inhibitors, and alpha-glucosidase inhibitors. In vitro research using leguminous plant extracts has confirmed their antidiabetic properties. Leguminous plants should be employed in the promotion of healthy lifestyles in terms of functional food.

  1. Candida albicans Berthout, 1923: hydrolases activity and own method of digestive tract strains biotyping. (United States)

    Kurnatowski, Marek; Wasowska-Królikowska, Krystyna; Kurnatowska, Alicja


    112 strains of Candida albicans were isolated from oral cavity and ontocenoses of the upper digestive tract (endoscopy) of children (age: 5-17) with gastrointestinal disorders. Axenic strains were differentiated with API 20C AUX and API ZYM tests (bioMérieux). Then enzymograms and biotypes were determined for all the strains based on the activity of 19 hydrolases. The highest activity was noted for: e2 - phosphatase alcaline, e6 - leucine arylamidase, e11 - phosphatase acid, e5 - lipase (c14); e7 - valine arylamidase, e12 - naphtol-AS-BI-phosphohydrolase, e16 - alpha-glucosidase and e18 - N-acetyl-beta-glucosamidase, and the latter four were used for biotyping procedures. Our own system was based on the mathematical binominal distribution formula (1 : 4 : 6 : 4 : 1): all "+"; one "-", three "+"; two "-", two "+"; three "-", one "+"; all "-". We have found the following biotypes: A (16.1 +/- 3.5%), B1 (2.7 +/- 2.53%), B3 (8.0 +/- 2.5%), B4 (22.3 +/- 3.9%), C2 (1.8 +/- 1.3%), C3 (7.1 +/- 2.4%), C6 (30.4 +/- 4.3%), D, (11.6 +/- 3.0%).

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

    Directory of Open Access Journals (Sweden)

    Zhang B


    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

  3. 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)


    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.)

  4. Diabetes mellitus in a patient with glycogen storage disease type Ia: a case report. (United States)

    Cohn, Aviva; Ohri, Anupam


    Glycogen storage disease type Ia is a genetic disorder that is associated with persistent fasting hypoglycemia and the inability to produce endogenous glucose. The development of diabetes with glycogen storage disease is exceedingly rare. The underlying pathogenesis for developing diabetes in these patients is unclear, and there are no guidelines for treatment. We describe a case of a 34-year-old woman of South Asian descent with glycogen storage disease type Ia, who developed uncontrolled diabetes mellitus as a young adult. Hyperglycemia was noted after childbirth, and worsened years later. Treatment for diabetes was difficult due to risks of hypoglycemia from her underlying glycogen storage disease. With minimal hypoglycemic events, the patient's blood glucose improved with exercise in combination with a sodium-glucose co-transporter 2 inhibitor and an alpha glucosidase inhibitor. We report a rare case of diabetes in the setting of glycogen storage disease-Ia. Based on the literature, there appears to be a relationship between glycogen storage disease and metabolic syndrome, which likely plays a role in the pathogenesis. The management of glycemic control remains a clinical challenge, requiring management of both fasting hypoglycemia from glycogen storage disease, as well as post-prandial hyperglycemia from diabetes mellitus.

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

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    Xiang-Zhou Li


    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.

  6. Identification a novel mononucleotide deletion mutation in GAA in pompe disease patients

    Directory of Open Access Journals (Sweden)

    Milad Ebrahimi


    Full Text Available Background: Mutations in the acid alpha-glucosidase (GAA gene usually lead to reduced GAA activity. In this study, we analyzed the mutations of GAA and GAA enzyme activity from one sibling suspected Pompe disease and their first-degree relatives. Materials and Methods: In this cross-sectional study, GAA enzyme activity assay was assessed using tandem mass spectrometry. Polymerase chain reaction and Sanger sequencing were performed for GAA analysis. Results: GAA enzyme activity was significantly decreased in patients compared to the normal range (P = 0.02. Two individuals showed ten alterations in the GAA sequence, in which one of them (c. 1650del G has not been previously described in the literature. A single Guanine deletion (del-G was detected at codon 551 in exon 12. Conclusion: According to the literature, the detected change is a novel mutation. We hypothesized that the discovered deletion in the GAA might lead to a reduced activity of the gene product.

  7. Diabetes Management and Hypoglycemia in Safety Sensitive Jobs

    Directory of Open Access Journals (Sweden)

    See-Muah Lee


    Full Text Available The majority of people diagnosed with diabetes mellitus are in the working age group in developing countries. The interrelationship of diabetes and work, that is, diabetes affecting work and work affecting diabetes, becomes an important issue for these people. Therapeutic options for the diabetic worker have been developed, and currently include various insulins, insulin sensitizers and secretagogues, incretin mimetics and enhancers, and alpha glucosidase inhibitors. Hypoglycemia and hypoglycaemic unawareness are important and unwanted treatment side effects. The risk they pose with respect to cognitive impairment can have safety implications. The understanding of the therapeutic options in the management of diabetic workers, blood glucose awareness training, and self-monitoring blood glucose will help to mitigate this risk. Employment decisions must also take into account the extent to which the jobs performed by the worker are safety sensitive. A risk assessment matrix, based on the extent to which a job is considered safety sensitive and based on the severity of the hypoglycaemia, may assist in determining one's fitness to work. Support at the workplace, such as a provision of healthy food options and arrangements for affected workers will be helpful for such workers. Arrangements include permission to carry and consume emergency sugar, flexible meal times, self-monitoring blood glucose when required, storage/disposal facilities for medicine such as insulin and needles, time off for medical appointments, and structured self-help rogams.

  8. Two staining methods for selectively detecting isomaltase and maltase activity in electrophoresis gels. (United States)

    Finlayson, S D; Moore, P A; Johnston, J R; Berry, D R


    Two methods for specifically detecting maltase, alpha-glucosidase, or isomaltase activity in electrophoresis gels are described. Both systems couple the formation of glucose by enzyme action on maltose or isomaltose to the generation of a colored product. System A uses an agarose overlay which contains substrate, glucose oxidase, peroxidase, 2,4-dichlorophenol, and 4-L-amino-phenazone. A purple color is produced at the site of enzyme activity. No hazardous chemicals are used at any stage. The stain is simple, rapid, sensitive, and inexpensive and does not interfere with subsequent protein staining. However, the stain is not permanent. System B was developed to give a permanent stain. The gel is overlaid with agarose containing substrate, glucose oxidase, phenazine methosulfate, and nitroblue tetrazolium. Glucose production results in the nitroblue tetrazolium being oxidized to an insoluble formazan with a dark blue color. This stain is also sensitive, rapid, and inexpensive but does use hazardous chemicals and if overstaining occurs this can interfere with subsequent protein staining. Neither system inactivates the localized enzymes which can be recovered from the gel if desired.

  9. The Active Role of Leguminous Plant Components in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Monika Gętek


    Full Text Available Diabetes appears to be one of the most frequent noncommunicable diseases in the world. A permanent growth in the incidence of diabetes can be observed and according to the International Diabetes Federation (IDF the year 2030 will mark the increase in the number of diabetics to 439 mln worldwide. Type 2 diabetes accounts for about 90% of all diabetes incidence. Nutrition model modification not only features the basic element in type 2 diabetes treatment but also constitutes the fundamental factor influencing a morbidity rate decrease. Leguminous plants are a key factor in the diabetic diet; plants such as pulses or soybeans are nutritious products valued highly in nutrition. These legumes are high in the content of wholesome protein and contain large amounts of soluble alimentary fiber fractions, polyunsaturated fatty acids, vitamins and minerals, and bioactive substances with antioxidant, anti-inflammatory, and anticancer activity. They are distinguished by the high amount of bioactive compounds that may interfere with the metabolism of glucose. The most significant bioactive compounds displaying antidiabetic activity in leguminous plants are as follows: genistein and daidzein, alpha-amylase inhibitors, and alpha-glucosidase inhibitors. In vitro research using leguminous plant extracts has confirmed their antidiabetic properties. Leguminous plants should be employed in the promotion of healthy lifestyles in terms of functional food.

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

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    Noormohammad Noori


    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.

  11. Rapid Identification of α-Glucosidase Inhibitors from Phlomis tuberosa by Sepbox Chromatography and Thin-Layer Chromatography Bioautography (United States)

    Yang, Yingbo; Gu, Lihua; Xiao, Ying; Liu, Qing; Hu, Haijun; Wang, Zhengtao; Chen, Kaixian


    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. PMID:25658100

  12. Inhibitory activities of Moringa oleifera leaf extract against α-glucosidase enzyme in vitro (United States)

    Natsir, H.; Wahab, A. W.; Laga, A.; Arif, A. R.


    Alpha-glucosidase is a key enzyme in the final process of breaking carbohydrates into glucose. Inhibition of α-glucosidase affected more absorption of glucose, so it can reduce hyperglycemia condition. The aims of this study is to determine the effectiveness of inhibition wet and dried Moringa oleifera leaf extract through α-glucosidase activity in vitro. The effectiveness study of inhibition on the activity of α-glucosidase enzyme obtained from white glutinous rice (Oryza sativa glutinosa) was carried out using wet and dried kelor leaf extract of 13% (w/v) with 10 mM α-D-glucopyranoside (PNPG) substrate. A positive control used 1% acarbose and substrate without addition of extract was a negative control. Inhibitory activity was measured using spectrophotometers at a wavelength of 400 nm. The result showed that the inhibition activity against α-glucosidase enzyme of dried leaf extract, wet leaf extract and acarbose was 81,39%, 83,94%, and 95,4%, respectively on pH 7,0. The effectiveness inhibition of the wet Moringa leaf extract was greater than the dried leaf extract. The findings suggest that M. oleifera leaf has the potential to be developed as an alternative food therapy for diabetics.

  13. Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing

    Energy Technology Data Exchange (ETDEWEB)

    Tropea, J.E.; Molyneux, R.J.; Kaushal, G.P.; Pan, Y.T.; Mitchell, M.; Elbein, A.D. (Univ. of Texas Health Science Center, San Antonio (USA))


    Australine is a polyhydroxylated pyrrolizidine alkaloid that was isolated from the seeds of the Australian tree Castanospermum australe and characterized by NMR and X-ray diffraction analysis. Since swainsonine and catanospermine are polyhydroxylated indolizidine alkaloids that inhibit specific glycosidases, the authors tested australine against a variety of exoglycosidases to determine whether it would inhibit any of these enzymes. This alkaloid proved to be a good inhibitor of the {alpha}-glucosidase amyloglucosidase (50% inhibition at 5.8 {mu}M), but it did not inhibit {beta}-glucosidase, {alpha}- or {beta}-mannosidase, or {alpha}- or {beta}-galactosidase. The inhibition of amyloglucosidase was of a competitive nature. Australine also inhibited the glycoprotein processing enzyme glucosidase I, but had only slight activity toward glucosidase II. When incubated with cultured cells, this alkaloid inhibited glycoprotein processing at the glucosidase I step and caused the accumulation of glycoproteins with Glc{sub 3}Man{sub 7-9}(GlcNAc){sub 2}-oligosaccharides.

  14. Mutation profile of the GAA gene in 40 Italian patients with late onset glycogen storage disease type II. (United States)

    Montalvo, A L E; Bembi, B; Donnarumma, M; Filocamo, M; Parenti, G; Rossi, M; Merlini, L; Buratti, E; De Filippi, P; Dardis, A; Stroppiano, M; Ciana, G; Pittis, M G


    Glycogen storage disease type II (GSDII) is a recessively inherited disorder due to the deficiency of acid alpha-glucosidase (GAA) that results in impaired glycogen degradation and its accumulation in the lysosomes. We report here the complete molecular analysis of the GAA gene performed on 40 Italian patients with late onset GSDII. Twelve novel alleles have been identified: missense mutations were functionally characterized by enzyme activity and protein processing in a human GAA-deficient cell line while splicing mutations were studied by RT-PCR and in silico analysis. A complex allele was also identified carrying three different alterations in cis. The c.-32-13T > G was the most frequent mutation, present as compound heterozygote in 85% of the patients (allele frequency 42.3%), as described in other late onset GSDII Caucasian populations. Interestingly, the c.-32-13T > G was associated with the c.2237G > A (p.W746X) in nine of the 40 patients. Genotype-phenotype correlations are discussed with particular emphasis on the subgroup carrying the c.-32-13T > G/c.2237G > A genotype.

  15. Actinomyces timonensis sp. nov., isolated from a human clinical osteo-articular sample. (United States)

    Renvoise, Aurélie; Raoult, Didier; Roux, Véronique


    Gram-positive, non-spore-forming rods were isolated from a human osteo-articular sample (strain 7400942(T)). Based on cellular morphology and the results of biochemical analysis, this strain was tentatively identified as a novel species of the genus Actinomyces. Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that the bacterium was closely related to the type strain of Actinomyces denticolens (96.9 % 16S rRNA gene sequence similarity). A comparison of biochemical traits showed that strain 7400942(T) was distinct from A. denticolens in a number of characteristics, i.e. in contrast with A. denticolens, strain 7400942(T) was negative for nitrate reduction and for beta-galactosidase, alpha-glucosidase and alanine arylamidase activities, it was positive for acid production from N-acetylglucosamine, melezitose and glycogen, and it was negative for acid production from turanose. Matrix-assisted laser-desorption/ionization time-of-flight MS protein analysis confirmed that strain 7400942(T) represents a novel species, as scores obtained for its spectra were significant (>2.2) only with strain 7400942(T). On the basis of phenotypic data and phylogenetic inference, it is proposed that this strain should be designated Actinomyces timonensis sp. nov.; the type strain is strain 7400942(T) (=CSUR P35(T)=CCUG 55928(T)).

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

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    Ali Zarei


    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.

  17. The cardiovascular effect of incretin-based therapies among type 2 diabetes: a systematic review and network meta-analysis. (United States)

    Wu, Shanshan; Cipriani, Andrea; Yang, Zhirong; Yang, Jun; Cai, Ting; Xu, Yang; Quan, Xiaochi; Zhang, Yuan; Chai, Sanbao; Sun, Feng; Zhan, Siyan


    To evaluate the comparative cardiovascular safety of incretin-based therapies in patients with type 2 diabetes mellitus (T2DM). Medline, Embase, the Cochrane Library and were searched for randomized controlled trials (RCTs) with duration≥12 weeks. Network meta-analysis was performed, followed by subgroup analysis and meta-regression. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence. The outcome of interest was a composite of cardiovascular death, myocardial infarction, stroke and heart failure. Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size. 281 RCTs (76.9% double-blinded) with 180,000 patients were included, comparing incretin-based therapies with other six classes of anti-diabetic drugs or placebo. A statistically significant reduction in the risk of cardiovascular events was found in favour of GLP-1RAs when compared with placebo (OR 0.89, 95%CI: 0.80-0.99) and sulfonylurea (OR 0.76, 95%CI: 0.59-0.99), whereas DPP-4 inhibitors showed a neutral effect compared with placebo (OR 0.92, 95%CI: 0.83-1.01). Incretin-based therapies show similar cardiovascular risk in comparison with metformin, insulin, thiazolidinediones, alpha-glucosidase inhibitor and sodium-glucose co-transporter 2. GLP-1RA could decrease the risk compared with sulfonylurea or placebo, while DPP-4I appears to have neutral effect on cardiovascular risk.

  18. Effects of acarbose on proinsulin and insulin secretion and their potential significance for the intermediary metabolism and cardiovascular system. (United States)

    Rosak, Christoph; Mertes, Gabriele


    The alpha-glucosidase inhibitor acarbose is administered to control blood glucose levels in type 2 diabetic patients and, in several countries, in those with impaired glucose tolerance. The efficacy and safety of the drug has been well established in these patient populations. Acarbose shows no weakening of efficacy in long-term diabetes treatment, reduces the development of type 2 diabetes in those with impaired glucose tolerance, and also appears to reduce the risk of cardiovascular disease. The underlying mechanisms of its effect on the risk of developing macrovascular complications have still to be elucidated. The mode of action of acarbose, which precedes all other metabolic processes involved in blood glucose regulation, inhibits high increases in postprandial blood glucose. Due to this early mode of action, acarbose also modifies insulin and proinsulin secretion which are both involved in ss-cell dysfunction and insulin resistance and may be independent risk factors for cardiovascular mortality. Based on the literature available the present state of knowledge on insulin and proinsulin as risk factors for cardiovascular mortality is reviewed as well as the effect of acarbose on the regulation of the ss-cells as monotherapy and in combination regimens. Possible associated interactions with the cardiovascular system are identified.

  19. Phytochemicals Content, Antioxidant and α-Glucosidase Inhibition Activity of Bouea Macrophylla Griff Seed Extract

    International Nuclear Information System (INIS)

    Zainah Adam; Hazlina Ahmad Hassali; Rosniza Razali


    Bouea macrophylla Griff or locally known as kundang is one of the common fruit plant available in Malaysia. This plant from Anacardiaceae family is native to Southeast Asia particularly in Malaysia, Thailand and Indonesia. Medicinal values of this plant is not yet been explored. The present study was done to evaluate phytochemicals constituents in B. macrophylla seed extract qualitatively and quantitatively. Biological evaluations focusing on antioxidant and α-glucosidase inhibition were also performed. Qualitative phytochemicals screening revealed the presence of anthraquinones, terpenoids, flavanoids, tannins, alkaloids, glycosides, reducing sugar, steroids, triterpenes, phenolic, coumarine and proteins in B. macrophylla seed extract. Quantitative determination showed that B. macrophylla seed extract contains high amount of phenolic compounds (689.17±37.50 mg GAE/ g extract), but low amount of flavonoids (2.78±0.01 mg QE/ g extract), suggesting that most of the phenolics in B. macrophylla seed extract were non-flavonoids. Antioxidant assays showed that the extract possesses strong reducing power and DPPH radical scavenging activity (IC 50 : 4.73±0.51 μg/ ml). These activities were almost comparable to that of vitamin C. α-Glucosidase inhibition study showed that the extract inhibited alpha-glucosidase activity potently with the IC 50 value of 0.55±0.04 mg/ ml, suggesting the ability of the plant to delay glucose absorption in small intestine, hence reduces hyperglycemia in diabetic condition. Potent antioxidant and α-glucosidase inhibitory activity of the extract might be attributed to the presence of high amount of phenolic compounds. In conclusion, this study showed that B. macrophylla seed extract contains various phytochemicals, possess strong antioxidant property and showed promising antidiabetic activity. These results indicate that B. macrophylla might have the potential to be developed as new pharmacological agent targeting on oxidative stress

  20. 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.


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    Made Dwi Purnami


    Full Text Available Hypertrophic cardiomyopathy (HCM is an autosomal dominant cardiac disorder marked with muscular hypertrophy of the left ventricle, associated obstruction of left ventricular outflow. About 0.2% of all cases worldwide. The majority of patients are asymptomatic, and some present with severe activity- limiting symptoms. The diagnosis of HCM before the age of 2 years is rare and usually discovered by chance, during the investigation of a murmur. Progressive disease characterized by prominent cardiomegaly, cadiomyopathy, hepatomegaly, musle weakness or hypotonia, respiratory distress, feeding difficulties and failure to thrive as presenting sign and symptoms are often referred to infantile Pompe disease. A deficiency of of the enzyme acid alpha glucosidase disease, result in lysosomal accumulation of glycogen in heart and skeletal muscle. Cardiorespiratory failure is the cause of significant morbidity and mortality in the first year of life. We reported a rare case, 8 month-old female with frequent respiratory distress since 2 months before admission. Physical examination showed dyspnea with chest wall retraction, no cyanosis, with grade III systolic murmur at midclavicular line sinistra, ICS IV- V and floopy infant. Chest films showed   pneumonia and cardiomegaly. The echocardiogram demonstrated bi-ventricular and interventricular hypertrophy with left ventricular obstruction. Laboratory finding there was increased levels of glutamic oxaloacetic acid transferase, alanin aminotransferase, and lactate dehydrogenase. Patient was diagnosed with hypertrophic obstructive cardiomyopathy of suspected infantile onset pompe disease. Despite medical treatment with propanolol dan diuretics, there was no significant improvement and she was died after 26th days of treatment in intermediate ward. [MEDICINA 2014;45:108-14]    

  2. Single nucleotide deletion of cqm1 gene results in the development of resistance to Bacillus sphaericus in Culex quinquefasciatus. (United States)

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


    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. Copyright © 2013. Published by Elsevier Ltd.

  3. Novel method for detection of glycogen in cells. (United States)

    Skurat, Alexander V; Segvich, Dyann M; DePaoli-Roach, Anna A; Roach, Peter J


    Glycogen, a branched polymer of glucose, functions as an energy reserve in many living organisms. Abnormalities in glycogen metabolism, usually excessive accumulation, can be caused genetically, most often through mutation of the enzymes directly involved in synthesis and degradation of the polymer leading to a variety of glycogen storage diseases (GSDs). Microscopic visualization of glycogen deposits in cells and tissues is important for the study of normal glycogen metabolism as well as diagnosis of GSDs. Here, we describe a method for the detection of glycogen using a renewable, recombinant protein which contains the carbohydrate-binding module (CBM) from starch-binding domain containing protein 1 (Stbd1). We generated a fusion protein containing g lutathione S-transferase, a cM c eptitope and the tbd1 BM (GYSC) for use as a glycogen-binding probe, which can be detected with secondary antibodies against glutathione S-transferase or cMyc. By enzyme-linked immunosorbent assay, we demonstrate that GYSC binds glycogen and two other polymers of glucose, amylopectin and amylose. Immunofluorescence staining of cultured cells indicate a GYSC-specific signal that is co-localized with signals obtained with anti-glycogen or anti-glycogen synthase antibodies. GYSC-positive staining inside of lysosomes is observed in individual muscle fibers isolated from mice deficient in lysosomal enzyme acid alpha-glucosidase, a well-characterized model of GSD II (Pompe disease). Co-localized GYSC and glycogen signals are also found in muscle fibers isolated from mice deficient in malin, a model for Lafora disease. These data indicate that GYSC is a novel probe that can be used to study glycogen metabolism under normal and pathological conditions. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail:

  4. Knock down of Whitefly Gut Gene Expression and Mortality by Orally Delivered Gut Gene-Specific dsRNAs. (United States)

    Vyas, Meenal; Raza, Amir; Ali, Muhammad Yousaf; Ashraf, Muhammad Aleem; Mansoor, Shahid; Shahid, Ahmad Ali; Brown, Judith K


    Control of the whitefly Bemisia tabaci (Genn.) agricultural pest and plant virus vector relies on the use of chemical insecticides. RNA-interference (RNAi) is a homology-dependent innate immune response in eukaryotes, including insects, which results in degradation of the corresponding transcript following its recognition by a double-stranded RNA (dsRNA) that shares 100% sequence homology. In this study, six whitefly 'gut' genes were selected from an in silico-annotated transcriptome library constructed from the whitefly alimentary canal or 'gut' of the B biotype of B. tabaci, and tested for knock down efficacy, post-ingestion of dsRNAs that share 100% sequence homology to each respective gene target. Candidate genes were: Acetylcholine receptor subunit α, Alpha glucosidase 1, Aquaporin 1, Heat shock protein 70, Trehalase1, and Trehalose transporter1. The efficacy of RNAi knock down was further tested in a gene-specific functional bioassay, and mortality was recorded in 24 hr intervals, six days, post-treatment. Based on qPCR analysis, all six genes tested showed significantly reduced gene expression. Moderate-to-high whitefly mortality was associated with the down-regulation of osmoregulation, sugar metabolism and sugar transport-associated genes, demonstrating that whitefly survivability was linked with RNAi results. Silenced Acetylcholine receptor subunit α and Heat shock protein 70 genes showed an initial low whitefly mortality, however, following insecticide or high temperature treatments, respectively, significantly increased knockdown efficacy and death was observed, indicating enhanced post-knockdown sensitivity perhaps related to systemic silencing. The oral delivery of gut-specific dsRNAs, when combined with qPCR analysis of gene expression and a corresponding gene-specific bioassay that relates knockdown and mortality, offers a viable approach for functional genomics analysis and the discovery of prospective dsRNA biopesticide targets. The approach can

  5. Aglycone specificity of Escherichia coli alpha-xylosidase investigated by transxylosylation. (United States)

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


    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.

  6. Effects of Lactobacillus acidophilus on gut microflora metabolic biomarkers in fed and fasted rats. (United States)

    Mountzouris, Konstantinos C; Kotzampassi, Katerina; Tsirtsikos, Panagiotis; Kapoutzis, Konstantinos; Fegeros, Konstantinos


    Little is known about fasting effects on gut bacterial metabolism. As probiotics are purported to be beneficial for health, this study aimed to investigate the response of gut microbial metabolism on fasting with or without probiotic administration. Sixty male adult Wistar rats were allocated to six experimental treatments, for 6 days, arranged under three nutritional schemes namely: (a) ad libitum feeding (control), (b) fasting for 3 days and re-feeding for the remainder (re-fed) and (c) fasting for 6 days combined with parenteral liquid treatment during the last 3 days (starved). Each nutritional scheme had one non-probiotic and one probiotic treatment receiving orally Lactobacillus acidophilus. Rat caecal digesta were analyzed for bacterial enzyme activities and volatile fatty acids (VFA). Fasted rats had significantly lower activities of alpha-galactosidase, alpha-glucosidase and beta-glucosidase and higher activities of beta-galactosidase and azoreductase compared to control and re-fed rats, irrespective of probiotic administration. Results were variable regarding cholylglycine hydrolase (CGH), while there were no differences between treatments regarding beta-glucuronidase and arylsulfatase activity. Fasted rats had significantly lower caecal VFA concentration and different fermentation patterns. L. acidophilus resulted in significantly reduced azoreductase activity and increased caecal acetate levels in fasted rats. Re-feeding appeared to restore most enzyme activities, fermentation intensity and to some extent fermentation patterns at control treatment levels. L. acidophilus resulted in significantly reduced CGH activity and increased butyrate levels in re-fed rats. The results indicate a health beneficial potential of L. acidophilus in fasted and re-fed nutritional states via reduction of harmful azoreductase and CGH activities and promotion of useful VFA components for colonic function and health.

  7. 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.

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

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    Mansouri, S.


    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.

  9. Carbohydrate involvement in cellular interactions in sea urchin gastrulation. (United States)

    Khurrum, Maria; Hernandez, Astrid; Eskalaei, Melika; Badali, Oliver; Coyle-Thompson, Cathy; Oppenheimer, Steven B


    The sea urchin embryo is a model for studying cellular interactions that occur in higher organisms because of its availability, transparency, and accessibility to molecular probes. In previous studies, we found that the mannose/glucose-binding lectin Lens culinaris agglutinin entered living sea urchin embryos, bound to specific cell types and caused exogastrulation, when the developing gut (archenteron) falls out of the embryo proper. We have proposed that the lectin bound to sugar-containing ligands, thus preventing attachment of the archenteron to the blastocoel roof, resulting in exogastrulation. Here, we have continued our study of cellular interactions in this model using Lytechinus pictus sea urchin embryos, and have found that inhibitors of glycoprotein/proteoglycan synthesis, tunicamycin and sodium selenate, and the specific glycosidases, beta-amylase, alpha-glucosidase, and alpha-mannosidase, all inhibit archenteron organization, elongation, and attachment to the blastocoel roof in viable swimming embryos. We also show that single cells obtained by disaggregation of 32-h-old sea urchin embryos bind to L. culinaris agglutinin- and concanavalin A-derivatized beads; the binding is blocked by alpha-methyl mannose, but not l-fucose. These cells also bind to beads derivatized with mannan. These results provide evidence for a role of carbohydrate-containing molecules in cellular interactions in sea urchin gastrulation. In a second set of experiments, we found that the supernatant obtained by disaggregation of 24-32-h-old L. pictus embryos in calcium- and magnesium-free sea water contains molecules that cause exogastrulation, archenteron disorganization, inhibition of archenteron elongation and inhibition of archenteron attachment to the blastocoel roof in viable swimming embryos. We propose that the supernatant contains ligands and/or receptors that mediate archenteron development and attachment to the blastocoel roof and are released when embryos are

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

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    Jeong-A eLim


    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

  11. Coordination of sucrose uptake and respiration in the yeast Debaryomyces yamadae. (United States)

    Kaliterna, J; Weusthuis, R A; Castrillo, J I; van Dijken, J P; Pronk, J T


    Screening in batch cultures identified Debaryomyces yamadae as a yeast that exhibits the Kluyver effect for sucrose: this disaccharide can be respired but, even under oxygen-limited conditions, alcoholic fermentation of sucrose does not occur. Ethanol, glycerol and arabitol were the main fermentation products during oxygen-limited growth on glucose in chemostat cultures. None of these fermentation products were produced in oxygen-limited chemostat cultures grown on sucrose and the fraction of the sucrose that could not be respired remained unused in the culture medium. This absence of alcoholic fermentation was not due to repression of the key fermentative enzymes pyruvate decarboxylase and alcohol dehydrogenase. In contrast to some other yeasts that exhibit a Kluyver effect, D. yamadae did not exhibit a preference for ethanol in batch cultures grown on mixtures of ethanol and sucrose. Sucrose metabolism in D. yamadae involves intracellular hydrolysis by an alpha-glucosidase. Incubation of weakly buffered cell suspensions with sucrose led to a rapid transient alkalinization, indicating the presence of a sucrose-proton symport system. The apparent substrate saturation constant of the sucrose-uptake system was 0.2 mmol l-1. Sucrose-dependent alkalinization rates were much lower in samples from oxygen-limited cultures than in samples from aerobic cultures. Transient responses of D. yamadae to oxygen limitation were investigated by applying a sudden decrease in the oxygen feed to aerobic sugar-limited chemostat cultures. In glucose-grown cultures, this led to alcoholic fermentation and no significant accumulation of sugar occurred after the switch. In sucrose-limited cultures, sugar accumulation occurred instantaneously after the switch, and ethanol formation was virtually absent.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Biochemical properties of digestive carbohydrases from the sugar beet weevil, Lixus incanescens (Coleoptera: Curculionidae

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    Seyed Mohammad Ahsaei


    Full Text Available The sugar beet weevil, Lixus incanescens B., is one of the most important pests of sugar beet plant in Iran. The petioles and leaves of sugar beet are attacked by larvae and adults of the sugar beet weevil. Chemical application is currently used for controlling the pest. Digestion in the alimentary canal of the sugar beet weevil is facilitated by some carbohydrases. Results of the in vitro studies indicated the presence of alpha-amylase, beta-glucosidase and beta-galactosidase in the digestive tract of the pest. Highest activities of alpha-amylase, beta-glucosidase and beta-galactosidase were at pH 5, pH 5 and pH 4, respectively. No significant alpha-glucosidase and alpha-galactosidase activity was detected in the pest's digestive system. Optimum temperatures for alpha-amylase, beta-glucosidase and beta-galactosidase activity were determined at 45, 50 and 40 oC, respectively. alpha-amylase was more stable under acidic condition (pH 4 to pH 6 than under highly acidic and alkaline condition. Na+ and K+ increased alpha-amylase activity, but sodium dodecyl sulfate significantly decreased amylase activity. Also, the activity of alpha-amylase was inhibited by the other compounds such as MgCl2, CaCl2 and EDTA. Zymogram analysis using native-PAGE revealed one band of alpha-amylase activity in Lixus incanescens. High activity of carbohydrases in the digestive system of adults was determined and further researches are needed to be applied to design new strategies for controlling the sugar beet weevil based on natural carbohydrase inhibitors.

  13. Activity of hydrolytic enzymes of Candida albicans strains isolated from patients with periodontal and membrane mucosae of oral cavity diseases. (United States)

    Kurnatowska, A J


    Fungi are elements of the ontocenosis of the oral cavity and causal factors of inflammatory lesions in its mucous membrane. The objective of the study was to find differences in the activity of hydrolytic enzymes of Candida albicans isolated from patients with diseases of the periodontium and mucous membrane of the oral cavity. Of 235 patients examined, 31 were diagnosed with gingivitis, 38 with glossitis, 28 with leucoplakia, 37 with adult periodontitis, 25 with juvenile periodontitis, 36 stomatitis prothetica and 40 with stomatitis atrophica. In 196 patients (83.4 +/- 2.4%), fungi belonging to Candida species were detected. In the evaluation of Candida albicans strains (146) properties, bioMerieux API ZYM tests containing substrates for the detection of 19 hydrolases were used. All the investigated strains were characterized by the activity of 14 enzymes, i.e. phosphatase alcaline, esterase (C4), esterase lipase (C8), leucine and valine arylamidase, phosphatase acid, naphthol-AS-BI-phosphohydrolase, alpha galactosidase, beta galactosidase, alpha glucosidase, beta glucosidase, N-acetyl-beta-glucosaminidase, alpha mannosidase and alpha fucosidase. Strains isolated from the oral cavity of patients with disease of periodontium and mucous membrane are characterised by the highest phosphatase acid activity. The greatest enzymatic activity is characteristic of Candida albicans isolated from patients with stomatitis atrophica or stomatitis prothetica, and the lowest in strains from gingivitis or juvenile periodontitis cases. Differences in the activity of hydrolases are statistically significant (p phosphatase acid, naphthol-AS-BI-phosphohydrolase, beta glucosidase, N-acetyl-beta-glucosaminidase, of fungi isolated from patients with particular clinical diagnoses.

  14. Effect of Acarbose on Control of Metabolic Parameters in Patients with Diabetes Type 1

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    A. Ziaee


    Full Text Available Introduction & Objective: Acarbose is an intestinal alpha-glucosidase inhibitor that delays absorption of carbohydrates. Findings of some studies show that it has been effective in better control of blood glucose in patients with diabetes type 1. The goal of this study is to investigate the effect of administration of acarbose on glycemic & lipid parameters and daily insulin requirements and tolerability in type 1 diabetic patient.Materials & Methods: This was a clinical trial randomized double blind placebo controlled study. Performed on patients with history of at least 1 year diabetes type 1 and had HbA1c≥7.5%. Patients with Cr≥2, partial GI obstruction or IBD were excluded from the study. 45 patients were randomized to be administered acarbose or placebo for 12 weeks. Initial dose of acarbose was 25 mg T.D.S for 2 weeks, and then it was increased to 50 mg T.D.S for 10 weeks. BMI, FBS, 2hpp, HbA1c, Total cholesterol, HDL, LDL, TG and Insulin dosage were investigated monthly.Results: The values of BMI, FBS, 2hpp, HbA1c, Total cholesterol, and TG & Insulin requirements decreased significantly in the case group compared to the controls (P=0.003, P=0.005, P<0.001, P=0.001, P=0.003, P<0.001, P<0.001, respectively; but no significant changes were observed in HDL &LDL levels. Conclusion: Administration of acarbose together with insulin to type 1 diabetic patient can be valuable in improving metabolic control (BMI, FBS, 2hpp, HbA1c, Total cholesterol and TG.(Sci J Hamadan Univ Med Sci 2012;19(2:5-10

  15. Reguladores prandiales de la glucemia Prandial glycemia regulators

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    José A. Mesa Pérez


    Full Text Available Se hizo una revisión actualizada sobre un nuevo grupo de drogas que actúan por vías diferentes y por distintos mecanismos de acción regulan la hiperglucemia posprandial en los pacientes con diabetes mellitus. Se destacó la repaglinida, agente secretagogo insulínico independiente de las sulfonilureas, que ayuda a restaurar la fisiología del fallo en el pico secretor insulínico inicial, en pacientes con diabetes tipo 2 y de la acarbosa, agente inhibidor de las alfas glucosidadas intestinales. La hiperglucemia posprandial es determinante en la aparición de las complicaciones vasculares, por lo cual se concluyó que estos grupos de medicamentos ayudarían a alcanzar un mejor control metabólico y representan nuevas opciones medicamentosas en el arsenal terapéutico para la diabetes mellitus tipo 2.An updated review on a new group of drugs that act by different ways and that regulate postprandial hyperglycemia in diabetic patiens by different mechanisms of action was made. The roles played by repaglinide, an insulin secretagogue agent independent of sulphonilureas that helps to restore the physiology of the failure in the initial insulin secreting peak in type 2 diabetics, and by acarbose, an intestinal alpha-glucosidase inhibitor, were stressed. As postprandial hyperglycemia is determinant in the appearance of vascular complications, it was concluded that these groups of drugs may help to attain a better metabolic control and that they represent new drug options to treat type 2 diabetes mellitus.

  16. Effects on Diabetes Medications, Weight and Glycated Hemoglobin Among Adult Patients With Obesity and Type 2 Diabetes: 6-Month Observations From a Full Meal Replacement, Low-Calorie Diet Weight Management Program. (United States)

    Shiau, Judy Y; So, Derek Y F; Dent, Robert R


    A 6-month weight-management program with full meal replacement, low-calorie diet (full MR-LCD) (900 kcal/day for 6 to 12 weeks) follows a protocol for patients with diabetes for decreasing or discontinuing weight-gaining diabetes medications first (Group WG) and then titrating weight-neutral medications (Group WN). This is a retrospective cohort study (1992 to 2009) of weight, glycemic control and diabetes medications changes in 317 patients with obesity and type 2 diabetes who were taking medications. Group WG and Group WN were similar at baseline, except that glycated hemoglobin (A1C) levels were significantly lower in Group WN (7.5% vs. 6.6%; p<0.001). At 6 months, both groups had lost 16% of their weight, and the decreases or discontinuations of medications were 92.1% sulfonureas, 86.5% insulins, 78.8% thiazolidinediones, 77.8% alpha-glucosidase inhibitors, 50% meglitinides, 33.3% dipeptidyl peptidase-4 (DPP-4) inhibitors and 32.8% metformin. At 6 months, compared with baseline, A1C levels improved in Group WG and Group WN (6-month A1C levels 6.7% and 5.8%, respectively; p<0.0001), and Group WN had significantly better A1C levels than Group WG. At 6 months, 30% of patients were no longer taking diabetes medications and had significantly better percentages of weight loss compared with those taking medications (18.6% vs. 16%; p=0.002); both groups had improved glycemic control at 6 months (A1C 6.0% vs. A1C 6.6%; NS). In patients with obesity and type 2 diabetes taking medications, a full MR-LCD program appears to be safe and includes improvement in A1C levels. At 6 months, the percentage of weight loss can be significantly better in patients who no longer require diabetes medications, and A1C levels are best controlled in patients who are on WN medications. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  17. Improvement of both fasting and postprandial glycemic control by the two-step addition of miglitol and mitiglinide to basal insulin therapy: a pilot study. (United States)

    Ihana, Noriko; Tsujimoto, Tetsuro; Yamamoto-Honda, Ritsuko; Kishimoto, Miyako; Kajio, Hiroshi; Noto, Hiroshi; Kakei, Masafumi; Noda, Mitsuhiko


    Combination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) is effective for the treatment of type 2 diabetes (T2DM) that cannot be adequately controlled using OHAs alone. Though basal insulin with metformin or sulfonylurea is an effective therapy, it cannot reduce postprandial glycemia without the risk of hypoglycemia. We examined a two-step regimen consisting of the addition of postprandial hypoglycemic agents (an alpha-glucosidase inhibitor and a glinide) in patients whose T2DM was poorly controlled using basal insulin therapy. Inpatients between the ages of 30-79 years who had T2DM and an HbA1c level of more than 7.0% were recruited. The patients were treated with once-daily insulin glargine with or without metformin, depending on the patient's age and renal function. Insulin glargine was titrated to achieve a target fasting glucose level of 70-130 mg/dL as a first step (STEP0). If the 2-hour postprandial glucose (PBG) level was higher than the target of 180 mg/dL, miglitol treatment (150 mg/day) was initiated, with dose adjustments (75-225 mg) allowed depending on abdominal symptoms and the PBG (STEP1). If the PBG of the patients remained higher than the target after 3 days of treatment, mitiglinide (30 mg/day, titrated up to 60 mg) was added (STEP2). We then evaluated the proportion of patients who achieved the target PBG before and after the two-step regimen. Continuous Glucose Monitoring (CGM) was performed throughout the two-step protocol in most of the patients. Of the 16 patients who were recruited (median age, 67.0 [58.0-71.0] years; body mass index, 25.0 [22.0-27.9] kg/m(2); HbA1c level at admission, 9.1% [8.35-10.4%]), 1 patient (6.25%) achieved the target PBG at STEP 0 and 14 patients (87.5%) had achieved the target PBG at the end of the treatment protocol (P = 0.002). CGM showed a significant decrease in the glucose level at each step of the protocol. The standard deviations in the CGM glucose levels for 24

  18. In vitro biological assessment of Homalium zeylanicum and isolation of lucidenic acid A triterpenoid

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    Atish Kumar Sahoo

    Full Text Available Homalium zeylanicum (Gardner Benth. (Flacourtiaceae is a medicinal plant useful in controlling rheumatism, inflammation and diabetes. The objective of this work evaluates in vitro antioxidant, antidiabetic, and antiinflammatory properties of hydroalcohol extract of bark of H. zeylanicum (HAHZ. It also describes isolation and structure determination of lucidenic acid A, which is the first report in this plant. In order to explain the role of antioxidant principles, DPPH, nitric oxide, hydroxyl, superoxide and metal chelating assays were performed. Antidiabetic and anti-inflammatory activities were investigated by quantifying α-amylase, α-glucosidase and protein denaturation inhibitory activities of HAHZ. Biochemical estimations were performed. The chemical structure of the triterpenoid was elucidated using 1H, 13C NMR and high resolution-MS. IC50 of DPPH, nitric oxide, hydroxyl, superoxide and metal chelating activities were of 36.23 ± 0.27, 40.11 ± 0.32, 35.23 ± 0.57, 43.34 ± 0.22 and 11.54 ± 0.08 μg/mL, respectively. IC50 of α-amylase and α-glucosidase activities were 29.12 ± 0.54, and 18.55 ± 0.15 μg/mL. Total phenolic and total flavonoid contents were recorded at 233.65 mg/g GAE and 172.7 mg/g QE. Regarding kinetic behaviour, HAHZ showed competitive inhibition on α-glucosidase and mixed competitive inhibition on α-amylase. Lucidenic acid A was confirmed by spectroscopic studies. Anti-inflammatory activity of lucidenic acid A was determined by using protein denaturation assay with IC50 13 μg/mL but HAHZ showed 30.34 ± 0.13 μg/mL. Phenols and flavonoids could be attributed to inhibition of intestinal carbohydrases for anti-diabetic activities whereas triterpenoids could be responsible for anti-inflammatory activity of H. zeylanicum. Keywords: Homalium zeylanicum, Lucidenic acid a, Antidiabetic, Antiinflammatory, &alpha

  19. The association of yogurt starters with Lactobacillus casei DN 114.001 in fermented milk alters the composition and metabolism of intestinal microflora in germ-free rats and in human flora-associated rats. (United States)

    Djouzi, Z; Andrieux, C; Degivry, M C; Bouley, C; Szylit, O


    The aim of this study was to compare the effects of milk and of various fermented milks on the composition and metabolic activities of the intestinal microflora. Groups of eight rats were fed for 6 wk a diet containing 30% nonfermented milk (M), yogurt (Y), milk fermented with Lactobacillus casei (LcFM) or milk fermented with the association of L. casei DN 114.001 and yogurt starters (LcYFM). In the first study, the survival of the lactic acid bacteria from the fermented milks was assessed by bacterial enumeration in feces of germ-free rats (GF rats) fed milk or fermented milks. The metabolic activities of the lactic acid bacteria were studied in these rats by the measurement of glycolytic activities and products of bacterial fermentation, i.e., acetate and lactate (isoforms L and D). In a second study, the effects of fermented milks on the composition and metabolism [gas, glycolytic activities, short-chain fatty acids (SCFA), alcohol and ammonia] of human flora were studied using human flora-associated rats (HF rats). In GF rats, the survival of L. casei in the feces did not differ between those fed the LcFM and LcYFM diets. L. bulgaricus was detected in the feces of the rats fed Y, whereas Streptoccus thermophilus was found in the feces of the LcYFM group. In HF rats, fecal concentration of Bifidobacteria was greater in the LcFM group than in the others. beta-Glucuronidase (EC activity was lower in rats fed LcFM and Y than in those fed M and LcYFM, whereas beta-galactosidase (, alpha-glucosidase (EC 3.2.1 20) and beta-glucosidase (EC activities were higher in the LcYFM group compared with the others. Methane excretion was higher in rats fed Y than in other groups. Cecal SCFA concentrations did not differ in LcFM, Y and M groups, but total SCFA, acetate, propionate and butyrate were significantly greater in the LcYFM group. These results suggest that milk fermented with the combination of L. casei and yogurt starters leads to specific

  20. Modulation of adipocyte lipoprotein lipase expression as a strategy for preventing or treating visceral obesity. (United States)

    McCarty, M F


    As compared to subcutaneous adipocytes, visceral adipocytes have high basal lipolysis, are highly sensitive to catecholamines, and are poorly sensitive to insulin; these traits are amplified when visceral adipocytes hypertrophy. As a result, enlarged visceral fat stores tend to flood the portal circulation with free fatty acids at metabolically inappropriate times when fatty acids are unlikely to be oxidized, thus exposing tissues to excessive free fatty acid levels and giving rise to the insulin resistance syndrome. A logical approach to preventing or correcting visceral obesity is to down-regulate the lipoprotein lipase (LPL) activity of visceral adipocytes relative to that expressed in subcutaneous adipocytes and skeletal muscle. IGF-I activity appears to be a primary determinant of visceral LPL activity in humans; systemic IGF-I activity is decreased when diurnal insulin secretion is low, when hepatocytes detect a relative paucity of certain essential amino acids, and when estrogens are administered orally. The ability of alpha-glucosidase inhibitor therapy to selectively reduce visceral adiposity suggests that down-regulation of diurnal insulin secretion and/or IGF-I activity may indeed have a greater impact on LPL activity in visceral fat than in subcutaneous fat. Thus, low-glycemic-index, vegan, high-protein, or hypocaloric diets can be expected to decrease visceral LPL activity, as can postmenopausal estrogen therapy. Furthermore, estrogen enhances the LPL activity of non-pathogenic gluteofemoral fat cells, whereas testosterone decreases visceral LPL activity in men; this may explain why sex hormone replacement in middle-aged people of both sexes has a favorable impact on visceral fat and insulin sensitivity. Beta-adrenergic activity suppresses transcription of LPL in adipocytes; this phenomenon may contribute to the favorable impact of exercise training on visceral obesity; conceivably, preadministration of safe drugs that boost catecholamine activity

  1. Seasonal variation in phytochemicals and nutraceutical potential of Begonia nelumbiifolia consumed in Puebla, México. (United States)

    Villa-Ruano, Nemesio; Pacheco-Hernández, Yesenia; Cruz-Durán, Ramiro; Lozoya-Gloria, Edmundo; Betancourt-Jiménez, Martha G


    Begonia nelumbiifolia is a traditional edible plant consumed and commercialized in the northern highlands of Puebla, México. The present study reports the seasonal variation in proximate analysis as well as organic acids, carotenoids and flavonoids content in both leaves and stalks of this plant. The stalks contained low concentrations of protein (~3%), fiber (~1.5%) and nitrogen free extract (~0.26%) during the time of study. Both organs showed contents of oxalic acid (91-103 mg 100 g -1 FW), ascorbic acid (50-65 mg 100 g -1 FW), lutein (1-2.5 mg 100 g -1 FW), β-carotene (1-3 mg 100 g -1 FW), quercetin (1.3-2.7 mg 100 g -1 DW) and rutin (0.5-1.7 mg 100 g -1 DW). Antioxidant activity against DPPH was observed by the stalk extracts from 30% methanol (IC 50 , 0.21-0.37 mg L -1 ), pure methanol (IC 50 , 0.14-0.21 mg L -1 ) and hexane: acetone (IC 50 , 0.77-1.21 mg L -1 ). In vitro anti-HMG-CoA reductase (IC 50 , 0.07-0.36 mg L -1 ) and anti-alpha-glucosidase (IC 50 , 0.28-0.43 mg L -1 ) activities were observed in extracts from the edible stalks from pure methanol and 30% methanol. The leaf extracts from 30% methanol inhibited the growth of Pseudomonas syringae pv. tabaci TBR2004 (MIC, 254 µg mL -1 ), P. syringae pv. tomato DC3000 (MIC, 423 µg mL -1 ), P. syringae pv. glycinea (MIC, 605 µg mL -1 ) and Clavibacter michiganensis AB299158 (MIC, 162 µg mL -1 ). B. nelumbiifolia contained valuable phytochemicals associated to nutraceutical and biological properties. However, the consumption of the fresh stalks must be carefully considered because of the high oxalate content.

  2. Impact of Voglibose on of Metabolic Control Indicators in Patients with Diabetes Mellitus Type 1

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    V.I. Pankiv


    Full Text Available New therapeutic options to control diabetes mellitus (DM emerged with the discovery of alpha-glucosidase inhibitors which slow the absorption of carbohydrates in the small intestine. The objective of the study — to investigate the effect of voglibose administration on parameters of glycemic control, lipid metabolism and tolerability in patients with DM type 1. Materials and Methods. Criteria for inclusion in the study: DM type 1, age from 26 to 48 years, the level of glycated hemoglobin (HbA1c from 8 to 9 %. 19 patients were examined (7 men and 12 women, mean age 37.2 ± ± 3.9 years, DM duration 8.5 ± 1.4 years. Results. During the follow-up period (12 weeks, the level of HbA1c significantly decreased from 9.4 ± 0.6 % to 7.8 ± 0.4 % (p < 0.05. On the background of additional administration of voglibose, we observed a significant reduction in fasting glucose level from 10.37 ± 0.36 mmol/l to 7.39 ± 0.28 mmol/l (p < 0.01 and postprandial — from 12.29 ± 1.42 mmol/l to 8.46 ± 0.64 mmol/l (p < 0.01. At that, we have noted a significant reduction of total cholesterol (from 5.83 ± 0.11 mmol/l to 5.38 ± 0.08 mmol/l, p < 0.05, triglycerides (from 1.82 ± 0.03 mmol/l to 1.46 ± 0.03 mmol/l, p < 0.05 and low-density lipoprotein cholesterol (from 3.41 ± 0.05 mmol/l to 3.37 ± ± 0.04 mmol/l, p < 0.05. There were no significant changes in high-density lipoprotein cholesterol parameters. In two surveyed persons, we have detected adverse effects (bloating, which did not require discontinuation of therapy. Conclusion. Additional administration of voglibose at a dose of 0.9 mg/day on a background of insulin therapy helps to improve glycemic control and lipid metabolism, to reduce the daily dose of exogenous insulin and hypoglycemic reactions incidence in patients with DM type 1.

  3. Recent developments and emerging therapies for type 2 diabetes mellitus. (United States)

    Evans, A J; Krentz, A J


    Most patients with type 2 (non-insulin-dependent) diabetes mellitus require pharmacotherapy, initially as monotherapy and subsequently in combination, as adjuncts to diet and exercise. Exogenous insulin is ultimately required in a substantial proportion, reflecting the progressive natural history of the disease. Sulphonylureas and biguanides have been employed for over 4 decades as oral antidiabetic agents, but they have a limited capacity to provide long term glycaemic control and can cause serious adverse effects. Thus, more efficacious and tolerable antidiabetic agents are required. Recent years have witnessed the introduction of agents with novel modes of action, that is, the alpha-glucosidase inhibitors acarbose and miglitol (which reduce postprandial hyperglycaemia) and the first of the thiazolidinedione insulinsensitising drugs--troglitazone and rosiglitazone. Although the former has been withdrawn in some countries due to adverse effects, another 'glitazone' pioglitazone is expected to be approved in the near future. Other recently introduced drugs include glimepiride and the meglitinide insulin secretagogue, repaglinide. Attention is also focusing increasingly on combination therapy using insulin together with sulphonylureas, metformin or troglitazone. Rapid-acting insulin analogues are now being used as alternatives to conventional insulins; their role in the management of type 2 diabetes mellitus is presently uncertain but reports of a reduced frequency of hypoglycaemia are encouraging. The development of new drugs aims to counter the principal metabolic defects of the disorder, respectively, relative insulin deficiency and insulin resistance. Novel classes of rapid-acting secretagogues under evaluation include the morphilinoguanide BTS 67582 and the meglitinides mitiglinide (KAD 1229) and senaglinide (A-4166). Succinate ester derivatives represent a potential novel approach to improving beta-cell function through enhancement of insulin biosynthesis and

  4. Aislamiento y caracterización bioquímica de la α-glucosidasa II del hongo patógeno Candida albicans Aislamiento y caracterización bioquímica de la α-glucosidasa II del hongo patógeno Candida albicans

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    Arturo Flores Carreón


    Full Text Available Alpha-glucosidase II participates in N-linked glycosylation of proteins. A soluble 47 kDa α-glucosidase II has been previously isolated from C. albicans; however, bioinformatics analysis indicate that native enzyme has a molecular mass of 100 kDa. In this study we assessed the effect of protease inhibitors on intracellular distribution of α-glucosidase II. Despite there was not a significant change in the enzyme distribution, α-glucosidase II activity was associated to a 83 or 47 kDa polypeptide in absence or presence of inhibitors, respectively. Soluble 83-kDa protein was purified by conventional methodology and its biochemical characteristics were similar to those reported for the 47 kDa enzyme. Thus, these results indicated the 83 kDa protein is an α-glucosidase II and also suggested it is a precursor of the 47 kDa enzyme previously reported. La α-glucosidasa II participa en la ruta de la N-glicosilación de proteínas. En Candida albi­cans se ha aislado un polipéptido soluble de 47 kDa con actividad de α-glucosidasa II; sin embargo, análisis bioinformáticos indican que la enzima nativa pudiera tener un peso mo­lecular de 100 kDa. En este trabajo se estudió el efecto de inhibidores de proteasas sobre la distribución intracelular de la α-glucosidasa II. Se demostró que la distribución intracelular no fue afectada significativamente, pero la actividad de la α-glucosidasa II estuvo asociada a una proteína de 83 ó 47 kDa en ausencia o presencia de inhibidores de proteasas, res­pectivamente. La enzima soluble de 83 kDa se purificó por métodos convencionales y se demostró que presenta características bioquímicas similares a la enzima de 47 kDa. Estos datos confirmaron que la proteína de 83 kDa es una α-glucosidasa II y sugieren que es precursora de la enzima de 47 kDa previamente descrita.

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

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    Lineu Cesar Werneck


    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

  6. The anti-diabetic drug miglitol is protective against anginal ischaemia through a mechanism independent of regional myocardial blood flow in the dog. (United States)

    Uno, Yoshihiro; Minatoguchi, Shinya; Arai, Masazumi; Wang, Ningyuan; Chen, Xue-Hai; Hashimoto, Kazuaki; Lu, Cuanjiang; Takemura, Genzou; Fujiwara, Hisayoshi


    1. In the present study, we attempted to clarify whether the antidiabetic drug miglitol, an alpha-glucosidase inhibitor, has a protective effect against anginal ischaemia. We had reported previously that miglitol reduces myocardial infarct size through inhibition of glycogenolysis during ischaemia in rabbits. However, the effect of miglitol on anginal ischaemia remains unknown. 2. In open-chest beagle dogs with a severely stenosed left anterior descending coronary artery, an epicardial electrode was attached to the surface of the risk area of the left ventricle and a microdialysis probe was implanted into the myocardium to measure ST segment changes and interstitial lactate accumulation. The first episode of anginal ischaemia was induced by atrial pacing and phenylephrine infusion (50-100 microg/min) for 10 min. The second episode of anginal ischaemia was induced 210 min after the first episode. Miglitol (10 mg/kg, i.v.) was administered to the miglitol group (n = 10) 30 min before the second episode of anginal ischaemia, whereas saline was administered to the control group (n = 10). Regional myocardial blood flow was measured using coloured microspheres. 3. There was no significant difference in regional myocardial blood flow in the risk and non-risk areas between the first and second episodes of anginal ischaemia and between the miglitol and control groups. During the first and second episodes of anginal ischaemia, the ST segment was decreased to a similar extent in the control group. Although ST segment depression during the first episode of anginal ischaemia was similar in both groups, ST segment depression during the second episode of anginal ischaemia was significantly attenuated in the miglitol-treated group compared with the control group (1.3 +/- 0.4 vs 2.2 +/- 0.4 mV, respectively). Miglitol significantly attenuated myocardial interstitial lactate accumulation in the risk area. 4. In conclusion, in the present study miglitol improved ST segment depression

  7. Comparing Seminal Plasma Biomarkers between Normospermic and Azoospermic Men (United States)

    Sabetian, Soudabeh; Ardekani, Ali M.; Hodjat, Mahshid; Akhondi, Mohammad Mehdi; Soltanghoraee, Haleh; Amirjannati, Naser; Lakpour, Niknam; Sadeghi, Mohammad Reza


    Introduction Azoospermia affects more than 10% - 15% of infertile male subjects attending infertilty clinics. At present, testicular biopsy is the golden standard procedure for evaluating spermatogenesis status in men with azoospermia. Semen collection and analysis is a non-invasive method and has proven to be valuable in the evaluation of spermatogenesis. Identification of seminal plasma markers with testicular or extra-testicular origins have a great value in predicting the prescence of sperm in testicular tissue and presumptive cause of azoospermia. The aim of this study was to find such markers by comparing the content of seminal plasma using different methods in normospermic and azoospermic men. Materials and Methods Semen samples were collected from 200 men attending Avicenna Infertility Clinic (AIC) in Tehran, Iran. Semen samples were analysed according to WHO guidlines. The subjects were divided into two groups: normospermic (n = 100; group one) and azoospermic men (n = 100; group two) according to semen analysis results. Seminal plasma was separated by high speed centrifuagation and stored in -20° C. Four markers including fructose, neutral alpha glucosidase (NαG), inhibin B and anti-Müllerian hormone (AMH) were measured in seminal plasma. Fructose and NαG were evaluated by spectrophotometry, while inhibin B and AMH were assessed by ELISA method. The spermatogenesis status in the azoospermic group was evaluated by histopathological method following testicular biopsy. Results Fructose concentration showed no difference between the two groups. However, it was significantly correlated with sperm count (p < 0.01, r = -0.408). Seminal plasma inhibin B (OR: 1.01; 95%: CI: 1.005 - 1.016), AMH (OR: 1.63; 95% CI: 1.17 - 2.28) and NαG, (OR: 1.07; 95% CI: 1.04 - 1.1) levels were higher in normospermic subjects compared to azoospermic men. There were significant differences in inhibin B and AMH concentrations between the two groups based on the presence or

  8. Positive effects of acarbose in the diabetic rat are not altered by feeding schedule. (United States)

    Wright, B E; Vasselli, J R; Katovich, M J


    We previously demonstrated that chronic dietary treatment with acarbose, an alpha-glucosidase inhibitor, improves glucose homeostasis in the streptozotocin (STZ)-induced diabetic rat. In this study we evaluated the effects of 4 weeks of acarbose treatment on glucose homeostasis in STZ-diabetic rats for both meal-fed (three times daily) and ad libitum feeding conditions. Sprague Dawley male rats (n = 58) were started on a daily meal-feeding paradigm consisting of three 2-h feeding periods: 0700 to 0900 hours, 1300 to 1500 hours, and 1900 to 2100 hours. Following 2 weeks of adaptation, half of the animals were switched to ad libitum feeding. The feeding paradigm itself (meal fed versus ad lib.) affected neither body weight nor daily food intake. Twenty animals from each feeding group then received STZ (60 mg/kg i.v.), whereas control animals received vehicle injections only. Two days later, the diet of 10 STZ-treated animals from each paradigm was supplemented with acarbose (40 mg of BAY G 5421/100-g diet), and the groups were treated for 4 weeks. Untreated diabetic rats had lower body weight than vehicle-injected control rats at all time points after STZ treatment. Acarbose treatment delayed this effect on body weight. STZ treatment induced hyperphagia regardless of feeding paradigm, which was significantly attenuated by acarbose only for the first week of treatment. Untreated diabetic rats had fasting blood glucose values 4 times those of vehicle-injected controls in both the meal-fed and ad libitum-fed conditions. Acarbose significantly lowered fasting blood glucose in the treated STZ groups. Blood glucose was also assessed 0, 90, and 180 min following the start of a meal. The postprandial rise in blood glucose was significantly reduced in acarbose-treated meal-fed diabetic rats, to values not significantly different from those of vehicle-injected control rats. During the fourth week of treatment glycated hemoglobin levels were significantly higher in untreated

  9. Bacterial and enzymatic bioassays for toxicity testing in the environment. (United States)

    Bitton, G; Koopman, B


    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. Bacterial toxicity tests are based on bioluminescence, motility, growth, viability, ATP, oxygen uptake, nitrification, or heat production. An important aspect of bacterial tests is the permeability of cells to environmental toxicants, particularly organic chemicals of hydrophobic nature. Physical, chemical, and genetic alterations of the outer membrane of E. coli have been found to affect test sensitivity to organic toxicants. Several microbioassays are now commercially available. The names of the assays and their basis are: Microtox (bioluminescence), Polytox (respiration), ECHA Biocide Monitor (dehydrogenase activity), Toxi-Chromotest (enzyme biosynthesis), and MetPAD (enzyme activity). An important feature common to these tests is the provision of standardized cultures of bacteria in freeze-dried form. Two of the more recent applications of microbioassays are in sediment toxicity testing and toxicity reduction evaluation. Sediment pore water may be assayed directly or


    Directory of Open Access Journals (Sweden)

    V. G. Kadzharyan


    Full Text Available Diabetes mellitus (DM is a major medical and social problem almost in all countries of the world. Currently, there are more and more various pharmacological agents that make management of the glycaemia in patients with type 2 diabetes extremely difficult. Therefore, when the physician is faced with the choice of glucose-lowering therapy, he should be clearly aware of all the options in contemporary treatment. 11 groups of hypoglycemic agents are used for the treatment of type 2 diabetes The biguanides. According to modern concepts, biguanides inhibit the oxidation of glucose by stimulating anaerobic glycolysis. Both in the consensus of ADA / EASD, and in the IDF recommendations metformin may be the drug of the choice for hypoglycemic therapy of diabetes type 2. Sulfonylurea derivatives: glibenclamide, glimepiride, gliquidone, Glipizide. They belong to a group of secretagogues, as their action is based on the ability to stimulate the secretion of insulin by ß-cells of the pancreas. Prandial glucose regulators. Meglitinides (repaglinide and nateglinide stimulate insulin secretion by ß-cells. Due to the rapid normalization of stimulated insulin level after taking the drugs the risk of hypoglycaemia between meals is minimized. Insulin sensitayzers. Thiazolidinediones (rosiglitazone, pioglitazone reduce insulin resistance of peripheral tissues by binding to receptors, activating peroxisome proliferation (PPARg in the nuclear membrane. Alpha-glucosidase inhibitors (acarbose, miglitol, voglibose competitively inhibits intestinal enzymes (α-glucosidase. It consequently slows carbohydrate absorption from foods and supply of glucose into the blood. Incretin mimetics. Analogues of glucagon-like peptide 1 (GLP-1 stimulate the biosynthesis and secretion of insulin, regulate food consumption, support ß-cells in a healthy state, suppress glucagon secretion, depending on the glucose levels, affect the rate of gastric emptying, stimulat proliferation of

  11. Patrones de prescripción de antidiabéticos en un grupo de pacientes colombianos Antidiabetic drugs prescription patterns among a group of patients in Colombia

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    Jorge Enrique Machado Alba


    prescribed from two to four. The medications prescribed were: biguanides (67.5%, sulphonylureas (64.9%, insulin (23.5%, and thiazolidinediones (0.1%. The most common oral combination-therapies were: glibenclamide and metformin (n = 2 847, metformin and insulin (n = 510, glibenclamide and insulin (n = 148, and metformin, insulin, and glibenclamide (n = 288. Of the total, 94.3% had comorbid conditions for which they had been prescribed medication: antihypertensive drugs (in 74.4% of the cases, anti-inflammatories (61.5%, hypolipemiants (45.5%, antiulcer medications (21.0%, psychoactive drugs (16.8%, antimicrobials (14.4%, asthma medication (5.3%, and salicylic acid (2.8%. Prescriptions for comorbid conditions were more common among women than men (95.6% vs. 92.7%, P < 0.001. Undertreatment with certain medications (metformin, thiazolidinediones, alpha-glucosidase inhibitors, and salicylic acid, and overtreatment with others (antiulcer drugs, probably exist. CONCLUSIONS: There are significant differences in oral therapies prescribed for diabetes across the 19 cities studied, but overall, prescription patterns are appropriate. Educational strategies should be developed to address those prescribing practices that are not appropriate, and the clinical results of the medications studied should be explored.

  12. Salivary gland proteins of the human malaria vector, Anopheles dirus B (Diptera: Culicidae Proteínas das glândulas salivares do Anopheles dirus B (Diptera: Culicidae, vetor da malária humana

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    Narissara Jariyapan


    Full Text Available Salivary gland proteins of the human malaria vector, Anopheles dirus B were determined and analyzed. The amount of salivary gland proteins in mosquitoes aged between 3 - 10 days was approximately 1.08 ± 0.04 µg/female and 0.1 ± 0.05 µg/male. The salivary glands of both sexes displayed the same morphological organization as that of other anopheline mosquitoes. In females, apyrase accumulated in the distal regions, whereas alpha-glucosidase was found in the proximal region of the lateral lobes. This differential distribution of the analyzed enzymes reflects specialization of different regions for sugar and blood feeding. SDS-PAGE analysis revealed that at least seven major proteins were found in the female salivary glands, of which each morphological region contained different major proteins. Similar electrophoretic protein profiles were detected comparing unfed and blood-fed mosquitoes, suggesting that there is no specific protein induced by blood. Two-dimensional polyacrylamide gel analysis showed the most abundant salivary gland protein, with a molecular mass of approximately 35 kilodaltons and an isoelectric point of approximately 4.0. These results provide basic information that would lead to further study on the role of salivary proteins of An. dirus B in disease transmission and hematophagy.Proteínas das glândulas salivares do Anopheles dirus B (Diptera: Culicidae, vetor da malária humana foram determinadas e analisadas. A quantidade de proteínas das glândulas salivares em mosquitos com três a 10 dias de idade foi de aproximadamente 1,08 ± 0,04 µg/ fêmea e de 0,1 ± 0,05 µg/macho. As glândulas salivares de ambos os sexos mostraram organização morfológica semelhante à de outros mosquitos anofelinos. Em fêmeas, apirase acumula-se nas regiões distais, enquanto alfa-glucosidase foi encontrada na região proximal dos lóbulos laterais. Esta distribuição diferencial das enzimas analisadas reflete a especialização de

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

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    P Zlotowski


    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.


    Directory of Open Access Journals (Sweden)

    Santhosh Kumar S. S


    Full Text Available BACKGROUND This was an open label study. Although, honey has been used for centuries in wound care, now only it is being integrated into modern medical practice. The resurgence of interest in honey as a medicine for modern wound dressing offers opportunities for both patients and clinicians. The aim of this study is to show the advantage of honey dressing over conventional saline dressing in the management of chronic non-healing ulcer. This property of honey is mentioned in papyruses traced to 3500 years ago among ancient Egyptians and the Hebrews 3000 years ago. Honey naturally contains small amounts of enzymes. The predominant enzymes in honey are diastase (amylase, invertase (alpha-glucosidase and glucose oxidase. Honey has been proven to have significant antibacterial properties and is a useful constituent in wound and burn care. The stimulation of cell growth seen with honey is probably also responsible for ‘kick-starting’ the healing process in chronic wounds that have remained non-healing for long periods. Honey has a broad spectrum of activity against bacteria and fungi. Many randomised and non-randomised study has shown the efficacy of honey as a healing agent and excellent dressing material. MATERIALS AND METHODS Study was conducted in medical college, Trivandrum, which is a tertiary care centre. Patients are selected from orthopaedic and general surgical wards. The study period was one year extending from July 2014 to June 2015. Saline dressing was given for the patients admitted in the first 6 months of study. Honey dressing was given for the next 6 months of study. Outcome was assessed on duration of hospital stay, difference of outcome in different distribution of grades of ulcer, difference of outcome in patients with vascular compromise, which is found out by Doppler ultrasound and difference of outcome in patients with diabetes mellitus. RESULTS Most significant observations made were in regard to duration of hospital stay

  15. Enzyme replacement therapy for infantile-onset Pompe disease. (United States)

    Chen, Min; Zhang, Lingli; Quan, Shuyan


    Infantile-onset Pompe disease is a rare and progressive autosomal-recessive disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Current treatment involves enzyme replacement therapy (with recombinant human alglucosidase alfa) and symptomatic therapies (e.g. to control secretions). Children who are cross-reactive immunological material (CRIM)-negative require immunomodulation prior to commencing enzyme replacement therapy.Enzyme replacement therapy was developed as the most promising therapeutic approach for Pompe disease; however, the evidence is lacking, especially regarding the optimal dose and dose frequency. To assess the effectiveness, safety and appropriate dose regimen of enzyme replacement therapy for treating infantile-onset Pompe disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register, which is compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the Cochrane Central Register of Controlled Trials (CENTRAL), Embase (Ovid), PubMed and LILACS, and CBM, CNKI, VIP, and WANFANG for literature published in Chinese. In addition, we searched three online registers: WHO International Clinical Trials Registry Platform, and We also searched the reference lists of relevant articles and reviews.Date of last search of the Group's Inborn Errors of Metabolism Trials Register: 24 November 2016. Randomized and quasi-randomized controlled trials of enzyme replacement therapy in children with infantile-onset Pompe disease. Two authors independently selected relevant trials, assessed the risk of bias and extracted data. We contacted investigators to obtain important missing information. We found no trials comparing the effectiveness and safety of enzyme replacement therapy to another intervention, no intervention or placebo.We found one trial (18 participants

  16. Chemometrics Optimized Extraction Procedures, Phytosynergistic Blending and in vitro Screening of Natural Enzyme Inhibitors Amongst Leaves of Tulsi, Banyan and Jamun. (United States)

    De, Baishakhi; Bhandari, Koushik; Singla, Rajeev K; Katakam, Prakash; Samanta, Tanmoy; Kushwaha, Dilip Kumar; Gundamaraju, Rohit; Mitra, Analava


    targeted enzymes expressed in terms of IC50 values have shown that hydro-ethanolic extracts in all cases whether individual species or composites in varying ratios gave higher IC50 values thus showing greater effectivity. Current research provides the state-of-the-art of search of NEIs amongst three species by in-vitro assays which can be further utilized for bioactivity-guided isolations of such enzyme inhibitors. Further, it reports the optimized phyto-blend ratios so as to achieve synergistic anti-oxidative actions. The current research work focuses on the optimization of the extraction process parameters and the ratios of phyto-synergistic blends of the leaves of three common medicinal plants viz. banyan, jamun and tulsi by chemometrics. Qualitative and quantitative chemo profiling of the extracts were done by different phytochemical tests and UV spectrophotometric methods. Enzymes like alpha amylase, alpha glucosidase, aldose reductase, dipeptidyl peptidase 4, angiotensin converting enzymes are found to be pathogenic in type 2 diabetes. In vitro screening of natural enzyme inhibitors amongst individual extracts and composite blends were carried out by different assay procedures and the potency expressed in terms of IC50 values. Antioxidant potentials were estimated by DPPH radical scavenging, ABTS, FRAP and Dot Blot assay. Hydroalcoholic solvent (50:50) gave maximal yield of bio-actives with minimal chlorophyll leaching. Hydroethanolic extract of tulsi showed maximal antioxidant effect. Though all composites showed synergism, maximal effects were shown by the composite (1:1:2) in terms of polyphenol yield, antioxidant effect and inhibitory actions against the targeted enzymes. Abbreviations used: DPP4- dipeptidyl peptidase 4; AR- aldose reductase; ACE- angiotensin converting enzyme; PPAR-γ- peroxisome proliferator activated receptor-γ; NEIs- natural enzyme inhibitors; BE- binding energy; GLP-1- Glucagon like peptide -1; ROS- Reactive oxygen species; CAT- catalase