ABSTRACT
Phosphorus has an essential role in cellular and extracellular metabolism; maintenance of normal phosphorus homeostasis is critical. Phosphorus homeostasis can be affected by diet and certain medications; some intravenous iron formulations can induce renal phosphate excretion and hypophosphatemia, likely through increasing serum concentrations of intact fibroblast growth factor 23. Case studies provide insights into two types of hypophosphatemia: acute symptomatic and chronic hypophosphatemia, while considering the role of pre-existing conditions and comorbidities, medications, and intravenous iron. This review examines phosphorus homeostasis and hypophosphatemia, with emphasis on effects of iron deficiency and iron replacement using intravenous iron formulations.
Subject(s)
Hypophosphatemia/etiology , Iron/adverse effects , Phosphorus/metabolism , Anemia, Hypochromic/drug therapy , Calcitriol/physiology , Ferric Compounds/administration & dosage , Ferric Compounds/adverse effects , Ferric Compounds/pharmacology , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/biosynthesis , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/physiology , Homeostasis/drug effects , Homeostasis/physiology , Humans , Hypophosphatemia/chemically induced , Hypophosphatemia/diagnosis , Hypophosphatemia/therapy , Infusions, Parenteral , Iron/administration & dosage , Iron Deficiencies , Kidney/metabolism , Malabsorption Syndromes/complications , Maltose/administration & dosage , Maltose/adverse effects , Maltose/analogs & derivatives , Maltose/pharmacology , Osteomalacia/etiology , Parathyroid Hormone/physiology , Phosphorus, Dietary/pharmacokineticsABSTRACT
INTRODUCTION: Frequent blood donation often leads to iron deficiency and even anemia but appropriate strategies for detection and prevention are currently not mandatory. At the Medical University of Graz, we conducted a single-center prospective clinical trial to compare oral and IV iron supplementation in iron deficient blood donors including Austrian regular whole blood and platelet apheresis donors. We aimed to determine the difference of transferrin saturation between the treatment groups 8-12 weeks iron administration besides other parameters of iron status and blood count. METHODS: 176 healthy male and female blood donors with iron deficiency (ferritin ≤30 ng/mL) were randomized to either a single dose of IV ferric carboxymaltose (1000 mg, n = 86) or oral iron (II)fumarate (100 tablets of 100 mg [10 per week], n = 90). RESULTS: Between 2014 and 2016, 172 donors (137 women) completed the study; 4 in the oral group were lost to follow-up. At follow-up, median (IQR) transferrin saturation and ferritin were significantly higher in the intravenous group (27 [23-35]%, vs 21.0 [16-32]%; p < 0.001 and 105 [75-145] ng/mL vs 25 [17-34] ng/mL; p < 0.001, respectively) while median (IQR) hemoglobin levels were comparable (IV, 13.6 [13.0-14.4] g/dL vs oral, 13.6 [13.0-14.2] g/dL). The frequency of adverse effects was comparable (38% in both groups) and no serious adverse events occurred. CONCLUSIONS: A single dose of 1000 mg of intravenous iron is highly effective to counteract iatrogenic iron deficiency in blood donors. Oral iron appears to be an acceptable alternative. The assessment of body iron stores should play a key role in maintaining blood donors' health. This trial was registered at www.clinicaltrials.gov as NCT01787526 on February 8, 2013 and at www.clinicaltrialsregister.eu (EudraCT identifier: 2013-000327-14) on September 24, 2013.
Subject(s)
Anemia, Iron-Deficiency/drug therapy , Blood Donors/statistics & numerical data , Ferric Compounds/pharmacology , Ferrous Compounds/pharmacology , Maltose/analogs & derivatives , Administration, Intravenous , Administration, Oral , Adolescent , Adult , Aged , Female , Ferric Compounds/administration & dosage , Ferritins/blood , Ferrous Compounds/administration & dosage , Follow-Up Studies , Humans , Male , Maltose/administration & dosage , Maltose/pharmacology , Middle Aged , Prospective Studies , Transferrin/metabolism , Young AdultABSTRACT
Iron deficiency anaemia (IDA) is the most common nutritional deficiency affecting pregnant women worldwide. This study aims to compare the efficacy and safety of a newly available intravenous (IV) iron preparation, ferric carboxymaltose (FCM), against IV iron polymaltose (IPM), and standard oral iron (ferrous sulphate) for the treatment of IDA in pregnancy. This is an open-labelled prospective randomised controlled trial (RCT) with intention-to-treat analysis conducted at a primary health care facility with a single tertiary referral centre in Launceston. Tasmania, Australia. A 3-arm randomised controlled trial was conducted comparing a single IV infusion of 1000mg of FCM (n = 83 patients) over 15 minutes against a single IV infusion of 1000mg of IPM (n = 82) over 2 hours against 325mg daily oral ferrous sulphate (n = 81) until delivery, for the treatment of IDA in pregnancy. A total of 246 consecutive pregnant women were recruited between September 2013 and July 2014. The median age was 28 years, with a median and mean gestation of 27 weeks. The median serum ferritin was 9µg/L, with a mean of 13µg/L. The mean haemoglobin (Hb) was 114g/L. The primary outcome was the change in ferritin and Hb levels at 4 weeks after intervention. Secondary outcomes included ferritin and Hb improvements at predelivery, safety, tolerability, quality of life (QoL), cost utility, and fetal outcomes. The mean Hb level differences between the baseline intervention time point and 4 weeks thereafter were significantly higher in the FCM versus the oral group by 4.35g/L (95% CI: 1.64-7.05; P = 0.0006) and in the IPM vs the oral group by 4.08g/L (95% CI: 1.57-6.60; P = 0.0005), but not different between the FCM and IPM groups (0.26g/L; 95% CI: -2.59 to 3.11; P = 0.9740). The mean ferritin level differences were significantly higher at 4 weeks in the FCM vs oral iron group by 166µg/L (95% CI: 138-194; P < 0.0001) and in the IPM vs oral iron group by 145µg/L (95% CI: 109-1180, P < 0.0001), but not between the 2 IV groups (21.5µg/L; 95% CI: -23.9 to 66.9; P = 0.4989). Administration of IV FCM during pregnancy was safe and better tolerated than IV IPM or oral iron. Compliance to oral iron was the lowest amongst treatment groups with one-third of the patients missing doses of daily iron tablets. Significant improvement in overall QoL scores was observed in both IV iron supplement groups by achieving normal ferritin following effective and prompt repletion of iron stores, compared to the oral iron group (P = 0.04, 95% CI: 21.3, 1.8). The overall cost utility of IV FCM and IV IPM appear to be similar to oral iron. There were no differences in the fetal outcomes between the 3 trial arms. In conclusion, this study demonstrates that a single IV iron infusion is an effective and safe option for treatment of IDA during pregnancy. FCM was more convenient than other treatments. Rapid parenteral iron repletion can improve iron stores, Hb levels and QoL in pregnant women, with ongoing benefits until delivery. Integration of IV iron for IDA in pregnancy can potentially improve pregnancy outcomes for the mother. Update of guidelines to integrate the use of new IV iron preparations in pregnancy is warranted.
Subject(s)
Anemia, Iron-Deficiency/drug therapy , Ferric Compounds/therapeutic use , Ferrous Compounds/therapeutic use , Infusions, Intravenous/methods , Maltose/analogs & derivatives , Administration, Oral , Adolescent , Adult , Female , Ferric Compounds/pharmacology , Ferrous Compounds/pharmacology , Humans , Maltose/pharmacology , Maltose/therapeutic use , Middle Aged , Pregnancy , Prospective Studies , Young AdultABSTRACT
Microbial amylases are used to produce ethanol, glucose and can be applied in textiles products, detergents and other industries. This study aimed to determine the best carbon source concentration to induce the amylase production by A. japonicus, and its purification and biochemical characterization. For that, this fungus was cultivated in Khanna medium, pH 5.5, for 4 days, at 25°C, in static condition, supplemented with potato starch and maltose in different concentrations. The fungal crude enzymatic extract was purified in a unique elution in DEAE-cellulose column and the molecular mass was determined as 72kDa. The optimum temperature and pH was 65°C and 5.0, respectively. Amylase remained 75% of its activity after one hour at 50°C and was stable in the pH range 3.0-7.0. The analysis of the end-products by thin layer chromatography showed only glucose formation, which characterizes the purified enzyme as a glucoamylase. Amylopectin was the best substrate for the enzyme assay and Mn+2 and Pb+2 were good glucoamylase activators. This activation, in addition to the biochemical characteristics are important results for future biotechnological applications of this glucoamylase in the recycling and deinking process by the paper industries.
Subject(s)
Aspergillus/enzymology , Glucan 1,4-alpha-Glucosidase/isolation & purification , Glucan 1,4-alpha-Glucosidase/metabolism , Lead/pharmacology , Manganese/pharmacology , Amylose/metabolism , Dose-Response Relationship, Drug , Edetic Acid/pharmacology , Enzyme Activation/drug effects , Glucan 1,4-alpha-Glucosidase/chemistry , Hydrogen-Ion Concentration , Hydrolysis , Kinetics , Maltose/pharmacology , Mercaptoethanol/pharmacology , Molecular Weight , Phylogeny , TemperatureABSTRACT
In animals, the accepted model of carbohydrate digestion and absorption involves reduction of disaccharides into the monosaccharides glucose, fructose, and galactose followed by their individual transmembrane transport into cells. In 2011, a gene for a distinct disaccharide sucrose transporter (SCRT) was found in Drosophila melanogaster and characterized in a yeast expression system. The purpose of the present investigation was to functionally identify and characterize a putative disaccharide transporter analog in the hepatopancreas of the American lobster, Homarus americanus. Purified hepatopancreatic brush-border membrane vesicles (BBMV) were used in transport experiments using 14C-sucrose and a Millipore filter isolation technique. In the absence of sodium, an external pH of 4 significantly stimulated the uptake of 14C-sucrose compared to that occurring at pH 5, 6, or 7. At pH 7, increasing external concentrations of sodium increased 14C-sucrose uptake by BBMV in a hyperbolic fashion and this stimulation was significantly reduced when the pH was changed to 4, suggesting that both protons and sodium ions were each capable of driving the uptake of the sugar. In experiments with a variety of monosaccharides, disaccharides, and trisaccharides, used as potential inhibitors of 14C-sucrose uptake, only maltose and trehalose inhibited carrier-mediated 14C-sucrose transport. An additional experiment showed that 20 mM maltose was a competitive inhibitor of 14C-sucrose uptake. The use of a putative lobster SCRT by both maltose and trehalose is nutritionally appropriate for lobsters as they commonly digest glycogen and chitin, polymers of maltose and trehalose, respectively. These findings suggest there is a brush-border proton- or sodium-dependent, hepatopancreatic carrier process, shared by sucrose, maltose, and trehalose, that may function to absorb disaccharides that are produced from digestion of naturally occurring dietary constituents.
Subject(s)
Carrier Proteins/metabolism , Disaccharides/metabolism , Hepatopancreas/metabolism , Nephropidae/metabolism , Animals , Biological Transport/drug effects , Carbon Radioisotopes/metabolism , Carrier Proteins/antagonists & inhibitors , Carrier Proteins/chemistry , Disaccharides/pharmacology , Hydrogen-Ion Concentration , Maltose/metabolism , Maltose/pharmacology , Microvilli/metabolism , Nephropidae/chemistry , Sodium/metabolism , Sucrose/metabolism , Trehalose/metabolismABSTRACT
Aims: Iron deficiency (ID) is associated with adverse outcomes in heart failure (HF) but the underlying mechanisms are incompletely understood. Intracellular iron availability is secured by two mRNA-binding iron-regulatory proteins (IRPs), IRP1 and IRP2. We generated mice with a cardiomyocyte-targeted deletion of Irp1 and Irp2 to explore the functional implications of ID in the heart independent of systemic ID and anaemia. Methods and results: Iron content in cardiomyocytes was reduced in Irp-targeted mice. The animals were not anaemic and did not show a phenotype under baseline conditions. Irp-targeted mice, however, were unable to increase left ventricular (LV) systolic function in response to an acute dobutamine challenge. After myocardial infarction, Irp-targeted mice developed more severe LV dysfunction with increased HF mortality. Mechanistically, the activity of the iron-sulphur cluster-containing complex I of the mitochondrial electron transport chain was reduced in left ventricles from Irp-targeted mice. As demonstrated by extracellular flux analysis in vitro, mitochondrial respiration was preserved at baseline but failed to increase in response to dobutamine in Irp-targeted cardiomyocytes. As shown by 31P-magnetic resonance spectroscopy in vivo, LV phosphocreatine/ATP ratio declined during dobutamine stress in Irp-targeted mice but remained stable in control mice. Intravenous injection of ferric carboxymaltose replenished cardiac iron stores, restored mitochondrial respiratory capacity and inotropic reserve, and attenuated adverse remodelling after myocardial infarction in Irp-targeted mice but not in control mice. As shown by electrophoretic mobility shift assays, IRP activity was significantly reduced in LV tissue samples from patients with advanced HF and reduced LV tissue iron content. Conclusions: ID in cardiomyocytes impairs mitochondrial respiration and adaptation to acute and chronic increases in workload. Iron supplementation restores cardiac energy reserve and function in iron-deficient hearts.
Subject(s)
Heart Failure/prevention & control , Iron Deficiencies , Iron-Regulatory Proteins/physiology , Myocytes, Cardiac/metabolism , Animals , Cardiotonic Agents/pharmacology , Dopamine/pharmacology , Ferric Compounds/pharmacology , Ferritins/metabolism , Heart Failure/metabolism , Heart Failure/physiopathology , Humans , Iron/metabolism , Iron-Regulatory Proteins/deficiency , Magnetic Resonance Angiography , Maltose/analogs & derivatives , Maltose/pharmacology , Mitochondria, Heart/physiology , Phenotype , RNA, Messenger/physiology , Ventricular Function, Left/physiologyABSTRACT
Intravenous iron supplementation is an effective therapy in iron deficiency anemia (IDA), but controversial in anemia of inflammation (AI). Unbound iron can be used by bacteria and viruses for their replication and enhance the inflammatory response. Nowadays available high molecular weight iron complexes for intravenous iron substitution, such as ferric carboxymaltose, might be useful in AI, as these pharmaceuticals deliver low doses of free iron over a prolonged period of time. We tested the effects of intravenous iron carboxymaltose in murine AI: Wild-type mice were exposed to the heat-killed Brucella abortus (BA) model and treated with or without high molecular weight intravenous iron. 4h after BA injection followed by 2h after intravenous iron treatment, inflammatory cytokines were upregulated by BA, but not enhanced by iron treatment. In long term experiments, mice were fed a regular or an iron deficient diet and then treated with intravenous iron or saline 14 days after BA injection. Iron treatment in mice with BA-induced AI was effective 24h after iron administration. In contrast, mice with IDA (on iron deficiency diet) prior to BA-IA required 7d to recover from AI. In these experiments, inflammatory markers were not further induced in iron-treated compared to vehicle-treated BA-injected mice. These results demonstrate that intravenous iron supplementation effectively treated the murine BA-induced AI without further enhancement of the inflammatory response. Studies in humans have to reveal treatment options for AI in patients.
Subject(s)
Anemia/drug therapy , Ferric Compounds/administration & dosage , Ferric Compounds/pharmacology , Maltose/analogs & derivatives , Administration, Intravenous , Anemia/complications , Anemia/metabolism , Anemia/microbiology , Animals , Biomarkers/blood , Brucella abortus/physiology , Cytokines/blood , Diet , Ferric Compounds/therapeutic use , Hepcidins/metabolism , Inflammation/complications , Iron/blood , Maltose/administration & dosage , Maltose/pharmacology , Maltose/therapeutic use , Mice , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reticulocytes/drug effects , Reticulocytes/metabolismABSTRACT
SCOPE: Expression of intercellular adhesion molecule-1 (ICAM-1) on vascular smooth muscle cells (VSMCs) plays an important role in the progression of atherosclerosis. We investigated the effects of bamboo stem extract (BSE) on motility and ICAM-1 expression by using mouse MOVAS-1 cells. Active constituents of BSE exhibiting an inhibitory activity on TNF-α-induced ICAM1 expression were identified using HPLC. METHODS AND RESULTS: The effects of BSE on platelet-derived growth factor (PDGF)-BB-induced migration, tumor necrosis factor alpha (TNF-α)-induced expression of ICAM-1, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation were investigated. BSE inhibited migration of MOVAS-1 cells and sprout formation by mouse aorta explants. Reverse transcription PCR analysis and promoter reporter assays revealed that BSE suppressed ICAM-1 expression by inhibiting NF-κB activity. In addition, BSE reduced adhesion between VSMCs and monocytes. Several oligosaccharides were identified in BSE. Among the oligosaccharides contained in BSE, maltotetraose and stachyose were potent inhibitors of TNF-α-induced ICAM-1 expression. We confirmed that maltotetraose reduced PDGF-induced sprout formation by mouse aorta explants and inhibited TNF-α-induced NF-κB activation and ICAM-1 expression in MOVAS-1 cells. CONCLUSION: The BSE constituent maltotetraose may be beneficial in the suppression of early atherosclerosis development and could be developed as a dietary supplement for cardiovascular health.
Subject(s)
Cell Movement/drug effects , Maltose/analogs & derivatives , Muscle, Smooth, Vascular/cytology , Sasa/chemistry , Tumor Necrosis Factor-alpha/pharmacology , Animals , Aorta/cytology , Aorta/drug effects , Cell Line , Chromatography, High Pressure Liquid , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , Male , Maltose/pharmacology , Mice, Inbred BALB C , Muscle, Smooth, Vascular/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Plant Extracts/chemistry , Platelet-Derived Growth Factor/pharmacology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
A new thermostable and solvent-tolerant lipase was isolated from newly isolated Staphylococcus warneri from oil-contaminated soil. Optimization of the fermentation media for production of thermostable and organic solvent-tolerant lipase was carried out using two statistical methods, i.e., Plackett-Burman design (PBD) and central composite design (CCD) were used for the optimization of the media components. PBD was used to efficiently select important medium components affecting the lipase production. Out of 15 medium components screened, four components, i.e., olive oil, peptone, maltose, and K2HPO4 were found to contribute positively to lipase production. CCD and response surface methodology (RSM) were used to determine the optimum levels of the selected components using Design-Expert 8.0 software. Production medium with olive oil (1.45 %), peptone (0.28 %), maltose (0.054 %), and K2HPO4 (0.091 %) was optimized with a maximum lipase production of 10.43 IU/ml/min. Similarly, production conditions for the lipase production were optimized by using CCD and RSM. Optimized conditions were found to have an incubation temperature of 55 °C, medium pH of 8.0, agitation of 120 rpm, and inoculum volume of 2 %. RSM revealed the maximum lipase production of 17.21 IU/ml using these optimized production conditions. Crude lipase showed enhanced activity in organic solvents such as diethyl ether, hexane, and cyclohexane.
Subject(s)
Bacterial Proteins/biosynthesis , Lipase/biosynthesis , Soil Microbiology , Staphylococcus/enzymology , Bacterial Proteins/chemistry , Bacterial Proteins/isolation & purification , Environmental Pollutants/metabolism , Enzyme Stability , Factor Analysis, Statistical , Fermentation , Hydrogen-Ion Concentration , Industrial Oils/analysis , Kinetics , Lipase/chemistry , Lipase/isolation & purification , Maltose/metabolism , Maltose/pharmacology , Olive Oil , Peptones/metabolism , Peptones/pharmacology , Phosphates/metabolism , Phosphates/pharmacology , Plant Oils/metabolism , Plant Oils/pharmacology , Potassium Compounds/metabolism , Potassium Compounds/pharmacology , Solvents/chemistry , Staphylococcus/chemistry , Staphylococcus/drug effects , Staphylococcus/growth & development , TemperatureABSTRACT
PURPOSE: To determine the effect of intravenous iron supplementation on performance, fatigue and overall mood in runners without clinical iron deficiency. METHODS: Fourteen distance runners with serum ferritin 30-100 µg · L(-1) were randomly assigned to receive three blinded injections of intravenous ferric-carboxymaltose (2 ml, 100 mg, IRON) or normal saline (PLACEBO) over four weeks (weeks 0, 2, 4). Athletes performed a 3,000 m time trial and 10 × 400 m monitored training session on consecutive days at week 0 and again following each injection. Hemoglobin mass (Hbmass) was assessed via carbon monoxide rebreathing at weeks 0 and 6. Fatigue and mood were determined bi-weekly until week 6 via Total Fatigue Score (TFS) and Total Mood Disturbance (TMD) using the Brief Fatigue Inventory and Brunel Mood Scale. Data were analyzed using magnitude-based inferences, based on the unequal variances t-statistic and Cohen's Effect sizes (ES). RESULTS: Serum ferritin increased in IRON only (Week 0: 62.8 ± 21.9, Week 4: 128.1 ± 46.6 µg · L(-1); p = 0.002) and remained elevated two weeks after the final injection (127.0 ± 66.3 µg · L(-1), p = 0.01), without significant changes in Hbmass. Supplementation had a moderate effect on TMD of IRON (ES -0.77) with scores at week 6 lower than PLACEBO (ES -1.58, p = 0.02). Similarly, at week 6, TFS was significantly improved in IRON vs. PLACEBO (ES -1.54, p = 0.05). There were no significant improvements in 3,000 m time in either group (Week 0 vs. Week 4; Iron: 625.6 ± 55.5 s vs. 625.4 ± 52.7 s; PLACEBO: 624.8 ± 47.2 s vs. 639.1 ± 59.7 s); but IRON reduced their average time for the 10 × 400 m training session at week 2 (Week 0: 78.0 ± 6.6 s, Week 2: 77.2 ± 6.3; ES-0.20, p = 0.004). CONCLUSION: During 6 weeks of training, intravenous iron supplementation improved perceived fatigue and mood of trained athletes with no clinical iron deficiency, without concurrent improvements in oxygen transport capacity or performance.
Subject(s)
Fatigue/drug therapy , Ferric Compounds/therapeutic use , Hemoglobins/analysis , Maltose/analogs & derivatives , Mood Disorders/drug therapy , Running/physiology , Adolescent , Adult , Fatigue/blood , Fatigue/physiopathology , Female , Ferric Compounds/pharmacology , Ferritins/blood , Humans , Injections, Intravenous , Male , Maltose/pharmacology , Maltose/therapeutic use , Mood Disorders/blood , Mood Disorders/physiopathology , Psychiatric Status Rating Scales , Treatment Outcome , Young AdultABSTRACT
Anemia and iron deficiency anemia are very common in inflammatory bowel disease (IBD). In most cases, anemia is a consequence of mixed pathogenesis; inflammation and iron deficiency being the most important factors. Iron status should be evaluated carefully, as ferritin is unreliable in the presence of inflammation. It is always necessary to control disease activity; however, supplementation is usually required to fully correct iron deficiencies. Oral iron, intravenous iron, erythropoietin, and blood transfusions can be used in different clinical scenarios. Oral iron may be used in mild cases if the disease has no clinical activity. Intravenous iron should be preferred where oral iron is poorly tolerated or where it has failed in moderate to severe anemia, and in combination with erythropoietin. Iron sucrose is very safe and effective, but not very convenient, as the total needed dose must be divided into several infusions. Ferric carboxymaltose is much more convenient, and has been shown to be more effective than iron sucrose in a large randomized trial. Iron isomaltose shows theoretical promise, but very limited data are available from IBD populations. Blood transfusion can be necessary, especially in acute life-threatening situations, but the trigger for indication should be in the low range. With the correct use of available resources, anemia and iron deficiency should be well controlled in practically all IBD patients.
Subject(s)
Anemia, Iron-Deficiency/drug therapy , Anemia, Iron-Deficiency/etiology , Inflammatory Bowel Diseases/complications , Anemia, Iron-Deficiency/blood , Animals , Ferric Compounds/pharmacology , Humans , Inflammatory Bowel Diseases/blood , Iron/pharmacology , Maltose/analogs & derivatives , Maltose/pharmacologyABSTRACT
An efficient in vitro plant regeneration system was established for elite, recalcitrant Malaysian indica rice, Oryza sativa L. CV. MR 219 using mature seeds as explant on Murashige and Skoog and Chu N6 media containing 2,4-dichlorophenoxy acetic acid and kinetin either alone or in different combinations. L-proline, casein hydrolysate and L-glutamine were added to callus induction media for enhancement of embryogenic callus induction. The highest frequency of friable callus induction (84%) was observed in N6 medium containing 2.5 mg l(-1) 2,4-dichlorophenoxy acetic acid, 0.2 mg l(-1) kinetin, 2.5 mg l(-1) L-proline, 300 mg l(-1) casein hydrolysate, 20 mg l(-1) L-glutamine and 30 g l(-1) sucrose under culture in continuous lighting conditions. The maximum regeneration frequency (71%) was observed, when 30-day-old N6 friable calli were cultured on MS medium supplemented with 3 mg l(-1) 6-benzyl aminopurine, 1 mg l(-1) naphthalene acetic acid, 2.5 mg l(-1) L-proline, 300 mg l(-1) casein hydrolysate and 3% maltose. Developed shoots were rooted in half strength MS medium supplemented with 2% sucrose and were successfully transplanted to soil with 95% survival. This protocol may be used for other recalcitrant indica rice genotypes and to transfer desirable genes in to Malaysian indica rice cultivar MR219 for crop improvement.
Subject(s)
Oryza/physiology , 2,4-Dichlorophenoxyacetic Acid/pharmacology , Benzyl Compounds , Caseins/pharmacology , Culture Media/chemistry , Culture Techniques , Kinetin/pharmacology , Malaysia , Maltose/pharmacology , Naphthaleneacetic Acids/pharmacology , Oryza/drug effects , Oryza/growth & development , Plant Growth Regulators/pharmacology , Proline/pharmacology , Purines , Regeneration/drug effects , Regeneration/physiology , Seeds/drug effects , Seeds/growth & development , Seeds/physiologyABSTRACT
The maltose transporter gene is situated at the MAL locus, which consists of genes for a transporter, maltase, and transcriptional activator. Five unlinked MAL loci (MAL1, MAL2, MAL3, MAL4, and MAL6) constitute a gene family in Saccharomyces cerevisiae. The expression of the maltose transporter is induced by maltose and repressed by glucose. The activity of the maltose transporter is also regulated post-translationally; Mal61p is rapidly internalized from the plasma membrane and degraded by ubiquitin-mediated proteolysis in the presence of glucose. We found that S. cerevisiae strain ATCC20598 harboring MAL21 could grow in maltose supplemented with a non- assimilable glucose analogue, 2-deoxyglucose, whereas strain ATCC96955 harboring MAL61 and strain CB11 with MAL31 and AGT1 could not. These observations implied a Mal21p-specific resistance against glucose-induced degradation. Mal21p found in ATCC20598 has 10 amino acids, including Gly-46 and His-50, that are inconsistent with the corresponding residues in Mal61p. The half-life of Mal21p for glucose-induced degradation was 118 min when expressed using the constitutive TPI1 promoter, which was significantly longer than that of Mal61p (25 min). Studies with mutant cells that are defective in endocytosis or the ubiquitination process indicated that Mal21p was less ubiquitinated than Mal61p, suggesting that Mal21p remains on the plasma membrane because of poor susceptibility to ubiquitination. Mutational studies revealed that both residues Gly-46 and His-50 in Mal21p are essential for the full resistance of maltose transporters against glucose-induced degradation.
Subject(s)
Glucose/pharmacology , Glycine , Histidine , Monosaccharide Transport Proteins/genetics , Saccharomyces cerevisiae Proteins/genetics , Symporters/genetics , Amino Acid Sequence , Cloning, Molecular , DNA Mutational Analysis , DNA Primers , Maltose/pharmacology , Molecular Sequence Data , Monosaccharide Transport Proteins/drug effects , Monosaccharide Transport Proteins/metabolism , Multigene Family , Mutagenesis , Polymerase Chain Reaction , Recombinant Proteins/drug effects , Recombinant Proteins/metabolism , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/growth & development , Saccharomyces cerevisiae Proteins/drug effects , Saccharomyces cerevisiae Proteins/metabolism , Symporters/drug effects , Symporters/metabolism , Trans-Activators/metabolismABSTRACT
The effect of Daikenchuto, a traditional herbal medicine, on gastrointestinal hypoperistalsis in postoperative ileus (POI) was investigated. POI was induced by laparotomy with manipulation of the gastrointestine under anesthesia, and gastrointestinal transit was calculated by migration of Evans blue. Daikenchuto (270 - 2,700 mg/kg, p.o.) dose-dependently improved the delayed gastrointestinal transit in POI. This effect of Daikenchuto was partially inhibited by SB204070 (1 mg/kg, s.c.), a 5-hydroxytriptamine(4) (5-HT(4))-receptor antagonist and completely abolished by atropine (1 mg/kg, s.c.), a muscarine-receptor antagonist. Among the constituents of Daikenchuto, the medical herb zanthoxylum fruit (60 mg/kg, p.o.) and maltose syrup (2,400 mg/kg, p.o.) significantly ameliorated the delayed gastrointestinal transit, but ginseng and processed ginger did not affect the gastrointestinal transit in the rat POI. The improvement induced by zanthoxylum fruit was also inhibited by atropine or SB204070. In addition, the high osmotic pressure of the maltose syrup (2400 mg/10 mL per kg) was related to the improvement of delayed gastrointestinal transit. These results demonstrated that Daikenchuto ameliorates postoperative hypoperistalsis via cholinergic nerves and 5-HT(4) receptors and that osmotic pressure also may be involved in this action. Moreover, zanthoxylum fruit and maltose syrup were crucial medical herbs contributing to the ability of Daikenchuto.
Subject(s)
Gastrointestinal Transit/drug effects , Ileus/drug therapy , Plant Extracts/pharmacology , Postoperative Complications/drug therapy , Animals , Cholinergic Fibers/drug effects , Cholinergic Fibers/metabolism , Dose-Response Relationship, Drug , Evans Blue , Zingiber officinale/chemistry , Laparotomy/adverse effects , Male , Maltose/chemistry , Maltose/pharmacology , Medicine, East Asian Traditional , Osmotic Pressure , Panax/chemistry , Peristalsis/drug effects , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Rats , Rats, Sprague-Dawley , Receptors, Serotonin, 5-HT4/drug effects , Receptors, Serotonin, 5-HT4/metabolism , Zanthoxylum/chemistry , ZingiberaceaeABSTRACT
Maltose, a disaccharide composed of two glucose molecules, is used in a number of biological preparations as a stabilizing agent or osmolality regulator. Icodextrin, which is converted to maltose, is present in a peritoneal dialysis solution. Galactose and xylose are found in some foods, herbs, and dietary supplements; they are also used in diagnostic tests. When some blood glucose monitoring systems are used--specifically, those that use test strips containing the enzymes glucose dehydrogenase-pyrroloquinolinequinone or glucose dye oxidoreductase--in patients receiving maltose, icodextrin, galactose, or xylose, interference of blood glucose levels can occur. Maltose, icodextrin, galactose, and xylose are misinterpreted as glucose, which can result in erroneously elevated serum glucose levels. This interference can result in the administration of insulin, which may lead to hypoglycemia. In severe cases of hypoglycemia, deaths have occurred. If patients are receiving maltose, icodextrin, galactose, or xylose, clinicians must review the package inserts of all test strips to determine the type of glucose monitoring system being used and to use only those systems whose tests strips contain glucose oxidase, glucose dehydrogenase-nicotinamide adenine dinucleotide, or glucose dehydrogenase-flavin adenine dinucleotide.
Subject(s)
Blood Glucose Self-Monitoring , Blood Glucose/analysis , Maltose/analysis , Reagent Strips , Diabetes Mellitus , Dialysis Solutions/adverse effects , Drug Labeling , Galactose/analysis , Glucans/analysis , Glucose/analysis , Humans , Icodextrin , Maltose/pharmacokinetics , Maltose/pharmacology , Reproducibility of Results , Xylose/analysisABSTRACT
The present study investigated the effect of Daikenchuto (DKT) on postoperative intestinal adhesion in rats. We evaluated the effects of DKT, constituent medical herbs and active compounds on talc-induced intestinal adhesion in rats and DKT-induced contractions using isolated guinea pig ileum. DKT significantly prevented adhesion formation, and this action was inhibited by pretreatment with atropine or ruthenium red. The constituent medical herbs, Zanthoxylum Fruit and Maltose Syrup Powder significantly prevented adhesion formation. Moreover, hydroxy sanshool (HS) prevented adhesion formation, and this action was inhibited by pretreatment with ruthenium red. In contrast, DKT-induced contractions were inhibited by tetrodotoxin, atropine, and capsazepine. These results suggested that DKT had a preventive action on postoperative adhesive intestinal obstruction, and that this action was mediated by sensory and cholinergic nerves. Furthermore, HS was found to be one of the active compound of DKT, and its action was mediated by sensory nerves.
Subject(s)
Amides/pharmacology , Intestinal Obstruction/prevention & control , Plant Extracts/pharmacology , Postoperative Complications/prevention & control , Amides/isolation & purification , Animals , Disease Models, Animal , Fruit , Guinea Pigs , Ileum/drug effects , Intestinal Obstruction/etiology , Maltose/pharmacology , Medicine, East Asian Traditional , Muscle Contraction/drug effects , Nervous System Physiological Phenomena , Panax , Rats , Talc , Tissue Adhesions/etiology , Tissue Adhesions/prevention & control , Zanthoxylum/chemistry , ZingiberaceaeABSTRACT
A screening of 5 plants used for making drinks in Vietnam revealed a Cleistocalyx operculatus (Roxb.) Merr and Perry flower bud extract to have the highest inhibitory activity against the alpha-glucosidase enzyme. The anti-hyperglycemic effects of an aqueous extract from flower buds of Cleistocalyx operculatus (CO), a commonly used material for drink preparation in Vietnam, were therefore investigated in vitro and in vivo. In vitro, the CO extract inhibited the rat-intestinal maltase and sucrase activities, with IC50 values of 0.70 and 0.47 mg/ml, respectively. These values are lower than those for a guava leaf extract (GE; IC50 0.97 and 1.28 mg/ml, respectively). Postprandial blood glucose testing of normal mice and STZ-induced diabetic rats by maltose loading (2 g/kg body weight (bw)) showed that the blood glucose reduction with CO (500 mg/kg bw) was slightly less than that with acarbose (25 mg/kg bw) but was more potent than that with GE (500 mg/kg bw). In an 8-week experiment, the blood glucose level of STZ diabetic rats treated with 500 mg of CO/kg bw/day was markedly decreased in comparison with that of non-treated diabetic rats. Consequently, CO is considered to be a promising material for preventing and treating diabetes.
Subject(s)
Flowers/chemistry , Hypoglycemic Agents/pharmacology , Pongamia/chemistry , Animals , Blood Glucose/metabolism , Body Weight/drug effects , Diabetes Mellitus/blood , Diabetes Mellitus/chemically induced , Diabetes Mellitus/drug therapy , Enzyme Inhibitors/pharmacology , Flavonoids/chemistry , Flavonoids/pharmacology , Glycoside Hydrolase Inhibitors , Hypoglycemic Agents/therapeutic use , Male , Maltose/pharmacology , Mice , Phenols/chemistry , Phenols/pharmacology , Phytotherapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Polyphenols , Rats , Sucrase/pharmacology , Time Factors , alpha-Glucosidases/metabolismABSTRACT
Tournefortia hartwegiana is a Mexican medicinal plant that is used for the treatment of diabetes, diarrhea and kidney pain. In a previous investigation, the methanolic extract of Tournefortia hartwegiana (METh) showed significant hypoglycemic and anti-diabetic properties on normoglycemic and alloxanized rats. In this context, the purpose of the present study was to establish one of the possible modes of action of METh to induce anti-diabetic activity. METh (310mg/kg) effect on alpha-glucosidase activity was investigated. METh intragastric administration was conducted to determine oral glucose tolerance test (OGTT), using different substrates: glucose, sucrose and maltose. The increase in plasma glucose level was significantly suppressed (P<0.05) by the extract after substrates administration. On the other hand, METh inhibited alpha-glucosidase activity in vitro, in a concentration-dependent manner (IC(50) of 3.16mg/mL). These results suggest that METh might exert its anti-diabetic effect by suppressing carbohydrate absorption from intestine, and thereby reducing the post-prandial increase of blood glucose. On the other hand, the bio-guided fractionation of this extract led to the isolation of: beta-sitosterol (1), stigmasterol (2), lupeol (3), ursolic acid (4), oleanolic acid (5), saccharose (6) and myo-inositol (7), using various chromatographic techniques.
Subject(s)
Boraginaceae/chemistry , Enzyme Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors , Hypoglycemic Agents/pharmacology , Animals , Blood Glucose/metabolism , Chromatography, Gas , Gas Chromatography-Mass Spectrometry , Glucose/pharmacology , Male , Maltose/pharmacology , Methanol , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats , Rats, Wistar , Solvents , Sucrose/pharmacology , Triterpenes/isolation & purificationABSTRACT
The characteristics of NO donors, NOC5 [3-(2-hydroxy-1-(1-methylethyl-2-nitrosohydrazino)-1-propanamine), NOC12 [N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine] and SNAP [S-nitroso-N-acetyl-DL-penicillamine] as absorption enhancers for poorly absorbable drugs were examined in rats using an in situ closed loop method. They were compared with a group of conventional absorption enhancers including sodium glycocholate (NaGC), sodium caprate (NaCap), sodium salicylate (NaSal) and n-dodecyl-beta-D-maltopyranoside (LM). 5(6)-carboxyfluorescein (CF) was used as a model drug to investigate effectiveness, site-dependency, and concentration-dependency of the tested enhancers. Overall, the NO donors can improve the intestinal absorption of CF at low concentration (5 mM), whereas higher concentration was required for the conventional absorption enhancers to elicit the absorption enhancing effect. In the small intestine, SNAP was the most effective absorption enhancers, although its concentration (5 mM) was lower than the conventional absorption enhancers (20 mM). On the other hand, LM and NaCap as well as the three NO donors were effective to improve the colonic absorption of CF. In the regional difference in the absorption enhancing effects, the NO donors showed significant effects in all intestinal regions, whereas we observed a regional difference in the absorption enhancing effect of the other conventional absorption enhancers. In the conventional enhancers, the absorption enhancing effects were generally greater in the large intestine than those in the small intestine. LM and NaCap were ineffective in the jejunum, although they were effective for improving the absorption of CF in the colon. NaSal was ineffective in both the jejunum and the colon. The absorption enhancement produced by NO donors was greatly affected by increasing the enhancer concentration from 3 to 5 mM, but only a slight increase was obtained when the concentration was raised to 10 mM. Similar results were obtained for the other enhancers over the range of 10 to 20 mM, but the absorption enhancing effects of these enhancers were almost saturated above these concentrations. These results suggest that NO donors possess excellent effectiveness as absorption enhancers for poorly absorbable drugs compared with the conventional enhancers. They can enhance intestinal absorption of CF from all intestinal regions and they are effective at very low concentrations.
Subject(s)
Adjuvants, Pharmaceutic/pharmacology , Fluoresceins/pharmacokinetics , Intestinal Absorption/drug effects , Nitric Oxide Donors/pharmacology , Animals , Area Under Curve , Colon/drug effects , Colon/metabolism , Decanoic Acids/metabolism , Decanoic Acids/pharmacokinetics , Dose-Response Relationship, Drug , Fluoresceins/metabolism , Fluorescent Dyes/metabolism , Fluorescent Dyes/pharmacokinetics , Glycocholic Acid/pharmacology , Hydrazines/pharmacology , Jejunum/drug effects , Jejunum/metabolism , Male , Maltose/analogs & derivatives , Maltose/pharmacology , Nitroso Compounds/pharmacology , Penicillamine/analogs & derivatives , Penicillamine/pharmacology , Rats , Rats, Wistar , Sodium Salicylate/pharmacologyABSTRACT
Recent studies have shown that surfactant components, in particular the collectins surfactant protein (SP)-A and -D, modulate the phagocytosis of various pathogens by alveolar macrophages. This interaction might be important not only for the elimination of pathogens but also for the elimination of inhaled allergens and might explain anti-inflammatory effects of SP-A and SP-D in allergic airway inflammation. We investigated the effect of surfactant components on the phagocytosis of allergen-containing pollen starch granules (PSG) by alveolar macrophages. PSG were isolated from Dactylis glomerata or Phleum pratense, two common grass pollen allergens, and incubated with either rat or human alveolar macrophages in the presence of recombinant human SP-A, SP-A purified from patients suffering from alveolar proteinosis, a recombinant fragment of human SP-D, dodecameric recombinant rat SP-D, or the commercially available surfactant preparations Curosurf and Alveofact. Dodecameric rat recombinant SP-D enhanced binding and phagocytosis of the PSG by alveolar macrophages, whereas the recombinant fragment of human SP-D, SP-A, or the surfactant lipid preparations had no effect. In addition, recombinant rat SP-D bound to the surface of the PSG and induced aggregation. Binding, aggregation, and enhancement of phagocytosis by recombinant rat SP-D was completely blocked by EDTA and inhibited by d-maltose and to a lesser extent by d-galactose, indicating the involvement of the carbohydrate recognition domain of SP-D in these functions. The modulation of allergen phagocytosis by SP-D might play an important role in allergen clearance from the lung and thereby modulate the allergic inflammation of asthma.