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Sample records for erythromycin ethyl succinate

  1. Design, synthesis, and evaluation of stable and taste-free erythromycin proprodrugs.

    PubMed

    Bhadra, Pranab K; Morris, Gareth A; Barber, Jill

    2005-06-02

    Erythromycin A is normally formulated for children as its 2'-ethyl succinate, a taste-free prodrug. Unfortunately, the prodrug hydrolyzes at a measurable rate in the medicine bottle, leading to the vile-tasting erythromycin. We have prepared derivatives of erythromycin B as putative paediatric prodrugs, taking advantage of the much improved acid stability of erythromycin B relative to erythromycin A. Thus, erythromycin B enol ether ethyl succinate is very poorly soluble in water, and its hydrolysis is undetectable in conditions resembling the medicine bottle. In acid, however, it converts rapidly to erythromycin B 2'-ethyl succinate, and this is in turn hydrolyzed to erythromycin B in neutral and basic conditions. Derivatives of erythromycin B enol ether are therefore proposed as taste-free proprodrugs of erythromycin B.

  2. Erythromycin

    MedlinePlus

    ... is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including ... antibiotics. It works by stopping the growth of bacteria.Antibiotics such as erythromycin will not work for ...

  3. Effect of succinic acid and tween-80 on glucuronidation of 2-ethyl-6-methyl-3-hydroxypyridine.

    PubMed

    Baranov, P A; Kravtsova, O U; Sariev, A K; Sherdev, V P

    2008-07-01

    We studied the effect of succinic acid on the process of glucuronidation of 2-ethyl-6-methyl-3-hydroxypyridine after peroral and intraperitoneal administration in the form of succinate or a base. Since the basic form of 2-ethyl-6-methyl-3-hydroxypyridine is insoluble in water, it was administered in 5% Tween-80. It was necessary to evaluate also the effect of Tween-80 on glucuronidation of 2-ethyl-6-methyl-3-hydroxypyridine in different administration routes. Quantitative assay of glucuronidated fractions was performed by the method of reversed-phase HPLC with fluorometrical detection. The detection limit for this method was 10 ng/ml. We confirmed that the major excretion pathway for 2-ethyl-6-methyl-3-hydroxypyridine is conjugation with glucuronic acid. It was found that succinic acid increased excretion of glucuronidated metabolite after both peroral and intraperitoneal administration of 2-ethyl-6-methyl-3-hydroxypyridine in the form of succinate and base in 5% Tween-80. The effect of Tween-80 was detected only after peroral administration, which was probably related to its effect on absorption of this compound. Tween-80 increased excretion of glucuronate after peroral administration of 2-ethyl-6-methyl-3-hydroxypyridine in the form of succinate and in 5% Tween solution.

  4. [Role of mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) in the obtaining of stabilized magnetite nanoparticles for biomedical application].

    PubMed

    Vazhnichaya, Ye M; Mokliak, Ye V; Kurapov, Yu A; Zabozlaev, A A

    2015-01-01

    Magnetite nanoparticles (NPs) are studied as agents for magnetic resonance imaging, hyperthermia of malignant tumors, targeted drug delivery as well as anti-anemic action. One of the main problems of such NPs is their aggregation that requires creation of methods for magnetite NPs stabilization during preparation of liquid medicinal forms on their basis. The present work is devoted to the possibility of mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) use for solubilization of magnetite NPs in hydrophilic medium. For this purpose, the condensate produced by electron-beam evaporation and condensation, with magnetite particles of size 5-8 nm deposited into the crystals of sodium chloride were used in conjunction with substance of mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate), and low molecular weight polyvinylpyrrolidone (PVP). The NP condensate was dispersed in distilled water or PVP or mexidol solutions. NPs size distribution in the liquid phase of the systems was determined by photon correlation spectroscopy, iron (Fe) concentration was evaluated by atomic emission spectrometry. It is shown that in the dispersion prepared in distilled water, the major amount of NPs was of 13-120 nm in size, in mexidol solution - 270-1700 nm, in PVP solution - 30-900 nm. In the fluid containing magnetite NPs together with mexidol and PVP, the main fraction (99.9%) was characterized by the NPs size of 14-75 nm with maximum of 25 nm. This system had the highest iron concentration: it was similar to that in the sample with mexidol solution and 6.6-7.3 times higher than the concentration in the samples with distilled water or PVP. Thus, in the preparation of aqueous dispersions based on magnetite NPs condensate, mexidol provides a transition of Fe to the liquid phase in amount necessary to achieve its biological activity, and PVP stabilizes such modified NPs.

  5. Erythromycin Ophthalmic

    MedlinePlus

    ... to prevent bacterial infections of the eye in newborn babies. Erythromycin is in a class of medications ... soon after delivery to prevent eye infections in newborn babies. Follow the directions on your prescription label ...

  6. [Erythromycin ethylsuccinate obtaining possibilities].

    PubMed

    Stan, Cătălina Daniela; Stefanache, Alina; Tântaru, Gladiola; Poiată, Antonia; Dumitrache, M; Diaconu, D E; Profire, Lenuţa

    2008-01-01

    In this study we tried to improve the erythromycin ethylsuccinate obtaining, having in view to separate the erythromycin ester by crystallization in water. The erythromycin acylation and the erythromycin ethylsuccinate crystallization were realized, following the next steps: 1. the acylation of the erythromycin with a methylene chloride solution of monoethylsuccinyl chloride, at 25-28 degrees C for 3 hours in the presence of NaHCO3; 2. the transfer of the erythromycin ethylsuccinate from methylene chloride solution in acetone solution by distillation of mixture methylene chloride: acetone 1:1 at 25-28 degrees C; 3. erythromycin ethylsuccinate separation by crystallization in water at pH = 8-8.5 and 5 degrees C for 90 minutes. The quality control for the erythromycin ester was performed according to the Xth edition of Romanian Pharmacopoeia standards using national standard for erythromycin ethylsuccinate and national standard for erythromycin with an activity of 1: 937 U and 2.02% humidity. The Micrococcus luteus ATCC 9341 was used as a test microorganism and a thin layer cromatography was performed for qualitative control. 13.1 g of erythromycin ethylsuccinate were obtained with an output of the process of 82.02%. Using water for the separation of erythromycin ethylsuccinate the output of the process is greater (82.02%) than in case of using petroleum ether (74.14%) or hexane (80.25%). The thin layer cromatography revealed an Rf = 0.56 and the microbiological activity of the erythromycin ethylsuccinate was 98.7% compared with the standard. Using water instead of hexane or petroleum ether is gainful for the separation of erythromycin ethylsuccinate from the reaction medium. The obtained erythromycin ethylsuccinate corresponds to the Xth edition of Romanian Pharmacopoeia standards. So, the raw materials consumption is decreased, the costs are cut down, the obtained product purity is high and the output of the process is greater.

  7. Urticaria from erythromycin.

    PubMed

    López Serrano, C; Quiralte Enríquez, J; Martínez Alzamora, F

    1993-01-01

    We report an adverse cutaneous reaction (urticaria) due to erythromycin. A positive skin prick and leukocyte histamine release tests, as well as a positive single-blind, placebo controlled oral challenge to erythromycin, strongly suggest an IgE mediated hypersensitivity mechanism.

  8. Erythromycin and Benzoyl Peroxide Topical

    MedlinePlus

    The combination of erythromycin and benzoyl peroxide is used to treat acne. Erythromycin and benzoyl peroxide are in a class of medications called topical antibiotics. The combination of erythromycin ...

  9. Desvenlafaxine succinate monohydrate.

    PubMed

    Venu, Nalivela; Sreekanth, Bukkapattanam R; Ram, Thaimattam; Devarakonda, Surya

    2008-05-01

    The title compound {systematic name: [2-(1-hydroxycyclohexyl)-2-(4-hydroxyphenyl)ethyl]dimethylammonium 3-carboxypropanoate monohydrate}, C(16)H(26)NO(2)(+) x C(4)H(5)O(4)(-) x H(2)O, is a succinate salt of O-desmethylvenlafaxine (desvenlafaxine). The present structure is one of four reported polymorphs of this salt, which is a new antidepressant drug. The carboxyl group of the succinate anion adopts a rare anti conformation and is engaged in a very short O-H...O(-) hydrogen-bond contact. Both cations and anions are involved separately in the formation of distinct O-H...O hydrogen-bonded networks. Desvenlafaxine cations and water molecules self-assemble to generate a honeycomb layer, while the succinate anions form a linear tape structure. These hydrogen-bonded networks are interlinked via N-H...O and O-H...O hydrogen bonds. The hydrogen-bonding network is so strong that desolvation and melting occur together at approximately 402 K. Thus, the crystal structure may be used to understand the thermal stability and solubility of the compound at the molecular level.

  10. Erythromycin estolate and jaundice.

    PubMed Central

    Inman, W H; Rawson, N S

    1983-01-01

    Using prescription-event monitoring to determine whether erythromycin estolate was a more frequent cause of jaundice than erythromycin stearate or tetracycline 12 208 patients, for whom 5343 doctors had prescribed one of the three drugs, were identified by the Prescription Pricing Authority. Of the questionnaires sent to general practitioners about the possible occurrence of jaundice, 76% were returned. There were 16 reports of jaundice, of which four were attributable to gall stones, three to cancer, six to viral hepatitis, and only three were possibly related to an antibiotic. All three patients, in whom the antibiotic was a possible cause, had been treated with erythromycin stearate. No case was attributable to the estolate which had previously been suspected of being a more frequent cause of jaundice. Although the incidence is unknown, it is very unlikely to be more than one in 100. PMID:6407653

  11. Erythromycin and the gut.

    PubMed Central

    Catnach, S M; Fairclough, P D

    1992-01-01

    The commonly reported gastrointestinal side effects that occur with erythromycin are related to its prokinetic action on the gut, mediated, at least in part, by its motilin receptor stimulating activity. This action may be of clinical use in conditions associated with gastrointestinal hypomotility such as diabetic gastroparesis and intestinal pseudo-obstruction, although further work needs to be done to establish the long term therapeutic uses of erythromycin in these disorders. Macrolide compounds with no antibacterial properties but which have a pronounced prokinetic action on the gut have already been synthesised and are currently being developed for future use in man. These 'motilides' should provide a useful addition to our rather limited armamentarium of effective gastrointestinal prokinetic agents. PMID:1568663

  12. Erythromycin Seromadesis in Orthopedic Surgery

    PubMed Central

    Salgado, Martin; Fernández, Felipe; Avilés, Carolina; Cordova, Cecilia

    2016-01-01

    Introduction: The presence of postoperative seromadesis is common, corresponding to the presence of serum in the subcutaneous tissue post a surgical event. Erythromycin has been reported as sclerosing, although not in orthopedic surgery. We report a case of erythromycin seromadesis in orthopedic surgery. Case Presentation: We present a case of a 63-year-old woman having undergone femoral prosthesis surgery and total hip replacement with a subfacial seroma without findings of infection, refractory to standard treatment of compression bandages, massage and cleaning surgery in two oportunities. A literature review was undertaken to obtain the therapeutic alternatives where erythromycin seromadesis is chosen with excellent response. Conclusion: Erythromycin sclerotherapy should be considered as an effective and safe option in the treatment of seroma in general surgery and traumatology. More studies are necessary to get a better evidence. We believe that this is the first study of use of erythromycin as sclerotherapy in a traumatology case. PMID:27703947

  13. Erythromycin Resistance in Borrelia burgdorferi

    PubMed Central

    Terekhova, Darya; Sartakova, Marina L.; Wormser, Gary P.; Schwartz, Ira; Cabello, Felipe C.

    2002-01-01

    Susceptibility testing of laboratory strains and clinical isolates of Borrelia burgdorferi indicates that resistance to erythromycin is present in them. Evaluation of the MICs, minimal bactericidal concentrations, and kinetics of bacterial killing of erythromycin suggests that this resistance is increased by preexposure to the antibiotic, is dependent on inoculum size, and may be the result of selection of subpopulations of bacterial cells with increased resistance. PMID:12384380

  14. The Succinated Proteome

    SciTech Connect

    Merkley, Eric D.; Metz, Thomas O.; Smith, Richard D.; Baynes, John; Frizell, Norma

    2014-03-30

    Succination is a chemical modification of cysteine in protein by the Krebs cycle intermediate, fumarate, yielding S-(2-succino)cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of the inner mitochondrial membrane, in concert with mitochondrial, endoplasmic reticulum (ER) and oxidative stress in adipocytes grown in high glucose medium and in adipose tissue in obesity and diabetes. Increased succination of proteins is also detected in the kidney of a fumarase conditional knock-out mouse which develops renal tumors. Keap1, the gatekeeper of the antioxidant response, was identified as a major succinated protein in renal cancer cells, suggesting that succination may play a role in activation of the antioxidant response. A wide range of proteins is subject to succination, including enzymes, adipokines, cytoskeletal proteins and ER chaperones with functional cysteine residues. There is also significant overlap between succinated and glutathionylated proteins, and with proteins containing cysteine residues that are readily oxidized to the sulfenic (cysteic) acid. Succination of adipocyte proteins is inhibited by uncouplers, which discharge the mitochondrial membrane potential (Δψm) and by ER stress inhibitors. 2SC serves as a biomarker of mitochondrial stress or dysfunction in chronic diseases, such as obesity, diabetes and cancer, and recent studies suggest that succination is a mechanistic link between mitochondrial dysfunction, oxidative and ER stress, and cellular progression toward apoptosis. In this article, we review the history of the succinated proteome and the challenges associated with measuring this non-enzymatic post-translational modification of proteins by proteomics approaches.

  15. Significant decrease of broth viscosity and glucose consumption in erythromycin fermentation by dynamic regulation of ammonium sulfate and phosphate.

    PubMed

    Chen, Yong; Wang, Zejian; Chu, Ju; Zhuang, Yingping; Zhang, Siliang; Yu, Xiaoguang

    2013-04-01

    In this study, the effects of nitrogen sources on broth viscosity and glucose consumption in erythromycin fermentation were investigated. By controlling ammonium sulfate concentration, broth viscosity and glucose consumption were decreased by 18.2% and 61.6%, respectively, whereas erythromycin biosynthesis was little affected. Furthermore, erythromycin A production was increased by 8.7% still with characteristics of low broth viscosity and glucose consumption through the rational regulations of phosphate salt, soybean meal and ammonium sulfate. It was found that ammonium sulfate could effectively control proteinase activity, which was correlated with the utilization of soybean meal as well as cell growth. The pollets formation contributed much to the decrease of broth viscosity. The accumulation of extracellular propionate and succinate under the new regulation strategy indicated that higher propanol consumption might increase the concentration of methylmalonyl-CoA and propionyl-CoA and thus could increase the flux leading to erythromycin A. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. THE SUCCINATED PROTEOME

    PubMed Central

    Merkley, Eric D.; Metz, Thomas O.; Smith, Richard D.; Baynes, John W.; Frizzell, Norma

    2014-01-01

    The post-translational modifications (PTMs) of cysteine residues include oxidation, S-glutathionylation, S-nitrosylation, and succination, all of which modify protein function or turnover in response to a changing intracellular redox environment. Succination is a chemical modification of cysteine in proteins by the Krebs cycle intermediate, fumarate, yielding S-(2-succino) cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of the inner mitochondrial membrane, in concert with mitochondrial, endoplasmic reticulum (ER) and oxidative stress in 3T3 adipocytes grown in high glucose medium and in adipose tissue in obesity and diabetes in mice. Increased succination of proteins is also detected in the kidney of a fumarase deficient conditional knock-out mouse which develops renal cysts. A wide range of proteins are subject to succination, including enzymes, adipokines, cytoskeletal proteins, and ER chaperones with functional cysteine residues. There is also some overlap between succinated and glutathionylated proteins, suggesting that the same low pKa thiols are targeted by both. Succination of adipocyte proteins in diabetes increases as a result of nutrient excess derived mitochondrial stress and this is inhibited by uncouplers, which discharge the mitochondrial membrane potential (ΔΨm) and relieve the electron transport chain. 2SC therefore serves as a biomarker of mitochondrial stress or dysfunction in chronic diseases, such as obesity, diabetes, and cancer, and recent studies suggest that succination is a mechanistic link between mitochondrial dysfunction, oxidative and ER stress, and cellular progression toward apoptosis. In this article, we review the history of the succinated proteome and the challenges associated with measuring this non-enzymatic PTM of proteins by proteomics approaches. PMID:24115015

  17. Pitted keratolysis, erythromycin, and hyperhidrosis.

    PubMed

    Pranteda, Guglielmo; Carlesimo, Marta; Pranteda, Giulia; Abruzzese, Claudia; Grimaldi, Miriam; De Micco, Sabrina; Muscianese, Marta; Bottoni, Ugo

    2014-01-01

    Pitted keratolysis (PK) is a plantar skin disorder mainly caused by coryneform bacteria. A common treatment consists of the topical use of erythromycin. Hyperhidrosis is considered a predisposing factor for bacterial proliferation and, consequently, for the onset of PK. The aim of this study was to evaluate the relationship between PK erythromycin and hyperhidrosis. All patients with PK seen in Sant'Andrea Hospital, between January 2009 and December 2011, were collected. PK was clinically and microscopically diagnosed. All patients underwent only topical treatment with erythromycin 3% gel twice daily. At the beginning of the study and after 5 and 10 days of treatment, a clinical evaluation and a gravimetric measurement of plantar sweating were assessed. A total of 97 patients were diagnosed as PK and were included in the study. Gravimetric measurements showed that in 94 of 97 examined patients (96.90%) at the time of the diagnosis, there was a bilateral excessive sweating occurring specifically in the areas affected by PK. After 10 days of antibiotic therapy, hyperhidrosis regressed together with the clinical manifestations. According to these data, we hypothesize that hyperhidrosis is due to an eccrine sweat gland hyperfunction, probably secondary to bacterial infection.

  18. Succinate oxidase in Neurospora.

    PubMed

    West, D J; Woodward, D O

    1973-02-01

    Two kinetically distinct states of succinate oxidase have been detected in the mitochondria of Neruospora crassa. One state has a K(m) for succinate of 4.1 x 10(-3)m, and the other has a K(m) for succinate of 3.5 x 10(-4)m. The high K(m) state was found in freshly extracted mitochondria from either 20- or 72-hr mycelium. However, the succinate oxidase activity in mitochondria from 20-hr mycelium rapidly deteriorated in vitro, leaving a stable residual activity with the lower K(m) for succinate. Adenosine triphosphate (ATP) plus Mg(2+) stabilized the high K(m) state in these preparations. The high K(m) state of succinate oxidase was further characterized by a two- to threefold increase in activity over the pH range 6.6 to 8.0 and by classical competitive inhibition by fumarate and malonate. By contrast, the low K(m) state of succinate oxidase showed a relatively flat response to pH over the range 6.6 to 8.0 and a nonclassical pattern of inhibition by fumarate and malonate, as shown by nonlinear plots of reciprocal velocity versus reciprocal substrate concentration in the presence of inhibitor or reciprocal velocity versus inhibitor concentration at fixed substrate concentrations. The relationship of mycelial age to the in vitro stability of succinate oxidase is considered with reference to probable changes in the relative pool sizes of extra- and intramitochondrial ATP in response to changes in the rate of glycolysis.

  19. A novel erythromycin, 6-desmethyl erythromycin D, made by substituting an acyltransferase domain of the erythromycin polyketide synthase.

    PubMed

    Petkovic, Hrvoje; Lill, Rachel E; Sheridan, Rose M; Wilkinson, Barrie; McCormick, Ellen L; McArthur, Hamish A I; Staunton, James; Leadlay, Peter F; Kendrew, Steven G

    2003-06-01

    The acyltransferase (AT) domain in module 4 of the erythromycin polyketide synthase (PKS) was substituted with an AT domain from the rapamycin PKS module 2 in order to alter the substrate specificity from methylmalonyl-CoA to malonyl-CoA. The resulting strain produced 6-desmethyl erythromycin D as the predominant product. This AT domain swap completes the library of malonyl-CoA AT swaps on the erythromycin PKS and reinforces PKS engineering as a robust and generic tool.

  20. 21 CFR 556.230 - Erythromycin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.230 Erythromycin. Tolerances for residues of erythromycin in food are...

  1. 21 CFR 556.230 - Erythromycin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.230 Erythromycin. Tolerances for residues of erythromycin in food are...

  2. 21 CFR 556.230 - Erythromycin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.230 Erythromycin. Tolerances for residues of erythromycin in food are...

  3. 21 CFR 556.230 - Erythromycin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.230 Erythromycin. Tolerances for residues of erythromycin in food are...

  4. 21 CFR 556.230 - Erythromycin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.230 Erythromycin. Tolerances for residues of erythromycin in food are...

  5. Succinic anhydrides from epoxides

    DOEpatents

    Coates, Geoffrey W.; Rowley, John M.

    2013-07-09

    Catalysts and methods for the double carbonylation of epoxides are disclosed. Each epoxide molecule reacts with two molecules of carbon monoxide to produce a succinic anhydride. The reaction is facilitated by catalysts combining a Lewis acidic species with a transition metal carbonyl complex. The double carbonylation is achieved in single process by using reaction conditions under which both carbonylation reactions occur without the necessity of isolating or purifying the product of the first carbonylation.

  6. Succinic anhydrides from epoxides

    DOEpatents

    Coates, Geoffrey W.; Rowley, John M.

    2016-06-28

    Catalysts and methods for the double carbonylation of epoxides are disclosed. Each epoxide molecule reacts with two molecules of carbon monoxide to produce a succinic anhydride. The reaction is facilitated by catalysts combining a Lewis acidic species with a transition metal carbonyl complex. The double carbonylation is achieved in single process by using reaction conditions under which both carbonylation reactions occur without the necessity of isolating or purifying the product of the first carbonylation.

  7. Succinic anhydrides from epoxides

    DOEpatents

    Coates, Geoffrey W; Rowley, John M

    2014-12-30

    Catalysts and methods for the double carbonylation of epoxides are disclosed. Each epoxide molecule reacts with two molecules of carbon monoxide to produce a succinic anhydride. The reaction is facilitated by catalysts combining a Lewis acidic species with a transition metal carbonyl complex. The double carbonylation is achieved in single process by using reaction conditions under which both carbonylation reactions occur without the necessity of isolating or purifying the product of the first carbonylation.

  8. Penetration of erythromycin through Staphylococcus epidermidis biofilm.

    PubMed

    Lin, Mao-hu; He, Lei; Gao, Jie; Liu, Yun-xi; Suo, Ji-jiang; Xing, Yu-bin; Jia, Ning

    2013-07-01

    The catheter related infection caused by Staphylococcus epidermidis biofilm is increasing and difficult to treat by antimicrobial chemotherapy. The properties of biofilms that give rise to antibiotic resistance are only partially understood. This study aimed to elucidate the penetration of erythromycin through Staphylococcus epidermidis biofilm. The penetration ratio of erythromycin through Staphylococcus epidermidis biofilms of 1457, 1457-msrA, and wild isolate S68 was detected by biofilm penetration model at different time points according to the standard regression curve. The RNA/DNA ratio and the cell density within the biofilms were observed by confocal laser microscope and transmission electromicroscope, respectively. The penetration ratios of erythromycin through the biofilms of 1457, 1457-msrA, and S68 after cultivation for 36 hours were 0.93, 0.55 and 0.4, respectively. The erythromycin penetration ratio through 1457 biofilm (0.58 after 8 hours) was higher than that through the other two (0.499 and 0.31 after 24 hours). Lower growth rate of the cells in biofilm was shown, with reduction of RNA/DNA proportion observed by confocal laser microscope through acridine orange stain. Compared with the control group observed by transmission electrmicroscope, the cell density of biofilm air face was lower than that of agar face, with more cell debris. Erythromycin could penetrate to the Staphylococcus epidermidis biofilm, but could not kill the cells thoroughly. The lower growth rate of the cells within biofilm could help decreasing the erythromycin susceptibility.

  9. In vivo bioavailability studies of sumatriptan succinate buccal tablets

    PubMed Central

    Shivanand, K; Raju, SA; Nizamuddin, S; Jayakar, B

    2011-01-01

    Back ground and the purpose of study Sumatriptan succinate is a Serotonin 5- HT1 receptor agonist, used in treatment of migraine. It is absorbed rapidly but incompletely when given orally and undergoes first-pass metabolism, resulting in a low absolute bioavailability of about 15%. The aim of this work was to design mucoadhesive bilayered buccal tablets of sumatriptan succinate to improve its bioavailability. Methods Mucoadhesive polymers carbopol 934 (Carbopol), HPMC K4M, HPMC K15M along with ethyl cellulose as an impermeable backing layer were used for the preparation of mucoadhesive bilayered tablets. In vivo bioavailability studies was also conducted in rabbits for optimized formulation using oral solution of sumatriptan succinate as standard. Results Bilayered buccal tablets (BBT) containing the mixture of Carbopol and HPMC K4M in the ratio 1:1 (T1) had the maximum percentage of in vitro drug release within 6 hrs. The optimized formulation (T1) followed non-Fickian release mechanism. The percentage relative bioavailability of sumatriptan succinate from selected bilayered buccal tablets (T1) was found to be 140.78%. Conclusions Bilayered buccal tablets of sumatriptan succinate was successfully prepared with improved bioavailability. PMID:22615661

  10. Ethyl chloride

    Integrated Risk Information System (IRIS)

    Ethyl chloride ; CASRN 75 - 00 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  11. Ethyl carbamate

    Integrated Risk Information System (IRIS)

    Ethyl carbamate ; CASRN 51 - 79 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  12. Ethyl acetate

    Integrated Risk Information System (IRIS)

    Ethyl acetate ; CASRN 141 - 78 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  13. Ethyl ether

    Integrated Risk Information System (IRIS)

    Ethyl ether ; CASRN 60 - 29 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effect

  14. Succination of proteins in diabetes.

    PubMed

    Frizzell, Norma; Lima, Maria; Baynes, John W

    2011-01-01

    Cysteine is arguably the most reactive amino acid in protein. A wide range of cysteine derivatives is formed in vivo, resulting from oxidation, nitrosation, alkylation and acylation reactions. This review describes succination of proteins, an irreversible chemical modification of cysteine by the Krebs cycle intermediate, fumarate, yielding S-(2-succinyl)cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of the inner mitochondrial membrane and develop in concert with mitochondrial and oxidative stress in diabetes. Increased succination of glyceraldehyde-3-phosphate dehydrogenase explains the loss in specific activity of this enzyme in muscle of streptozotocin-diabetic rats and increased succination of adiponectin may explain the decreased secretion of adiponectin from adipose tissue in type 2 diabetes. In addition to GAPDH and adiponectin, other succinated proteins identified in adipocytes include cytoskeletal proteins (tubulin, actin) and chaperone proteins in the endoplasmic reticulum. Succination of adipocyte protein in vitro is inhibited by uncouplers of oxidative phosphorylation and by inhibitors of ER stress. 2SC serves as a biomarker of mitochondrial stress and recent studies suggest that succination is the mechanistic link between mitochondrial and ER stress in diabetes.

  15. 21 CFR 558.248 - Erythromycin thiocyanate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS Specific New Animal Drugs for Use in Animal Feeds § 558.248 Erythromycin thiocyanate. (a) Approvals. Type A medicated...

  16. 21 CFR 520.823 - Erythromycin phosphate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... chapter. (d) Conditions of use. It is used in drinking water as follows: (1) Broiler and replacement... for 5 days; do not use in replacement pullets over 16 weeks of age; do not use in chickens producing... erythromycin. (iii) Limitations. Administer for 7 days; do not use in replacement pullets over 16 weeks of age...

  17. 21 CFR 520.823 - Erythromycin phosphate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... chapter. (d) Conditions of use. It is used in drinking water as follows: (1) Broiler and replacement... for 5 days; do not use in replacement pullets over 16 weeks of age; do not use in chickens producing... erythromycin. (iii) Limitations. Administer for 7 days; do not use in replacement pullets over 16 weeks of age...

  18. 21 CFR 520.823 - Erythromycin phosphate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... chapter. (d) Conditions of use. It is used in drinking water as follows: (1) Broiler and replacement... for 5 days; do not use in replacement pullets over 16 weeks of age; do not use in chickens producing... erythromycin. (iii) Limitations. Administer for 7 days; do not use in replacement pullets over 16 weeks of age...

  19. 21 CFR 520.823 - Erythromycin phosphate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... chapter. (d) Conditions of use. It is used in drinking water as follows: (1) Broiler and replacement... for 5 days; do not use in replacement pullets over 16 weeks of age; do not use in chickens producing... erythromycin. (iii) Limitations. Administer for 7 days; do not use in replacement pullets over 16 weeks of age...

  20. 21 CFR 520.823 - Erythromycin phosphate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... chapter. (d) Conditions of use. It is used in drinking water as follows: (1) Broiler and replacement... for 5 days; do not use in replacement pullets over 16 weeks of age; do not use in chickens producing... erythromycin. (iii) Limitations. Administer for 7 days; do not use in replacement pullets over 16 weeks of age...

  1. Childhood pityriasis lichenoides and oral erythromycin.

    PubMed

    Hapa, Asli; Ersoy-Evans, Sibel; Karaduman, Ayşen

    2012-01-01

    Pityriasis lichenoides (PL) is not uncommon in childhood, but current knowledge about the efficacy of oral erythromycin therapy for its treatment in children is limited. To investigate the role of oral erythromycin therapy in the treatment of PL in children, the records of 24 children with PL who had been started on oral erythromycin treatment at our institution between 2005 and 2008 were retrospectively reviewed. The study included 24 patients (14 male, 10 female) with a median age of 7 years (range 2-14) of whom 15 (62.5%) had PL chronica (PLC), six (25%) PL et varioliformis acuta (PLEVA), and three (2.5%) PLEVA-PLC overlap. History of upper respiratory tract infection was reported in 33% (n = 8) of the patients. History of drug intake and vaccination was noted in 20% (n = 5) and 20% (n = 5), respectively. The disease began during spring (30%, n = 7) or fall (30%, n = 7) in the majority of patients. The median duration of the disease was 11 months (range 1-48 months). Fifteen (68.2%) patients had more than 100 lesions. Distribution was diffuse in 82% (n = 18) of the cases and peripheral in the remainder (n = 6). Oral erythromycin was started at a dosage of 30 to 50 mg/kg per day in three to four divided dosages for 1 to 4 months. Good response was recorded in 64% and 73% of patients in the first and second months of therapy, respectively. Response rate rose to 83% in the third month. In those for whom follow-up data were available (n = 16), relapse was recorded in 12.5% (n = 3). Oral erythromycin may be an effective and well-tolerated treatment option for PL in children and should be continued for at least 3 months.

  2. [Bioavailability of erythromycin and colistin in calves (author's transl)].

    PubMed

    Escoula, L; Coste, M; Larrieu, G

    1981-01-01

    Bioavailability of erythromycin and colistin was studied in plasma, ruminal liquid and nasal mucus after simultaneous injection by intraruminal or intramuscular route. After intramuscular injection, erythromycin was found in plasma and respiratory tract, colistin in plasma. After oral administration, only erythromycin was found in nasal cavity secretions but nitrogen metabolism and volatile fatty acid production were modified in rumen.

  3. Fulminant hepatic failure associated with intravenous erythromycin lactobionate.

    PubMed

    Gholson, C F; Warren, G H

    1990-01-01

    Fatal fulminant hepatic failure accompanied by brisk hemolysis developed in an elderly man after intravenous administration of erythromycin lactobionate for a lower respiratory infection. To our knowledge, this is the first case of fatal hepatotoxicity associated with intravenous erythromycin therapy. Erythromycin should be added to the list of drugs that can cause fulminant hepatic failure.

  4. Postantibiotic effects and postantibiotic sub-MIC effects of tilmicosin, erythromycin and tiamulin on erythromycin-resistant Streptococcus suis.

    PubMed

    Wang, Liping; Zhang, Yuanshu

    2009-10-01

    The postantibiotic effects (PAEs) and postantibiotic sub-MIC effects (PA SMEs) of tilmicosin, erythromycin and tiamulin on erythromycin-susceptible and erythromycin-resistant strains of Streptococcus suis (M phenotype) were investigated in vitro. Tilmicosin and tiamulin induced significantly longer PAE and PA SME against both erythromycin-susceptible and erythromycin-resistant strains than did erythromycin. The durations of PAE and PA SMEs were proportional to the concentrations of drugs used for exposure. The PA SMEs were substantially longer than PAEs on S. suis (P<0.05) regardless of the antimicrobial used for exposure. The results indicated that the PAE and PA SME could help in the design of efficient control strategies for infection especially caused by erythromycin-resistant S. suis and that they may provide additional valuable information for the rational drug use in clinical practice.

  5. Succinate production in Escherichia coli

    PubMed Central

    Thakker, Chandresh; Martínez, Irene; San, Ka-Yiu; Bennett, George N.

    2012-01-01

    Succinate has been recognized as an important platform chemical that can be produced from biomass. While a number of organisms are capable of succinate production naturally, this review focuses on the engineering of Escherichia coli for production of the four-carbon dicarboxylic acid. Important features of a succinate production system are to achieve optimal balance of reducing equivalents generated by consumption of the feedstock, while maximizing the amount of carbon that is channeled to the product. Aerobic and anaerobic production strains have been developed and applied to production from glucose as well as other abundant carbon sources. Metabolic engineering methods and strain evolution have been used and supplemented by the recent application of systems biology and in silico modeling tools to construct optimal production strains. The metabolic capacity of the production strain, as well as the requirement for efficient recovery of succinate and the reliability of the performance under scale-up are important in the overall process. The costs of the overall biorefinery compatible process will determine the economical commercialization of succinate and its impact in larger chemical markets. PMID:21932253

  6. Ethyl glucuronide and ethyl sulfate.

    PubMed

    Walsham, Natalie E; Sherwood, Roy A

    2014-01-01

    Alcohol misuse is associated with significant morbidity and mortality. Although clinical history, examination, and the use of self-report questionnaires may identify subjects with harmful patterns of alcohol use, denial or under-reporting of alcohol intake is common. Existing biomarkers for detecting alcohol misuse include measurement of blood or urine ethanol for acute alcohol consumption, and carbohydrate-deficient transferrin and gamma-glutamyl transferase for chronic alcohol misuse. There is a need for a biomarker that can detect excessive alcohol consumption in the timeframe between 1 day and several weeks. Ethyl glucuronide (EtG) is a direct metabolite of ethanol detectable in urine for up to 90 h and longer in hair. Because EtG has high specificity for excess alcohol intake, it has great potential for use in detecting "binge" drinking. Using urine or hair, this noninvasive marker has a role in a variety of clinical and forensic settings. © 2014 Elsevier Inc. All rights reserved.

  7. Succinic acid: technology development and commercialization

    USDA-ARS?s Scientific Manuscript database

    Succinic acid is a precursor of many important, large volume industrial chemicals and consumer products. It was common knowledge that many ruminant microorganisms accumulated succinic acid under anaerobic conditions. However, it was not until the discovery of Anaerobiospirillum succiniciproducens at...

  8. Biological properties of ER 42859, a novel erythromycin derivative.

    PubMed

    Wilson, J M; Hannan, P C; Shillingford, C; Knowles, D J

    1989-03-01

    The antimicrobial activity of a new semi-synthetic oral erythromycin derivative, ER 42859, was evaluated in vitro and in vivo in comparison with erythromycin, spiramycin, josamycin, oleandomycin and the newer semi-synthetic derivatives flurithromycin, roxithromycin and A-56268. MIC values of ER 42859 were superior to those of roxithromycin, oleandomycin, josamycin and spiramycin but generally 2-fold poorer than those of erythromycin. The activity equalled that of erythromycin against Haemophilus influenzae and was superior to that of roxithromycin and A-56268 against this organism. MIC values of the compound were greatly influenced by pH due to the dibasic nature of the molecule. ER 42859 had markedly superior activity to erythromycin, spiramycin, josamycin, oleandomycin and flurithromycin against experimental infections in mice and similar activity to roxithromycin and A-56268. Blood and tissue levels were high and prolonged in rodents. In volunteers, blood levels were prolonged but inferior to those of erythromycin.

  9. 21 CFR 582.1091 - Succinic acid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Succinic acid. 582.1091 Section 582.1091 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1091 Succinic acid. (a) Product. Succinic acid. (b) Conditions of use. This substance is generally...

  10. 21 CFR 582.1091 - Succinic acid.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Succinic acid. 582.1091 Section 582.1091 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1091 Succinic acid. (a) Product. Succinic acid. (b) Conditions of use. This substance is generally...

  11. 21 CFR 582.1091 - Succinic acid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Succinic acid. 582.1091 Section 582.1091 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1091 Succinic acid. (a) Product. Succinic acid. (b) Conditions of use. This substance is generally...

  12. 21 CFR 582.1091 - Succinic acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Succinic acid. 582.1091 Section 582.1091 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1091 Succinic acid. (a) Product. Succinic acid. (b) Conditions of use. This substance is generally...

  13. 21 CFR 582.1091 - Succinic acid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Succinic acid. 582.1091 Section 582.1091 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1091 Succinic acid. (a) Product. Succinic acid. (b) Conditions of use. This substance is generally...

  14. Succinate in the cancer-immune cycle.

    PubMed

    Jiang, Shuai; Yan, Wei

    2017-04-01

    Succinate is an important intermediate of the tricarboxylic acid (TCA) cycle. In mitochondria, it plays a crucial role in generating adenosine triphosphate. Succinate metabolism is also intertwined with the metabolism of other metabolites and with the "GABA shunt" of the glutamine pathway. Recently, it has become increasingly apparent that the roles of succinate extend into the realms of immunity and cancer. Succinate is a key modulator of the hypoxic response, an important player in tumorigenesis; succinate is also involved in protein succinylation, a novel posttranslational modification pathway. This expanding repertoire of succinate functions suggests that it has broad roles in cellular contexts. Mutations in enzymes such as succinate dehydrogenase (SDH) that participate in succinate-related pathways lead to various pathologies, including tumor formation and innate inflammatory processes. Succinate can have both pro- or anti-tumor effectiveness. Therefore, investigation of succinate as an inflammatory signal may increase our understanding of the cancer-immunity cycle involved in both inflammatory diseases and cancer. Here, we briefly review the emerging roles of succinate, extending beyond metabolism, into anti-cancer immunity. This expansion of succinate roles suggests that it may represent a novel class of regulators in inflammation, which act as key signals in human cancers.

  15. Erythromycin contracts rabbit colon myocytes via occupation of motilin receptors.

    PubMed

    Hasler, W L; Heldsinger, A; Chung, O Y

    1992-01-01

    Erythromycin stimulates gastroduodenal motility via action on motilin receptors. We evaluated erythromycin as a colonic muscle motilin agonist using in vitro rabbit colon studies. Isolated myocytes contracted to erythromycin with a half-maximal effective concentration of 2 pM and peak shortening of 22.4 +/- 2.5% at 1 nM, which was superimposable with the response to motilin. 125I-labeled motilin binding to colon muscle homogenates was saturable and specific with a dissociation constant (Kd) of 0.39 nM and maximal binding (Bmax) of 41 +/- 3 fmol/mg protein. Motilin displaced specifically bound 125I-motilin, with a Kd of 0.31 nM. Erythromycin displaced 125I-motilin but was less potent, with an inhibitory constant of 84.0 nM. Bmax values from displacement studies were similar to the Scatchard data. Motilin receptor protection from alkylation by N-ethylmaleimide preserved contraction to motilin and erythromycin but not acetylcholine or cholecystokinin, whereas protection with erythromycin preserved contraction to motilin but not other agonists. In conclusion, erythromycin binds to colon muscle motilin receptors present in densities similar to reported values for the upper gut. Furthermore, erythromycin contracts colonic myocytes via specific action on motilin receptors. Thus erythromycin may have colonic motor-stimulating properties by action on motilin receptors.

  16. [Progress in microbial production of succinic acid].

    PubMed

    Liu, Rongming; Liang, Liya; Wu, Mingke; Jiang, Min

    2013-10-01

    Succinic acid is one of the key intermediates in the tricarboxylic acid cycle (TCA)and has huge potentials in biopolymer, food, medicine applications. This article reviews recent research progress in the production of succinic acid by microbial fermentation, including discovery and screening of the succinic-acid-producing microbes, the progress of genetic engineering strategy and metabolic engineering technology for construction of succinic acid-producing strains, and fermentation process control and optimization. Finally, we discussed the limitation of current progress and proposed the future research needs for microbial production of succinic acid.

  17. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ethyl alcohol containing ethyl acetate. 584.200... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100...

  18. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ethyl alcohol containing ethyl acetate. 584.200... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100...

  19. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ethyl alcohol containing ethyl acetate. 584.200... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100...

  20. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ethyl alcohol containing ethyl acetate. 584.200... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100...

  1. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethyl alcohol containing ethyl acetate. 584.200... Ethyl alcohol containing ethyl acetate. The feed additive ethyl alcohol containing ethyl acetate meets the requirement of 27 CFR 21.62, being not less than 92.5 percent ethyl alcohol, each 100...

  2. Succinate: a metabolic signal in inflammation.

    PubMed

    Mills, Evanna; O'Neill, Luke A J

    2014-05-01

    Succinate is an intermediate of the tricarboxylic acid (TCA) cycle, and plays a crucial role in adenosine triphosphate (ATP) generation in mitochondria. Recently, new roles for succinate outside metabolism have emerged. Succinate stabilizes the transcription factor hypoxia-inducible factor-1α (HIF-1α) in specific tumors and in activated macrophages, and stimulates dendritic cells via its receptor succinate receptor 1. Furthermore, succinate has been shown to post-translationally modify proteins. This expanding repertoire of functions for succinate suggests a broader role in cellular activation. We review the new roles of succinate and draw parallels to other metabolites such as NAD(+) and citrate whose roles have expanded beyond metabolism and into signaling. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Escherichia coli yjjPB genes encode a succinate transporter important for succinate production.

    PubMed

    Fukui, Keita; Nanatani, Kei; Hara, Yoshihiko; Yamakami, Suguru; Yahagi, Daiki; Chinen, Akito; Tokura, Mitsunori; Abe, Keietsu

    2017-09-01

    Under anaerobic conditions, Escherichia coli produces succinate from glucose via the reductive tricarboxylic acid cycle. To date, however, no genes encoding succinate exporters have been established in E. coli. Therefore, we attempted to identify genes encoding succinate exporters by screening an E. coli MG1655 genome library. We identified the yjjPB genes as candidates encoding a succinate transporter, which enhanced succinate production in Pantoea ananatis under aerobic conditions. A complementation assay conducted in Corynebacterium glutamicum strain AJ110655ΔsucE1 demonstrated that both YjjP and YjjB are required for the restoration of succinate production. Furthermore, deletion of yjjPB decreased succinate production in E. coli by 70% under anaerobic conditions. Taken together, these results suggest that YjjPB constitutes a succinate transporter in E. coli and that the products of both genes are required for succinate export.

  4. Use and safety of erythromycin and metoclopramide in hospitalized infants

    PubMed Central

    Ericson, Jessica E.; Arnold, Christopher; Cheeseman, Jomani; Cho, Jordan; Kaneko, Sarah; Wilson, Ele’na; Clark, Reese H.; Benjamin, Daniel K.; Chu, Vivian; Smith, P. Brian; Hornik, Christoph P.

    2015-01-01

    Objective Prokinetic medications are used in premature infants to promote motility and decrease time to full enteral feeding. Erythromycin and metoclopramide are the most commonly used prokinetic medications in the neonatal intensive care unit (NICU), but their safety profile is not well defined. Methods We conducted a large retrospective cohort study using data from 348 NICUs managed by the Pediatrix Medical Group. All infants exposed to ≥1 dose of erythromycin, metoclopramide, or both, from a cohort of 887,910 infants discharged between 1997 and 2012 were included. We collected laboratory and clinical information while infants were exposed to erythromycin or metoclopramide and described the frequency of laboratory abnormalities and clinical adverse events. Results Metoclopramide use increased from 1997–2005 and decreased from 2005–2012, while erythromycin use remained stable. Erythromycin use was most often associated with a diagnosis of feeding problem (40%), while metoclopramide was most often associated with a diagnosis of gastroesophageal reflux (59%). The most common laboratory adverse event during exposure to erythromycin or metoclopramide was hyperkalemia (8.6/1000 infant days on erythromycin and 11.0/1000 infant days on metoclopramide). Incidence of pyloric stenosis was greater with erythromycin than with metoclopramide (10/1095, 0.9% vs. 76/19,001, 0.4%, p=0.01), but odds were not significantly increased after adjusting for covariates (odds ratio=0.52 [95% CI: 0.26, 1.02], p=0.06). More infants experienced an adverse event while treated with metoclopramide than with erythromycin (odds ratio=1.21 [95% CI: 1.03, 1.43]). Conclusion Metoclopramide was associated with increased risk of adverse events compared to erythromycin. Studies are needed to confirm safety and effectiveness of both drugs in infants. PMID:25806675

  5. Use and Safety of Erythromycin and Metoclopramide in Hospitalized Infants.

    PubMed

    Ericson, Jessica E; Arnold, Christopher; Cheeseman, Jomani; Cho, Jordan; Kaneko, Sarah; Wilson, Ele'na; Clark, Reese H; Benjamin, Daniel K; Chu, Vivian; Smith, P Brian; Hornik, Christoph P

    2015-09-01

    Prokinetic medications are used in premature infants to promote motility and decrease time to full enteral feeding. Erythromycin and metoclopramide are the most commonly used prokinetic medications in the neonatal intensive care unit (NICU), but their safety profile is not well defined. We conducted a large retrospective cohort study using data from 348 NICUs managed by the Pediatrix Medical Group. All of the infants exposed to ≥1 dose of erythromycin, metoclopramide, or both, from a cohort of 8,87,910 infants discharged between 1997 and 2012 were included. We collected laboratory and clinical information while infants were exposed to erythromycin or metoclopramide and described the frequency of laboratory abnormalities and clinical adverse events (AEs). Metoclopramide use increased from 1997 to 2005 and decreased from 2005 to 2012, whereas erythromycin use remained stable. Erythromycin use was most often associated with a diagnosis of feeding problem (40%), whereas metoclopramide was most often associated with a diagnosis of gastroesophageal reflux (59%). The most common laboratory AE during exposure to erythromycin or metoclopramide was hyperkalemia (8.6/1000 infant days on erythromycin and 11.0/1000 infant days on metoclopramide). Incidence of pyloric stenosis was greater with erythromycin than with metoclopramide (10/1095, 0.9% vs 76/19,001, 0.4%; P = 0.01), but odds were not significantly increased after adjusting for covariates (odds ratio 0.52, 95% confidence interval [CI] 0.26-1.02, P = 0.06). More infants experienced an AE while treated with metoclopramide than with erythromycin (odds ratio 1.21, 95% CI 1.03-1.43). Metoclopramide was associated with increased risk of AEs compared with erythromycin. Studies are needed to confirm safety and effectiveness of both the drugs in infants.

  6. Improved succinate production by metabolic engineering.

    PubMed

    Cheng, Ke-Ke; Wang, Gen-Yu; Zeng, Jing; Zhang, Jian-An

    2013-01-01

    Succinate is a promising chemical which has wide applications and can be produced by biological route. The history of the biosuccinate production shows that the joint effort of different metabolic engineering approaches brings successful results. In order to enhance the succinate production, multiple metabolical strategies have been sought. In this review, different overproducers for succinate production, including natural succinate overproducers and metabolic engineered overproducers, are examined and the metabolic engineering strategies and performances are discussed. Modification of the mechanism of substrate transportation, knocking-out genes responsible for by-products accumulation, overexpression of the genes directly involved in the pathway, and improvement of internal NADH and ATP formation are some of the strategies applied. Combination of the appropriate genes from homologous and heterologous hosts, extension of substrate, integrated production of succinate, and other high-value-added products are expected to bring a desired objective of producing succinate from renewable resources economically and efficiently.

  7. Improved Succinate Production by Metabolic Engineering

    PubMed Central

    Cheng, Ke-Ke; Wang, Gen-Yu; Zeng, Jing; Zhang, Jian-An

    2013-01-01

    Succinate is a promising chemical which has wide applications and can be produced by biological route. The history of the biosuccinate production shows that the joint effort of different metabolic engineering approaches brings successful results. In order to enhance the succinate production, multiple metabolical strategies have been sought. In this review, different overproducers for succinate production, including natural succinate overproducers and metabolic engineered overproducers, are examined and the metabolic engineering strategies and performances are discussed. Modification of the mechanism of substrate transportation, knocking-out genes responsible for by-products accumulation, overexpression of the genes directly involved in the pathway, and improvement of internal NADH and ATP formation are some of the strategies applied. Combination of the appropriate genes from homologous and heterologous hosts, extension of substrate, integrated production of succinate, and other high-value-added products are expected to bring a desired objective of producing succinate from renewable resources economically and efficiently. PMID:23691505

  8. 21 CFR 184.1091 - Succinic acid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Succinic acid. 184.1091 Section 184.1091 Food and... Substances Affirmed as GRAS § 184.1091 Succinic acid. (a) Succinic acid (C4H6O4, CAS Reg. No. 110-15-6), also referred to as amber acid and ethylenesuccinic acid, is the chemical 1,4-butanedioic acid. It is...

  9. 21 CFR 184.1091 - Succinic acid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Succinic acid. 184.1091 Section 184.1091 Food and... Substances Affirmed as GRAS § 184.1091 Succinic acid. (a) Succinic acid (C4H6O4, CAS Reg. No. 110-15-6), also referred to as amber acid and ethylenesuccinic acid, is the chemical 1,4-butanedioic acid. It is...

  10. 21 CFR 184.1091 - Succinic acid.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Succinic acid. 184.1091 Section 184.1091 Food and... Substances Affirmed as GRAS § 184.1091 Succinic acid. (a) Succinic acid (C4H6O4, CAS Reg. No. 110-15-6), also referred to as amber acid and ethylenesuccinic acid, is the chemical 1,4-butanedioic acid. It is...

  11. 21 CFR 184.1091 - Succinic acid.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Succinic acid. 184.1091 Section 184.1091 Food and... Substances Affirmed as GRAS § 184.1091 Succinic acid. (a) Succinic acid (C4H6O4, CAS Reg. No. 110-15-6), also referred to as amber acid and ethylenesuccinic acid, is the chemical 1,4-butanedioic acid. It is...

  12. 21 CFR 184.1091 - Succinic acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Succinic acid. 184.1091 Section 184.1091 Food and....1091 Succinic acid. (a) Succinic acid (C4H6O4, CAS Reg. No. 110-15-6), also referred to as amber acid and ethylenesuccinic acid, is the chemical 1,4-butanedioic acid. It is commercially prepared by...

  13. [The in vivo penetration of erythromycin into alveolar macrophages].

    PubMed

    Carré, P; Piva, F; Aerts, C; Voisin, C; Wallaert, B

    1990-01-01

    In order to appreciate the in vivo penetration of erythromycin the alveolar spaces a broncho-alveolar lavage was carried out in 24 guinea pigs, 30 minutes, 1 hour 30 minutes and three hours after a single intraperitoneal injection of 50 mgms. of erythromycin. The erythromycin dose was assessed by a microbiological method in the alveolar macrophages and the supernatant of the broncho-alveolar lavage liquid. The intramacrophage concentrations of erythromycin were 3.9, 11.5 and 12 times higher than the serum concentrations at 30 minutes, 1 hour 30 and three hours respectively. The concentrations in the broncho-alveolar lavage liquid was always higher than the serum concentrations tacking account of the different dilutions estimated with relation to the glucose concentrations. At 30 minutes, 1 hour 30 minutes and three hours the alveolar macrophages contained 1.9; 7.6 and 6 times more erythromycin respectively than the lavage supernatant. From the first half hour of its administration the erythromycin was concentrated in the alveolar spaces, in particular within the macrophages. Already noted in vitro, this rapidity of erythromycin concentration in vivo in alveolar macrophages appears to be one of the reasons to explain its activity against micro-organisms developing within macrophages.

  14. The effects of erythromycin on theophylline elimination in normal males.

    PubMed

    May, D C; Jarboe, C H; Ellenburg, D T; Roe, E J; Karibo, J

    1982-01-01

    The effects of three erythromycin preparations on theophylline elimination kinetics were examined in 23 male subjects. Subjects received 6 mg/kg of the theophylline elixir orally and elimination kinetics were determined. The population was then randomized to receive either a lactose placebo, erythromycin base, erythromycin stearate, or erythromycin ethylsuccinate. Each 250-mg preparation was given four times a day for six days. On day seven, a repeat kinetic study was performed. The mean theophylline half-life of controls was 7.8 +/- 2.6 hours. The half-life increased significantly in all erythromycin treatment groups. The increase for the base, stearate, and ethylsuccinate groups was 51.7, 21.3, and 60.3 per cent, respectively. The total body theophylline clearance decreased significantly in all treatment groups. This was not associated with biochemical evidence of hepatitis. Three of four smokers who received erythromycin manifested no increase in theophylline half-life, in contrast to one of 13 nonsmokers. There was no difference in the percentage theophylline bound to serum protein for any of the erythromycin treatment groups or controls as determined by ultracentrifugation.

  15. Genetics Home Reference: succinic semialdehyde dehydrogenase deficiency

    MedlinePlus

    ... National Institute of Neurological Disorders and Stroke: Epilepsy Information Page Educational Resources (5 links) Boston Children's Hospital: Seizures and Epilepsy Disease InfoSearch: Succinic ...

  16. Acyltransferase domain substitutions in erythromycin polyketide synthase yield novel erythromycin derivatives.

    PubMed Central

    Ruan, X; Pereda, A; Stassi, D L; Zeidner, D; Summers, R G; Jackson, M; Shivakumar, A; Kakavas, S; Staver, M J; Donadio, S; Katz, L

    1997-01-01

    The methylmalonyl coenzyme A (methylmalonyl-CoA)-specific acyltransferase (AT) domains of modules 1 and 2 of the 6-deoxyerythronolide B synthase (DEBS1) of Saccharopolyspora erythraea ER720 were replaced with three heterologous AT domains that are believed, based on sequence comparisons, to be specific for malonyl-CoA. The three substituted AT domains were "Hyg" AT2 from module 2 of a type I polyketide synthase (PKS)-like gene cluster isolated from the rapamycin producer Streptomyces hygroscopicus ATCC 29253, "Ven" AT isolated from a PKS-like gene cluster of the pikromycin producer Streptomyces venezuelae ATCC 15439, and RAPS AT14 from module 14 of the rapamycin PKS gene cluster of S. hygroscopicus ATCC 29253. These changes led to the production of novel erythromycin derivatives by the engineered strains of S. erythraea ER720. Specifically, 12-desmethyl-12-deoxyerythromycin A, which lacks the methyl group at C-12 of the macrolactone ring, was produced by the strains in which the resident AT1 domain was replaced, and 10-desmethylerythromycin A and 10-desmethyl-12-deoxyerythromycin A, both of which lack the methyl group at C-10 of the macrolactone ring, were produced by the recombinant strains in which the resident AT2 domain was replaced. All of the novel erythromycin derivatives exhibited antibiotic activity against Staphylococcus aureus. The production of the erythromycin derivatives through AT replacements confirms the computer predicted substrate specificities of "Hyg" AT2 and "Ven" AT and the substrate specificity of RAPS AT14 deduced from the structure of rapamycin. Moreover, these experiments demonstrate that at least some AT domains of the complete 6-deoxyerythronolide B synthase of S. erythraea can be replaced by functionally related domains from different organisms to make novel, bioactive compounds. PMID:9335291

  17. Protective role of tetrahydrocurcumin against erythromycin estolate-induced hepatotoxicity.

    PubMed

    Pari, L; Murugan, P

    2004-05-01

    Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, was investigated for its possible hepatoprotective effect in Wistar rats against erythromycin estolate-induced toxicity. Oral administration of THC significantly prevented the occurrence of erythromycin estolate-induced liver damage. The increased level of serum enzymes (aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP)), bilirubin, cholesterol, triglycerides, phospholipids, free fatty acids and plasma thiobarbituric acid reactive substances (TBARS) and hydroperoxides observed in rats treated with erythromycin estolate were very much reduced in rats treated with THC and erythromycin estolate. This biochemical observation were supplemented by histopathological examination of liver section. Results of this study revealed that THC could afford a significant protection against erthromycin estolate-induced hepatocellular damage. Tetrahydrocurcumin had a better protective effect when compared with Silymarin, a reference drug.

  18. Autobacteriographic studies of clarithromycin and erythromycin in mice

    SciTech Connect

    Kohno, Y.; Ohta, K.; Suwa, T.; Suga, T. )

    1990-04-01

    The antimicrobial activity of clarithromycin was compared with that of erythromycin in experimentally infected mice by whole-body autobacteriography. In mice with systemic staphylococcal infections, the number of vital microbes in the body was relatively low in the early period after oral administration of erythromycin, but increased thereafter to the levels found in nonmedicated control mice. On the other hand, with clarithromycin treatment, a significantly smaller number of microbes was evident throughout the body. The microbes were scarcely seen in the parenchyma of any organs during the examination period. This potent antimicrobial activity of clarithromycin compared with that of erythromycin was further demonstrated in mice with respiratory infections. On the other hand, to examine the distribution properties of both antibiotics in the whole body, an autoradiographic study was carried out with (N-methyl-14C)clarithromycin and (N-methyl-14C)erythromycin. Both labeled antibiotics were distributed widely throughout the body after oral administration in both uninfected control mice and mice with systemic infections. However, the radioactivity was more marked and persistent for (14C)clarithromycin than it was for (14C)erythromycin, particularly in the lungs. The observations described above indicate the superior in vivo antimicrobial activity of clarithromycin compared with that of erythromycin and suggest that the superiority of clarithromycin is largely attributed to its favorable distribution properties. The advantages of whole-body autobacteriography, coupled with whole-body autoradiography, are discussed.

  19. Production of Succinic Acid for Lignocellulosic Hydrolysates

    SciTech Connect

    Davison, B.H.; Nghiem, J.

    2002-06-01

    The purpose of this Cooperative Research and Development Agreement (CRADA) is to add and test new metabolic activities to existing microbial catalysts for the production of succinic acid from renewables. In particular, they seek to add to the existing organism the ability to utilize xylose efficiently and simultaneously with glucose in mixtures of sugars or to add succinic acid production to another strain and to test the value of this new capability for production of succinic acid from industrial lignocellulosic hydrolyasates. The Contractors and Participant are hereinafter jointly referred to as the 'Parties'. Research to date in succinic acid fermentation, separation and genetic engineering has resulted in a potentially economical process based on the use of an Escherichia coli strain AFP111 with suitable characteristics for the production of succinic acid from glucose. Economic analysis has shown that higher value commodity chemicals can be economically produced from succinic acid based on repliminary laboratory findings and predicted catalytic parameters. The initial target markets include succinic acid itself, succinate salts, esters and other derivatives for use as deicers, solvents and acidulants. The other commodity products from the succinic acid platform include 1,4-butanediol, {gamma}-butyrolactone, 2-pyrrolidinone and N-methyl pyrrolidinone. Current economic analyses indicate that this platform is competitive with existing petrochemical routes, especially for the succinic acid and derivatives. The report presents the planned CRADA objectives followed by the results. The results section has a combined biocatalysis and fermentation section and a commercialization section. This is a nonproprietary report; additional proprietary information may be made available subject to acceptance of the appropriate proprietary information agreements.

  20. Designing green plasticizers: influence of alkyl chain length on biodegradation and plasticization properties of succinate based plasticizers.

    PubMed

    Erythropel, Hanno C; Dodd, Patrick; Leask, Richard L; Maric, Milan; Cooper, David G

    2013-04-01

    Phthalate diesters such as di (2-ethylhexyl) phthalate (DEHP) are considered ubiquitous contaminants and are poorly biodegraded in the environment. Moreover, both the parent compound and stable metabolites such as mono (2-ethylhexyl) phthalate (MEHP) are linked to several negative impacts on the environment and human health. Earlier work established that saturated diester compounds, such as succinates, showed better biodegradation characteristics and comparable plasticizer properties compared to DEHP. In this work we examine the effect of alkyl chain length of succinate molecules on plasticizer and biodegradation properties. This included both the side chains (n-ethyl to n-octyl) as well as substituents on the middle part of the succinate molecule. We showed that the common soil bacterium Rhodococcus rhodocrous could rapidly break down all unsubstituted succinates, without the appearance of stable metabolites. Furthermore, the organisms used the plasticizer metabolites as carbon source. The introduction of a large cyclohexyl substituent on the succinate resulted in a poorer degradation rate. Glass Transition Temperature (Tg) measurements were performed to evaluate plasticizer properties and showed that longer side chains reduced the Tg more efficiently, while large cyclohexyl substituents on the succinate decreased this effect. However, all compounds performed better or equal to DEHP at reducing the Tg.

  1. Microarray analysis of erythromycin resistance determinants.

    PubMed

    Volokhov, D; Chizhikov, V; Chumakov, K; Rasooly, A

    2003-01-01

    To develop a DNA microarray for analysis of genes encoding resistance determinants to erythromycin and the related macrolide, lincosamide and streptogramin B (MLS) compounds. We developed an oligonucleotide microarray containing seven oligonucleotide probes (oligoprobes) for each of the six genes (ermA, ermB, ermC, ereA, ereB and msrA/B) that account for more than 98% of MLS resistance in Staphylococcus aureus clinical isolates. The microarray was used to test reference and clinical S. aureus and Streptococcus pyrogenes strains. Target genes from clinical strains were amplified and fluorescently labelled using multiplex PCR target amplification. The microarray assay correctly identified the MLS resistance genes in the reference strains and clinical isolates of S. aureus, and the results were confirmed by direct DNA sequence analysis. Of 18 S. aureus clinical strains tested, 11 isolates carry MLS determinants. One gene (ermC) was found in all 11 clinical isolates tested, and two others, ermA and msrA/B, were found in five or more isolates. Indeed, eight (72%) of 11 clinical isolate strains contained two or three MLS resistance genes, in one of the three combinations (ermA with ermC, ermC with msrA/B, ermA with ermC and msrA/B). Oligonucleotide microarray can detect and identify the six MLS resistance determinants analysed in this study. Our results suggest that microarray-based detection of microbial antibiotic resistance genes might be a useful tool for identifying antibiotic resistance determinants in a wide range of bacterial strains, given the high homology among microbial MLS resistance genes.

  2. Improved succinate production in Corynebacterium glutamicum by engineering glyoxylate pathway and succinate export system.

    PubMed

    Zhu, Nianqing; Xia, Huihua; Yang, Jiangang; Zhao, Xueming; Chen, Tao

    2014-03-01

    A dual route for anaerobic succinate production was engineered into Corynebacterium glutamicum. The glyoxylate pathway was reconstructed by overexpressing isocitrate lyase, malate synthase and citrate synthase. The engineered strain produced succinate with a yield of 1.34 mol (mol glucose)(-1). Further overexpression of succinate exporter, SucE, increased succinate yield to 1.43 mol (mol glucose)(-1). Metabolic flux analysis revealed that the glyoxylate pathway was further activated by engineering succinate export system. Using an anaerobic fed-batch fermentation process, the final strain produced 926 mM succinate (= 109 g l(-1)) with an overall volumetric productivity of 9.4 mM h(-1) and an average yield of 1.32 mol (mol glucose)(-1).

  3. Molecular subtyping and erythromycin resistance of Campylobacter in China.

    PubMed

    Zhang, A; Song, L; Liang, H; Gu, Y; Zhang, C; Liu, X; Zhang, J; Zhang, M

    2016-07-01

    To investigate the erythromycin resistance patterns and mechanism for Campylobacter isolates in China. The minimum inhibitory concentrations of erythromycin on 858 Chinese Campylobacter isolates were analysed. PCR and DNA sequencing were used to identify mutations in the 23S rRNA and the presence of the ermB gene in the 158 erythromycin resistance isolates (18·4%). About 83% (131/158) had A2075G mutation in their 23S rRNA; no A2074C/G mutants were found. The ermB gene was identified in 30 Campylobacter coli isolates (19%). Four types of multidrug-resistant gene islands (MDRGIs) were found. Fifty-three types were identified by multilocus sequence typing among the resistant isolates. All isolates of STs 6322 and 1145 had the ermB gene. The erythromycin resistance rate of Camp. coli (58·56%) was much higher than Campylobacter jejuni (0·67%). The insertion sites between cadF and CCO1582 and between nfsB and cinA on the chromosome might be hot spots for MDRGI transformation. Point mutation in domain V of the 23S rRNA and the ermB gene accounted for 100% of the erythromycin resistance of Campylobacter in China. Journal of Applied Microbiology © 2016 The Society for Applied Microbiology.

  4. Inhibition of membrane-bound succinate dehydrogenase by disulfiram.

    PubMed

    Jay, D

    1991-04-01

    The effect of disulfiram on succinate oxidase and succinate dehydrogenase activities of beef heart submitochondrial particles was studied. Results show that disulfiram inhibits both functions. Succinate and malonate suppress the inhibitory action of disulfiram when succinate dehydrogenase is stabilized in an active conformation. Disulfiram is not able to inhibit the enzyme when succinate dehydrogenase is inactivated by oxaloacetate. The inhibitory effect of disulfiram is reverted by the addition of dithiothreitol. From these results, it is proposed that disulfiram inhibits the utilization of succinate by a direct modification of an -SH group located in the catalytically active site of succinate dehydrogenase.

  5. Role of succinic acid in chemical evolution

    NASA Technical Reports Server (NTRS)

    Negron-Mendoza, A.; Ponnamperuma, C.

    1982-01-01

    Succinic acid is converted into other carboxylic acids by ionizing radiation. The results obtained have been correlated with the ready formation of this compound in prebiotic experiments. Its role in biological systems may be related to its prebiotic occurrence.

  6. Role of succinic acid in chemical evolution

    NASA Technical Reports Server (NTRS)

    Negron-Mendoza, A.; Ponnamperuma, C.

    1982-01-01

    Succinic acid is converted into other carboxylic acids by ionizing radiation. The results obtained have been correlated with the ready formation of this compound in prebiotic experiments. Its role in biological systems may be related to its prebiotic occurrence.

  7. [Interaction of succinate dehydrogenase and oxaloacetate].

    PubMed

    Kotliar, A B; Vinogradov, A D

    1984-04-01

    The equilibrium and rate constants for interaction of the reduced and oxidized membrane-bound succinate dehydrogenase (EC 1.3.99.1) with oxaloacetate were determined. The 10-fold decrease in the oxaloacetate affinity for the reduced enzyme was shown to be due to the 10-fold increase of the enzyme-inhibitor complex dissociation rate, which occurs upon its reduction. The rate of dissociation induced by succinate is 10 times higher than that induced by malonate in the submitochondrial particles, being equal in the soluble enzyme preparations. The rates of dissociation induced by malonate excess, or by the enzyme irreversibly utilizing oxaloacetate (transaminase in the presence of glutamate) are also equal. The data obtained suggest that succinate dehydrogenase interaction with succinate and oxaloacetate results from the competition for a single dicarboxylate-specific site. In submitochondrial particles all succinate dehydrogenase molecules are in redox equilibrium provided for by endogenous ubiquinone. No electronic equilibrium between the individual enzyme molecules exists, when succinate dehydrogenase is solubilized.

  8. Organization of a cluster of erythromycin genes in Saccharopolyspora erythraea.

    PubMed Central

    Weber, J M; Leung, J O; Maine, G T; Potenz, R H; Paulus, T J; DeWitt, J P

    1990-01-01

    We used a series of gene disruptions and gene replacements to mutagenically characterize 30 kilobases of DNA in the erythromycin resistance gene (ermE) region of the Saccharopolyspora erythraea chromosome. Five previously undiscovered loci involved in the biosynthesis of erythromycin were found, eryBI, eryBII, eryCI, eryCII, and eryH; and three known loci, eryAI, eryG, and ermE, were further characterized. The new Ery phenotype, EryH, was marked by (i) the accumulation of the intermediate 6-deoxyerythronolide B (DEB), suggesting a defect in the operation of the C-6 hydroxylase system, and (ii) a block in the synthesis or addition reactions for the first sugar group. Analyses of ermE mutants indicated that ermE is the only gene required for resistance to erythromycin, and that it is not required for production of the intermediate erythronolide B (EB) or for conversion of the intermediate 3-alpha-mycarosyl erythronolide B (MEB) to erythromycin. Mutations in the eryB and eryC loci were similar to previously reported chemically induced eryB and eryC mutations blocking synthesis or attachment of the two erythromycin sugar groups. Insertion mutations in eryAI, the macrolactone synthetase, defined the largest (at least 9-kilobase) transcription unit of the cluster. These mutants help to define the physical organization of the erythromycin gene cluster, and the eryH mutants provide a source for the production of the intermediate DEB. Images PMID:2185216

  9. Chlorimuron-ethyl

    Integrated Risk Information System (IRIS)

    Integrated Risk Information System ( IRIS ) Chemical Assessment Summary U.S . Environmental Protection Agency National Center for Environmental Assessment This IRIS Summary has been removed from the IRIS database and is available for historical reference purposes . ( July 2016 ) Chlorimuron - ethyl

  10. Development and Validation of HPTLC Method for Simultaneous Determination of Amlodipine Besylate and Metoprolol Succinate in Bulk and Tablets

    PubMed Central

    Jain, P. S.; Patel, M. K.; Bari, S. B.; Surana, S. J.

    2012-01-01

    A simple, selective, precise high-performance thin-layer chromatographic method for simultaneous determination of amlodipine besylate and metoprolol succinate in bulk and pharmaceutical combined dosage form was developed and validated. The method employed HPTLC aluminum plates precoated with silica gel 60F-254 (10×10) as the stationary phase. The solvent system consisted of toluene:ethyl acetate:methanol:triethylamine (4:1:1:0.4 v/v/v). The system was found to give a compact spot for amlodipine besylate (Rf = 0.39±0.02) and metoprolol succinate (Rf = 0.59±0.02). Densitometric analysis of amlodipine besylate and metoprolol succinate was carried out in the absorbance mode at 254 nm. Linear regression analysis data for the calibration plots showed good linear relationship with r2 = 0.9990±0.0013 with respect to peak area in the concentration range 400-1400 ng per spot for amlodipine besylate and r2 = 0.9993±0.0013 with respect to peak area in the concentration range 3800–13300 ng per spot for metoprolol succinate. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 39.99 and 121.20 ng per spot for amlodipine besylate and 234.31 and 710.03 ng per spot for metoprolol succinate, respectively. Statistical analysis proved that the method is selective, precise and accurate for the estimation of amlodipine and metoprolol. PMID:23325996

  11. Characterization of the effects of erythromycin estolate and erythromycin base on the excretory function of the isolated rat liver

    SciTech Connect

    Gaeta, G.B.; Utili, R.; Adinolfi, L.E.; Abernathy, C.O.; Giusti, G.

    1985-09-15

    To investigate the mechanisms of erythromycin cholestasis, the effects of erythromycin estolate (EE) on the excretory function of the isolated perfused rat liver and on liver plasma membrane (LM) preparations were studied and compared to those of erythromycin base (EB) and lauryl sulfate (LS), added alone or in combination. EE (at 125 to 200 microM) caused dose-dependent reductions of bile and perfusate flows, bile acid (BA) excretion, and biliary BA concentration. The alterations of the excretory function were only in part due to the decreased perfusate flow. In contrast, both 200 and 300 microM concentrations of EB elicited similar choleretic responses, which were presumably related to the osmotic activity of the drug excreted in the bile. LS did not affect hepatic excretory functions. However, the simultaneous addition of EB and LS resulted in a rate of bile flow lower than that observed with EB alone. EE, but not EB, increased canalicular permeability to (/sup 14/C)sucrose as measured by bile to plasma (B:P) ratio. Neither drugs altered (/sup 14/C)erythritol B:P ratio. In LM preparations both Na+,K+- and Mg2+-ATPase activities were inhibited in a dose-dependent manner by EE, but not by EB. The data suggest that EE could affect bile flow by inhibiting cotransport of Na+ and BA and by altering LM permeability and support the view that the effect of erythromycins on the liver may be related to their surface activity.

  12. Methylmalonate inhibits succinate-supported oxygen consumption by interfering with mitochondrial succinate uptake.

    PubMed

    Mirandola, S R; Melo, D R; Schuck, P F; Ferreira, G C; Wajner, M; Castilho, R F

    2008-02-01

    The effect of methylmalonate (MMA) on mitochondrial succinate oxidation has received great attention since it could present an important role in energy metabolism impairment in methylmalonic acidaemia. In the present work, we show that while millimolar concentrations of MMA inhibit succinate-supported oxygen consumption by isolated rat brain or muscle mitochondria, there is no effect when either a pool of NADH-linked substrates or N,N,N',N'-tetramethyl-p-phenylendiamine (TMPD)/ascorbate were used as electron donors. Interestingly, the inhibitory effect of MMA, but not of malonate, on succinate-supported brain mitochondrial oxygen consumption was minimized when nonselective permeabilization of mitochondrial membranes was induced by alamethicin. In addition, only a slight inhibitory effect of MMA was observed on succinate-supported oxygen consumption by inside-out submitochondrial particles. In agreement with these observations, brain mitochondrial swelling experiments indicate that MMA is an important inhibitor of succinate transport by the dicarboxylate carrier. Under our experimental conditions, there was no evidence of malonate production in MMA-treated mitochondria. We conclude that MMA inhibits succinate-supported mitochondrial oxygen consumption by interfering with the uptake of this substrate. Although succinate generated outside the mitochondria is probably not a sig-nificant contributor to mitochondrial energy generation, the physiopathological implications of MMA-induced inhibition of substrate transport by the mitochondrial dicarboxylate carrier are discussed.

  13. Erythromycin resistance features and biofilm formation affected by subinhibitory erythromycin in clinical isolates of Staphylococcus epidermidis.

    PubMed

    He, Hong-Jing; Sun, Feng-Jun; Wang, Qian; Liu, Yao; Xiong, Li-Rong; Xia, Pei-Yuan

    2016-02-01

    Subminimal inhibitory concentration (sub-MIC) of antibiotics can modify the phenotype of biofilm formation in bacteria. However, the relationship between resistance phenotypes, genotypes, and the biofilm formation phenotype in response to sub-MIC antibiotics remains unclear. Here, we collected 96 clinical isolates of Staphylococcus epidermidis (S. epidermidis) and investigated the erythromycin (ERY) susceptibility, the biofilm formation in respond to sub-MIC ERY, the presence and transcription expression of erm genes. Serial passage of induction resistance was used against ERY-susceptible isolates and biofilm formation in response to their new sub-MIC ERY was determined. The incidence of biofilm phenotype modification in ERY-resistant isolates was significantly higher than that of ERY-susceptible isolates [27/85 (31.8%) vs. 0/11 (0%), p = 0.031]. Yet, ERY-susceptible isolates displayed the phenomenon of biofilm phenotype modification (7/11), after induction of resistance to ERY. The ermC gene was absolutely dominant among the three macrolide resistant genes including erm (A, B, C) [6/96 (6.2%), 6/96 (6.2%), and 91/96 (94.8%), respectively]. With statistic stratification analysis, a linear and positive correlation was identified between the two factors in the biofilm-enhanced strains, a linear and negative correlation in biofilm-inhibited strains, and a weakly positive correlation in biofilm-unaffected strains (R(2) = 0.4992, 0.3686, and 0.0512, respectively). The results suggest that the ERY resistance phenotype and the transcription expression of ermC gene could be considered as important signs to estimate whether the biofilm formation phenotype in S. epidermidis clinical isolates can be easily affected by sub-MIC ERY. Copyright © 2014. Published by Elsevier B.V.

  14. Recovery of succinic acid from fermentation broth.

    PubMed

    Kurzrock, Tanja; Weuster-Botz, Dirk

    2010-03-01

    Succinic acid is of high interest as bio-feedstock for the chemical industry. It is a precursor for a variety of many other chemicals, e.g. 1,4-butandiol, tetrahydrofuran, biodegradable polymers and fumaric acid. Besides optimized production strains and fermentation processes it is indispensable to develop cost-saving and energy-effective downstream processes to compete with the current petrochemical production process. Various methods such as precipitation, sorption and ion exchange, electrodialysis, and liquid-liquid extraction have been investigated for the recovery of succinic acid from fermentation broth and are reviewed critically here.

  15. Erythromycins H and I From Actinopolyspora sp. YIM90600, a New Halophilic Actinomycete

    PubMed Central

    Huang, Sheng-Xiong; Zhao, Li-Xing; Tang, Shu-Kun; Jiang, Cheng-Lin; Shen, Ben

    2009-01-01

    Erythromycins H and I, shunt metabolites of the clinically important antibacterial drug erythromycin A, have been isolated from the new actinomycete Actinopolyspora sp. YIM90600. A. sp. YIM90600 joins Saccharopolyspora erythraea and Aeromicrobium erythreum as only the third actinomycete reported capable of producing erythromycins. In addition to producing new erythromycins, A. sp. YIM90600, even under suboptimal conditions, is a high titer producer of erythromycin C. The presence of the C-14 hydroxyl moiety and the 6,18-epoxide in the 14-membered lactone nucleus of erythromycin H and the spiro-fused dipyran moiety of erythomycin I sheds new insight into the size and structural diversity of erythromycin analog libraries accessible by combinatorial biosynthesis. PMID:19228040

  16. 21 CFR 520.784 - Doxylamine succinate tablets.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Doxylamine succinate tablets. 520.784 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.784 Doxylamine succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate as...

  17. 21 CFR 520.784 - Doxylamine succinate tablets.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Doxylamine succinate tablets. 520.784 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.784 Doxylamine succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate as...

  18. 21 CFR 520.784 - Doxylamine succinate tablets.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Doxylamine succinate tablets. 520.784 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.784 Doxylamine succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate as...

  19. Succinic Acid Turnover and Propionate Production in the Bovine Rumen

    PubMed Central

    Blackburn, T. H.; Hungate, R. E.

    1963-01-01

    High velocity constants for conversion of added succinate to propionate, together with estimations of pool size, showed that extracellular succinate is the major precursor of the propionate formed in the rumen. Some bacteria give off succinate as a final fermentation product which is decarboxylated by others to propionate. PMID:13971386

  20. 21 CFR 520.784 - Doxylamine succinate tablets.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Doxylamine succinate tablets. 520.784 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.784 Doxylamine succinate tablets. (a) Specifications. The drug is in tablet form and contains doxylamine succinate as...

  1. Increase of cellular hypoxic tolerance by erythromycin and other antibiotics.

    PubMed

    Huber, R; Kasischke, K; Ludolph, A C; Riepe, M W

    1999-05-14

    Antibiotics are used extensively, but in addition to their anti-infectious effects some inhibit cellular energy metabolism. We investigated hypoxic tolerance following in vivo pretreatment with erythromycin and kanamycin, or in vitro pretreatment with ampicillin. Recovery of the CA1 population spike amplitude in hippocampal slices upon 15 min hypoxia improved time-dependently following single i.p. in vivo pretreatment with erythromycin (maximum at 6 h: recovery 90+/-7% (mean s.d.) vs 30% in untreated controls; p<0.01). The hypoxia-induced increase in NADH was smaller in slices that recovered from hypoxia. We conclude that antibiotics increase cellular hypoxic tolerance to a varying extent. Use of antibiotics in experimental studies may, therefore, distort conclusions about hypoxic sensitivity and confounding mechanisms. In contrast, antibiotics may provide an effective strategy to induce chemical preconditioning in humans.

  2. Methyl ethyl ketone (MEK)

    Integrated Risk Information System (IRIS)

    Methyl ethyl ketone ( MEK ) ( CASRN 78 - 93 - 3 ) Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Nonc

  3. Ethyl alcohol production

    SciTech Connect

    Hofman, V.; Hauck, D.

    1980-11-01

    Recent price increases and temporary shortages of petroleum products have caused farmers to search for alternate sources of fuel. The production of ethyl alcohol from grain is described and the processes involved include saccharification, fermentation and distillation. The resulting stillage has potential as a livestock feed.

  4. A simplified erythromycin resistance cassette for Treponema denticola mutagenesis

    PubMed Central

    Goetting-Minesky, M. Paula; Fenno, J. Christopher

    2010-01-01

    The primary selectable marker for genetic studies of Treponema denticola is a hybrid gene cassette containing both ermF and ermAM (ermB) genes. ErmB functions in Escherichia coli, while ErmF has been assumed to confer resistance in T. denticola. We demonstrate here that ErmB is sufficient for erythromycin selection in T. denticola and that the native ermB promoter drives ErmB expression. PMID:20691222

  5. Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels.

    PubMed

    Cordes, Thekla; Wallace, Martina; Michelucci, Alessandro; Divakaruni, Ajit S; Sapcariu, Sean C; Sousa, Carole; Koseki, Haruhiko; Cabrales, Pedro; Murphy, Anne N; Hiller, Karsten; Metallo, Christian M

    2016-07-01

    Metabolic reprogramming is emerging as a hallmark of the innate immune response, and the dynamic control of metabolites such as succinate serves to facilitate the execution of inflammatory responses in macrophages and other immune cells. Immunoresponsive gene 1 (Irg1) expression is induced by inflammatory stimuli, and its enzyme product cis-aconitate decarboxylase catalyzes the production of itaconate from the tricarboxylic acid cycle. Here we identify an immunometabolic regulatory pathway that links Irg1 and itaconate production to the succinate accumulation that occurs in the context of innate immune responses. Itaconate levels and Irg1 expression correlate strongly with succinate during LPS exposure in macrophages and non-immune cells. We demonstrate that itaconate acts as an endogenous succinate dehydrogenase inhibitor to cause succinate accumulation. Loss of itaconate production in activated macrophages from Irg1(-/-) mice decreases the accumulation of succinate in response to LPS exposure. This metabolic network links the innate immune response and tricarboxylic acid metabolism to function of the electron transport chain.

  6. Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels*

    PubMed Central

    Cordes, Thekla; Wallace, Martina; Michelucci, Alessandro; Divakaruni, Ajit S.; Sapcariu, Sean C.; Sousa, Carole; Koseki, Haruhiko; Cabrales, Pedro; Murphy, Anne N.; Hiller, Karsten; Metallo, Christian M.

    2016-01-01

    Metabolic reprogramming is emerging as a hallmark of the innate immune response, and the dynamic control of metabolites such as succinate serves to facilitate the execution of inflammatory responses in macrophages and other immune cells. Immunoresponsive gene 1 (Irg1) expression is induced by inflammatory stimuli, and its enzyme product cis-aconitate decarboxylase catalyzes the production of itaconate from the tricarboxylic acid cycle. Here we identify an immunometabolic regulatory pathway that links Irg1 and itaconate production to the succinate accumulation that occurs in the context of innate immune responses. Itaconate levels and Irg1 expression correlate strongly with succinate during LPS exposure in macrophages and non-immune cells. We demonstrate that itaconate acts as an endogenous succinate dehydrogenase inhibitor to cause succinate accumulation. Loss of itaconate production in activated macrophages from Irg1−/− mice decreases the accumulation of succinate in response to LPS exposure. This metabolic network links the innate immune response and tricarboxylic acid metabolism to function of the electron transport chain. PMID:27189937

  7. Succinic acid production with Actinobacillus succinogenes ZT-130 in the presence of succinic acid.

    PubMed

    Corona-Gonzalez, Rosa Isela; Bories, Andre; González-Alvarez, Víctor; Snell-Castro, Raul; Toriz-González, Guillermo; Pelayo-Ortiz, Carlos

    2010-01-01

    Glucose fermentation with Actinobacillus succinogenes was carried out at different initial concentrations of succinic acid (SA(0)) to determine its effect on growth and on the production of succinic acid itself. The specific rates of biomass production, succinic, formic and acetic acids decreased with SA(0) (0-40 g/l). The partially dissociated form of succinic acid had a higher effect on cell growth and production of succinic acid as compared to the non-dissociated forms of the acids, a fact that has not been reported until now. Cell growth fitted the Jerusalimski model, and the Aiba-Shoda model was suitable for quantification of the inhibition for the production of succinic acid. The growth inhibition constants K(is) and K(ip) and their summatory were consistent with the experimental values obtained, i.e., 22 g/l for the produced acids and 38 g/l for total acids that were the limits at which the biomass formation ceased.

  8. Distribution of genes encoding erythromycin ribosomal methylases and an erythromycin efflux pump in epidemiologically distinct groups of staphylococci.

    PubMed

    Eady, E A; Ross, J I; Tipper, J L; Walters, C E; Cove, J H; Noble, W C

    1993-02-01

    Erythromycin-resistant staphylococci can be divided into two phenotypic classes based on their pattern of cross-resistance to other macrolides, lincosamides and type B streptogramins. Strains inducibly or constitutively resistant to all MLS antibiotics possess erythromycin ribosomal methylase (erm) genes, whereas strains inducibly resistant to only 14 and 15-membered ring macrolides and type B streptogramins harbour msrA, which encodes an ATP-dependent efflux pump. Dot-blot hybridization was used to study the distribution of ermA, ermB, ermC and msrA in five epidemiologically distinct groups of staphylococci. The most widely-distributed resistance determinant was ermC, which was detected in 112 (50.6%) of 221 isolates, alone in 106 isolates and in combination with a second erythromycin resistance determinant in six strains. MsrA was detected in 73 (33%) of isolates, alone in 65 and in combination with a methylase gene in eight strains. This determinant was responsible for erythromycin resistance in over one-third (36.4%) of clinical isolates of coagulase-negative staphylococci. ErmA and ermB were present in only a minority of isolates (5.9 and 7.2% of strains, respectively). The resistance determinants present in ten strains did not hybridize to any of the four probes although, in all cases, their resistance phenotype was consistent with the possession of a methylase gene. Interestingly, ermB was found exclusively in animal isolates of Staphylococcus intermedius, Staphylococcus xylosus and Staphylococcus hyicus, but not in coagulase-negative staphylococci of human origin. This determinant has previously only been found in a small number of epidemiologically related strains of Staphylococcus aureus.

  9. Pharmacokinetic advantages of erythromycin estolate over ethylsuccinate as determined by high-pressure liquid chromatography.

    PubMed Central

    Croteau, D; Bergeron, M G; LeBel, M

    1988-01-01

    The pharmacokinetics of erythromycin estolate (500 mg) and erythromycin ethylsuccinate (600 mg) were compared in 12 healthy volunteers after single doses and after repeated oral doses (every 8 h). High-pressure liquid chromatography with electrochemical detection was used to determine concentrations in plasma and urine of estolate, ethylsuccinate, and erythromycin base. The maximum concentration of drug in the serum, the half-life, and the area under the curve for erythromycin estolate were significantly greater than those of erythromycin ethylsuccinate after both regimens. After single and multiple doses, the respective areas under the curve of erythromycin base generated by estolate formulation were 3 and 1.6 times greater (P less than 0.05) than those of ethylsuccinate. The lower percentage of hydrolysis of erythromycin estolate (41 versus 69%) combined with its longer half-life (5.47 versus 2.72 h) and its larger area under the curve (30.61 versus 4.68 micrograms/h/ml, after multiple doses) could explain these differences. This study underscores the need for a specific high-pressure liquid chromatography assay and the importance of wide variability, rate-limited processes, changes with multiple doses, and the appearance of a second peak when one studies the pharmacokinetics of erythromycin esters. The pharmacokinetic data presented in this study reinforce the clinical advantages of erythromycin estolate over erythromycin ethylsuccinate. PMID:3259856

  10. Alternative system of succinate oxidation in glyoxysomes of higher plants.

    PubMed

    Igamberdiev, A U; Popov, V N; Falaleeva, M I

    1995-07-03

    Succinate oxidation in scutella of germinating seeds of wheat and maize was investigated. Besides oxidation via succinate dehydrogenase (SDH; EC 1.3.99.1), an alternative path of succinate oxidation insensitive to SDH inhibitors--malonate and thenoyltrifluoroacetone (TTFA)--was revealed. Using isopicnic sucrose gradient it was shown that this path is localized in glyoxysomal membranes. Glyoxysomal succinate oxidase (GSO) converts succinate directly into malate with the production of hydrogen peroxide identified using auxiliary enzymes malate dehydrogenase and peroxidase. GSO is most active during the intensive operation of the glyoxylate cycle (3-5 days of germination). Quinacrine, the inhibitor of flavine-containing oxidases, strongly suppressed the activity of GSO. Km for succinate is 18 mM for GSO from maize scutellum. It is concluded that in scutella of cereal seeds the glyoxysomal succinate oxidation non-linked with ATP synthesis operates.

  11. Differential protonation and dynamic structure of doxylamine succinate in solution using 1H and 13C NMR.

    PubMed

    Somashekar, B S; Nagana Gowda, G A; Ramesha, A R; Khetrapal, C L

    2004-07-01

    A protonation and dynamic structural study of doxylamine succinate, a 1:1 salt of succinic acid with dimethyl-[2-(1-phenyl-1-pyridin-2-yl-ethoxy)ethyl]amine, in solution using one- and two-dimensional 1H and 13C NMR experiments at variable temperature and concentration is presented. The two acidic protons of the salt doxylamine succinate are in 'intermediate' exchange at room temperature, as evidenced by the appearance of a broad signal. This signal evolves into two distinct signals below about -30 degrees C. A two-dimensional 1H-1H double quantum filtered correlation experiment carried out at -55 degrees C shows protonation of one of the acidic protons to the dimethylamine nitrogen. A two-dimensional rotating frame 1H-1H NOE experiment at the same temperature reveals that the other proton remains with the succinate moiety. Comparison of the 1H and 13C chemical shifts and the 13C T1 relaxation times of the salt with those of the free base further substantiate the findings.

  12. Double-blind study comparing erythromycin and mupirocin for treatment of impetigo in children: implications of a high prevalence of erythromycin-resistant Staphylococcus aureus strains.

    PubMed Central

    Dagan, R; Bar-David, Y

    1992-01-01

    Staphylococcus aureus has been consistently isolated from a high proportion of impetiginous lesions, and in several recent studies, it was present in the majority of the cases. Since recently a large proportion of S. aureus strains in our community showed erythromycin resistance, we undertook a prospective double-blind controlled study comparing topical mupirocin with oral erythromycin to determine (i) the prevalence of erythromycin-resistant S. aureus strains in impetigo and (ii) whether an increased rate of failure of erythromycin treatment was associated with such resistance. A total of 102 patients 3 to 185 months old (median = 49 months) were enrolled. Culture was positive for 97 of 102 (95%) patients, and S. aureus was present in 93% of the patients for whom cultures were positive. S. aureus was the single pathogen in 64% of these patients. Erythromycin-resistant S. aureus strains were present in 27 of 91 (28%) patients for whom cultures were positive. In all cases but one, S. aureus was resistant to penicillin, and in all cases it was sensitive to mupirocin. A marked difference was observed in favor of mupirocin in the clinical courses of the disease. However, only patients with erythromycin-resistant S. aureus strains had unfavorable courses compared with those treated with mupirocin (failure rate, 47 versus 2%, respectively). Patients with erythromycin-susceptible S. aureus strains who received erythromycin had a failure rate of 8%. In four patients, S. aureus strains initially susceptible to erythromycin became resistant during treatment. We conclude that erythromycin-resistant S. aureus strains are commonly isolated from impetigo in our region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1605593

  13. Regulation of insulin secretion and proinsulin biosynthesis by succinate.

    PubMed

    Attali, Veronique; Parnes, Marcela; Ariav, Yafa; Cerasi, Erol; Kaiser, Nurit; Leibowitz, Gil

    2006-11-01

    Succinate stimulates insulin secretion and proinsulin biosynthesis. We studied the effects of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-modulating pathways on glucose- and succinate-stimulated insulin secretion and proinsulin biosynthesis in the rat and the insulin-resistant Psammomys obesus. Disruption of the anaplerotic pyruvate/malate shuttle by phenylacetic acid inhibited glucose- and succinate-stimulated insulin secretion and succinate-stimulated proinsulin biosynthesis in both species. In contrast, phenylacetic acid failed to inhibit glucose-stimulated proinsulin biosynthesis in P. obesus islets. Inhibition of the NADPH-consuming enzyme neuronal nitric oxide synthase (nNOS) with l-N(G)-nitro-l-arginine methyl ester or with N(G)-monomethyl-l-arginine(G) doubled succinate-stimulated insulin secretion in rat islets, suggesting that succinate- and nNOS-derived signals interact to regulate insulin secretion. In contrast, nNOS inhibition had no effect on succinate-stimulated proinsulin biosynthesis in both species. In P. obesus islets, insulin secretion was not stimulated by succinate in the absence of glucose, whereas proinsulin biosynthesis was increased 5-fold. Conversely, under stimulating glucose levels, succinate doubled insulin secretion, indicating glucose-dependence. Pyruvate ester and inhibition of nNOS partially mimicked the permissive effect of glucose on succinate-stimulated insulin secretion, suggesting that anaplerosis-derived signals render the beta-cells responsive to succinate. We conclude that beta-cell anaplerosis via pyruvate carboxylase is important for glucose- and succinate-stimulated insulin secretion and for succinate-stimulated proinsulin biosynthesis. In P. obesus, pyruvate/malate shuttle dependent and independent pathways that regulate proinsulin biosynthesis coexist; the latter can maintain fuel stimulated biosynthetic activity when the succinate-dependent pathway is inhibited. nNOS signaling is a negative regulator

  14. Ethyl N-phenyloxamate.

    PubMed

    García-Báez E, Efrén V; Gómez-Castro, Carlos Z; Höpfl, Herbert; Martínez-Martínez, Francisco J; Padilla-Martínez, Itzia I

    2003-10-01

    The oxamate group in the title compound, C(10)H(11)NO(3), is almost coplanar with the phenyl ring because of intramolecular hydrogen-bonding interactions, and the structure can be described as an anilide single bonded to an ethyl carboxylate group. The supramolecular structure is achieved through intermolecular hard N-H...O and soft C-H...X (X = O and phenyl) hydrogen-bonding interactions.

  15. Erythromycin- and chloramphenicol-induced ribosomal assembly defects are secondary effects of protein synthesis inhibition.

    PubMed

    Siibak, Triinu; Peil, Lauri; Xiong, Liqun; Mankin, Alexander; Remme, Jaanus; Tenson, Tanel

    2009-02-01

    Several protein synthesis inhibitors are known to inhibit ribosome assembly. This may be a consequence of direct binding of the antibiotic to ribosome precursor particles, or it could result indirectly from loss of coordination in the production of ribosomal components due to the inhibition of protein synthesis. Here we demonstrate that erythromycin and chloramphenicol, inhibitors of the large ribosomal subunit, affect the assembly of both the large and small subunits. Expression of a small erythromycin resistance peptide acting in cis on mature ribosomes relieves the erythromycin-mediated assembly defect for both subunits. Erythromycin treatment of bacteria expressing a mixture of erythromycin-sensitive and -resistant ribosomes produced comparable effects on subunit assembly. These results argue in favor of the view that erythromycin and chloramphenicol affect the assembly of the large ribosomal subunit indirectly.

  16. Edoxaban drug–drug interactions with ketoconazole, erythromycin, and cyclosporine

    PubMed Central

    Parasrampuria, Dolly A.; Mendell, Jeanne; Shi, Minggao; Matsushima, Nobuko; Zahir, Hamim

    2016-01-01

    Aims Edoxaban, a novel factor Xa inhibitor, is a substrate of cytochrome P450 3 A4 (CYP3A4) and the efflux transporter P‐glycoprotein (P‐gp). Three edoxaban drug–drug interaction studies examined the effects of P‐gp inhibitors with varying degrees of CYP3A4 inhibition. Methods In each study, healthy subjects received a single oral dose of 60 mg edoxaban with or without an oral dual P‐gp/CYP3A4 inhibitor as follows: ketoconazole 400 mg once daily for 7 days, edoxaban on day 4; erythromycin 500 mg four times daily for 8 days, edoxaban on day 7; or single dose of cyclosporine 500 mg with edoxaban. Serial plasma samples were obtained for pharmacokinetics and pharmacodynamics. Safety was assessed throughout the study. Results Coadministration of ketoconazole, erythromycin, or cyclosporine increased edoxaban total exposure by 87%, 85%, and 73%, respectively, and the peak concentration by 89%, 68%, and 74%, respectively, compared with edoxaban alone. The half‐life did not change appreciably. Exposure of M4, the major active edoxaban metabolite, was consistent when edoxaban was administered alone or with ketoconazole and erythromycin. With cyclosporine, M4 total exposure increased by 6.9‐fold and peak exposure by 8.7‐fold, suggesting an additional interaction. Pharmacodynamic effects were reflective of increased edoxaban exposure. No clinically significant adverse events were observed. Conclusions Administration of dual inhibitors of P‐gp and CYP3A4 increased edoxaban exposure by less than two‐fold. This effect appears to be primarily due to inhibition of P‐gp. The impact of CYP3A4 inhibition appears to be less pronounced, and its contribution to total clearance appears limited in healthy subjects. PMID:27530188

  17. Mechanism and diversity of the erythromycin esterase family of enzymes.

    PubMed

    Morar, Mariya; Pengelly, Kate; Koteva, Kalinka; Wright, Gerard D

    2012-02-28

    Macrolide antibiotics such as azithromycin and erythromycin are mainstays of modern antibacterial chemotherapy, and like all antibiotics, they are vulnerable to resistance. One mechanism of macrolide resistance is via drug inactivation: enzymatic hydrolysis of the macrolactone ring catalyzed by erythromycin esterases, EreA and EreB. A genomic enzymology approach was taken to gain insight into the catalytic mechanisms and origins of Ere enzymes. Our analysis reveals that erythromycin esterases comprise a separate group in the hydrolase superfamily, which includes homologues of uncharacterized function found on the chromosome of Bacillus cereus, Bcr135 and Bcr136, whose three-dimensional structures have been determined. Biochemical characterization of Bcr136 confirms that it is an esterase that is, however, unable to inactivate macrolides. Using steady-state kinetics, homology-based structure modeling, site-directed mutagenesis, solvent isotope effect studies, pH, and inhibitor profiling performed in various combinations for EreA, EreB, and Bcr136 enzymes, we identified the active site and gained insight into some catalytic features of this novel enzyme superfamily. We rule out the possibility of a Ser/Thr nucleophile and show that one histidine, H46 (EreB numbering), is essential for catalytic function. This residue is proposed to serve as a general base in activation of a water molecule as the reaction nucleophile. Furthermore, we show that EreA, EreB, and Bcr136 are distinct, with only EreA inhibited by chelating agents and hypothesized to contain a noncatalytic metal. Detailed characterization of these esterases allows for a direct comparison of the resistance determinants, EreA and EreB, with their prototype, Bcr136, and for the discussion of their potential connections.

  18. Mechanism of Penicillin-Erythromycin Synergy on Antibiotic-Resistant Staphylococcus aureus

    PubMed Central

    Allen, Norris E.; Epp, Janet K.

    1978-01-01

    Clinically isolated strains of Staphylococcus aureus that are inducibly resistant to both erythromycin and penicillin were susceptible to a combination of the two antibiotics. The synergistic effect of the combination results from an inhibition of penicillinase induction by erythromycin, sparing penicillin and allowing this drug to inhibit growth. When resistance to erythromycin is constitutive rather than inducible, the combination is no longer synergistic. PMID:248271

  19. Succinate transport by free-living forms of Rhizobium japonicum.

    PubMed Central

    McAllister, C F; Lepo, J E

    1983-01-01

    We have demonstrated that the transport of succinate into the cells of Rhizobium japonicum strains USDA 110 and USDA 217 is severely inhibited by cyanide, azide, and 2,4-dinitrophenol, but not by arsenate. These results suggest an active mechanism of transport that is dependent on an energized membrane, but does not directly utilize ATP. The apparent Km for succinate was 3.8 microM for strain USDA 110 and 1.8 microM for strain USDA 217; maximal transport velocities were 1.5 and 3.3 nmol of succinate per min per mg of protein, respectively. The expression of the succinate uptake activity was inducible rather than constitutive, with succinate and structurally related compounds being the most effective inducers. The mechanism showed some specificity for succinate and similar organic acids; fumarate and L-malate were classical competitive inhibitors of the system. In general, the best competing compounds were also the best carbon substrates for induction of succinate uptake activity. EDTA inhibited the transport of succinate, implying a role for divalent cations in the system. When various divalent cations were used to reconstitute EDTA-inhibited activity, Ca2+ was most effective, followed by Mg2+, which restored activity at about half the efficiency of Ca2+. Growth media that were supplemented with increased Ca2+ concentration supported more rapid growth with succinate as the carbon substrate, and cells from such media showed higher specific activities of succinate transport. PMID:6402487

  20. Enhanced succinate production from glycerol by engineered Escherichia coli strains.

    PubMed

    Li, Qing; Wu, Hui; Li, Zhimin; Ye, Qin

    2016-10-01

    In this study, an engineered strain Escherichia coli MLB (ldhA(-)pflB(-)) was constructed for production of succinate from glycerol. The succinate yield was 0.37mol/mol in anaerobic culture, however, the growth and glycerol consumption rates were very slow, resulting in a low succinate level. Two-stage fermentation was performed in flasks, and the succinate yield reached 0.93mol/mol, but the succinate titer was still low. Hence, overexpression of malate dehydrogenase, malic enzyme, phosphoenolpyruvate (PEP) carboxylase and PEP carboxykinase (PCK) from E. coli, and pyruvate carboxylase from Corynebacterium glutamicum in MLB was investigated for improving succinate production. Overexpression of PCK resulted in remarkable enhancement of glycerol consumption and succinate production. In flask experiments, the succinate concentration reached 118.1mM, and in a 1.5-L bioreactor the succinate concentration further increased to 360.2mM. The highest succinate yield achieved 0.93mol/mol, which was 93% of the theoretical yield, in the anaerobic stage.

  1. Nuclear inheritance of erythromycin resistance in human cells: New class of mitochondrial protein synthesis mutants

    SciTech Connect

    Doersen, C.J.; Stanbridge, E.J.

    1982-06-01

    The characterization of two new erythromycin-resistant mutants of HeLa cells is described. The strains ERY2305 and ERY2309 both exhibited resistance to erythromycin in growth assays and cell-free mitochondrial protein synthesis assays. The erythromycin resistance phenotype could not be transferred by cybridization. The mutation appeared to be encoded in the nucleus and inherited as a recessive trait. These two mutants, therefore, represent a new class of erythromycin-resistant mutants in human cells that is distinct from the cytoplasmically inherited mutation in strain ERY2301 described previously.

  2. Antimicrobial activity of essential oils and carvacrol, and synergy of carvacrol and erythromycin, against clinical, erythromycin-resistant Group A Streptococci.

    PubMed

    Magi, Gloria; Marini, Emanuela; Facinelli, Bruna

    2015-01-01

    In the present study, we have evaluated the in vitro antibacterial activity of essential oils from Origanum vulgare, Thymus vulgaris, Lavandula angustifolia, Mentha piperita, and Melaleuca alternifolia against 32 erythromycin-resistant [Mininum Inhibitory Concentration (MIC) ≥1 μg/mL; inducible, constitutive, and efflux-mediated resistance phenotype; erm(TR), erm(B), and mef(A) genes] and cell-invasive Group A streptococci (GAS) isolated from children with pharyngotonsillitis in Italy. Over the past decades erythromycin resistance in GAS has emerged in several countries; strains combining erythromycin resistance and cell invasiveness may escape β-lactams because of intracellular location and macrolides because of resistance, resulting in difficulty of eradication and recurrent pharyngitis. Thyme and origanum essential oils demonstrated the highest antimicrobial activity with MICs ranging from 256 to 512 μg/mL. The phenolic monoterpene carvacrol [2-Methyl-5-(1-methylethyl) phenol] is a major component of the essential oils of Origanum and Thymus plants. MICs of carvacrol ranged from 64 to 256 μg/mL. In the live/dead assay several dead cells were detected as early as 1 h after incubation with carvacrol at the MIC. In single-step resistance selection studies no resistant mutants were obtained. A synergistic action of carvacrol and erythromycin was detected by the checkerboard assay and calculation of the Fractional Inhibitory Concentration (FIC) Index. A 2- to 2048-fold reduction of the erythromycin MIC was documented in checkerboard assays. Synergy (FIC Index ≤0.5) was found in 21/32 strains and was highly significant (p < 0.01) in strains where resistance is expressed only in presence of erythromycin. Synergy was confirmed in 17/23 strains using 24-h time-kill curves in presence of carvacrol and erythromycin. Our findings demonstrated that carvacrol acts either alone or in combination with erythromycin against erythromycin-resistant GAS and could potentially

  3. BER-Myriant Succinic Acid Biorefinery

    SciTech Connect

    Shmorhun, Mark

    2015-12-31

    Myriant Corporation (Myriant) has successfully produced the bioproduct succinic acid by the fermentation of glucose at a commercial scale operation in Lake Providence, Louisiana. The MySAB facility (Myriant Succinic Acid Biorefinery) came on stream in May 2013 and has been producing product since then. The MySAB facility is a demonstration-scale plant, capable of utilizing sorghum grits and commercially available dextrose, to ferment glucose into succinic acid. A downstream processing train has demonstrated the ability to produce an industrial, a standard and a polymer grade product. It consists of cell separation, membrane filtration, continuous chromatography, polishing to remove ionic and color bodies impurities, and final evaporation and crystallization. A by-product of the process is ammonium sulfate which is sold as a liquid fertilizer product. Since 2007 when development work began in the Woburn, Massachusetts R&D laboratories, the succinic acid bio-process has evolved through: Process development (microbiology, fermentation, and downstream) – R&D development laboratories; Piloting efforts at Fermic S.A. de C.V., Mexico City, Mexico – upstream and downstream processes; Design, construction, commissioning, and commercial production operations at the MySAB facility Additionally, Myriant became a wholly-owned subsidiary of the PTT Global Chemical Plc., Thailand, in late 2015, their investment into and support of Myriant goes back to 2011. The support of PTT Global Chemical Plc. helped to improve the upstream and downstream processes, and produce significant metric ton quantities of high quality bio-based succinic acid. The product has gone into a number of commercial markets worldwide for customer applications, development and production. The experience base gained via operations at the MySAB facility since May 2013, along with continued R&D development efforts involving Microbiology, Fermentation, and Downstream processes, at both the Woburn, Massachusetts

  4. [Compound erythromycin sustained release preparation and its in vitro release].

    PubMed

    Chen, Hai-xia; Chen, Zhi-peng; Wang, Qi-rong; Liu, Ze-kun; Ma, Quan-long

    2011-11-01

    Using the weight-average molecular weight 50 000 polylactic acid (PLA) as a carrier, and a certain proportion of erythromycin (EM) and prednisone acetate (PNA) to mixed prepare the compound erythromycin sustained release preparation (sustained-release tablets). Using ultraviolet spectrophotometry and high performance liquid chromatography (HPLC) to detect separately the release amount of EM and PNA in vitro medium. The sustained-release tablets release for about 21 days, the average content of EM is 99.7 mg/table, RSD = 0.82%; and the average content of PNA is 10.03 mg/table, RSD = 0.93%. Within 21 days, the cumulative releases of EM and PNA are 86.1% and 78.3%, respectively. The drug release is steady and slow after 5 days, the burst release phenomenon in early stage is more significant. The results showed that the sustained-release tablet preparation method is feasible, the release performance is good and the clinical efficacy is significant.

  5. Acute pancreatitis and acute renal failure complicating doxylamine succinate intoxication.

    PubMed

    Lee, Yang Deok; Lee, Soo Teik

    2002-06-01

    Doxylamine succinate is an antihistaminic drugwith additional hypnotic, anticholinergic and local anesthetic effects first described in 1948. In Korea and many other countries, it is a common-over-the counter medication frequently involved in overdoses. Clinical symtomatology of doxylamine succinate overdose includes somnolence, coma, seizures, mydriasis, tachycardia, psychosis, and rhabdomyolysis. A serious complication may be rhabdomyolysis with subsequent impairment of renal function and acute renal failure. We report a case of acute renal failure and acute pancreatitis complicating a doxylamine succinate intoxication.

  6. Maternal administration of erythromycin fails to eradicate intrauterine ureaplasma infection in an ovine model.

    PubMed

    Dando, Samantha J; Nitsos, Ilias; Newnham, John P; Jobe, Alan H; Moss, Timothy J M; Knox, Christine L

    2010-10-01

    Erythromycin is the standard antibiotic used for treatment of infection with Ureaplasma spp. during pregnancy; however, maternally administered erythromycin may be ineffective at eliminating intra-amniotic ureaplasma infections. We examined whether erythromycin would eradicate intra-amniotic ureaplasma infections in pregnant sheep. At Gestational Day (GD) 50 (term, GD 150), pregnant ewes received intra-amniotic injections of erythromycin-sensitive Ureaplasma parvum serovar 3 (n = 16) or 10B medium (n = 16). At GD 100, amniocentesis was performed; five fetal losses (ureaplasma group, n = 4; 10B group, n = 1) had occurred by this time. Remaining ewes were allocated into treatment subgroups: medium only (n = 7), medium and erythromycin (n = 8), ureaplasma only (Up; n = 6), or ureaplasma and erythromycin (Up/E; n = 6). Erythromycin was administered intramuscularly (500 mg) every 8 h for 4 days (GDs 100-104). Amniotic fluid samples were collected at GD 105. At GD 125, preterm fetuses were surgically delivered, and specimens were collected for culture and histology. Erythromycin was quantified in amniotic fluid by liquid chromatography-mass spectrometry. Ureaplasmas were isolated from the amniotic fluid, chorioamnion, and fetal lung of animals from the Up and Up/E groups, however, the numbers of U. parvum recovered were not different between these groups. Inflammation in the chorioamnion, cord, and fetal lung was increased in ureaplasma-exposed animals compared to controls but was not different between the Up and Up/E groups. Erythromycin was detected in amniotic fluid samples, although concentrations were low (<10-76 ng/ml). This study demonstrates that maternally administered erythromycin does not eradicate chronic, intra-amniotic ureaplasma infections or improve fetal outcomes in an ovine model, potentially because of the poor placental passage of erythromycin.

  7. Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor.

    PubMed

    Deecher, Darlene C; Beyer, Chad E; Johnston, Grace; Bray, Jenifer; Shah, S; Abou-Gharbia, M; Andree, Terrance H

    2006-08-01

    The purpose of this study was to characterize a new chemical entity, desvenlafaxine succinate (DVS). DVS is a novel salt form of the isolated major active metabolite of venlafaxine. Competitive radioligand binding assays were performed using cells expressing either the human serotonin (5-HT) transporter (hSERT) or norepinephrine (NE) transporter (hNET) with K(i) values for DVS of 40.2 +/- 1.6 and 558.4 +/- 121.6 nM, respectively. DVS showed weak binding affinity (62% inhibition at 100 microM) at the human dopamine (DA) transporter. Inhibition of [3H]5-HT or [3H]NE uptake by DVS for the hSERT or hNET produced IC50 values of 47.3 +/- 19.4 and 531.3 +/- 113.0 nM, respectively. DVS (10 microM), examined at a large number of nontransporter targets, showed no significant activity. DVS (30 mg/kg orally) rapidly penetrated the male rat brain and hypothalamus. DVS (30 mg/kg orally) significantly increased extracellular NE levels compared with baseline in the male rat hypothalamus but had no effect on DA levels using microdialysis. To mimic chronic selective serotonin reuptake inhibitor treatment and to block the inhibitory 5-HT(1A) autoreceptors, a 5-HT(1A) antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclo hexanecarboxamide maleate salt (WAY-100635) (0.3 mg/kg s.c.), was administered with DVS (30 mg/kg orally). 5-HT increased 78% compared with baseline with no additional increase in NE or DA levels. In conclusion, DVS is a new 5-HT and NE reuptake inhibitor in vitro and in vivo that demonstrates good brain-to-plasma ratios, suggesting utility in a variety of central nervous system-related disorders.

  8. Purification process for succinic acid produced by fermentation

    SciTech Connect

    Glassner, D.A.; Elankovan, P.; Beacom, D.R.

    1995-12-31

    Succinic acid is a versatile four-carbon dicarboxylic acid. It can be used commercially as an intermediate chemical for the manufacture of 1,4-butanediol, maleic anhydride, and many other chemicals. Succinic acid can be produced by the fermentation of carbohydrates. A complete process for the production and purification of succinic acid from carbohydrates has been developed. The process includes fermentation, desalting electrodialysis, water-splitting electrodialysis, and crystallization to produce a pure crystalline succinic acid. This article will present experimental work performed in the development of this process.

  9. 21 CFR 184.1295 - Ethyl formate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Substances Affirmed as GRAS § 184.1295 Ethyl formate. (a) Ethyl formate (C3H6O2, CAS Reg. No. 109-94-4) is also referred to as ethyl methanoate. It is an ester of formic acid and is prepared by esterification of formic acid with ethyl alcohol or by distillation of ethyl acetate and formic acid in the...

  10. 21 CFR 184.1295 - Ethyl formate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Substances Affirmed as GRAS § 184.1295 Ethyl formate. (a) Ethyl formate (C3H6O2, CAS Reg. No. 109-94-4) is also referred to as ethyl methanoate. It is an ester of formic acid and is prepared by esterification of formic acid with ethyl alcohol or by distillation of ethyl acetate and formic acid in the...

  11. Combination of azelaic acid 5% and erythromycin 2% in the treatment of acne vulgaris.

    PubMed

    Pazoki-Toroudi, Hamidreza; Nassiri-Kashani, Mansour; Tabatabaie, Hossein; Ajami, Marjan; Habibey, Rouhollah; Shizarpour, Mohammad; Babakoohi, Shahab; Rahshenas, Makan; Firooz, Alireza

    2010-05-01

    Acne vulgaris is a common problem, particularly among adolescents, which is usually resistant to monotherapy. We evaluated the efficacy and safety of a combination of azelaic acid (AA) 5% and erythromycin 2% gel (AzE) compared with AA 20% or erythromycin 2% gels in facial acne vulgaris. We conducted a 12-week, multicenter, randomized double-blind study on 147 patients with mild-to-moderate acne vulgaris. Four treatment group were determined (placebo, erythromycin, AA and AzE) and followed in 4-week intervals for 12 weeks, except the placebo group which was changed to routine treatment after 4 weeks. The combination of AA 5% and erythromycin 2% gel significantly reduced the number of papules, pustules and comedones compared with placebo (p < 0.001), erythromycin 2% (p < 0.01) or AA 20% (p < 0.05). The incidence of adverse effects observed in patients treated with AzE (27%) was less than that with erythromycin 2% (54%) and AA 20% (45%). The combination of AA 5% and erythromycin 2% produced more potent therapeutic effects in comparison with erythromycin 2% or AA 20% alone, and with fewer side effects.

  12. Gastrointestinal behavior of orally administered radiolabeled erythromycin pellets in man as determined by gamma scintigraphy

    SciTech Connect

    Digenis, G.A.; Sandefer, E.P.; Parr, A.F.; Beihn, R.; McClain, C.; Scheinthal, B.M.; Ghebre-Sellassie, I.; Iyer, U.; Nesbitt, R.U.; Randinitis, E. )

    1990-07-01

    The behavior of single 250-mg doses of a multiparticulate form of erythromycin base (ERYC(R)), each including five pellets radiolabeled with neutron-activated samarium-153, was observed by gamma scintigraphy in seven male subjects under fasting and nonfasting conditions. The residence time and locus of radiolabeled pellets within regions of the gastrointestinal tract were determined and were correlated with plasma concentrations of erythromycin at coincident time points. Administration of food 30 minutes postdosing reduced fasting plasma erythromycin Cmax and area under the plasma erythromycin versus time curve (AUC) values by 43% and 54%, respectively. Mean peak plasma concentration of erythromycin (Cmax) in the fasting state was 1.64 micrograms/mL versus 0.94 micrograms/mL in the nonfasting state. Total oral bioavailability, as determined by mean AUC (0-infinity) of the plasma erythromycin concentration versus time curve, was 7.6 hr/micrograms/mL in the fasted state, versus 3.5 hr/micrograms/mL in the nonfasting state. Mean time to peak plasma erythromycin concentration (tmax) in the fasting state was 3.3 hours, versus 2.3 hours in the nonfasting state. Plasma concentrations of erythromycin in both fasting and nonfasting states were within acceptable therapeutic ranges.

  13. Erythromycin bioactivity is stable in ophthalmic ointment used for prophylaxis of neonatal gonococcal conjunctivitis.

    PubMed Central

    Bialer, M G; Baron, E J; Harper, R G

    1987-01-01

    Erythromycin ophthalmic ointment (E. Fougera & Co., Melville, N.Y.) and erythromycin gluceptate standards prepared in ointment base were stored at room temperature and heated at temperatures up to 45 degrees C for as long as 6 h before being assayed for bioactivity. We were unable to detect any significant loss of antibiotic bioactivity. PMID:3619431

  14. [Effect of combination of sub-MIC sodium houttuyfonate and erythromycin on biofilm of Staphylococcus epidermidis].

    PubMed

    Guan, Yan; Li, Chun; Shi, Jing-Jin; Zhou, Hua-Na; Liu, Li; Wang, Yan; Pu, Yan-Ping

    2013-03-01

    To observe the effect of the combination of sub-MIC sodium houttuyfonate and erythromycin on biofilm of Staphylococcus epidermidis. The serial dilution method was adopted to determine MIC of the combination of sodium houttuyfonate and erythromycin on S. epidermidis; the checkerboard method was used to evaluate the combination of sodium houttuyfonate and erythromycin on suspended bacteria of S. epidermidis; S. epidermidis biofilm was built in vitro, and XTT reduction assay was used to evaluate the effect of the combination of sub-MIC sodium houttuyfonate and erythromycin on the adhesion of S. epidermidis and bacterial metabolism inside the biofilm. Microscope was applied to observe the impact the single administration and combination of the two medicines under sub-MIC on biofilm morphology of S. epidermidis. The MIC of sodium houttuyfonate and erythromycin were 62.5, 7.812 5 mg x L(-1), respectively. The combination of 1/8MIC sodium houttuyfonate and 1/2MIC erythronmycin showed a synergistic effect on S. epidermidis. Sodium houttuyfonate, erythromycin and their combination had an inhibitory effect on the adhesion and metabolism of S. epidermidis biofilm bacteria, and made impact on the morphology of S. epidermidis biofilm. The sub-MIC sodium houttuyfonate and erythromycin have an inhibitory effect on S. epidermidis biofilm. The combination of sodium houttuyfonate and erythromycin shows a synergistic effect in inhibiting suspended bacteria and biofilm of S. epidermidis, particularly in inhibiting the metabolism of S. epidermidis biofilm bacteria and impacting the morphology of biofilm.

  15. [The application of succine in sports].

    PubMed

    S V, Okovityi; S V, Rad'Ko

    2015-01-01

    The development of energy deficiency in the course of physical exercises that eventually leads to serious derangement of the energy metabolism is an important component of the deterioration of physical and intellectual working capacity. The most promising approach to the correction of impaired physical and intellectual working capacity associated with energy deficiency consists in the application of pharmaceutical preparations containing intermediate products of the tricarbonic acid cycle. Of great promise in this context is succinic acid by virtue of its oxidation in endogenous reactions that constitutes the physiological adaptive mechanism by which resistance of the organism to oxygen deficiency is promoted.

  16. Succinic acid adsorption from fermentation broth and regeneration.

    PubMed

    Davison, Brian H; Nghiem, Nhuan P; Richardson, Gerald L

    2004-01-01

    More than 25 sorbents were tested for uptake of succinic acid from aqueous solutions. The best resins were then tested for successive loading and regeneration using hot water. The key desired properties for an ideal sorbent are high capacity, complete stable regenerability, and specificity for the product. The best resins have a stable capacity of about 0.06 g of succinic acid/g of resin at moderate concentrations (1-5 g/L) of succinic acid. Several sorbents were tested more exhaustively for uptake of succinic acid and for successive loading and regeneration using hot water. One resin, XUS 40285, has a good stable isotherm capacity, prefers succinate over glucose, and has good capacities at both acidic and neutral pH. Succinic acid was removed from simulated media containing salts, succinic acid, acetic acid, and sugar using a packed column of sorbent resin, XUS 40285. The fermentation byproduct, acetate, was completely separated from succinate. A simple hot water regeneration successfully concentrated succinate from 10 g/L (inlet) to 40-110 g/L in the effluent. If successful, this would lower separation costs by reducing the need for chemicals for the initial purification step. Despite promising initial results of good capacity (0.06 g of succinic/g of sorbent), 70% recovery using hot water, and a recovered concentration of >100 g/L, this regeneration was not stable over 10 cycles in the column. Alternative regeneration schemes using acid and base were examined. Two (XUS 40285 and XFS-40422) showed both good stable capacities for succinic acid over 10 cycles and >95% recovery in a batch operation using a modified extraction procedure combining acid and hot water washes. These resins showed comparable results with actual broth.

  17. Loss of erythromycin resistance genes from strains of Streptococcus pyogenes that have developed resistance to levofloxacin.

    PubMed

    Billal, Dewan Sakhawat; Hotomi, Muneki; Yan, Steve S; Fedorko, Daniel P; Shimada, Jun; Fujihara, Keiji; Yamanaka, Noboru

    2009-06-01

    In the past 2 to 3 decades, erythromycin resistance in Streptococcus pyogenes has been decreasing, whereas fluoroquinolone resistance (or reduction in its susceptibility) has been reported often. Although a shift of M-type prevalence and decreased pressure from macrolides have been suggested for the decrease in erythromycin resistance, we hypothesized that this might also be a result of increased antimicrobial pressure from fluoroquinolone use. Levofloxacin resistance for 4 erythromycin-resistant parent strains was induced in vitro. Their mutants became highly resistant to the fluoroquinolones but lost their erythromycin resistance trait. Erythromycin resistance was fully restored by transconjugation with respective parent strains with either mefA- or ermTR-mediated mechanisms.

  18. Investigation on the chemical stability of erythromycin in solutions using an optimization system.

    PubMed

    Brisaert, M; Heylen, M; Plaizier-Vercammen, J

    1996-10-01

    Erythromycin, an antibiotic commonly used topically in the treatment of acne, is unstable in solution. The stability is influenced by the pH and by the presence of water. The influence of the pH on the stability of erythromycin was investigated even with the use of dimethyl isosorbide as co-solvent instead of water. The addition of zinc was attempted to ameliorate erythromycin stability as suggested in the literature. To investigate these three factors and their interactions, an optimization technique was carried out consisting of a 2(3) factorial analysis and a rotative central composite design. The erythromycin solutions were analysed with an HPLC method. The pH and the concentration of dimethyl isosorbide had a significant influence on the stability of erythromycin but the addition of zinc was not a significant factor. Moreover, there was a significant interaction between the pH and dimethyl isosorbide.

  19. Sub-inhibitory and post-antibiotic effects of spiramycin and erythromycin on Staphylococcus aureus.

    PubMed

    Webster, C; Ghazanfar, K; Slack, R

    1988-07-01

    The antibacterial responses of clinical isolates of Staphylococcus aureus to spiramycin and erythromycin were compared. Conventional MICs showed erythromycin-sensitive strains to be 16-32 times less sensitive to spiramycin. MBCs were only four to eight times higher for spiramycin. Erythromycin resistant S. aureus were more frequently encountered. Concentrations of both macrolides at 1/4 MIC produced antibacterial effects. Post-antibiotic effects were more marked with spiramycin. After 3 h exposure to 4 x MIC of antibiotic the delay in regrowth of S. aureus was 5 h for erythromycin and 9 h for spiramycin. In a continuous cultivation model, spiramycin produced an inhibitory effect on S. aureus for 12 h whereas the effect of erythromycin was only apparent for 6 h. In conclusion, spiramycin is more active against staphylococci in vitro than would be expected by its modest MICs.

  20. [Mechanism of hetero-erythromycin resistant Staphylococcus aureus and a comparison of detection methods].

    PubMed

    Chen, Dong-ke; Lai, Hui-ying; Yang, Dong-mei; Xu, Hong-tao

    2013-12-24

    To explore the phenotypes and genotypes of Staphylococcus aureus (S. aureus) hetero-resistant to erythromycin and clindamycin and compare their detection methods so as to report results accurately to guide clinical rational use of antibiotics. D test was used to detect the phenotypes of S. aureus hetero-resistant to erythromycin. And then the results of two methods (automated instrument and disk diffusion) were analyzed. All strains were continuously passaged for 50 generations to verify the phenotypic and genotypic stability of hetero-resistance. ErmA, ermC and msrA genes were amplified by multiplex polymerase chain reaction (PCR). Among 95 erythromycin-sensitive strains, there were 70 strains hetero-resistant to erythromycin (73.7%). The primary 70 strains were all susceptive to erythromycin (MIC ≤ 0.25 µg/ml) and clindamycin (MIC ≤ 0.25 µg/ml) with the cards of GP-67 of VITEK2 Compact. With D tests, the results were difficult to observe. The passaged 70 strains were all resistant to erythromycin (MIC >8 µg/ml) and susceptible to clindamycin (MIC ≤ 0.25 µg/ml) and D test positive with the cards of GP-67 of VITEK2 Compact. The primary and 50(th) generation of herero-erythromycin resistant strains were stable in susceptibility test results. The primary and the 50(th)th generation strains were all ermA gene positive, ermC and msrA negative with PCR results. The phenotypes and genotypes of hetreo-erythromycin resistant S. aureus strains were stable. Missed detection with VITEK2 Compact may affect the proper use of erythromycin and clindamycin. Laboratory technicians should identify the erythromycin-susceptible strains by disk diffusion method.

  1. Adaptive mechanisms of Campylobacter jejuni to erythromycin treatment

    PubMed Central

    2013-01-01

    Background Macrolide is the drug of choice to treat human campylobacteriosis, but Campylobacter resistance to this antibiotic is rising. The mechanisms employed by Campylobacter jejuni to adapt to erythromycin treatment remain unknown and are examined in this study. The transcriptomic response of C. jejuni NCTC 11168 to erythromycin (Ery) treatment was determined by competitive microarray hybridizations. Representative genes identified to be differentially expressed were further characterized by constructing mutants and assessing their involvement in antimicrobial susceptibility, oxidative stress tolerance, and chicken colonization. Results Following the treatment with an inhibitory dose of Ery, 139 genes were up-regulated and 119 were down-regulated. Many genes associated with flagellar biosynthesis and motility was up-regulated, while many genes involved in tricarboxylic acid cycle, electron transport, and ribonucleotide biosynthesis were down-regulated. Exposure to a sub-inhibitory dose of Ery resulted in differential expression of much fewer genes. Interestingly, two putative drug efflux operons (cj0309c-cj0310c and cj1173-cj1174) were up-regulated. Although mutation of the two operons did not alter the susceptibility of C. jejuni to antimicrobials, it reduced Campylobacter growth under high-level oxygen. Another notable finding is the consistent up-regulation of cj1169c-cj1170c, of which cj1170c encodes a known phosphokinase, an important regulatory protein in C. jejuni. Mutation of the cj1169c-cj1170c rendered C. jejuni less tolerant to atmospheric oxygen and reduced Campylobacter colonization and transmission in chickens. Conclusions These findings indicate that Ery treatment elicits a range of changes in C. jejuni transcriptome and affects the expression of genes important for in vitro and in vivo adaptation. Up-regulation of motility and down-regulation of energy metabolism likely facilitate Campylobacter to survive during Ery treatment. These findings

  2. Hypromellose succinate-crosslinked chitosan hydrogel films for potential wound dressing.

    PubMed

    Jiang, Qiong; Zhou, Wei; Wang, Jun; Tang, Rupei; Zhang, Di; Wang, Xin

    2016-10-01

    The objective of this study was to develop novel hydrogel films based on carboxyl-modified hypromellose-crosslinked chitosan for potential wound dressing. Hypromellose (HPMC) was grafted with succinic acid to yield hypromellose succinate (HPMCS), and then the reinforced hydrogel films of HPMCS-crosslinked chitosan (HPMCS-CS) were prepared through amide bond formation using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N- hydroxysuccinimide (NHS) as a catalyst. Compared to that of blend film, mechanical properties of HPMCS-CS hydrogel films were significantly enhanced both in dry and swollen state. To assess the applicability of HPMCS-CS hydrogel films as wound dressing, the swelling behavior, water vapor transmission rate (WVTR), oxygen permeability, biocompatibility (cytotoxicity and hemolysis), in vitro drug release and bactericidal properties were analyzed. The results indicated that HPMCS-CS hydrogel films with good biocompatibility possess high swelling ratio, proper WVTR, and oxygen permeability, which might accelerate tissue regeneration. Meanwhile, gentamycin sulfate release from drug-loaded HPMCS-CS hydrogel films were sustained, which would help to protect wound from infection.

  3. Evaluation of hypromellose acetate succinate (HPMCAS) as a carrier in solid dispersions.

    PubMed

    Tanno, Fumié; Nishiyama, Yuichi; Kokubo, Hiroyasu; Obara, Sakaé

    2004-01-01

    The utility of hypromellose acetate succinate (HPMCAS), a cellulosic enteric coating agent, as a carrier in a solid dispersion of nifedipine (NP) was evaluated in comparison with other polymers, including hypromellose (HPMC), hypromellose phthalate (HPMCP), methacrylic acid ethyl acrylate copolymer (MAEA), and povidone (PVP). An X-ray diffraction study showed that the minimum amount of HPMCAS required to make the drug completely amorphous was the same as that of other cellulosic polymers, and less than that in dispersions using non-cellulosic polymers. Hypromellose acetate succinate showed the highest drug dissolution level from its solid dispersion in a dissolution study using a buffer of pH 6.8. This characteristic was unchanged after a storage test at high temperature and high humidity. The inhibitory effect of HPMCAS on recrystallization of NP from a supersaturated solution was the greatest among all the polymers examined. Further, the drug release pattern could be modulated by altering the ratio of succinoyl and acetyl moieties in the polymer chain. Our results indicate that HPMCAS is an attractive candidate for use as a carrier in solid dispersions.

  4. Materials and methods for efficient succinate and malate production

    SciTech Connect

    Jantama, Kaemwich; Haupt, Mark John; Zhang, Xueli; Moore, Jonathan C; Shanmugam, Keelnatham T; Ingram, Lonnie O'Neal

    2014-04-08

    Genetically engineered microorganisms have been constructed to produce succinate and malate in mineral salt media in pH-controlled batch fermentations without the addition of plasmids or foreign genes. The subject invention also provides methods of producing succinate and malate comprising the culture of genetically modified microorganisms.

  5. Effect of erythromycin exposure on the growth, antioxidant system and photosynthesis of Microcystis flos-aquae.

    PubMed

    Wan, Jinjin; Guo, Peiyong; Peng, Xiaofang; Wen, Keqi

    2015-01-01

    Erythromycin, a macrolide antibiotic, is commonly used in human life. This compound and its derivatives have been detected in various aquatic compartments and may pose a serious threat to aquatic organisms. This study investigated the effects of erythromycin on the growth, antioxidant system and photosynthesis of Microcystis flos-aquae. The results showed that at 0.001-0.1 μg L(-1), erythromycin could stimulate the growth of M. flos-aquae and increase its photosynthetic activity; however, it did not significantly increase the activities of superoxide dismutase (SOD) and catalase (CAT) or the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). In contrast, the growth of M. flos-aquae was significantly inhibited (p<0.01) at high levels of erythromycin, reaching an inhibition rate of 81.6% at 40 μg L(-1) erythromycin. At the same time, the activities of SOD and CAT along with MDA content also increased significantly (p<0.01), indicating that the high concentrations of erythromycin caused a severe oxidative stress on algae. However, the balance between oxidants and antioxidant enzymes were disrupted because ROS content simultaneously increased. In addition, the fluorescence parameters of M. flos-aquae decreased significantly with both exposure time and increasing concentration of erythromycin, indicating that photosynthesis was inhibited.

  6. Crystal structure of the bis­(cyclo­hexyl­ammonium) succinate succinic acid salt adduct

    PubMed Central

    Sarr, Modou; Diasse-Sarr, Aminata; Diop, Libasse; Plasseraud, Laurent; Cattey, Hélène

    2015-01-01

    The crystal structure of the title salt adduct, 2C6H14N+·C4H4O4 2−·C4H6O4, consists of two cyclo­hexyl­ammonium cations, one succcinate dianion and one neutral succinic acid mol­ecule. Succinate dianions and succinic acid mol­ecules are self-assembled head-to-tail through O—H⋯O hydrogen bonds and adopt a syn–syn configuration, leading to a strand-like arrangement along [101]. The cyclo­hexyl­ammonium cations have a chair conformation and act as multidentate hydrogen-bond donors linking adjacent strands through inter­molecular N—H⋯O inter­actions to both the succinate and the succinic acid components. This results in two-dimensional supra­molecular layered structures lying parallel to (010). PMID:26396750

  7. The effect of tetracycline and erythromycin in a model of acne-type inflammation.

    PubMed Central

    Dalziel, K.; Dykes, P. J.; Marks, R.

    1987-01-01

    The effects of systemically administered oxytetracycline and erythromycin in a guinea pig model of acne-type inflammation were assessed histologically and by tissue measurement techniques. It was found that oxytetracycline significantly reduced the volume and maximum area of inflammation compared with both control and erythromycin treated groups. Oxytetracycline also altered the morphology of the inflammatory infiltrate significantly reducing the proportion of polymorphonuclear leucocytes present. In this model, erythromycin did not alter the inflammatory response but did seem to reduce the amount of transepidermal elimination of inflammatory debris. PMID:2949771

  8. Tocopheramine succinate and tocopheryl succinate: mechanism of mitochondrial inhibition and superoxide radical production.

    PubMed

    Gruber, Julia; Staniek, Katrin; Krewenka, Christopher; Moldzio, Rudolf; Patel, Anjan; Böhmdorfer, Stefan; Rosenau, Thomas; Gille, Lars

    2014-01-15

    Tocopherols (TOH) are lipophilic antioxidants which require the phenolic OH group for their redox activity. In contrast, non-redox active esters of α-TOH with succinate (α-TOS) were shown to possess proapoptotic activity in cancer cells. It was suggested that this activity is mediated via mitochondrial inhibition with subsequent O2(-) production triggering apoptosis and that the modification of the linker between the succinate and the lipophilic chroman may modulate this activity. However, the specific mechanism and the influence of the linker are not clear yet on the level of the mitochondrial respiratory chain. Therefore, this study systematically compared the effects of α-TOH acetate (α-TOA), α-TOS and α-tocopheramine succinate (α-TNS) in cells and submitochondrial particles (SMP). The results showed that not all cancer cell lines are highly sensitive to α-TOS and α-TNS. In HeLa cells α-TNS did more effectively reduce cell viability than α-TOS. The complex I activity of SMP was little affected by α-TNS and α-TOS while the complex II activity was much more inhibited (IC50=42±8μM α-TOS, 106±8μM α-TNS, respectively) than by α-TOA (IC50 >1000μM). Also the complex III activity was inhibited by α-TNS (IC50=137±6μM) and α-TOS (IC50=315±23μM). Oxygen consumption of NADH- or succinate-respiring SMP, involving the whole electron transfer machinery, was dose-dependently decreased by α-TOS and α-TNS, but only marginal effects were observed in the presence of α-TOA. In contrast to the similar inhibition pattern of α-TOS and α-TNS, only α-TOS triggered O2(-) formation in succinate- and NADH-respiring SMP. Inhibitor studies excluded complex I as O2(-) source and suggested an involvement of complex III in O2(-) production. In cancer cells only α-TOS was reproducibly able to increase O2(-) levels above the background level but neither α-TNS nor α-TOA. Furthermore, the stability of α-TNS in liver homogenates was significantly lower than that

  9. 21 CFR 173.228 - Ethyl acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl acetate. 173.228 Section 173.228 Food and..., Lubricants, Release Agents and Related Substances § 173.228 Ethyl acetate. Ethyl acetate (CAS Reg. No. 141-78... the specifications of the Food Chemicals Codex, 1 (Ethyl Acetate; p. 372, 3d Ed., 1981), which are...

  10. 21 CFR 173.228 - Ethyl acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Ethyl acetate. 173.228 Section 173.228 Food and..., Lubricants, Release Agents and Related Substances § 173.228 Ethyl acetate. Ethyl acetate (CAS Reg. No. 141-78... the specifications of the Food Chemicals Codex, 1 (Ethyl Acetate; p. 372, 3d Ed., 1981), which are...

  11. Method to produce succinic acid from raw hydrolysates

    DOEpatents

    Donnelly, Mark I.; Sanville-Millard, Cynthia Y.; Nghiem, Nhuan Phu

    2004-06-01

    A method for producing succinic acid from industrial-grade hydrolysates is provided, comprising supplying an organism that contains mutations for the genes ptsG, pflB, and ldhA, allowing said organism to accumulate biomass, and allowing said organism to metabolize the hydrolysate. Also provided is a bacteria mutant characterized in that it produces succinic acid from substrate contained in industrial-grade hydrolysate in a ratio of between 0.6:1 and 1.3:1 succinic acid to substrate.

  12. 3,4-Diamino­pyridinium hydrogen succinate

    PubMed Central

    Fun, Hoong-Kun; Balasubramani, Kasthuri

    2009-01-01

    In the title compound, C5H8N3 +·C4H5O4 −, the pyridine N atom of the 3,4-diamino­pyridine mol­ecule is protonated. The protonated N atom participates in an N—H⋯O hydrogen bond to a succinate O atom of the singly deprotonated succinate anion. Each of the two amino groups are hydrogen-bonded to the O atoms of two different sets of succinate groups.. The crystal structure is further stabilized by O—H⋯O and C—H⋯O hydrogen bonds. PMID:21582821

  13. Radiographic appearance of nosocomial legionnaires' disease after erythromycin treatment.

    PubMed Central

    Domingo, C; Roig, J; Planas, F; Bechini, J; Tenesa, M; Morera, J

    1991-01-01

    Radiographic features of 71 patients (48 men, 23 women) with nosocomial Legionella pneumophila pneumonia were assessed and compared with those of other nosocomial series of L pneumophila pneumonia. Sixteen patients were assessed retrospectively and 55 prospectively. Chest radiographs were assessed at the onset of the illness, 10 days later, and at 3 months. Erythromycin was given to 67 patients at the time of the diagnosis and to the remaining four at a later stage. Forty eight patients were over the age of 60. On the initial chest radiograph 53 of the 71 patients had unilateral shadowing (23 of them in the right lung); 35 had unilobar shadowing and the remaining 36 had more than one affected lobe. Pleural effusion was present in 24 cases and cavitation in 2. One patient had evidence of a pericardial effusion. At 10 days 21 patients had evidence of radiographic progression (14 ipsilateral), but 28 had improved. At 3 months 36 patients had an abnormal radiograph, 30 showing residual scarring, 15 loss of volume, six pleural shadows and two cavitation. Our series shows a lesser incidence of unilateral shadowing and pleural effusion than other nosocomial series and a lesser tendency to progression, but more patients had radiographic abnormalities at long term follow up. PMID:1948796

  14. Genotyping of erythromycin resistant group C & G streptococci isolated in Chennai, south India

    PubMed Central

    Prabu, D.; Menon, Thangam

    2013-01-01

    Background & objectives: Increasing resistance to erythromycin has been observed worldwide in group C and group G streptococci (GCS/GGS). The information available from India is scanty. The aim of the study was to identify erythromycin resistant GCS/GGS isolates in Chennai, south India, and to compare erythromycin resistant genotypes with emm types. Methods: One hundred and thirty one GCS/GGS isolates were tested for erythromycin resistance by disc diffusion and agar dilution methods. Erythromycin resistance genotypes [erm(A), erm(B) and mef(A)] were determined by a multiplex PCR. emm types of erythromycin resistant GCS/GGS isolates was also assessed using emm gene sequencing method. Results: Sixteen of the 131 isolates (12.21%) were resistant to erythromycin. Majority of the isolates were GGS (15/16). Eight of the 16 (50%) were S. dysgalactiae subsps. equisimilis. Twelve isolates (75%) were MLSB phenotype and four (25%) were M phenotype. Of the 12 isolates which exhibited MLSB resistance, seven showed cMLSB phenotype and were positive for erm(B) gene. The remaining five were iMLSB phenotype of which three were positive for erm(A) gene and two for erm(B) gene. erm(A) was common among carriers whereas erm(B) was common among clinical isolates. Interpretation & conclusions: MLSB was the predominant phenotype and erm(B) was the common genotype in the present study. The emm type stC1400.0 was frequently associated with erythromycin resistant GCS/GGS in our study. PMID:23481067

  15. Enhanced Corneal Absorption of Erythromycin by Modulating P-Glycoprotein and MRP Mediated Efflux with Corticosteroids

    PubMed Central

    Hariharan, Sudharshan; Gunda, Sriram; Mishra, Gyan P.; Pal, Dhananjay; Mitra, Ashim K.

    2015-01-01

    Purpose The objectives were (i) to test in vivo functional activity of MRP2 on rabbit corneal epithelium and (ii) to evaluate modulation of P-gp and MRP2 mediated efflux of erythromycin when co-administered with corticosteroids. Methods Cultured rabbit primary corneal epithelial cells (rPCECs) was employed as an in vitro model for rabbit cornea. Cellular accumulation and bi-directional transport studies were conducted across Madin-Darby Canine Kidney (MDCK) cells overexpressing MDR1 and MRP2 proteins to delineate transporter specific interaction of steroids. Ocular pharmacokinetic studies were conducted in rabbits following a single-dose infusion of erythromycin in the presence of specific inhibitors and steroids. Results Bi-directional transport of erythromycin across MDCK-MDR1 and MDCK-MRP2 cells showed significant difference between BL-AP and AP-BL permeability, suggesting that erythromycin is a substrate for P-gp and MRP2. Cellular accumulation of erythromycin in rPCEC was inhibited by steroids in a dose dependent manner. MK571, a specific MRP inhibitor, modulated the aqueous humor concentration of erythromycin in vivo. Even, steroids inhibited P-gp and MRP2 mediated efflux with maximum increase in ka, AUC0−∞, Cmax and Clast values of erythromycin, observed with 6α-methyl prednisolone. Conclusion MRP2 is functionally active along with P-gp in effluxing drug molecules out of corneal epithelium. Steroids were able to significantly inhibit both P-gp and MRP2 mediated efflux of erythromycin. PMID:18958406

  16. Blood, Tissue, and Intracellular Concentrations of Erythromycin and Its Metabolite Anhydroerythromycin during and after Therapy

    PubMed Central

    Krasniqi, S.; Matzneller, P.; Kinzig, M.; Sörgel, F.; Hüttner, S.; Lackner, E.; Müller, M.

    2012-01-01

    For macrolides, clinical activity but also the development of bacterial resistance has been attributed to prolonged therapeutic and subtherapeutic concentrations. Although erythromycin is a long-established antimicrobial, concomitant determination of the pharmacokinetics of erythromycin and its metabolites in different compartments is limited. To better characterize the pharmacokinetics of erythromycin and its anhydrometabolite (anhydroerythromycin [AHE]) in different compartments during and after the end of treatment with 500 mg of erythromycin four times daily, concentration-time profiles were determined in plasma, interstitial space of muscle and subcutaneous adipose tissue, and white blood cells (WBCs) at days 1 and 3 of treatment and 2 and 7 days after end of therapy. In WBCs, concentrations of erythromycin exceeded those in plasma approximately 40-fold, while free concentrations in plasma and tissue were comparable. The observed delay of peak concentrations in tissue might be caused by fast initial cellular uptake. Two days after the end of treatment, subinhibitory concentrations were observed in plasma and interstitial space of both soft tissues, while 7 days after the end of treatment, erythromycin was not detectable in any compartment. This relatively short period of subinhibitory concentrations may be advantageous compared to other macrolides. The ratio of erythromycin over AHE on day 1 was highest in plasma (2.81 ± 3.45) and lowest in WBCs (0.27 ± 0.22). While the ratio remained constant between single dose and steady state, after the end of treatment the concentration of AHE declined more slowly than that of the parent compound, indicating the importance of the metabolite for the prolonged drug interaction of erythromycin. PMID:22083477

  17. Erythromycin exerts in vivo anti-inflammatory activity downregulating cell adhesion molecule expression

    PubMed Central

    Sanz, María-Jesús; Nabah, Yafa Naim Abu; Cerdá-Nicolás, Miguel; O'Connor, José-Enrique; Issekutz, Andrew C; Cortijo, Julio; Morcillo, Esteban J

    2004-01-01

    Macrolides have long been used as anti-bacterial agents; however, there is some evidence that may exert anti-inflammatory activity. Therefore, erythromycin was used to characterize the mechanisms involved in their in vivo anti-inflammatory activity. Erythromycin pretreatment (30 mg kg−1 day−1 for 1 week) reduced the lipopolysaccharide (LPS; intratracheal, 0.4 mg kg−1)-induced increase in neutrophil count and elastase activity in the bronchoalveolar lavage fluid (BALF) and lung tissue myeloperoxidase activity, but failed to decrease tumor necrosis factor-α and macrophage-inflammatory protein-2 augmented levels in BALF. Erythromycin pretreatment also prevented lung P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) mRNA upregulation in response to airway challenge with LPS. Mesentery superfusion with LPS (1 μg ml−1) induced a significant increase in leukocyte–endothelial cell interactions at 60 min. Erythromycin pretreatment abolished the increases in these parameters. LPS exposure of the mesentery for 4 h caused a significant increase in leukocyte rolling flux, adhesion and emigration, which were inhibited by erythromycin by 100, 93 and 95%, respectively. Immunohistochemical analysis showed that LPS exposure of the mesentery for 4 h caused a significant enhancement in P-selectin, E-selectin, ICAM-1 and VCAM-1 expression that was downregulated by erythromycin pretreatment. Flow cytometry analysis indicated that erythromycin pretreatment inhibited LPS-induced CD11b augmented expression in rat neutrophils. In conclusion, erythromycin inhibits leukocyte recruitment in the lung and this effect appears mediated through downregulation of CAM expression. Therefore, macrolides may be useful in the control of neutrophilic pulmonary diseases. PMID:15665859

  18. Comparative study of effectiveness of oral acyclovir with oral erythromycin in the treatment of Pityriasis rosea.

    PubMed

    Amatya, A; Rajouria, E A; Karn, D K

    2012-01-01

    Pityriasis rosea is an acute, self-limiting disease, probably infective in origin, affecting mainly children and young adults, characterized by distinctive skin eruptions and minimal constitutional symptoms. Both oral Erythromycin and oral Acyclovir have been used in its management. To compare the effectiveness of oral Erythromycin and oral Acyclovir in the treatment of Pityriasis rosea. Forty two patients with clinical diagnosis of Pityriasis rosea were enrolled. They were randomized into two groups. One group was given high-dose oral Acyclovir and another group oral Erythromycin in standard dose. The participants were evaluated one, two, four, six and eight weeks and six months after commencement of the study. Forty two patients including 26 males and 16 females completed the study. After 8th week, all patients showed complete response in both the groups. The response to oral Acyclovir compared with that to oral Erythromycin was better and was statistically significant in 1st, 2nd, 4th and 6th weeks. Although it is a self-limiting disease which resolves within three weeks to three months, this study reveals that both oral Acyclovir and oral Erythromycin are helpful in decreasing the severity and duration of Pityriasis rosea. Moreover, the study also indicates that oral Acyclovir is more effective than oral Erythromycin in reducing the severity and duration of Pityriasis rosea.

  19. Erythromycin-induced stabilization of ermA messenger RNA in Staphylococcus aureus and Bacillus subtilis.

    PubMed

    Sandler, P; Weisblum, B

    1988-10-20

    Erythromycin-induced stabilization of ermA mRNA was studied in Staphylococcus aureus, its original host background, and in Bacillus subtilis, subcloned on plasmid vectors. By RNA blot analysis it was shown that 40 nM-erythromycin specifically increased the chemical half-life of ermA mRNA from 2.5 to 17.5 minutes whereas the half-life of cat-86 mRNA was not increased by erythromycin. While expression of ermA has been shown to be induced by erythromycin at the level of translation, our studies with three ermA constitutive mutants demonstrated that mRNA stabilization in growing cells occurred independently of induced gene expression, suggesting that the stabilized mRNA was not functional for protein synthesis. Studies of ermA/lacZ fusions demonstrated that the 5' end of the mRNA was sufficient to confer stabilization. Translation of specific amino acid codons in a leader peptide located at the extreme 5' end of the mRNA was required for the erythromycin-induced stabilization as a frameshift mutation introduced into the leader peptide determinant abolished stabilization. By S1 mapping, no differences were detected in the length of the 5' or 3' end of ermA mRNA with the addition of erythromycin, indicating that the stabilized transcript was not processed at its ends.

  20. Transfer of Erythromycin Resistance from Poultry to Human Clinical Strains of Staphylococcus aureus

    PubMed Central

    Khan, Saeed A.; Nawaz, Mohamed S.; Khan, Ashraf A.; Cerniglia, Carl E.

    2000-01-01

    The transfer of ermA and ermC genes, the two most common resistance determinants of erythromycin resistance, was studied with Luria-Bertani broth in the absence of additional Ca2+ or Mg2+ ions. Fifteen human and five poultry isolates of Staphylococcus aureus, which were resistant to erythromycin but carried different genetic markers for erythromycin resistance, were used for conjugation. Since both the donors (Amps-Tetr) and recipients (Ampr-Tets) were resistant to erythromycin, the transconjugants were initially picked up as ampicillin- and tetracycline-resistant colonies. The resistance transfer mechanisms of the chromosomally located erythromycin rRNA methylase gene ermA and the plasmid-borne ermC gene were monitored by a multiplex PCR and gene-specific internal probing assay. Four groups of transconjugants, based upon the transfer of the ermA and/or ermC gene, were distinguished from each other by the use of this method. Selective antibiotic screening revealed only one type of transconjugant that was resistant to ampicillin and tetracycline. A high frequency of transfer (4.5 × 10−3) was observed in all of the 23 transconjugants obtained, and the direction of tetracycline and erythromycin resistance marker transfer was determined to be from poultry to clinical isolates. The transfers of the ermA and ermC genes were via transposition and transformation, respectively. PMID:10790109

  1. Development and pharmacokinetic evaluation of erythromycin lipidic formulations for oral administration in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Serdoz, Francesca; Voinovich, Dario; Perissutti, Beatrice; Grabnar, Iztok; Hasa, Dritan; Ballestrazzi, Rodolfo; Coni, Ettore; Pellegrini, Enrico

    2011-08-01

    The aim of this work was to enhance the bioavailability of erythromycin base when administered orally in rainbow trout (Oncorhynchus mykiss). Since erythromycin is normally given in the form of medicated feed, in this study three new types of feed formulation were developed. A self-emulsifying system and two types of double microemulsions (O/W/O) were prepared, characterized and adsorbed on a commercial extruded diet for fish. The emulsified systems were based on saturated polyglycolized glycerides and mono- and diglycerides of medium-chain fatty acids (as oily phase), Tween 80 (as surfactant) and, in the case of double microemulsions, distilled water. The systems differed in percentage composition and for the amount and position of erythromycin in different phases. The three medicated feed were then administered orally by means of a gastric probe to rainbow trout and their relative bioavailability was estimated in comparison with that obtained after oral administration of feed with erythromycin powder. For each medicated feed, 80 fish were tested. Finally, plasma profiles of erythromycin after single administration of medicated feeds were used to predict profiles obtainable by administering once-daily medicated feeds for 7 consecutive days. The results proved that the feeds containing microemulsified erythromycin provided largely superior oral bioavailability and the advantage of obtaining the same efficacy against bacterial infections with a much lower dose of drug. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Perioperative Use of Erythromycin Reduces Cognitive Decline After Coronary Artery Bypass Grafting Surgery: A Pilot Study.

    PubMed

    Thomaidou, Evanthia; Argiriadou, Helena; Vretzakis, Georgios; Megari, Kalliopi; Taskos, Nikolaos; Chatzigeorgiou, Georgios; Anastasiadis, Kyriakos

    Adverse neurologic outcome can be a debilitating complication after cardiac surgery. The aim of this study was to investigate the potential neuroprotective action of erythromycin, a well known antibiotic agent, regarding postoperative cognitive decline in patients undergoing cardiac surgery. Forty patients scheduled for elective coronary artery bypass grafting surgery were prospectively randomly assigned in 2 groups: the erythromycin group (n = 19) who received erythromycin at a dose of 25 mg/kg before and after surgery and the control group (n = 21) who did not receive it. All patients were monitored with near-infrared spectroscopy during the operation. Interleukin (IL) 1 and IL-6 as inflammatory markers and tau protein as a marker of brain injury were measured before and after surgery. Neurocognitive assessment was performed before surgery, on the day of discharge, and at 3 months postoperatively. Both groups were comparable in terms of demographic and clinical data. Patients who took erythromycin presented with significantly better cognitive performance before discharge and 3 months after surgery. No significant differences between the 2 groups referring to IL-1 and IL-6 values were detected. Tau serum values were lower in the erythromycin group after surgery. Erythromycin administration attenuates cerebral damage and postoperative cognitive decline after coronary artery bypass grafting surgery. The study was retrospectively registered at ClinicalTrials.gov (NCT01274754). Study start day: November 2008.

  3. Removal of Penicillin G and Erythromycin with Ionizing Radiation Followed by Biological Treatment.

    PubMed

    Ben Salem, Issam; Mezni, Mohamed; Boulila, Abdennacer; Hamdi, Mokhtar; Saidi, Mouldi

    2016-10-01

    The decomposition of penicillin G and erythromycin antibiotics at concentration of 0.2 mg ml(-1) by gamma irradiation at 50 kGy followed by biological treatment with Cupriavidus metallidurans CH34 was evaluated. Degradation of penicillin G and erythromycin was analyzed using nuclear magnetic resonance analysis (NMR), fourier transform infrared spectroscopy (FTIR), and chemical oxygen demand (COD). The exposure to the absorbed dose of 50 kGy caused degradation of penicillin G and erythromycin in the aqueous solution. The complete disappearance of NMR and FTIR peaks following irradiation confirmed the breakage of the β-lactam ring in penicillin G, and the decarboxylation and cleavage of the thiazolidine ring and for erythromycin, the complete destruction of the three aromatic rings. Irradiation alone removed 52.8 and 65.5 % of penicillin G and erythromycin, respectively. Further reduction to 12.6 and 14 % of the original penicillin G and erythromycin COD, respectively, was achieved using treatment of the irradiation products with C. metallidurans.

  4. Randomized clinical trial of topical mupirocin versus oral erythromycin for impetigo.

    PubMed Central

    Goldfarb, J; Crenshaw, D; O'Horo, J; Lemon, E; Blumer, J L

    1988-01-01

    The safety and efficacy of a new topical antiinfective agent, mupirocin, was compared with that of oral erythromycin ethylsuccinate in the treatment of impetigo in children. Sixty-two children aged 5 months to 13 years with impetigo were assigned to be treated with either mupirocin in three daily applications or erythromycin ethylsuccinate (40 mg/kg of body weight per day divided into four doses) according to a randomized treatment schedule. On the initial visit, exudate or cleansed infected sites or both were cultured and therapy was begun. All patients were treated for 8 days. Patients were seen again on days 4 to 5 of therapy, at the end of therapy, and 7 days after the end of therapy. Sites of infection were comparable between the groups, as were bacteriologic responses. At the first visit, 24 of 30 children in the mupirocin group and 14 of 32 children in the erythromycin group were cured or had at least a 75% reduction in size of the lesions. At the end of the study, all 29 of the children in the mupirocin group who came to follow-up, compared with 27 of 29 in the erythromycin group, were cured. Side effects were few. Five children in the erythromycin group developed mild diarrhea. Thus, mupirocin appears to be safe and effective in treating impetigo in children. Our data show a trend toward more rapid clinical response with mupirocin than with erythromycin. PMID:3149884

  5. Erythromycin resistance by L4/L22 mutations and resistance masking by drug efflux pump deficiency

    PubMed Central

    Lovmar, Martin; Nilsson, Karin; Lukk, Eliisa; Vimberg, Vladimir; Tenson, Tanel; Ehrenberg, Måns

    2009-01-01

    We characterized the effects of classical erythromycin resistance mutations in ribosomal proteins L4 and L22 of the large ribosomal subunit on the kinetics of erythromycin binding. Our data are consistent with a mechanism in which the macrolide erythromycin enters and exits the ribosome through the nascent peptide exit tunnel, and suggest that these mutations both impair passive transport through the tunnel and distort the erythromycin-binding site. The growth-inhibitory action of erythromycin was characterized for bacterial populations with wild-type and L22-mutated ribosomes in drug efflux pump deficient and proficient backgrounds. The L22 mutation conferred reduced erythromycin susceptibility in the drug efflux pump proficient, but not deficient, background. This ‘masking' of drug resistance by pump deficiency was reproduced by modelling with input data from our biochemical experiments. We discuss the general principles behind the phenomenon of drug resistance ‘masking', and highlight its potential importance for slowing down the evolution of drug resistance among pathogens. PMID:19197244

  6. Desvenlafaxine succinate for major depressive disorder.

    PubMed

    Sproule, Beth A; Hazra, Monica; Pollock, Bruce G

    2008-07-01

    Desvenlafaxine (O-desmethylvenlafaxine) is the major active metabolite of venlafaxine. Desvenlafaxine succinate is now undergoing active evaluation for its therapeutic efficacy in a variety of disorders, including major depressive disorder, vasomotor symptoms associated with menopause, fibromyalgia and diabetic neuropathy. Desvenlafaxine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with similar activity to its parent compound venlafaxine, and little affinity for other brain targets, including muscarinic, cholinergic, histamine H(1) and alpha-adrenergic receptors. Desvenlafaxine has linear pharmacokinetics, low protein binding, a half-life of approximately 10 hours and is metabolized primarily via glucuronidation, and to a minor extent through CYP3A4. The desvenlafaxine succinate formulation appears to have good oral bioavailability. Clearance rates are reduced in the elderly, those with severe renal dysfunction and those with moderate to severe hepatic dysfunction, which may require dosage adjustments. Three published clinical trials have shown supportive but mixed results for the efficacy of desvenlafaxine in the treatment of major depressive disorder with daily doses ranging from 100 mg to 400 mg. One published clinical trial has shown mixed results for the efficacy of desvenlafaxine in the treatment of vasomotor symptoms associated with menopause with daily doses ranging from 50 mg to 200 mg. In these four clinical trials, desvenlafaxine was associated with several mild adverse effects, with the most common effect being nausea. Less common, but more serious, adverse effects reported in these trials included hypertension, QTc interval prolongation, exacerbation of ischemic cardiac disease, elevated lipids and elevated liver enzymes. The exact nature of these serious adverse effects, including the prevalence, clinical significance and potential risk factors, still needs to be fully elucidated. Desvenlafaxine has a low propensity for pharmacokinetic

  7. Succinate Dehydrogenase Loss in Familial Paraganglioma: Biochemistry, Genetics, and Epigenetics

    PubMed Central

    Her, Yeng F.; Maher, L. James

    2015-01-01

    It is counterintuitive that metabolic defects reducing ATP production can cause, rather than protect from, cancer. Yet this is precisely the case for familial paraganglioma, a form of neuroendocrine malignancy caused by loss of succinate dehydrogenase in the tricarboxylic acid cycle. Here we review biochemical, genetic, and epigenetic considerations in succinate dehydrogenase loss and present leading models and mysteries associated with this fascinating and important tumor. PMID:26294907

  8. Inhibition of membrane-bound succinate dehydrogenase by fluorescamine.

    PubMed

    Jay, D; Jay, E G; Garcia, C

    1993-12-01

    Fluorescamine rapidly inactivated membrane-bound succinate dehydrogenase. The inhibition of the enzyme by this reagent was prevented by succinate and malonate, suggesting that the group modified by fluorescamine was located at the active site. The modification of the active site sulfhydryl group by 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) did not alter the inhibitory action of fluorescamine. However, the protective effect of malonate against fluorescamine inhibition was abolished in the enzyme modified at the thiol.

  9. Succination of Thiol Groups in Adipose Tissue Proteins in Diabetes

    PubMed Central

    Frizzell, Norma; Rajesh, Mathur; Jepson, Matthew J.; Nagai, Ryoji; Carson, James A.; Thorpe, Suzanne R.; Baynes, John W.

    2009-01-01

    S-(2-Succinyl)cysteine (2SC) is formed by reaction of the Krebs cycle intermediate fumarate with cysteine residues in protein, a process termed succination of protein. Both fumarate and succination of proteins are increased in adipocytes cultured in high glucose medium (Nagai, R., Brock, J. W., Blatnik, M., Baatz, J. E., Bethard, J., Walla, M. D., Thorpe, S. R., Baynes, J. W., and Frizzell, N. (2007) J. Biol. Chem. 282, 34219–34228). We show here that succination of protein is also increased in epididymal, mesenteric, and subcutaneous adipose tissue of diabetic (db/db) mice and that adiponectin is a major target for succination in both adipocytes and adipose tissue. Cys-39, which is involved in cross-linking of adiponectin monomers to form trimers, was identified as a key site of succination of adiponectin in adipocytes. 2SC was detected on two of seven monomeric forms of adiponectin immunoprecipitated from adipocytes and epididymal adipose tissue. Based on densitometry, 2SC-adiponectin accounted for ∼7 and 8% of total intracellular adiponectin in cells and tissue, respectively. 2SC was found only in the intracellular, monomeric forms of adiponectin and was not detectable in polymeric forms of adiponectin in cell culture medium or plasma. We conclude that succination of adiponectin blocks its incorporation into trimeric and higher molecular weight, secreted forms of adiponectin. We propose that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes. PMID:19592500

  10. Identification of Protein Succination as a Novel Modification of Tubulin

    PubMed Central

    Piroli, Gerardo G.; Manuel, Allison M.; Walla, Michael D.; Jepson, Matthew J.; Brock, Jonathan W.C.; Rajesh, Mathur P.; Tanis, Ross M.; Cotham, William E.; Frizzell, Norma

    2015-01-01

    Protein succination is a stable post-translational modification that occurs when fumarate reacts with cysteine residues to generate S-(2-succino)cysteine (2SC). We demonstrate that both alpha (α) and beta (β) tubulin are increasingly modified by succination in 3T3-L1 adipocytes and in the adipose tissue of db/db mice. Incubation of purified tubulin from porcine brain with fumarate (50 mM) or the pharmacological compound dimethylfumarate (DMF, 500 μM) inhibited polymerization up to 35% and 59%, respectively. Using mass spectrometry we identified Cys347α, Cys376α, Cys12β and Cys303β as sites of succination in porcine brain tubulin and the relative abundance of succination at these cysteines increased in association with fumarate concentration. The increase in succination after incubation with fumarate altered tubulin recognition by an anti-α-tubulin antibody. Succinated tubulin in adipocytes cultured in high glucose vs. normal glucose also had reduced reactivity with the anti-αtubulin antibody; suggesting that succination may interfere with tubulin:protein interactions. DMF reacted rapidly with 11 of the 20 cysteines in the αβ tubulin dimer, decreased the number of free sulfhydryls and inhibited the proliferation of 3T3-L1 fibroblasts. Our data suggests that inhibition of tubulin polymerization is an important, undocumented mechanism of action of DMF. Taken together, our results demonstrate that succination is a novel post-translational modification of tubulin and suggest that extensive modification by fumarate, either physiologically or pharmacologically, may alter microtubule dynamics. PMID:24909641

  11. Biologically produced succinic acid: A new route to chemical intermediates

    SciTech Connect

    1995-09-01

    The national laboratory consortium has undertaken an R&D project with the Michigan Biotechnology Institute (MBI) to demonstrate the feasibility of producing a chemical intermediate, succinic acid, and various derivatives, from renewable agricultural resources. The projects near-term goal is to demonstrate an economically competetive process for producing 1,4-butanediol and other derivatives from biologically produced succinic acid without generating a major salt waste. The competitiveness to the petrochemical process must be demonstrated.

  12. Towards hyperpolarized 13C-succinate imaging of brain cancer

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Pratip; Chekmenev, Eduard Y.; Perman, William H.; Harris, Kent C.; Lin, Alexander P.; Norton, Valerie A.; Tan, Chou T.; Ross, Brian D.; Weitekamp, Daniel P.

    2007-05-01

    We describe a novel 13C enriched precursor molecule, sodium 1- 13C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1- 13C-glutamate, 5- 13C-glutamate, 1- 13C-glutamine and 5- 13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images.

  13. The Succinated Proteome of FH-Mutant Tumours

    PubMed Central

    Yang, Ming; Ternette, Nicola; Su, Huizhong; Dabiri, Raliat; Kessler, Benedikt M.; Adam, Julie; Teh, Bin Tean; Pollard, Patrick J.

    2014-01-01

    Inherited mutations in the Krebs cycle enzyme fumarate hydratase (FH) predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC). Loss of FH activity in HLRCC tumours causes accumulation of the Krebs cycle intermediate fumarate to high levels, which may act as an oncometabolite through various, but not necessarily mutually exclusive, mechanisms. One such mechanism, succination, is an irreversible non-enzymatic modification of cysteine residues by fumarate, to form S-(2-succino)cysteine (2SC). Previous studies have demonstrated that succination of proteins including glyceraldehyde 3-phosphate dehydrogenase (GAPDH), kelch-like ECH-associated protein 1 (KEAP1) and mitochondrial aconitase (ACO2) can have profound effects on cellular metabolism. Furthermore, immunostaining for 2SC is a sensitive and specific biomarker for HLRCC tumours. Here, we performed a proteomic screen on an FH-mutant tumour and two HLRCC-derived cancer cell lines and identified 60 proteins where one or more cysteine residues were succinated; 10 of which were succinated at cysteine residues either predicted, or experimentally proven, to be functionally significant. Bioinformatic enrichment analyses identified most succinated targets to be involved in redox signaling. To our knowledge, this is the first proteomic-based succination screen performed in human tumours and cancer-derived cells and has identified novel 2SC targets that may be relevant to the pathogenesis of HLRCC. PMID:25105836

  14. Towards hyperpolarized 13C-succinate imaging of brain cancer

    PubMed Central

    Bhattacharya, Pratip; Chekmenev, Eduard Y.; Perman, William H.; Harris, Kent C.; Lin, Alexander P.; Norton, Valerie A.; Tan, Chou T.; Ross, Brian D.; Weitekamp, Daniel P.

    2009-01-01

    We describe a novel 13C enriched precursor molecule, sodium 1-13C acetylenedicarboxylate, which after hydrogenation by PASADE-NA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1-13C-glutamate, 5-13C-glutamate, 1-13C-glutamine and 5-13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood–brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images. PMID:17303454

  15. Succination of thiol groups in adipose tissue proteins in diabetes: succination inhibits polymerization and secretion of adiponectin.

    PubMed

    Frizzell, Norma; Rajesh, Mathur; Jepson, Matthew J; Nagai, Ryoji; Carson, James A; Thorpe, Suzanne R; Baynes, John W

    2009-09-18

    S-(2-Succinyl)cysteine (2SC) is formed by reaction of the Krebs cycle intermediate fumarate with cysteine residues in protein, a process termed succination of protein. Both fumarate and succination of proteins are increased in adipocytes cultured in high glucose medium (Nagai, R., Brock, J. W., Blatnik, M., Baatz, J. E., Bethard, J., Walla, M. D., Thorpe, S. R., Baynes, J. W., and Frizzell, N. (2007) J. Biol. Chem. 282, 34219-34228). We show here that succination of protein is also increased in epididymal, mesenteric, and subcutaneous adipose tissue of diabetic (db/db) mice and that adiponectin is a major target for succination in both adipocytes and adipose tissue. Cys-39, which is involved in cross-linking of adiponectin monomers to form trimers, was identified as a key site of succination of adiponectin in adipocytes. 2SC was detected on two of seven monomeric forms of adiponectin immunoprecipitated from adipocytes and epididymal adipose tissue. Based on densitometry, 2SC-adiponectin accounted for approximately 7 and 8% of total intracellular adiponectin in cells and tissue, respectively. 2SC was found only in the intracellular, monomeric forms of adiponectin and was not detectable in polymeric forms of adiponectin in cell culture medium or plasma. We conclude that succination of adiponectin blocks its incorporation into trimeric and higher molecular weight, secreted forms of adiponectin. We propose that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes.

  16. Chloramphenicol succinate, a competitive substrate and inhibitor of succinate dehydrogenase: possible reason for its toxicity.

    PubMed

    Ambekar, C S; Lee, J S K; Cheung, B M Y; Chan, L C; Liang, R; Kumana, C R

    2004-08-01

    From our previous study [Eur. J. Clin. Pharmacol. 56 (2000) 405] we hypothesized that chloramphenicol succinate (CAPS) may be a competitive substrate for succinate dehydrogenase (SDH). It may be oxidized by SDH to release chloramphenicol (CAP), which may inhibit SDH by feed back mechanism. The present ex-vivo/in vitro study was aimed to investigate this possibility by using human tissues (bone marrow and liver samples) and animal tissues (rat liver and kidney). The effect of different SDH activators and specific inhibitors was studied on CAPS metabolism by SDH. The metabolites and reduction products were detected by using HPLC. In marrow samples, CAPS was slowly oxidized to form CAP. The formation of CAP (oxidation product) was enhanced by FAD and low malonate and inhibited by high malonate and 3-NPA. Similar results were obtained with mitochondria from human and rat tissues. These studies suggest that CAPS could be a competitive oxidative substrate and the metabolite CAP could be an inhibitor at the reduction site. Therefore, SDH could be a target molecule responsible for CAPS induced toxicity.

  17. Prevalence and mechanisms of erythromycin resistance in Streptococcus agalactiae from healthy pregnant women.

    PubMed

    Pinheiro, Sandra; Radhouani, Hajer; Coelho, Céline; Gonçalves, Alexandre; Carvalho, Eulália; Carvalho, José António; Ruiz-Larrea, Fernanda; Torres, Carmen; Igrejas, Gilberto; Poeta, Patrícia

    2009-06-01

    We sought to determine the resistance phenotypes for erythromycin and clindamycin and the mechanisms implicated in 93 Streptococcus agalactiae isolates recovered from healthy pregnant women. Susceptibility testing for erythromycin, clindamycin, penicillin, cefotaxime, vancomycin, quinupristin-dalfopristin, choramphenicol, ofloxacin, and meropenen was carried out by disc-diffusion test, and the E-test was also applied for erythromycin and clindamycin. The constitutive MLS(B) resistance (cMLS(B)) and inducible MLS(B) resistance (iMLS(B)) phenotypes, respectively, as well as the M resistance phenotype were determined by the erythromycin-clindamycin double-disc test. The presence of ermA, ermB, ermC, msrA, and mef(A/E) macrolide resistance genes was studied by PCR. Resistance to erythromycin and clindamycin was found in 15% and 9.6% of the isolates, respectively. The resistance phenotypes detected among the 14 erythromycin-resistant isolates were as follows (number of isolates): cMLS(B) (9), iMLS(B) (3), and M (2). The MICs for erythromycin and clindamycin were as follows: cMLS(B) isolates (128-256 and >or=32 mg/L, respectively), iMLS(B) isolates (16-256 and 1 mg/L), and M isolates (2-8 and 1 mg/L). The following combination of genes were detected among isolates with cMLS(B) or iMLS(B) phenotypes: erm(B) (6 isolates), ermA + ermTR (3), ermA + ermB + ermTR (1), and none of these genes (2). The two isolates with M phenotype harbored the mef(A/E), and msrA gene was also found in one of them.

  18. High Prevalence of Inducible Erythromycin Resistance among Streptococcus bovis Isolates in Taiwan

    PubMed Central

    Teng, Lee-Jene; Hsueh, Po-Ren; Ho, Shen-Wu; Luh, Kwen-Tay

    2001-01-01

    Susceptibilities to 13 antimicrobial agents were determined by measurement of MICs for 60 isolates of Streptococcus bovis from blood cultures. Thirty-eight isolates (63.3%) had high-level resistance to erythromycin (MICs, ≥128 μg/ml). Among the 38 erythromycin-resistant strains, 21 isolates (55%) had inducible resistance to macrolides-lincosamides-streptogramin B (iMLS isolates) and 17 (45%) had constitutive resistance to macrolides-lincosamides-streptogramin B (cMLS isolates). Tetracycline resistance was also found among all of the erythromycin-resistant strains. None of the strains displayed resistance to penicillin, chloramphenicol, or vancomycin. Detection of erythromycin resistance genes by PCR and sequencing indicated that all 17 cMLS isolates were positive for the ermB gene and that 7 of 21 iMLS isolates carried the ermB gene and the remaining 14 iMLS isolates carried the ermT gene. Sequence analysis of amplified partial ermB fragments (594 bp) from S. bovis isolates revealed a 99.8% nucleotide identity and a 100% amino acid homology compared with the sequences from gene banks. The sequences of amplified fragments with primers targeted for ermC were shown to be very similar to that of ermGT (ermT) from Lactobacillus reuteri (98.5% nucleotide identity). This is the first report to describe the detection of the ermT class of erythromycin resistance determinants in S. bovis. The high rate of inducible erythromycin resistance among S. bovis isolates in Taiwan was not reported before. The iMLS S. bovis isolates were shown to be heterogeneous by randomly amplified polymorphic DNA analysis. These results indicate that the prevalence of inducible erythromycin resistance in S. bovis in Taiwan is very high and that most of the resistant strains carry the ermT or the ermB gene. PMID:11709309

  19. The use of erythromycin as a gastrointestinal prokinetic agent in adult critical care: benefits versus risks.

    PubMed

    Hawkyard, Catherine V; Koerner, Roland J

    2007-03-01

    Erythromycin A, the first macrolide, was introduced in the 1950s and after years of clinical experience it still remains a commonly relied upon antibiotic. In the past, pharmacodynamic characteristics of macrolides beyond antimicrobial action such as anti-inflammatory and immune-modulating properties have been of scientific and clinical interest. The function of erythromycin as a prokinetic agent has also been investigated for a range of gastrointestinal motility disorders and more recently within the context of critically ill patients. Prokinetic agents are drugs that increase contractile force and accelerate intraluminal transit. Whilst the anti-inflammatory action may be a desirable side effect to its antibiotic action, using erythromycin A merely for its prokinetic effect alone raises the concern about promoting emergence of macrolide resistance. The objectives of this review article are: (i) to briefly summarize the modes and epidemiology of macrolide resistance, particularly in respect to that found in the Streptococcus species (a potential reservoir for the dissemination of macrolide resistance on the critical care unit); (ii) to discuss in this context the evidence for conditions promoting bacterial resistance against macrolides; and (iii) to assess the potential clinical benefit of using erythromycin A as a prokinetic versus the risks of promoting emergence of macrolide resistance in the clinical setting. We conclude, that in view of the growing weight of evidence demonstrating the potential epidemiological impact of the increased use of macrolides upon the spread of resistance, versus a lack of sufficient and convincing evidence that erythromycin A is a superior prokinetic agent to potential alternatives in the critically ill patient population, at this stage we do not advocate the use of erythromycin A as a prokinetic agent in critically ill patients unless they have failed all other treatment for impaired gastrointestinal dysmotility and are intolerant

  20. [Mechanism reversing MDR of K562/A02 by garlicin combined with erythromycin].

    PubMed

    Yu, Min; Liu, Xin; Xu, Bo; Wang, Hui; Chen, Wei

    2008-10-01

    This study was purposed to investigate the reversal effect of garlicin, erythromycin alone or combination of garlicin with erythromycin on K562/A02 and its possible mechanisms, so as to provide experimental evidence for combination reversal strategies. Cytotoxicity and the reversal effect of garlicin and erythromycin alone and combination of this two drugs were detected by MTT assay. The expression of mdr1 gene of K562/A02 was detected by RT-PCR. The P-gp expression was observed by immunohistochemical technique. Flow cytometry was used to detect intracellular drug concentration. The results showed that the sensitivity of K562/A02 to ADM increased somewhat in the presence of 1, 4, 8 mg/L garlicin, the reversal multiples at 1, 4, 8 mg/L garlicin were 1.80, 2.26 and 2.82 respectively in dose-dependent manner. The reversal multiple of erythromycin 60 mg/L was 2.20. The combination of two drugs could increase the reversal multiple to 4.94, and had no more cytotoxin. Both of garlicin and erythromycin alone could down-regulate the expression of mdr1 and P-gp of K562/A02 and elevate the intracellular concentrations of ADM in K562/A02 cells. Meanwhile, the effects described above were enhanced when garlicin was combined with erythromycin. It is concluded that the garlicin and erythromycin alone under cytotoxic dose both can reverse the MDR of K562/A02 cells effectively. Moreover, the combination of two drugs is more effective than that in use alone. Combination of these two drugs shows synergistic actions in regulating the expression of mdr1/P-gp and increasing the intracellular concentrations of ADM in K562/A02 cell.

  1. Succinate dehydrogenase gene mutations in cardiac paragangliomas.

    PubMed

    Martucci, Victoria L; Emaminia, Abbas; del Rivero, Jaydira; Lechan, Ronald M; Magoon, Bindiya T; Galia, Analyza; Fojo, Tito; Leung, Steve; Lorusso, Roberto; Jimenez, Camilo; Shulkin, Barry L; Audibert, Jennifer L; Adams, Karen T; Rosing, Douglas R; Vaidya, Anand; Dluhy, Robert G; Horvath, Keith A; Pacak, Karel

    2015-06-15

    Pheochromocytomas and paragangliomas are chromaffin cell tumors arising from neuroendocrine cells. At least 1/3 of paragangliomas are related to germline mutations in 1 of 17 genes. Although these tumors can occur throughout the body, cardiac paragangliomas are very rare, accounting for <0.3% of mediastinal tumors. The purpose of this study was to determine the clinical characteristics of patients with cardiac paragangliomas, particularly focusing on their genetic backgrounds. A retrospective chart analysis of 15 patients with cardiac paragangliomas was performed to determine clinical presentation, genetic background, diagnostic workup, and outcomes. The average age at diagnosis was 41.9 years. Typical symptoms of paraganglioma (e.g., hypertension, sweating, palpitations, headache) were reported at initial presentation in 13 patients (86.7%); the remaining 2, as well as 4 symptomatic patients, initially presented with cardiac-specific symptoms (e.g., chest pain, dyspnea). Genetic testing was done in 13 patients (86.7%); 10 (76.9%) were positive for mutations in succinate dehydrogenase (SDHx) subunits B, C, or D. Thirteen patients (86.7%) underwent surgery to remove the paraganglioma with no intraoperative morbidity or mortality; 1 additional patient underwent surgical resection but experienced intraoperative complications after removal of the tumor due to co-morbidities and did not survive. SDHx mutations are known to be associated with mediastinal locations and malignant behavior of paragangliomas. In this report, the investigators extend the locations of predominantly SDHx-related paragangliomas to cardiac tumors. In conclusion, cardiac paragangliomas are frequently associated with underlying SDHx germline mutations, suggesting a need for genetic testing of all patients with this rare tumor. Published by Elsevier Inc.

  2. Succinate Dehydrogenase Gene Mutations in Cardiac Paragangliomas

    PubMed Central

    Martucci, Victoria L.; Emaminia, Abbas; del Rivero, Jaydira; Lechan, Ronald M.; Magoon, Bindiya T.; Galia, Analyza; Fojo, Tito; Leung, Steve; Lorusso, Roberto; Jimenez, Camilo; Shulkin, Barry L.; Audibert, Jennifer L.; Adams, Karen T.; Rosing, Douglas R.; Vaidya, Anand; Dluhy, Robert G.; Horvath, Keith A.; Pacak, Karel

    2015-01-01

    Pheochromocytomas and paragangliomas are chromaffin cell tumors arising from neuroendocrine cells. At least one third of paragangliomas are related to germline mutations in one of 17 genes. While these tumors can occur throughout the body, cardiac paragangliomas are very rare, accounting for less than 0.3% of mediastinal tumors. The purpose of this study was to determine the clinical characteristics of patients with cardiac paragangliomas, particularly focusing on their genetic backgrounds. A retrospective chart analysis of fifteen patients with cardiac paraganglioma was performed to determine clinical presentation, genetic background, diagnostic work-up, and outcomes. The average age at diagnosis was 41.9 years. Typical symptoms of paraganglioma (e.g., hypertension, sweating, palpitations, headache) were reported at initial presentation in 13 patients (86.7%); the remaining 2, as well as 4 symptomatic patients, initially presented with cardiac-specific symptoms (e.g., chest pain, dyspnea). Genetic testing was done in 13 cases (86.7%); 10 (76.9%) were positive for mutations in succinate dehydrogenase (SDHx) subunits B, C, or D. Thirteen cases (86.7%) underwent surgery to remove the paraganglioma with no intraoperative morbidity or mortality; one additional patient underwent surgical resection but experienced intraoperative complications after removal of the tumor due to comorbities and did not survive. SDHx mutations are known to be associated with mediastinal locations and malignant behavior of paragangliomas. In this report, we extend the locations of predominantly SDHx-related paragangliomas to cardiac tumors. In conclusion, cardiac paragangliomas are frequently associated with underlying SDHx germline mutations, suggesting a need for genetic testing of all patients with this rare tumor. PMID:25896150

  3. S-Ethyl dipropylthiocarbamate (EPTC)

    Integrated Risk Information System (IRIS)

    S - Ethyl dipropylthiocarbamate ( EPTC ) ; CASRN 759 - 94 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessme

  4. Detection of interstellar ethyl cyanide

    NASA Technical Reports Server (NTRS)

    Johnson, D. R.; Lovas, F. J.; Gottlieb, C. A.; Gottlieb, E. W.; Litvak, M. M.; Thaddeus, P.; Guelin, M.

    1977-01-01

    Twenty-four millimeter-wave emission lines of ethyl cyanide (CH3CH2CN) have been detected in the Orion Nebula (OMC-1) and seven in Sgr B2. To derive precise radial velocities from the astronomical data, a laboratory measurement of the rotational spectrum of ethyl cyanide has been made at frequencies above 41 GHz. In OMC-1, the rotational temperature of ethyl cyanide is 90 K (in good agreement with other molecules), the local-standard-of-rest radial velocity is 4.5 + or - 1.0 km/s (versus 8.5 km/s for most molecules), and the column density is 1.8 by 10 to the 14th power per sq cm (a surprisingly high figure for a complicated molecule). The high abundance of ethyl cyanide in the Orion Nebula suggests that ethane and perhaps larger saturated hydrocarbons may be common constituents of molecular clouds and have escaped detection only because they are nonpolar or only weakly polar.

  5. Determination of erythromycin and tylosin residues in honey by LC/MS/MS.

    PubMed

    Granja, Rodrigo; Niño, Alfredo Montes; Zucchetti, Roberto; Niño, Rosario Montes; Patel, Raj; Salerno, Alessandro Gonzalez

    2009-01-01

    Antibiotics are used in apiculture to protect bees against a variety of brood diseases. As a result of the development of resistance to oxytetracycline, erythromycin and tylosin are increasingly used for the prevention and treatment of these diseases. Therefore, Brazilian authorities have added these antibiotics to the National Regulatory Monitoring Program for the control of residues in honey. An analytical method has been developed for the determination of residues of erythromycin and tylosin in honey. The procedure involves solid-phase extraction of diluted honey samples with Bond Elut cartridges, followed by LC/MS with electrospray positive ionization in the multiple reaction monitoring mode. Two characteristic transitions were monitored for both drugs. Average analyte recoveries of erythromycin and tylosin ranged from 99 to 109% from sets of replicate honey samples fortified with drug concentrations of 5, 10, 15, and 20 microg/kg. The method decision limits were determined to be 1.27 and 0.59 microg/kg for erythromycin and tylosin, respectively. The detection capabilities were 5 and 5.2 microg/kg for erythromycin and tylosin, respectively.

  6. Comparative erythromycin and tylosin susceptibility testing of streptococci from bovine mastitis.

    PubMed

    Entorf, Monika; Feßler, Andrea T; Kaspar, Heike; Kadlec, Kristina; Peters, Thomas; Schwarz, Stefan

    2016-10-15

    Tylosin, a 16-membered macrolide, is - besides other indications - used for the treatment of bovine mastitis. So far, there is only limited information available on the tylosin susceptibility of streptococci isolated from mastitis. The aim of the present study was to comparatively investigate 303 streptococci from bovine mastitis, including 101 Streptococcus agalactiae, 100 Streptococcus dysgalactiae and 102 Streptococcus uberis, for their tylosin and erythromycin susceptibility by broth microdilution and agar disk diffusion. Both tests followed the recommendations of the Clinical and Laboratory Standards Institute (CLSI). For erythromycin, the results were interpreted using the CLSI-approved clinical breakpoints. Moreover, erythromycin-resistant isolates were tested for the presence of macrolide resistance genes and for inducible macrolide resistance. In general, both testing methods showed a good correlation for the three streptococcal species, although for the erythromycin susceptibility testing 11 S. uberis isolates fell into the very major error category. All but one of the erythromycin-resistant isolates harbored at least one macrolide resistance gene, with the erm(B) gene being most common. Moreover, single isolates of S. agalactiae and S. dysgalactiae proved to be inducibly macrolide-resistant. Since inducible macrolide resistance can easily switch to constitutive resistance, tylosin should not be used for the treatment of infections caused by inducibly resistant streptococci. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Effect of parenteral administration of erythromycin, tilmicosin, and tylosin on abomasal emptying rate in suckling calves.

    PubMed

    Nouri, Mohammad; Constable, Peter D

    2007-12-01

    To determine the effect of parenteral administration of erythromycin, tilmicosin, and tylosin on abomasal emptying rate in suckling calves. 8 male Holstein-Friesian calves < 35 days old. Calves received each of 4 treatments in random order (2 mL of saline [0.9% NaCl] solution, IM [control treatment]; erythromycin, 8.8 mg/kg, IM; tilmicosin, 10 mg/kg, SC; and tylosin, 17.6 mg/kg, IM). Calves were fed 2 L of milk replacer containing acetaminophen (50 mg/kg) 30 minutes later. Jugular venous blood samples and transabdominal ultrasonographic abomasal dimensions were obtained periodically after suckling. Abomasal emptying rate was assessed on the basis of the time to maximal plasma acetaminophen concentration and ultrasonographic determination of the halftime of abomasal emptying. One-tailed Dunnett post tests were conducted whenever the F value for group was significant. Emptying rate was faster for erythromycin, tilimicosin, and tylosin than for the control treatment, as determined on the basis of time to maximal plasma acetaminophen concentration. Ultrasonography indicated that the half-time of abomasal emptying was significantly shorter for erythromycin than for the control treatment. Tylosin and tilmicosin accelerated the abomasal emptying rate, but not significantly, relative to the emptying rate for the control treatment. Administration of erythromycin, tilmicosin, and tylosin at the label dosage increased abomasal emptying rate in calves. The clinical importance of an increase in abomasal emptying rate in cattle remains to be determined.

  8. Feed restriction enhances the depressive effects of erythromycin on equine hindgut microbial metabolism in vitro.

    PubMed

    Kuhn, Manuela; Guschlbauer, Maria; Feige, Karsten; Schluesener, Michael; Bester, Kai; Beyerbach, Martin; Breves, Gerhard

    2012-01-01

    Equine typholocolitis is a sporadic diarrheal disease causing high mortality rates. One of the risk factors responsible for this is the oral application of the macrolide antibiotic erythromycin. The aim of the present in vitro study was to investigate whether erythromycin in combination with feed restriction provokes changes in microbial hindgut metabolism and could therefore be involved in the pathogenesis of equine typhlocolitis. As application of erythromycin and feed restriction are risk factors for equine typhlocolitis, both factors were chosen to investigate their individual and combined effects on hindgut microbial metabolism. The colon simulation technique (Cositec) was used to evaluate biochemical parameters of microbial metabolism. Production rates of the acetate, proprionate and butyrate were measured as quantitative parameters of microbial fermentation. Application of erythromycin (10 mg/d) predominantly decreased the production rates of propionate. Reducing the fermentable substrate to 30% induced an even more pronounced impairment. The detrimental effects of feed restriction on the production rates of short-chain fatty acids (SCFA) were enhanced when feed restriction was combined with the application of erythromycin. Irrespective of erytrhomycin, the butyrate fermentation rate was completely inhibited by feed restriction within two days after start of restriction. The reduction in butyrate fermentation rate has to be discussed as a pathophysiological factor for the onset of acute typhlocolitis.

  9. Molecular Basis for Erythromycin Resistance in Group A Streptococcus Isolated From Skin and Soft Tissue Infections

    PubMed Central

    Menon, Thangam

    2015-01-01

    Background In recent years there has been an increase in the use of erythromycin in the treatment of infections caused by bacteria other than Group A Streptococcus (GAS), which has resulted in increased resistance to this antibiotic. Erythromycin and other macrolides are alternative agents for treating GAS infections in patients, who are allergic to penicillin and its derivatives. Aim The main aim of this study was to identify frequency, pattern and genetic determinant of erythromycin resistance among the GAS isolated from skin and soft tissue infections. Materials and Methods A total 100 isolates of GAS were screened for erythromycin resistance by phenotypic and genotypic method. Results The results of the present study showed that 38% isolates were resistant to erythromycin. The iMLS (inducible macrolide-lincosamide-streptogramin) phenotype was predominant (55.26%) followed by M phenotype (26.32%) and cMLS (constitutive macrolide-lincosamide-streptogramin) (18.42%). Conclusion Phenotypic and genotypic analysis showed that the MLSB phenotype with ermB mediated mechanism of resistance was found the most common (76.31%) followed by mefA (20.51%). The ermTR genes was absent in all the isolates. PMID:26672671

  10. Production of ultrafine sumatriptan succinate particles for pulmonary delivery.

    PubMed

    Yang, Zong-Yang; Le, Yuan; Hu, Ting-Ting; Shen, Zhigang; Chen, Jian-Feng; Yun, Jimmy

    2008-09-01

    Drug particle physical properties are critical for the efficiency of a drug delivered to the lung. The purpose of this study was to produce ultrafine sumatriptan succinate particles for inhalation. Sumatriptan succinate particles were produced via reactive precipitation without any surfactants. Several low toxic organic solvents such as acetone, isopropanol, and tetrahydrofuran were investigated as the reaction medium. And the dry powder was obtained via spray drying. FT-IR, HPLC, SEM and XRD were exploited to characterize the physicochemical properties of the ultrafine sumatriptan succinate dry powder. The aerosol performance of the powder was evaluated using an Aeroliser connected to a multi stage liquid impinger operating at 60 l/min. The mean particle size of the ultrafine sumatriptan succinate particles obtained under optimum conditions was in the range of 630-679 nm and consequently they were in the respirable range. The spray-dried powder whose fine particle fraction was increased up to 50.6 +/- 8.2% showed good aerosol performance whereas the vacuum-dried powder was approximate 18.2 +/- 3.0%. Good aerosol performance ultrafine sumatriptan succinate particles could be produced by reactive precipitation without any additives followed by spray drying at the optimum parameters.

  11. Reactivity of the sulfhydryl groups of soluble succinate dehydrogenase.

    PubMed

    Vinogradov, A D; Gavrikova, E V; Zuevsky, V V

    1976-04-01

    Soluble succinate dehydrogenase prepared by butanol extraction reacts with N-ethylmaleimide according to first-order kinetics with respect to both remaining active enzyme and the inhibitor concentration. Binding of the sulfhydryl groups of the enzyme prevents its alkylation by N-ethylmaleimide and inhibition by oxaloacetate. A kinetic analysis of the inactivation of alkylating reagent in the presence of succinate or malonate suggests that N-ethylmaleimide acts as a site-directed inhibitor. The apparent first-order rate constant of alkylation increases between pH 5.8 and 7.8 indicating a pKa value for the enzyme sulfhydryl group equal to 7.0 at 22 degrees C in 50 mM Tris-sufate buffer. Certain anions (phosphate, citrate, maleate and acetate) decrease the reactivity of the enzyme towards the alkylating reagent. Succinate/phenazine methosulfate reductase activity measured in the presence of a saturating concentration of succinate shows the same pH-dependence as the alkylation rate by N-ethylmaleimide. The mechanism of the first step of succinate oxidation, including a nucleophilic attack of substrate by the active-site sulfhydryl group, is discussed.

  12. [Malate oxidation by mitochondrial succinate:ubiquinone-reductase].

    PubMed

    Belikova, Iu O; Kotliar, A B

    1988-04-01

    Succinate:ubiquinone reductase was shown to catalyze the oxidation of L- and D-stereoisomers of malate by artificial electron acceptors and ubiquinone. The rate of malate oxidation by succinate:ubiquinone reductase is by two orders of magnitude lower than that for the natural substrate--succinate. The values of kinetic constants for the oxidation of D- and L-stereoisomers of malate are equal to: V infinity = 0.1 mumol/min/mg protein, Km = 2 mM and V infinity = 0.05 mumol/min/mg protein, Km = 2 mM, respectively. The malate dehydrogenase activity is fully inhibited by the inhibitors of the dicarboxylate-binding site of the enzyme, i.e., N-ethylmaleimide and malonate and is practically insensitive to carboxin, a specific inhibitor of the ubiquinone-binding center. The enol form of oxaloacetate was shown to be the product of malate oxidation by succinate:ubiquinone reductase. The kinetics of inhibition of the enzyme activity by the ketone and enol forms of oxaloacetate was studied. Both forms of oxaloacetate effectively inhibit the succinate:ubiquinone reductase reaction.

  13. Effects of succinate on ground beef color and premature browning.

    PubMed

    Mancini, R A; Ramanathan, R; Suman, S P; Dady, G; Joseph, P

    2011-10-01

    The objective of this experiment was to determine the effects of succinate on raw and cooked ground beef color. Chubs (n=10) were divided in half and assigned to either succinate (final w/w concentration of 2.5%) or distilled water. Patties (n=14 per chub half) were assigned to initial day 0 color and each of 6 treatment combinations, created by crossing 3 packaging types (vacuum, high-oxygen/80% O(2), and PVC) with 2 storage times (days 1 and 3). After storage, patties were cooked to either 66 °C or 71 °C. Succinate increased (P<0.05) ground beef pH and metmyoglobin reducing activity but had no effect (P>0.05) on raw a* and chroma values. Moreover, succinate decreased (P<0.05) raw L* values, lipid oxidation, and premature browning for patties packaged in PVC and high-oxygen. Succinate may increase cooked patty redness via its influence on meat pH.

  14. 21 CFR 172.868 - Ethyl cellulose.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Ethyl cellulose. 172.868 Section 172.868 Food and... Multipurpose Additives § 172.868 Ethyl cellulose. The food additive ethyl cellulose may be safely used in food in accordance with the following prescribed conditions: (a) The food additive is a cellulose...

  15. 21 CFR 172.868 - Ethyl cellulose.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Ethyl cellulose. 172.868 Section 172.868 Food and... Multipurpose Additives § 172.868 Ethyl cellulose. The food additive ethyl cellulose may be safely used in food in accordance with the following prescribed conditions: (a) The food additive is a cellulose...

  16. 21 CFR 172.868 - Ethyl cellulose.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Ethyl cellulose. 172.868 Section 172.868 Food and... Multipurpose Additives § 172.868 Ethyl cellulose. The food additive ethyl cellulose may be safely used in food in accordance with the following prescribed conditions: (a) The food additive is a cellulose...

  17. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Ethyl alcohol. 184.1293 Section 184.1293 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  18. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Ethyl alcohol. 184.1293 Section 184.1293 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  19. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Ethyl alcohol. 184.1293 Section 184.1293 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT FOOD....1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH. (b) The ingredient meets...

  20. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl alcohol. 184.1293 Section 184.1293 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  1. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Ethyl alcohol. 184.1293 Section 184.1293 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  2. 21 CFR 172.868 - Ethyl cellulose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl cellulose. 172.868 Section 172.868 Food and... Multipurpose Additives § 172.868 Ethyl cellulose. The food additive ethyl cellulose may be safely used in food in accordance with the following prescribed conditions: (a) The food additive is a cellulose...

  3. 49 CFR 173.322 - Ethyl chloride.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Ethyl chloride. 173.322 Section 173.322 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.322 Ethyl chloride. Ethyl chloride must...

  4. 49 CFR 173.322 - Ethyl chloride.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Ethyl chloride. 173.322 Section 173.322 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.322 Ethyl chloride. Ethyl chloride must...

  5. 49 CFR 173.322 - Ethyl chloride.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Ethyl chloride. 173.322 Section 173.322 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.322 Ethyl chloride. Ethyl chloride must...

  6. mefE is necessary for the erythromycin-resistant M phenotype in Streptococcus pneumoniae.

    PubMed Central

    Tait-Kamradt, A; Clancy, J; Cronan, M; Dib-Hajj, F; Wondrack, L; Yuan, W; Sutcliffe, J

    1997-01-01

    Recently, it was shown that a significant number of erythromycin-resistant Streptococcus pneumoniae and Streptococcus pyogenes strains contain a determinant that mediates resistance via a putative efflux pump. The gene encoding the erythromycin-resistant determinant was cloned and sequenced from three strains of S. pneumoniae bearing the M phenotype (macrolide resistant but clindamycin and streptogramin B susceptible). The DNA sequences of mefE were nearly identical, with only 2-nucleotide differences between genes from any two strains. When the mefE sequences were compared to the mefA sequence from S. pyogenes, the two genes were found to be closely related (90% identity). Strains of S. pneumoniae were constructed to confirm that mefE is necessary to confer erythromycin resistance and to explore the substrate specificity of the pump; no substrates other than 14- and 15-membered macrolides were identified. PMID:9333056

  7. A Novel Erythromycin Resistance Methylase Gene (ermTR) in Streptococcus pyogenes

    PubMed Central

    Seppälä, Helena; Skurnik, Mikael; Soini, Hanna; Roberts, Marilyn C.; Huovinen, Pentti

    1998-01-01

    Erythromycin resistance among streptococci is commonly due to target site modification by an rRNA-methylating enzyme, which results in coresistance to macrolide, lincosamide, and streptogramin B antibiotics (MLSB resistance). Genes belonging to the ermAM (ermB) gene class are the only erythromycin resistance methylase (erm) genes in Streptococcus pyogenes with MLSB resistance that have been sequenced so far. We identified a novel erm gene, designated ermTR, from an erythromycin-resistant clinical strain of S. pyogenes (strain A200) with an inducible type of MLSB resistance. The nucleotide sequence of ermTR is 82.5% identical to ermA, previously found, for example, in Staphylococcus aureus and coagulase-negative staphylococci. Our finding provides the first sequence of an erm gene other than ermAM that mediates MLSB resistance in S. pyogenes. PMID:9527769

  8. A case of fixed drug eruption due to doxycycline and erythromycin present in food.

    PubMed

    Lim, Won-Suk; Kim, Do-Hun; Jin, Sang-Yun; Choi, Yun-Seok; Lee, Seung-Ho; Huh, Hee-Jin; Chae, Seok-Lae; Lee, Ai-Young

    2013-09-01

    A fixed drug eruption (FDE) is not difficult to diagnose, given its clinical characteristics. However, the causative agent can be difficult to identify, particularly when the patient denies ingestion of any drugs. To the best of our knowledge, we present herein the first reported case of an FDE caused by antibiotics taken in food; doxycycline and erythromycin contained in pork and fish. A 57-year-old female experienced repeated episodes of well-demarcated erythematous patches covering her entire body. She denied taking any medications, but she thought that the lesions appeared after consuming pork and/or fish. An oral provocation test showed positive results for doxycycline and erythromycin, commonly used antibiotics in live-stock farming and in the fishing industry. Because of the antibiotics' thermostability, cooking does not guarantee the elimination of residual drugs. From the patient's history, we concluded that doxycycline and erythromycin contained in the pork and fish that she ate were the cause of the FDE.

  9. Tailoring pathway modularity in the biosynthesis of erythromycin analogs heterologously engineered in E. coli.

    PubMed

    Zhang, Guojian; Li, Yi; Fang, Lei; Pfeifer, Blaine A

    2015-05-01

    Type I modular polyketide synthases are responsible for potent therapeutic compounds that include avermectin (antihelinthic), rapamycin (immunosuppressant), pikromycin (antibiotic), and erythromycin (antibiotic). However, compound access and biosynthetic manipulation are often complicated by properties of native production organisms, prompting an approach (termed heterologous biosynthesis) illustrated in this study through the reconstitution of the erythromycin pathway through Escherichia coli. Using this heterologous system, 16 tailoring pathways were introduced, systematically producing eight chiral pairs of deoxysugar substrates. Successful analog formation for each new pathway emphasizes the remarkable flexibility of downstream enzymes to accommodate molecular variation. Furthermore, analogs resulting from three of the pathways demonstrated bioactivity against an erythromycin-resistant Bacillus subtilis strain. The approach and results support a platform for continued molecular diversification of the tailoring components of this and other complex natural product pathways in a manner that mirrors the modular nature of the upstream megasynthases responsible for aglycone polyketide formation.

  10. Erythromycin-resistant Bordetella pertussis--Yuma County, Arizona, May-October 1994.

    PubMed

    1994-11-11

    In 1993, a total of 6586 cases of pertussis was reported in the United States, including 70 in Arizona. On June 27, 1994, a case of Bordetella pertussis disease caused by a strain resistant to erythromycin was reported to the Arizona Department of Health Services (ADHS) from Yuma County (1990 population: 106,895). Susceptibility testing at CDC confirmed that the isolate was highly resistant to erythromycin with a minimum inhibitory concentration (MIC) > 64 micrograms/mL. The MIC of erythromycin against B. pertussis usually ranges from 0.02 micrograms/mL to 0.1 micrograms/mL, and resistant isolates have not been previously reported (1). This report summarizes the case investigation and describes efforts to enhance surveillance for pertussis in Arizona.

  11. Tailoring pathway modularity in the biosynthesis of erythromycin analogs heterologously engineered in E. coli

    PubMed Central

    Zhang, Guojian; Li, Yi; Fang, Lei; Pfeifer, Blaine A.

    2015-01-01

    Type I modular polyketide synthases are responsible for potent therapeutic compounds that include avermectin (antihelinthic), rapamycin (immunosuppressant), pikromycin (antibiotic), and erythromycin (antibiotic). However, compound access and biosynthetic manipulation are often complicated by properties of native production organisms, prompting an approach (termed heterologous biosynthesis) illustrated in this study through the reconstitution of the erythromycin pathway through Escherichia coli. Using this heterologous system, 16 tailoring pathways were introduced, systematically producing eight chiral pairs of deoxysugar substrates. Successful analog formation for each new pathway emphasizes the remarkable flexibility of downstream enzymes to accommodate molecular variation. Furthermore, analogs resulting from three of the pathways demonstrated bioactivity against an erythromycin-resistant Bacillus subtilis strain. The approach and results support a platform for continued molecular diversification of the tailoring components of this and other complex natural product pathways in a manner that mirrors the modular nature of the upstream megasynthases responsible for aglycone polyketide formation. PMID:26601183

  12. Erythromycin and position facilitated placement of postpyloric feeding tubes in burned patients.

    PubMed

    Komenaka, I K; Giffard, K; Miller, J; Schein, M

    2000-01-01

    One of the main difficulties encountered in enteral nutrition in critically ill patients is the impaired gastric emptying: while the small bowel is ready the stomach is still 'lazy'. This paper describes a simple bedside method for postpyloric feeding tube placement, using a gastric prokinetic agent, erythromycin, and patient positioning. In eight critically ill, burned patients a gastric feeding tube was placed in a reverse Trendelenburg, right lateral decubitus position. A dose of 250 mg of erythromycin was administered intravenously. In 13 out of 14 attempts, the tube passed into the duodenum, a success rate of 92%. Combining the prokinetic effects of erythromycin with proper patient positioning allows a rapid bedside transpyloric placement of feeding tubes. Copyright 2000 S. Karger AG, Basel.

  13. Inhibitory effect of erythromycin, tetracycline and sulfamethoxazole antibiotics on anaerobic treatment of a pharmaceutical wastewater.

    PubMed

    Aydın, Sevcan; Ince, Bahar; Ince, Orhan

    2015-01-01

    Pharmaceuticals enter ecosystems, which causes changes to microbial community structure and development of resistant genes. Anaerobic treatments can be an alternative application for treatment of pharmaceutical wastewaters, which has high organic content. This study aims to develop an understanding of the effects of sulfamethoxazole-erythromycin-tetracycline (ETS), sulfamethoxazole-tetracycline (ST), erythromycin-sulfamethoxazole (ES) and erythromycin-tetracycline (ET) combinations on the anaerobic treatment of pharmaceutical industry wastewater. The results of this investigation revealed that bacteria have a competitive advantage over archaea under all antibiotic combinations. The ET reactor showed a better performance compared to other reactors; this could be due to antagonistic effects of sulfamethoxazole. Acute inhibition in the microbial community was also strongly affected by antibiotics concentrations. This indicated that the composition of the microbial community changed in association with anaerobic sequencing batch reactor performances. The results of this research support the idea that an acute test could be used to control and improve the anaerobic treatment system.

  14. Uptake, accumulation, and egress of erythromycin by tissue culture cells of human origin.

    PubMed Central

    Martin, J R; Johnson, P; Miller, M F

    1985-01-01

    The ability of erythromycin A base to penetrate and accumulate in tissue culture cells of human origin was investigated. The antibiotic was highly concentrated by early passage cells of normal bronchus, kidney, liver, lung, and skin and by cancer cells derived from breast, liver, and lung. Intracellular levels 4 to 12 times that of the extracellular milieu were obtained in both early-passage and transformed cells. The total quantity of erythromycin accumulated depended on the extracellular concentration of antibiotic, but the cellular/extracellular ratios were, for the most part, independent of the initial extracellular drug concentration. In all cell types tested, the accumulated antibiotic rapidly egressed when cells were incubated in antibiotic-free medium. Bioactivity assays demonstrated that the expelled drug was unmetabolized, fully active antibiotic. The concentration of erythromycin by a variety of human cell types probably accounts, in part, for the effectiveness of the antibiotic against intracellular parasites such as Legionella and Chlamydia spp. PMID:3994346

  15. Concentrations of azidocillin, erythromycin, doxycycline and clindamycin in human mandibular bone.

    PubMed

    Bystedt, H; DAhlbäck, A; Dornbusch, K; Nord, C E

    1978-10-01

    Postoperative complications after surgery in the mandible are still a clinical problem. Levels of four antibiotics--azidocillin, erythromycin, doxycycline and clindamycin--were measured in serum, dental alveolar serum, saliva and mandibular bone in 24 patients undergoing surgical removal of mandibular third molars. The concentration in mandibular bone for azidocillin was 0.8 microgram/g +/- 0.4 microgram/g, erythromycin 0.2 microgram/g +/- 0.1 microgram/g, doxycycline 2.6 microgram/g +/- 2 microgram/g and clindamycin 0.6 microgram/g +/- 0.4 microgram/g. No saliva levels were achieved with azidocillin and erythromycin, whereas doxycycline and clindamycin gave measurable saliva levels.

  16. [Antipneumococcal activity of erythromycin and spiramycin in 2 experimental models in mice].

    PubMed

    Rolin, O; Bouanchaud, D H

    1987-06-01

    Macrolides often remain the first intention treatment in many chest infections caused by S. pneumoniae. Antipneumococcal activities of spiramycin and erythromycin have then been tested in a septicaemia model and in a pulmonary infection model in mice. In the septicaemia model, spiramycin has been found 5 to 15 times more active than erythromycin by subcutaneous route and 1.5 to 6 times by oral route. In the pneumonia model, spiramycin has been found as active (one strain) to 5 times more active than erythromycin (three strains) by both subcutaneous and oral route. These data might indicate that better tissular penetration of spiramycin is responsible for better in vivo activity. These facts also support the statement that MIC should not be the only choice standard of infectious chemotherapy.

  17. A facile synthesis of deuterium labeled 2,2-dimethyl-[2H6]-succinic acid and its anhydride.

    PubMed

    Srinivas, G; Unny, V K P; Mukkanti, K; Choudary, B M

    2013-05-30

    Deuterium labeled 2,2-dimethyl-[(2)H(6)]-succinic anhydride by a sequence of reactions involving Knoevenagel condensation of [(2)H(6)]-acetone with ethyl cyanoacetate in the presence of piperidine, Michael addition of cyanide, HCl hydrolysis, simultaneous decarboxylation, and subsequent dehydration using acetic anhydride in an overall yield of 34.23% based on [(2)H(6)]-acetone utilized in the reaction is reported. The title compounds were characterized and confirmed spectroscopically by Fourier transform infrared, (1) H-NMR, and Mass. The chemical purity as determined by HPLC was 99%. To the best of our knowledge, the synthesis of these specifically deuterium labeled compounds has not been reported so far. Copyright © 2013 John Wiley & Sons, Ltd.

  18. Erythromycin enhances oesophageal motility in patients with gastro-oesophageal reflux.

    PubMed

    Chrysos, E; Tzovaras, G; Epanomeritakis, E; Tsiaoussis, J; Vrachasotakis, N; Vassilakis, J S; Xynos, E

    2001-02-01

    Intravenous (i.v.) erythromycin enhances gastric emptying and oesophageal motility in both healthy and disease situations, acting either as a motilin or acetylcholine agonist. The purpose of the present paper was to investigate any possible effect of i.v. erythromycin on oesophageal motility in patients with gastro-oesophageal reflux (GOR). In 15 patients with GOR (proven on 24-h ambulatory oesophageal pH measurement), standard oesophageal manometry was performed after i.v. injection of placebo and 200 mg erythromycin, in a random blind fashion. Erythromycin significantly increased lower oesophageal sphincter (LOS) pressure from 17 +/- 5 to 41 +/- 10 mmHg (P < 0.001), without affecting the postdeglutition relaxation of LOS. Erythromycin also increased the amplitude (from 79 +/- 34 to 97 +/- 40 mmHg; P < 0.001), duration (from 3.4 +/- 0.6 to 3.8 +/- 0.6 s; P = 0.005), velocity (from 3.1 +/- 0.8 to 3.5 +/- 1.15 cm/s; P = 0.0047) and strength (from 149 +/- 84 to 201 +/- 103 mmHg.s; P < 0.001) of peristalsis at 5 cm proximal to the LOS. Similarly, the drug increased the amplitude of peristalsis at 10 and 15 cm proximal to the LOS (from 70 +/- 39 to 77.4 +/- 37 mmHg; P = 0.049 and from 36 +/- 20 to 49 +/- 36 mmHg; P = 0.004, respectively) and the duration of peristalsis at the same levels (from 3.1 +/- 0.6 to 3.3 +/- 0.5 s; P = 0.011, and from 2.7 +/- 0.6 to 3 +/- 0.5 s; P = 0.003, respectively). Intravenously administered erythromycin improves impaired oesophageal motility in patients with GOR. This observation might be of clinical use.

  19. Effect of the aqueous extract of Psidium guajava on erythromycin-induced liver damage in rats.

    PubMed

    Sambo, N; Garba, S H; Timothy, H

    2009-12-01

    The effect of Psidium guajava extract on erythromycin-induced liver damage in albino rats was investigated using 30 normal rats grouped into six. Group I and II served as the normal and treatment controls that were administered with normal saline and 100 mg/kg body weight of erythromycin stearate daily for 14 days respectively. Rats in group III were administered 450 mg/kg body weight of Psidium guajava only for 7 days while rats in groups IV, V and VI were administered Psidium guajava extract for 7 days and 100mg/kg body weight of erythromycin for 14 days. Histopathological investigation of the liver tissues revealed striking oedema and mild periportal mononuclear cell infiltration of hepatic cords in the liver of rats administered 100 mg/kg of erythromycin stearate and 300/450 mg/kg of Psidium guajava extract. Pretreatment with 150 mg/kg of Psidium guajava extract showed a slight degree of protection against the induced hepatic injury caused by 100 mg/kg of erythromycin stearate. Biochemical analysis of the serum obtained revealed a significant increase in serum levels of hepatic enzymes measured in the groups administered with 100 mg/kg of erythromycin stearate and 300/450 mg/kg of Psidium guajava extract compared to the control groups and those pretreated with 150 mg/kg of Psidium guajava extract. This study has shown that the aqueous extract of psidium guajava leaf possesses hepatoprotective property at lower dose and a hepatotoxic property at higher dose but further studies with prolonged duration is recommended.

  20. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS

    PubMed Central

    Gaude, Edoardo; Aksentijević, Dunja; Sundier, Stephanie Y.; Robb, Ellen L.; Logan, Angela; Nadtochiy, Sergiy M.; Ord, Emily N. J.; Smith, Anthony C.; Eyassu, Filmon; Shirley, Rachel; Hu, Chou-Hui; Dare, Anna J.; James, Andrew M.; Rogatti, Sebastian; Hartley, Richard C.; Eaton, Simon; Costa, Ana S.H.; Brookes, Paul S.; Davidson, Sean M.; Duchen, Michael R.; Saeb-Parsy, Kourosh; Shattock, Michael J.; Robinson, Alan J.; Work, Lorraine M.; Frezza, Christian; Krieg, Thomas; Murphy, Michael P.

    2014-01-01

    Ischaemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death, and aberrant immune responses through generation of mitochondrial reactive oxygen species (ROS)1-5. Although mitochondrial ROS production in IR is established, it has generally been considered a non-specific response to reperfusion1,3. Here, we developed a comparative in vivo metabolomic analysis and unexpectedly identified widely conserved metabolic pathways responsible for mitochondrial ROS production during IR. We showed that selective accumulation of the citric acid cycle (CAC) intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase (SDH), which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. Upon reperfusion, the accumulated succinate is rapidly re-oxidised by SDH, driving extensive ROS generation by reverse electron transport (RET) at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo IR injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of IR injury. Furthermore, these findings reveal a novel pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation upon subsequent reperfusion is a potential therapeutic target to decrease IR injury in a range of pathologies. PMID:25383517

  1. Succinate-dependent metabolism in Trypanosoma cruzi epimastigotes.

    PubMed

    Denicola-Seoane, A; Rubbo, H; Prodanov, E; Turrens, J F

    1992-08-01

    Trypanosoma cruzi epimastigotes permeabilized with digitonin (65 micrograms (mg protein)-1) to measure mitochondrial respiration were exposed to different substrates. Although none of the NADH-dependent substrates stimulated respiration, succinate supported not only oxygen consumption but also oxidative phosphorylation (respiratory control ratio of 1.9 +/- 0.3) indicating that the mitochondria were coupled. The rate of NADH-dependent oxygen consumption by membrane fractions (9.4 +/- 0.7 nmol min-1 (mg protein)-1) was reduced by 50% upon addition of catalase indicating that the electrons from NADH oxidation reduced oxygen to H2O2. NADH-dependent H2O2 production (16 +/- 1 nmol min-1 (mg protein)-1) was confirmed using cytochrome c peroxidase. This activity was inhibited by fumarate by 70%, suggesting a competition between fumarate and oxygen for the electrons from NADH, probably at the fumarate reductase level. The respiratory chain inhibitor antimycin blocked both respiration by intact cells and succinate-dependent cytochrome c by isolated membranes. No inhibition by antimycin was observed when NADH replaced succinate as an electron donor, indicating that the electrons from NADH oxidation reduced cytochrome c through a different route. Malonate blocked not only succinate-cytochrome c reductase and fumarate reductase, but also intact cell motility. These results suggest that succinate has a central role in the intermediate metabolism of i. cruzi, as it may be used for respiration or excreted to the extracellular space under anaerobic conditions. In addition, 2 potential sources of H2O2 were tentatively identified as: (a) the enzyme fumarate reductase; and (b) a succinate-dependent site, which may be the semiquinone form of Coenzyme Q9, as in mammalian mitochondria.

  2. Therapeutic Agents in Acne Vulgaris: Part II. D-Alpha Amino Benzyl Penicillin, Erythromycin and Sulfadimethoxine.

    PubMed

    Stewart, W D; Maddin, S; Nelson, A J; Danto, J L

    1965-06-26

    A total of 379 patients with pustular and cystic acne vulgaris were selected for study in three groups. Each group was assigned one of the following medications: benzyl penicillin, erythromycin, sulfadimethoxine, or placebo; these were to be compared with tetracycline, a medication whose effectiveness was previously demonstrated in this type of acne. The study revealed a larger number of favourable responses to tetracycline and erythromycin than to sulfadimethoxine. Sulfadimethoxine, however, produced a greater number of favourable responses than did the benzyl penicillin or the placebo; the last-named had equivalent results.

  3. [Effect of high performance liquid chromatographic instrument system on the analysis of erythromycin A oxime].

    PubMed

    Sun, Jing-gu; Yao, Guo-wei; Ou, Yu-xiang

    2004-09-01

    A HPLC chromatography for the determination of erythromycin A oxime and relative compounds was studied, and the effect of chromatography systems including a HITACHI L-7100, a Shimadzu LC-6A, a Waters 474 and relative columns was analyzed. It was revealed that different HPLC apparatus and columns have obvious impact on the peak separation and retention time under the general chromatographic condition. The suitable chromatographic conditions for several different chromatography systems were summarized with good linear relationship, which is very significant to the quality control of erythromycin A oxime and relative compounds.

  4. In vitro evaluation of josamycin, spiramycin, and erythromycin against Rickettsia rickettsii and R. conorii.

    PubMed

    Raoult, D; Roussellier, P; Tamalet, J

    1988-02-01

    The antimicrobial activities of josamycin, erythromycin, and spiramycin against Rickettsia conorii and R. rickettsii were evaluated in two tests: a dye-uptake assay and a plaque assay. The MIC of josamycin was 1 microgram/ml for both species; the MICs of erythromycin and spiramycin were 4 to 8 and 16 to 32 micrograms/ml, respectively, for both species. Only josamycin may be of clinical use in treating spotted fever rickettsiosis. It may be useful in treating pregnant women and young children.

  5. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2001-09-25

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  6. Simulating Succinate-Promoted Dissolution at Calcite {104} Steps

    NASA Astrophysics Data System (ADS)

    Mkhonto, D.; Sahai, N.

    2008-12-01

    Organic molecules of a wide range of molecular weights from small organic acids, amino-acids, acidic peptides and acidic proteins to humic and fulvic acids play a key role in modulating nucleation, crystal growth and dissolution of calcium carbonate polymorphs. In general, these acidic molecules inhibit calcite growth and, promote dissolution preferentially along specific crystallographic directions, in the process, regulating crystal shape and size, and even whether a metastable polymorph (e.g., vaterite or aragonite) is nucleated first. For example, chiral faces of calcite are selected by chiral amino-acids and the unusual {hk0} faces are expressed in the presence of amino-acids [Orme et al., 2001], and unusual heptagonal dissolution etch-pit are seen in the presence of succinate compared to the normal rhombohedral pits in water alone [Teng et al., 2006]. Thus, the presence of unusual crystal morphologies may indicate organic-mediated growth, thus serving as a biosignature. We have conducted the Molecular Dynamics (MD) simulations using the Consistent Valence Force Field (CVFF) as implemented in the FORCITE© module of the Materials Studio © software package (Accelrys, Inc. TM) to model the adsorption of succinate, a dicarboxylic acid, and charge- balancing Na+ ions on dry and hydrated steps in different directions on the {104} cleavage face of calcite [Mkhonto and Sahai, in prep.]. At the site of succinate adsorption, we find elongation of the interatomic distances (Ca-OCO3,i) between surface Ca2+ cation and the oxygen of the underlying inorganic CO32- anion the first surface layer of calcite, compared to the corresponding distances in the presence of water alone, suggesting greater ease of surface Ca2+ detachment. This result is consistent with the empirically observed increase in overall dissolution rate with succinate [Teng et al., 2006]. Furthermore, succinate adsorption lowers the step energies, which explains the appearance of steps in the unsusual [42

  7. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, M.; Millard, C.S.; Stols, L.

    1998-06-23

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria. 2 figs.

  8. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    1998-01-01

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  9. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2002-01-01

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  10. Metabolic engineering of Saccharomyces cerevisiae to improve succinic acid production based on metabolic profiling.

    PubMed

    Ito, Yuma; Hirasawa, Takashi; Shimizu, Hiroshi

    2014-01-01

    We performed metabolic engineering on the budding yeast Saccharomyces cerevisiae for enhanced production of succinic acid. Aerobic succinic acid production in S. cerevisiae was achieved by disrupting the SDH1 and SDH2 genes, which encode the catalytic subunits of succinic acid dehydrogenase. Increased succinic acid production was achieved by eliminating the ethanol biosynthesis pathways. Metabolic profiling analysis revealed that succinic acid accumulated intracellularly following disruption of the SDH1 and SDH2 genes, which suggests that enhancing the export of intracellular succinic acid outside of cells increases succinic acid production in S. cerevisiae. The mae1 gene encoding the Schizosaccharomyces pombe malic acid transporter was introduced into S. cerevisiae, and as a result, succinic acid production was successfully improved. Metabolic profiling analysis is useful in producing chemicals for metabolic engineering of microorganisms.

  11. Evaluation of regional limb perfusion with erythromycin using the saphenous, cephalic, or palmar digital veins in standing horses.

    PubMed

    Kelmer, G; Martin-Jimenez, T; Saxton, A M; Catasus, C; Elliot, S B; Lakritz, J

    2013-10-01

    There are no reported studies evaluating the use of erythromycin for regional limb perfusion (RLP) in horses. Our hypothesis was that using the cephalic and saphenous veins for RLP will enable delivery of therapeutic concentrations of erythromycin to the distal limb. Nineteen healthy horses participated in the study. The cephalic, saphenous or palmar digital (PD) vein was used to perfuse the limb with erythromycin. Synovial samples were collected from the metacarpo/metatarso-phalangeal (MCP/MTP) joint and blood samples were collected from the jugular vein. Maximum concentration (C(max)) of erythromycin in the MCP joint using the cephalic vein was 113 mg/L. The Cmax of erythromycin in the MTP joint using the saphenous vein was 38 mg/L. Erythromycin administered using the PD vein was not detectable in the MCP/MTP joint of four of six horses. Concentrations of erythromycin achieved in the synovial fluid of the MCP/MTP joint were between 152 and 452 times the minimal inhibitory concentration (MIC) for Rhodococcus equi (R. equi). In conclusion, the results indicate that when using the saphenous or cephalic veins for RLP, therapeutic concentrations of erythromycin in the MCP/MTP joint can be consistently reached [corrected].

  12. Evaluation of an integrated biorefinery based on fractionation of spent sulphite liquor for the production of an antioxidant-rich extract, lignosulphonates and succinic acid.

    PubMed

    Alexandri, Maria; Papapostolou, Harris; Komaitis, Michael; Stragier, Lutgart; Verstraete, Willy; Danezis, Georgios P; Georgiou, Constantinos A; Papanikolaou, Seraphim; Koutinas, Apostolis A

    2016-08-01

    Spent sulphite liquor (SSL) has been used for the production of lignosulphonates (LS), antioxidants and bio-based succinic acid. Solvent extraction of SSL with isopropanol led to the separation of approximately 80% of the total LS content, whereas the fermentations carried out using the pretreated SSL with isopropanol led to the production of around 19g/L of succinic acid by both Actinobacillus succinogenes and Basfia succiniciproducens. Fractionation of SSL via nanofiltration to separate the LS and solvent extraction using ethyl acetate to separate the phenolic compounds produced a detoxified sugar-rich stream that led to the production of 39g/L of succinic acid by B. succiniciproducens. This fractionation scheme resulted also in the production of 32.4g LS and 1.15g phenolic-rich extract per 100g of SSL. Both pretreatment schemes removed significant quantities of metals and heavy metals. This novel biorefinery concept could be integrated in acidic sulphite pulping mills. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Desvenlafaxine succinate identifies novel antagonist binding determinants in the human norepinephrine transporter.

    PubMed

    Mason, John N; Deecher, Darlene C; Richmond, Rhonda L; Stack, Gary; Mahaney, Paige E; Trybulski, Eugene; Winneker, Richard C; Blakely, Randy D

    2007-11-01

    Desvenlafaxine succinate (DVS) is a recently introduced antagonist of the human norepinephrine and serotonin transporters (hNET and hSERT, respectively), currently in clinical development for use in the treatment of major depressive disorder and vasomotor symptoms associated with menopause. Initial evaluation of the pharmacological properties of DVS (J Pharmacol Exp Ther 318:657-665, 2006) revealed significantly reduced potency for the hNET expressed in membranes compared with whole cells when competing for [(3)H]nisoxetine (NIS) binding. Using hNET in transfected human embryonic kidney-293 cells, this difference in potency for DVS at sites labeled by [(3)H]NIS was found to distinguish DVS, the DVS analog rac-(1-[1-(3-chloro-phenyl)-2-(4-methylpiperazin-1-yl)-ethyl]cyclohexanol (WY-46824), methylphenidate, and the cocaine analog 3beta-(4-iodophenyl)tropane-2beta-carboxylic acid methyl ester (RTI-55) from other hNET antagonists, such as NIS, mazindol, tricyclic antidepressants, and cocaine. These differences seem not to arise from preparation-specific perturbations of ligand intrinsic affinity or antagonist-specific surface trafficking but rather from protein conformational alterations that perturb the relationships between distinct hNET binding sites. In an initial search for molecular features that differentially define antagonist binding determinants, we document that Val148 in hNET transmembrane domain 3 selectively disrupts NIS binding but not that of DVS.

  14. Phenotypes and gene expression profiles of Saccharopolyspora erythraea rifampicin-resistant (rif) mutants affected in erythromycin production

    PubMed Central

    Carata, Elisabetta; Peano, Clelia; Tredici, Salvatore M; Ferrari, Francesco; Talà, Adelfia; Corti, Giorgio; Bicciato, Silvio; De Bellis, Gianluca; Alifano, Pietro

    2009-01-01

    Background There is evidence from previous works that bacterial secondary metabolism may be stimulated by genetic manipulation of RNA polymerase (RNAP). In this study we have used rifampicin selection as a strategy to genetically improve the erythromycin producer Saccharopolyspora erythraea. Results Spontaneous rifampicin-resistant (rif) mutants were isolated from the parental strain NRRL2338 and two rif mutations mapping within rpoB, S444F and Q426R, were characterized. With respect to the parental strain, S444F mutants exhibited higher respiratory performance and up to four-fold higher final erythromycin yields; in contrast, Q426R mutants were slow-growing, developmental-defective and severely impaired in erythromycin production. DNA microarray analysis demonstrated that these rif mutations deeply changed the transcriptional profile of S. erythraea. The expression of genes coding for key enzymes of carbon (and energy) and nitrogen central metabolism was dramatically altered in turn affecting the flux of metabolites through erythromycin feeder pathways. In particular, the valine catabolic pathway that supplies propionyl-CoA for biosynthesis of the erythromycin precursor 6-deoxyerythronolide B was strongly up-regulated in the S444F mutants, while the expression of the biosynthetic gene cluster of erythromycin (ery) was not significantly affected. In contrast, the ery cluster was down-regulated (<2-fold) in the Q426R mutants. These strains also exhibited an impressive stimulation of the nitrogen regulon, which may contribute to lower erythromycin yields as erythromycin production was strongly inhibited by ammonium. Conclusion Rifampicin selection is a simple and reliable tool to investigate novel links between primary and secondary metabolism and morphological differentiation in S. erythraea and to improve erythromycin production. At the same time genome-wide analysis of expression profiles using DNA microarrays allowed information to be gained about the mechanisms

  15. Correlation of Succinate Metabolism and Virulence in Salmonella typhimurium

    PubMed Central

    Herzberg, Mendel; Jawad, Mudhaffer J.; Pratt, Darrell

    1965-01-01

    Herzberg, Mendel (University of Florida, Gainesville), and Mudhaffer J. Jawad, and Darrell Pratt. Succinate metabolism and virulence in Salmonella typhimurium. J. Bacteriol. 89:185–192. 1965.—A virulent, smooth strain of Salmonella typhimurium (Wild-7) grew slowly with succinate as sole carbon source (Suc-L). Old stock cultures yielded a smooth variant which grew rapidly (Suc-E). Visible colonies of Suc-E appeared in 24 hr, whereas Suc-L required 48 hr. Differences other than the response to succinate were not demonstrable between the two strains; ld50 values of both strains were similar, but equivalent numbers of Suc-E required longer periods of time to kill mice. Recovery of bacteria from liver and spleen homogenates revealed that Suc-L remains as such in vivo, but Suc-E populations change to Suc-L. By the eighth day of infection, the organisms were 93 to 100% Suc-L; thus, mortality was due to the Suc-L population developed in vivo and not the Suc-E of the original inoculum. Animal passage of a number of stock cultures of S. typhimurium of diverse origin, all Suc-E type, invariably yielded Suc-L. Slow utilization of succinate appears to be correlated with virulence. Images PMID:14255661

  16. Molecular properties of succinate dehydrogenase isolated from Micrococcus luteus (lysodeikticus).

    PubMed Central

    Crowe, B A; Owen, P

    1983-01-01

    Succinate dehydrogenase (EC 1.3.99.1) of Micrococcus luteus was selectively precipitated from Triton X-100-solubilized membranes by using specific antiserum. The precipitated enzyme contained equimolar amounts of four polypeptides with apparent molecular weights of 72,000, 30,000, 17,000, and 15,000. The 72,000 polypeptide possessed a covalently bound flavin prosthetic group and appeared to be strongly antigenic as judged by immunoprinting experiments. Low-temperature absorption spectroscopy revealed the presence of cytochrome b556 in the antigen complex. By analogy with succinate dehydrogenase purified from other sources, the 72,000 and 30,000 polypeptides were considered to represent subunits of the succinate dehydrogenase enzyme, whereas one (or both) of the low-molecular-weight polypeptides was attributed to the apoprotein of the b-type cytochrome. A succinate dehydrogenase antigen cross-reacting with the M. luteus enzyme complex could be demonstrated in membranes of Micrococcus roseus, Micrococcus flavus, and Sarcina lutea, but not in the membranes isolated from a wide variety of other gram-positive and gram-negative bacteria. Images PMID:6402500

  17. Melatonin and succinate reduce rat liver mitochondrial dysfunction in diabetes.

    PubMed

    Zavodnik, I B; Lapshina, E A; Cheshchevik, V T; Dremza, I K; Kujawa, J; Zabrodskaya, S V; Reiter, R J

    2011-08-01

    Mitochondrial dysfunction and an increase in mitochondrial reactive oxygen species in response to hyperglycemia during diabetes lead to pathological consequences of hyperglycemia. The aim of the present work was to investigate the role of a specific functional damage in rat liver mitochondria during diabetes as well as to evaluate the possibility of metabolic and antioxidative correction of mitochondrial disorders by pharmacological doses of succinate and melatonin. In rat liver mitochondria, streptozotocin-induced diabetes was accompanied by marked impairments of metabolism: we observed a significant activation of α-ketoglutarate dehydrogenase (by 60%, p<0.05) and a damage of the respiratory function. In diabetic animals, melatonin (10 mg/kg b.w., 30 days) or succinate (50 mg/kg b.w., 30 days) reversed the oxygen consumption rate V(3) and the acceptor control ratio to those in nondiabetic animals. Melatonin enhanced the inhibited activity of catalase in the cytoplasm of liver cells and prevented mitochondrial glutathione-S-transferase inhibition while succinate administration prevented α-ketoglutarate dehydrogenase activation. The mitochondria dysfunction associated with diabetes was partially remedied by succinate or melatonin administration. Thus, these molecules may have benefits for the treatment of diabetes. The protective mechanism may be related to improvements in mitochondrial physiology and the antioxidative status of cells.

  18. 21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Synthetic paraffin and succinic derivatives. 172.275 Section 172.275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO...

  19. 21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Synthetic paraffin and succinic derivatives. 172.275 Section 172.275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO...

  20. 21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Synthetic paraffin and succinic derivatives. 172.275 Section 172.275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO...

  1. 21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Synthetic paraffin and succinic derivatives. 172.275 Section 172.275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Coatings...

  2. 21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Synthetic paraffin and succinic derivatives. 172.275 Section 172.275 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO...

  3. 21 CFR 522.784 - Doxylamine succinate injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Doxylamine succinate injection. 522.784 Section 522.784 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL...

  4. 76 FR 22904 - Ferm Solutions, Inc.; Filing of Food Additive Petition (Animal Use); Erythromycin Thiocyanate

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-25

    ... food additive regulations in part 573 Food Additives Permitted in Feed and Drinking Water of Animals... HUMAN SERVICES Food and Drug Administration Ferm Solutions, Inc.; Filing of Food Additive Petition (Animal Use); Erythromycin Thiocyanate AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY...

  5. Application of oxygen uptake rate and response surface methodology for erythromycin production by Saccharopolyspora erythraea.

    PubMed

    Zou, Xiang; Hang, Hai-feng; Chen, Chang-fa; Chu, Ju; Zhuang, Ying-ping; Zhang, Si-liang

    2008-12-01

    A process for efficient production of erythromycin by Saccharopolyspora erythraea using statistical designs and feeding strategy was developed. The critical nutrient components were selected in accordance with fractional factorial design and were further optimized via response surface methodology. Three significant components (ZnSO(4), citric acid threonine) were identified for the optimization study. The optimum levels of these significant variables were determined with Box-Behnken design, which were ZnSO(4) 0.039 g/l, citric acid 0.24 g/l and threonine 0.42 g/l, respectively. A novel feeding strategy based on oxygen uptake rate (OUR) measurement was developed successfully to increase the flux of erythromycin biosynthesis, in which the optimized nutrient components was fed in the 50 l stirred bioreactor when OUR began to decline at 46 h. The maximum erythromycin production reached 10,622 U/ml, which was 11.7% higher than the control in the same cultivation conditions. It was the first report to integrate physiological parameter OUR and statistical methods to optimize erythromycin production.

  6. [Rapid detection of oxacillin and erythromycin resistance genes in Staphylococcus aureus using multiplex PCR].

    PubMed

    Huang, Ge; Zhou, Xiao-hong; Jiang, Wen-ling; Rong, Ka-bin; Zhao, Yin

    2008-04-01

    To establish a rapid multiplex PCR (MPCR) detection system of oxacillin and erythromycin resistance genes in Staphylococcus aureus (S. aureus) and evaluate the genotype distribution of the genes associated to mecA, ermA and ermC resistance in Guangzhou. The S. aureus strains were identified and susceptibility tests were performed using VITEK-60 or PHOENIX-100 system. The inducible resistance to clindamycin of strains with of erythromycin resistance was conducted using D-test, and the MPCR system of for detecting the antibiotic resistance genes was optimized. The MPCR assay for detecting the resistance genes was constructed successfully. According to the results of MPCR, the positivity rates for mecA, ermA and ermC genes among the 124 strains of S. aureus isolated from clinical samples were 56.5%, 50% and 33.9%, respectively. Good correlation was observed between the antibiotic resistance phenotypes and the S. aureus genotypes. mecA were detected in all the methicillin-resistant S. aureus strains, and ermA and/or ermC in 97.7% of the S. aureus strains with erythromycin resistance. This MPCR system allows rapid and reliable analysis of antibiotic resistance genotypes of S. aureus isolated from clinical samples. mecA, ermA, and ermC genes are among the predominant genetic determinants for the resistance to oxacillin and erythromycin in S. aureus isolates in Guangzhou.

  7. Improving monitoring of erythromycin ribosome methylase genes in swine and cattle manures with gene targeted approaches

    USDA-ARS?s Scientific Manuscript database

    Macrolide antibiotics are often used in feed for animal industry to prevent diseases. Resistance to these antibiotics is associated with erythromycin ribosome methylase genes (erm genes), which were first discovered in Staphylococcus aureus. The erm gene confers resistance by methylating rRNA at the...

  8. Cj1199 Affect the Development of Erythromycin Resistance in Campylobacter jejuni through Regulation of Leucine Biosynthesis

    PubMed Central

    Hao, Haihong; Li, Fei; Han, Jing; Foley, Steven L.; Dai, Menghong; Wang, Xu; Wang, Yulian; Huang, Lingli; Sun, Yawei; Liu, Zhenli; Yuan, Zonghui

    2017-01-01

    The aim of this study was to reveal the biological function of Cj1199 which was overexpressed in the laboratory induced erythromycin resistant strains. The Cj1199 deletion mutant (ΦCj1199) was constructed via insertional inactivation from its parent strain Campylobacter jejuni NCTC11168. The ΦCj1199 and NCTC11168 were then subjected to microarray and real-time PCR to find gene pathway of Cj1199. The antimicrobial susceptibility, antimicrobial resistance development, growth characteristics and leucine metabolism were examined to confirm the biological function of Cj1199. Our result showed that a total of 20 genes were down-regulated in ΦCj1199. These genes were mainly involved in leucine biosynthesis, amino acid transport and periplasmic/membrane structure. Compared to NCTC11168, ΦCj1199 was difficult to acquire higher-level erythromycin resistance during the in vitro step-wise selection. The competition growth and leucine-dependent growth assays demonstrated that ΦCj1199 imposed a growth disadvantage under pressure of erythromycin and in the leucine-free medium. In conclusion, Cj1199 gene may directly regulate the leucine biosynthesis and transport and indirectly affect the development of erythromycin resistance in C. jejuni. PMID:28144238

  9. Preparation and characterization of erythromycin molecularly imprinted polymers based on distillation-precipitation polymerization.

    PubMed

    Liu, Jiang; Li, Le; Tang, Hui; Zhao, Feilang; Ye, Bang-Ce; Li, Yingchun; Yao, Jun

    2015-09-01

    Erythromycin-imprinted polymers with excellent recognition properties were prepared by an innovative strategy called distillation-precipitation polymerization. The interaction between erythromycin and methacrylic acid was studied by ultraviolet absorption spectroscopy, and the as-prepared materials were characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy. Moreover, their binding performances were evaluated in detail by static, kinetic and selective sorption tests. It was found that the molecularly imprinted polymers afforded good morphology, monodispersity, and high adsorption capacity when the fraction of the monomers was 7 vol% in the whole reaction system, and the adsorption data for imprinted polymers correlated well with the Langmuir model. The maximum capacity of the imprinted and the non-imprinted polymers for adsorbing erythromycin is 44.03 and 19.95 mg/g, respectively. The kinetic studies revealed that the adsorption process fitted a pseudo-second-order kinetic model. Furthermore, the imprinted polymers display higher affinity toward erythromycin, compared with its analogue roxithromycin.

  10. Erythromycin potentiates PR interval prolonging effect of verapamil in the rat: A pharmacodynamic drug interaction

    SciTech Connect

    Dakhel, Yaman; Jamali, Fakhreddin . E-mail: fjamali@ualberta.ca

    2006-07-01

    Calcium channel blockers and macrolide antibiotics account for many drug interactions. Anecdotal reports suggest interactions between the two resulting in severe side effects. We studied the interaction between verapamil and erythromycin in the rat to see whether it occurs at the pharmacokinetics or pharmacodynamic level. Adult male Sprague-Dawley rats received doses of 1 mg/kg verapamil or 100 mg/kg erythromycin alone or in combination (n = 6/group). Serial blood samples (0-6 h) were taken for determination of the drug concentrations using HPLC. Electrocardiograms were recorded (0-6 h) through subcutaneously inserted lead II. Binding of the drugs to plasma proteins was studied using spiked plasma. Verapamil prolonged PR but not QT interval. Erythromycin prolonged QT but not PR interval. The combination resulted in a significant increase in PR interval prolongation and AV node blocks but did not further prolong QT interval. Pharmacokinetics and protein binding of neither drug were altered by the other. Our rat data confirm the anecdotal human case reports that combination of erythromycin and verapamil can result in potentiation of the cardiovascular response. The interaction appears to be at the pharmacodynamic rather than pharmacokinetic level hence may be extrapolated to other calcium channel antagonists.

  11. Lack of Synergy of Erythromycin Combined with Penicillin or Cefotaxime against Streptococcus pneumoniae In Vitro

    PubMed Central

    Lin, Eugene; Stanek, Ronald J.; Mufson, Maurice A.

    2003-01-01

    We investigated a possible synergistic effect of a macrolide and β-lactams against Streptococcus pneumoniae strains with different resistance profiles. Checkerboard and time-kill assays of erythromycin combined with penicillin or cefotaxime essentially showed indifference, suggesting that these antibiotics in combinations in vitro act substantially as individuals in their activity against S. pneumoniae. PMID:12604560

  12. Structure and Function of the Macrolide Biosensor Protein, MphR(A), with and without Erythromycin

    SciTech Connect

    Zheng, Jianting; Sagar, Vatsala; Smolinsky, Adam; Bourke, Chase; LaRonde-LeBlanc, Nicole; Cropp, T. Ashton

    2009-09-02

    The regulatory protein MphR(A) has recently seen extensive use in synthetic biological applications, such as metabolite sensing and exogenous control of gene expression. This protein negatively regulates the expression of a macrolide 2{prime}-phosphotransferase I resistance gene (mphA) via binding to a 35-bp DNA operator upstream of the start codon and is de-repressed by the presence of erythromycin. Here, we present the refined crystal structure of the MphR(A) protein free of erythromycin and that of the MphR(A) protein with bound erythromycin at 2.00- and 1.76-{angstrom} resolutions, respectively. We also studied the DNA binding properties of the protein and identified mutants of MphR(A) that are defective in gene repression and ligand binding in a cell-based reporter assay. The combination of these two structures illustrates the molecular basis of erythromycin-induced gene expression and provides a framework for additional applied uses of this protein in the isolation and engineered biosynthesis of polyketide natural products.

  13. Occurrence of erythromycin and its degradation products residues in honey. Validation of an analytical method.

    PubMed

    Zhao, Liuwei; Cao, Weirui; Xue, Xiaofeng; Wang, Miao; Wu, Liming; Yu, Linsheng

    2017-03-01

    Erythromycin A, the main component of erythromycin, is widely used to treat and control foulbrood diseases in honey bees. In this study, we developed a fast and sensitive method to simultaneously determine erythromycin A and its degradation products in honey. The analytical methodology was based on dispersive liquid-liquid microextraction and liquid chromatography coupled with tandem mass spectrometry with advanced i-Funnel technology. The liquid-liquid microextraction and liquid chromatography coupled with tandem mass spectrometry parameters were optimized. The recoveries of erythromycin A and its degradation products from spiked honey samples were 76.1-102.1%, with reproducibility rates of 7.1-13.1% and correlation coefficients  >0.99. The decision limit and detection capability were 0.02-0.07 and 0.03-0.10 ng/g, respectively. The proposed method was validated and successfully applied to the determination of the target analytes in commercial honey samples. It was efficient and sensitive, and it lays the foundation for further research on honey safety.

  14. Biochemical parameters of Saccharopolyspora erythraea during feeding ammonium sulphate in erythromycin biosynthesis phase.

    PubMed

    Zou, X; Li, W-J; Zeng, W; Hang, H-F; Chu, J; Zhuang, Y P; Zhang, S L

    2013-01-01

    The physiology of feeding ammonium sulphate in erythromycin biosynthesis phase of Saccharopolyspora erythraea on the regulation of erythromycin A (Er-A) biosynthesis was investigated in 50 L fermenter. At an optimal feeding ammonium sulphate rate of 0.03 g/L per h, the maximal Er-A production was 8281 U/mL at 174 h of growth, which was increased by 26.3% in comparison with the control (6557 U/mL at 173 h). Changes in cell metabolic response of actinomycete were observed, i.e. there was a drastic increase in the level of carbon dioxide evolution rate and oxygen consumption. Assays of the key enzyme activities and organic acids of S. erythraea and amino acids in culture broth revealed that cell metabolism was enhanced by ammonium assimilation, which might depend on the glutamate transamination pathway. The enhancement of cell metabolism induced an increase of the pool of TCA cycle and the metabolic flux of erythromycin biosynthesis. In general, ammonium assimilation in the erythromycin biosynthesis phase of S. erythraea exerted a significant impact on the carbon metabolism and formation of precursors of the process for dramatic regulation of secondary metabolites biosynthesis.

  15. Genome Sequence of Aeromicrobium erythreum NRRL B-3381, an Erythromycin-Producing Bacterium of the Nocardioidaceae

    PubMed Central

    Harrell, Erin A.

    2016-01-01

    Aeromicrobium erythreum NRRL B-3381 has a 3,629,239-bp circular genome that has 72% G+C content. There are at least 3,121 coding sequences (CDSs), two rRNA gene operons, and 47 tRNAs. The genome and erythromycin (ery) biosynthetic gene sequences provide resources for metabolic and combinatorial engineering of polyketides. PMID:27103725

  16. The cyclosporin-erythromycin interaction: impaired first pass metabolism in the pig.

    PubMed Central

    Freeman, D. J.; Grant, D. R.; Carruthers, S. G.

    1991-01-01

    1. The pharmacokinetic interaction between cyclosporin (CsA) and erythromycin has been studied in the weanling pig model. 2. Blood CsA and metabolite-1 (M1) concentrations were monitored by high performance liquid chromatography in portal, hepatic and jugular venus blood before and after treatment with erythromycin stearate for 7 days. 3. Erythromycin significantly increased maximum concentration (Cmax) and area under the concentration-time curve from 0 to 24 h (AUC) of CsA in the peripheral circulation. This was accompanied by a significant reduction in the hepatic extraction ratio calculated from portal and hepatic Cmax and AUC data. 4. The extraction ratio appears to be concentration-dependent in that values derived from Cmax (high concentrations) were greater than those from AUC (average concentrations). 5. Time to Cmax (tmax) and t1/2 of CsA were essentially unchanged and no significant changes were observed in peripheral M1 kinetics apart from a small increase in tmax. 6. The pharmacokinetic changes observed in the pig suggest that the CsA-erythromycin interaction is caused by inhibition of hepatic metabolism and the impact of inhibition is greatest during first-pass when CsA concentrations are at their highest. PMID:1933135

  17. Erythromycin ameliorates cigarette-smoke-induced emphysema and inflammation in rats.

    PubMed

    Zhou, Yan; Tan, Xianshu; Kuang, Wenjuan; Liu, Litao; Wan, Lihong

    2012-06-01

    The exposure to cigarette smoke (CS) is associated with emphysema. In addition to chronic lung inflammation, emphysema is known mainly for the complex pathogenesis associated with imbalance of proteolytic and antiproteolytic activities, oxidative stress, and apoptosis of lung structural cells. Increasing evidence shows that erythromycin, which is a macrolide antibiotic, ameliorates chronic inflammation via mechanisms independent of its antibacterial activity. We hypothesize that erythromycin protects against CS-induced emphysema and inflammation in rats via its anti-inflammation and antiapoptosis action. Sprague-Dawley (SD) rats were administered lipopolysaccharide (LPS) intratracheally solution twice and exposed to the CS, the control rats were administered saline intratracheally and exposed to ambient air for 3 weeks. Then, all the CS rats were distributed randomly into 3 groups and, respectively, treated orally with saline (LPS + CS + saline), Guilongkechuanning capsule (450 mg/kg) (LPS + CS + GLKCN), or erythromycin (100 mg/kg) (LPS + CS + ERY) 0.5 h before CS exposure for 2 weeks. On day 36, the rats were killed. The cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). The middle lobe of the right lung was removed for histology and apoptosis analyses, respectively. Emphysematous lesions and inflammatory cell infiltrations in the CS group were evident by a histologic analysis. Erythromycin protected significantly against the alveolar enlargement levels (P = 0.0017), reduced the pathologic apoptosis (P = 0.0023) related with Bcl-2 (P = 0.0002) and Bax (P = 0.0002), and inhibited the expressions of matrix metalloproteinase (MMP)-9 (P = 0.0019) and TIMP-1 protein (P = 0.04) and the MMP-9/TIMP-1 ratio (P = 0.0002) in the lungs of CS-induced emphysema in rats. The protective effect of erythromycin on CS-induced emphysema and inflammation in rats is associated with a reduction in inflammation, imbalance of MMP-9/TIMP-1, and apoptosis of

  18. Nitrosation of glycine ethyl ester and ethyl diazoacetate to give the alkylating agent and mutagen ethyl chloro(hydroximino)acetate.

    PubMed

    Zhou, Lin; Haorah, James; Chen, Sheng C; Wang, Xiaojie; Kolar, Carol; Lawson, Terence A; Mirvish, Sidney S

    2004-03-01

    Whereas nitrosation of secondary amines produces nitrosamines, amino acids with primary amino groups and glycine ethyl ester were reported to react with nitrite to give unidentified agents that alkylated 4-(p-nitrobenzyl)pyridine to produce purple dyes and be direct mutagens in the Ames test. We report here that treatment of glycine ethyl ester at 37 degrees C with excess nitrite acidified with HCl, followed by ether extraction, gave 30-40% yields of a product identified as ethyl chloro(hydroximino)acetate [ClC(=NOH)COOEt, ECHA] and a 9% yield of ethyl chloroacetate. The ECHA was identical to that synthesized by a known method from ethyl acetoacetate, strongly alkylated nitrobenzylpyridine, and may have arisen by N-nitrosation of glycine ethyl ester to give ethyl diazoacetate, which was C-nitrosated and reacted with chloride to give ECHA. Nitrosation of ethyl diazoacetate also yielded ECHA. Ethyl nitroacetate was not an intermediate as its nitrosation did not produce ECHA. ECHA reacted with aniline to give ethyl (hydroxamino)(phenylimino)acetate [PhN=C(NHOH)CO2Et]. This product was different from ethyl [(phenylamino)carbonyl]carbamate [PhNHC(=O)NHCO2Et], which was synthesized by reacting ethyl isocyanatoformate (OCN.CO2Et) with aniline. ECHA reacted with guanosine to give a derivative, which may have been a guanine-C(=NOH)CO2Et derivative. ECHA showed moderate toxicity and weak but significant mutagenicity without activation in Salmonella typhimurium TA-100 (mean, 1.31 x control value for 12-18 microg/plats) and for V79 mammalian cells (1.5-1.7 x control value for 60-100 microM). In conclusion, gastric nitrosation of glycine derivatives such as peptides with a N-terminal glycine might produce ECHA analogues that alkylate bases of gastric mucosal DNA and thereby initiate gastric cancer.

  19. Nonezymatic formation of succinate in mitochondria under oxidative stress.

    PubMed

    Fedotcheva, Nadezhda I; Sokolov, Alexander P; Kondrashova, Mariya N

    2006-07-01

    The products of the reactions of mitochondrial 2-oxo acids with hydrogen peroxide and tert-butyl hydroperoxide (tert-BuOOH) were studied in a chemical system and in rat liver mitochondria. It was found by HPLC that the decarboxylation of alpha-ketoglutarate (KGL), pyruvate (PYR), and oxaloacetate (OA) by both oxidants results in the formation of succinate, acetate, and malonate, respectively. The two latter products do not metabolize in rat liver mitochondria, whereas succinate is actively oxidized, and its nonenzymatic formation from KGL may shunt the tricarboxylic acid (TCA) cycle upon inactivation of alpha-ketoglutarate dehydrogenase (KGDH) under oxidative stress, which is inherent in many diseases and aging. The occurrence of nonenzymatic oxidation of KGL in mitochondria was established by an increase in the CO(2) and succinate levels in the presence of the oxidants and inhibitors of enzymatic oxidation. H(2)O(2) and menadione as an inductor of reactive oxygen species (ROS) caused the formation of CO(2) in the presence of sodium azide and the production of succinate, fumarate, and malate in the presence of rotenone. These substrates were also formed from KGL when mitochondria were incubated with tert-BuOOH at concentrations that completely inhibit KGDH. The nonenzymatic oxidation of KGL can support the TCA cycle under oxidative stress, provided that KGL is supplied via transamination. This is supported by the finding that the strong oxidant such as tert-BuOOH did not impair respiration and its sensitivity to the transaminase inhibitor aminooxyacetate when glutamate and malate were used as substrates. The appearance of two products, KGL and fumarate, also favors the involvement of transamination. Thus, upon oxidative stress, nonenzymatic decarboxylation of KGL and transamination switch the TCA cycle to the formation and oxidation of succinate.

  20. Stepwise binding of tylosin and erythromycin to Escherichia coli ribosomes, characterized by kinetic and footprinting analysis.

    PubMed

    Petropoulos, Alexandros D; Kouvela, Ekaterini C; Dinos, George P; Kalpaxis, Dimitrios L

    2008-02-22

    Erythromycin and tylosin are 14- and 16-membered lactone ring macrolides, respectively. The current work shows by means of kinetic and chemical footprinting analysis that both antibiotics bind to Escherichia coli ribosomes in a two-step process. The first step established rapidly, involves a low-affinity binding site placed at the entrance of the exit tunnel in the large ribosomal subunit, where macrolides bind primarily through their hydrophobic portions. Subsequently, slow conformational changes mediated by the antibiotic hydrophilic portion push the drugs deeper into the tunnel, in a high-affinity site. Compared with erythromycin, tylosin shifts to the high-affinity site more rapidly, due to the interaction of the mycinose sugar of the drug with the loop of H35 in domain II of 23 S rRNA. Consistently, mutations of nucleosides U2609 and U754 implicated in the high-affinity site reduce the shift of tylosin to this site and destabilize, respectively, the final drug-ribosome complex. The weak interaction between tylosin and the ribosome is Mg2+ independent, unlike the tight binding. In contrast, both interactions between erythromycin and the ribosome are reduced by increasing concentrations of Mg2+ ions. Polyamines attenuate erythromycin affinity for the ribosome at both sequential steps of binding. In contrast, polyamines facilitate the initial binding of tylosin, but exert a detrimental, more pronounced, effect on the drug accommodation at its final position. Our results emphasize the role of the particular interactions that side chains of tylosin and erythromycin establish with 23 S rRNA, which govern the exact binding process of each drug and its response to the ionic environment.

  1. Effects of dietary sodium butyrate on hepatic biotransformation and pharmacokinetics of erythromycin in chickens.

    PubMed

    Csikó, G; Nagy, G; Mátis, G; Neogrády, Z; Kulcsár, Á; Jerzsele, A; Szekér, K; Gálfi, P

    2014-08-01

    Butyrate, a commonly applied feed additive in poultry nutrition, can modify the expression of certain genes, including those encoding cytochrome P450 (CYP) enzymes. In comparative in vitro and in vivo experiments, the effect of butyrate on hepatic CYP genes was examined in primary cultures of chicken hepatocytes and in liver samples of chickens collected from animals that had been given butyrate as a feed additive. Moreover, the effect of butyrate on the biotransformation of erythromycin, a marker substance for the activity of enzymes of the CYP3A family, was investigated in vitro and in vivo. Butyrate increased the expression of the avian-specific CYP2H1 both in vitro and in vivo. In contrast, the avian CYP3A37 expression was decreased in hepatocytes following butyrate exposure, but not in the in vivo model. CYP1A was suppressed by butyrate in the in vitro experiments, and overexpressed in vivo in butyrate-fed animals. The concomitant incubation of hepatocytes with butyrate and erythromycin led to an increased CYP2H1 expression and a less pronounced inhibition of CYP3A37. In in vivo pharmacokinetic experiments, butyrate-fed animals given a single i.m. injection of erythromycin, a slower absorption phase (longer T(half-abs) and delayed T(max)) but a rapid elimination phase of this marker substrate was observed. Although these measurable differences were detected in the pharmacokinetics of erythromycin, it is unlikely that a concomitant application of sodium butyrate with erythromycin or other CYP substrates will cause clinically significant feed-drug interaction in chickens.

  2. Minimum inhibitory concentrations of erythromycin and rifampin for Rhodococcus equi during the years 2007-2014.

    PubMed

    Fenton, Caitriona S; Buckley, Thomas C

    2015-01-01

    Rhodococcus equi is a gram positive, intracellular pathogen of foals worldwide. The aim of this study was to determine whether there was an increasing resistance occurring in Rhodococcus equi towards the antibiotics rifampin and erythromycin over a seven year period. The investigation was carried out with the use of E test strips (epsilometers) for rifampin and erythromycin in order to determine the Minimum Inhibitory Concentrations (MIC) values of Rhodococcus equi to these antibiotics. The main results of this study found that the mean MICs were higher for erythromycin than for rifampin for every year analysed apart from 2008. The results highlight that 75 % (6/8) of the mean MICs for erythromycin were above the threshold of susceptibility of 0.5 μg/ml and one of the yearly mean MICs for rifampin (2008) was above the level of ≤ 1 μg/ml. Two soil samples analysed had high MIC values of 2 μg/ml and 3 μg/ml for rifampin and erythromycin respectively. These samples can be said to have acquired resistance as they are above 1 μg/ml. The significance of these findings is that R. equi is already a problematic pathogen to treat and if the bacteria keeps gaining resistance to these antibiotics at rate that has been shown over the last decade, then a new form of treatment will have to be introduced. Further research into the genomics of Rhodococcus equi will, in time, shed more light on possible alternatives such as vaccines or new, more effective antimicrobials.

  3. Acute and chronic effects of erythromycin exposure on oxidative stress and genotoxicity parameters of Oncorhynchus mykiss.

    PubMed

    Rodrigues, S; Antunes, S C; Correia, A T; Nunes, B

    2016-03-01

    Erythromycin (ERY) is a macrolide antibiotic used in human and veterinary medicine, and has been detected in various aquatic compartments. Recent studies have indicated that this compound can exert biological activity on non-target organisms environmentally exposed. The present study aimed to assess the toxic effects of ERY in Oncorhynchus mykiss after acute and chronic exposures. The here adopted strategy involved exposure to three levels of ERY, the first being similar to concentrations reported to occur in the wild, thus ecologically relevant. Catalase (CAT), total glutathione peroxidase (GPx), glutathione reductase (GRed) activities and lipid peroxidation (TBARS levels) were quantified as oxidative stress biomarkers in gills and liver. Genotoxic endpoints, reflecting different types of genetic damage in blood cells, were also determined, by performing analysis of genetic damage (determination of the genetic damage index, GDI, measured by comet assay) and of erythrocytic nuclear abnormalities (ENAs). The results suggest the occurrence of a mild, but significant, oxidative stress scenario in gills. For acutely exposed organisms, significant alterations were observed in CAT and GRed activities, and also in TBARS levels, which however are modifications with uncertain biological interpretation, despite indicating involvement of an oxidative effect and response. After chronic exposure, a significant decrease of CAT activity, increase of GPx activity and TBARS levels in gills was noticed. In liver, significant decrease in TBARS levels were observed in both exposures. Comet and ENAs assays indicated significant increases on genotoxic damage of O. mykiss, after erythromycin exposures. This set of data (acute and chronic) suggests that erythromycin has the potential to induce DNA strand breaks in blood cells, and demonstrate the induction of chromosome breakage and/or segregational abnormalities. Overall results indicate that both DNA damaging effects induced by

  4. Ultraviolet reduction of erythromycin and tetracycline resistant heterotrophic bacteria and their resistance genes in municipal wastewater.

    PubMed

    Guo, Mei-Ting; Yuan, Qing-Bin; Yang, Jian

    2013-11-01

    Antibiotic resistance in wastewater is becoming a major public health concern, but poorly understood about impact of disinfection on antibiotic resistant bacteria and antibiotic resistance genes. The UV disinfection of antibiotic resistant heterotrophic bacteria and their relevant genes in the wastewater of a municipal wastewater treatment plant has been evaluated. Two commonly used antibiotics, erythromycin and tetracycline were selected because of their wide occurrences in regard to the antibiotic resistance problem. After UV treatment at a fluence of 5mJcm(-2), the log reductions of heterotrophic bacteria resistant to erythromycin and tetracycline in the wastewater were found to be 1.4±0.1 and 1.1±0.1, respectively. The proportion of tetracycline-resistant bacteria (5%) was nearly double of that before UV disinfection (3%). Tetracycline-resistant bacteria exhibited more tolerance to UV irradiation compared to the erythromycin-resistant bacteria (p<0.05). Gene copy numbers were quantified via qPCR and normalized to the volume of original sample. The total concentrations of erythromycin- and tetracycline-resistance genes were (3.6±0.2)×10(5) and (2.5±0.1)×10(5) copies L(-1), respectively. UV treatment at a fluence of 5mJcm(-2) removed the total erythromycin- and tetracycline-resistance genes by 3.0±0.1 log and 1.9±0.1 log, respectively. UV treatment was effective in reducing antibiotic resistance in the wastewater. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Erythromycin prevents the pulmonary inflammation induced by exposure to cigarette smoke.

    PubMed

    Mikura, Shinichiro; Wada, Hiroo; Higaki, Manabu; Yasutake, Tetsuo; Ishii, Haruyuki; Kamiya, Shigeru; Goto, Hajime

    2011-07-01

    The effect of erythromycin on the inflammation caused by exposure to cigarette smoke was investigated in this study. Mice were exposed either to cigarette smoke or to environmental air (control), and some mice exposed to cigarette smoke were treated with oral erythromycin (100 mg/kg/day for 8 days). Pulmonary inflammation was assessed by determining the cellular content of bronchoalveolar lavage (BAL) fluid. The messenger RNA (mRNA) levels of various mediators, including keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP)-2, surfactant protein (SP)-D, granulocyte macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-α, interleukin (IL)-6 in lung tissue were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. The exposure to cigarette smoke increased significantly the numbers of neutrophils (P = 0.029), macrophages (P = 0.029), and lymphocytes (P = 0.029) recovered in BAL fluid. Moreover, mRNA levels of KC (P = 0.029), MIP-2 (P = 0.029), SP-D (P = 0.029), and GM-CSF (P = 0.057) in the lung tissue were higher in mice exposed to cigarette smoke than in mice exposed to environmental air. In the erythromycin-treated mice that were exposed also to cigarette smoke, both neutrophil and lymphocyte counts were significantly lower in the BAL fluid than those in the vehicle-treated mice (P = 0.029). Erythromycin-treated mice exposed to cigarette smoke showed a trend of lower mRNA levels of KC and TNF-α in the lung tissue than those in the vehicle-treated mice, although the statistical significance was not achieved (P = 0.057). Our data demonstrated that erythromycin prevented lung inflammation induced by cigarette smoke, in parallel to the reduced mRNA levels of KC and TNF-α.

  6. HERG K+ channel expression-related chemosensitivity in cancer cells and its modulation by erythromycin.

    PubMed

    Chen, Shu-Zhen; Jiang, Min; Zhen, Yong-su

    2005-08-01

    Previous studies have found that the HERG K+ channel is highly expressed in some cancers. In the study reported here, we investigated HERG expression in various cancer cell lines, its correlation with chemosensitivity to vincristine, paclitaxel, and hydroxy-camptothecin, and its biochemical modulation. The MTT assay and clonogenic assay were used to detect the cytotoxicity of anticancer drugs in vitro. HERG expression was analyzed by Western blotting or immunocytochemistry. Gene transfection was used to examine the changes in HERG-related chemosensitivity. Cell cycle phase distribution was detected by flow cytometry and drug combinations were evaluated by the MTT assay. HERG expression levels differed widely between various human cancer cell lines and HT-29 cells expressing high levels of HERG were more sensitive than A549 cells expressing low levels of HERG to vincristine, paclitaxel, and hydroxy-camptothecin. In terms of IC50, the chemosensitivities of herg-transfected A549 cells to vincristine, paclitaxel and hydroxy-camptothecin were significantly increased. However, for cisplatin and 5-fluorouracil, no significant difference between herg-transfected A549 cells and parent A549 cells was detected. Erythromycin, a HERG K+ channel blocker, suppressed the growth of various cancer cells and the potency was correlated with HERG expression levels. Combinations of erythromycin and vincristine, paclitaxel or hydroxy-camptothecin showed synergy in cytotoxicity to HT-29 cells. Erythromycin also enhanced the G2/M arrest induced by vincristine in HT-29 cells. There were synergistic effects between erythromycin and vincristine, paclitaxel, and hydroxy-camptothecin, and chemosensitivity was correlated with HERG expression level. HERG expression levels and chemosensitivity were positively correlated for vincristine, paclitaxel, and hydroxy-camptothecin. Erythromycin was active as a modulator. These results suggest that HERG may serve as a molecular marker and modulating target

  7. Insights into the amplification of bacterial resistance to erythromycin in activated sludge.

    PubMed

    Guo, Mei-Ting; Yuan, Qing-Bin; Yang, Jian

    2015-10-01

    Wastewater treatment plants are significant reservoirs for antimicrobial resistance. However, little is known about wastewater treatment effects on the variation of antibiotic resistance. The shifts of bacterial resistance to erythromycin, a macrolide widely used in human medicine, on a lab-scale activated sludge system fed with real wastewater was investigated from levels of bacteria, community and genes, in this study. The resistance variation of total heterotrophic bacteria was studied during the biological treatment process, based on culture dependent method. The alterations of bacterial community resistant to erythromycin and nine typical erythromycin resistance genes were explored with molecular approaches, including high-throughput sequencing and quantitative polymerase chain reaction. The results revealed that the total heterotrophs tolerance level to erythromycin concentrations (higher than 32 mg/L) was significantly amplified during the activated sludge treatment, with the prevalence increased from 9.6% to 21.8%. High-throughput sequencing results demonstrated an obvious increase of the total heterotrophic bacterial diversity resistant to erythromycin. Proteobacteria and Bacteroidetes were the two dominant phyla in the influent and effluent of the bioreactor. However, the prevalence of Proteobacteria decreased from 76% to 59% while the total phyla number increased greatly from 18 to 29 through activated sludge treatment. The gene proportions of erm(A), mef(E) and erm(D) were greatly amplified after biological treatment. It is proposed that the transfer of antibiotic resistance genes through the variable mixtures of bacteria in the activated sludge might be the reason for the antibiotic resistance amplification. The amplified risk of antibiotic resistance in wastewater treatment needs to be paid more attention.

  8. Method for construction of bacterial strains with increased succinic acid production

    DOEpatents

    Donnelly, Mark I.; Sanville-Millard, Cynthia; Chatterjee, Ranjini

    2000-01-01

    A fermentation process for producing succinic acid is provided comprising selecting a bacterial strain that does not produce succinic acid in high yield, disrupting the normal regulation of sugar metabolism of said bacterial strain, and combining the mutant bacterial strain and selected sugar in anaerobic conditions to facilitate production of succinic acid. Also provided is a method for changing low yield succinic acid producing bacteria to high yield succinic acid producing bacteria comprising selecting a bacterial strain having a phosphotransferase system and altering the phosphotransferase system so as to allow the bacterial strain to simultaneously metabolize different sugars.

  9. Morpho-physiological response of Populus alba to erythromycin: A timeline of the health status of the plant.

    PubMed

    Pierattini, Erika Carla; Francini, Alessandra; Raffaelli, Andrea; Sebastiani, Luca

    2016-11-01

    Populus alba Villafranca clone was chosen for a proof of concept study to determine the potential uptake and accumulation of antibiotics by trees. Plants were grown hydroponically and irrigated with a recirculating Hoagland's nutrient solution (control) and Hoagland's nutrient solution fortified with erythromycin at 0.01, 0.1 and 1mgL(-1). After 3 and 28days of treatment, poplar plants were separated into roots, stem, and leaves. Plants showed good health all over the period of treatment, and no differences in poplar growth for all the concentrations of erythromycin tested were observed. Quantification of erythromycin was performed using liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS) in positive ion mode using multiple reaction ion monitoring. Erythromycin was detected in all organs analyzed. Roots showed an erythromycin concentration tenfold higher than leaves. The photochemical efficiency of photosystem II did not show a dose-dependant trend. From the quenching analysis of chlorophyll fluorescence, low nonphotochemical quenching (NPQ) and high photochemical quenching (qP) for the first week of erythromycin exposure was observed, depending on leaves position along the stem. Results suggest a short term adaptation of the photosynthetic apparatus of Populus alba in response to environmental realistic erythromycin concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Succinate dehydrogenase subunit D and succinate dehydrogenase subunit B mutation analysis in canine phaeochromocytoma and paraganglioma.

    PubMed

    Holt, D E; Henthorn, P; Howell, V M; Robinson, B G; Benn, D E

    2014-07-01

    Phaeochromocytomas (PCs) are tumours of the adrenal medulla chromaffin cells. Paragangliomas (PGLs) arise in sympathetic ganglia (previously called extra-adrenal PCs) or in non-chromaffin parasympathetic ganglia cells that are usually non-secretory. Parenchymal cells from these tumours have a common embryological origin from neural crest ectoderm. Several case series of canine PCs and PGLs have been published and a link between the increased incidence of chemoreceptor neoplasia in brachycephalic dog breeds and chronic hypoxia has been postulated. A similar link to hypoxia in man led to the identification of germline heterozygous mutations in the gene encoding succinate dehydrogenase subunit D (SDHD) and subsequently SDHA, SDHB and SDHC in similar tumours. We investigated canine PCs (n = 6) and PGLs (n = 2) for SDHD and SDHB mutations and in one PGL found a somatic SDHD mutation c.365A>G (p.Lys122Arg) in exon 4, which was not present in normal tissue from this brachycephalic dog. Two PCs were heterozygous for both c.365A>G (p.Lys122Arg) mutation and an exon 3 silent variant c.291G>A. We also identified the heterozygous SDHB exon 2 mutation c.113G>A (p.Arg38Gln) in a PC. These results illustrate that genetic mutations may underlie tumourigenesis in canine PCs and PGLs. The spontaneous nature of these canine diseases and possible association of PGLs with hypoxia in brachycephalic breeds may make them an attractive model for studying the corresponding human tumours. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. A Novel Erythromycin Resistance Plasmid from Bacillus Sp. Strain HS24, Isolated from the Marine Sponge Haliclona Simulans

    PubMed Central

    Leong, Dara; Morrissey, John P.; Adams, Claire; Dobson, Alan D. W.; O’Gara, Fergal

    2014-01-01

    A better understanding of the origin and natural reservoirs of resistance determinants is fundamental to efficiently tackle antibiotic resistance. This paper reports the identification of a novel 5.8 kb erythromycin resistance plasmid, from Bacillus sp. HS24 isolated from the marine sponge Haliclona simulans. pBHS24B has a mosaic structure and carries the erythromycin resistance gene erm(T). This is the first report of an erythromycin resistance plasmid from a sponge associated bacteria and of the Erm(T) determinant in the genus Bacillus. PMID:25548909

  12. Effectiveness of Combined Therapy with Pirfenidone and Erythromycin for Unclassifiable Interstitial Pneumonia Induced by HTLV-1-associated Bronchioloalveolar Disorder (HABA)

    PubMed Central

    Yokohori, Naoko; Sato, Akitoshi; Hasegawa, Mizue; Katsura, Hideki; Hiroshima, Kenzo; Takemura, Tamiko

    2017-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus involved in the pathogenesis of adult T-cell leukemia (ATL) and HTVL-1-associated bronchioloalveolar disorder (HABA). The clinical and pathological findings of HABA have been characterized as either a diffuse panbronchiolitis (DPB) pattern or idiopathic interstitial pneumonia (IIP) pattern. Treatments for HABA include corticosteroids for the IIP pattern and erythromycin for the DPB pattern. We herein report a case of HABA-associated unclassifiable interstitial pneumonia that improved with combined therapy with pirfenidone and erythromycin. This is the first report on the effectiveness of combined therapy with pirfenidone and erythromycin for HABA. PMID:28050003

  13. SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea

    PubMed Central

    2013-01-01

    Background Erythromycin is a medically important antibiotic, biosynthesized by the actinomycete Saccharopolyspora erythraea. Genes encoding erythromycin biosynthesis are organized in a gene cluster, spanning over 60 kbp of DNA. Most often, gene clusters encoding biosynthesis of secondary metabolites contain regulatory genes. In contrast, the erythromycin gene cluster does not contain regulatory genes and regulation of its biosynthesis has therefore remained poorly understood, which has for a long time limited genetic engineering approaches for erythromycin yield improvement. Results We used a comparative proteomic approach to screen for potential regulatory proteins involved in erythromycin biosynthesis. We have identified a putative regulatory protein SACE_5599 which shows significantly higher levels of expression in an erythromycin high-producing strain, compared to the wild type S. erythraea strain. SACE_5599 is a member of an uncharacterized family of putative regulatory genes, located in several actinomycete biosynthetic gene clusters. Importantly, increased expression of SACE_5599 was observed in the complex fermentation medium and at controlled bioprocess conditions, simulating a high-yield industrial fermentation process in the bioreactor. Inactivation of SACE_5599 in the high-producing strain significantly reduced erythromycin yield, in addition to drastically decreasing sporulation intensity of the SACE_5599-inactivated strains when cultivated on ABSM4 agar medium. In contrast, constitutive overexpression of SACE_5599 in the wild type NRRL23338 strain resulted in an increase of erythromycin yield by 32%. Similar yield increase was also observed when we overexpressed the bldD gene, a previously identified regulator of erythromycin biosynthesis, thereby for the first time revealing its potential for improving erythromycin biosynthesis. Conclusions SACE_5599 is the second putative regulatory gene to be identified in S. erythraea which has positive influence

  14. Studies on the interaction of fermentation and microfiltration operations: erythromycin recovery from Saccharopolyspora erythraea fermentation broths.

    PubMed

    Davies, J L; Baganz, F; Ison, A P; Lye, G J

    2000-08-20

    Changes in fermentation media not only affect the performance of the fermentation itself (with regard to the kinetics of biomass and product formation and the yields obtained) but also the initial product-recovery operations downstream of the fermentor. In this work, microfiltration experiments to remove Saccharopolyspora erythraea biomass from fermentation broth and to recover erythromycin were carried out using two fundamentally different media; a soluble complex medium (SCM) and an oil-based process medium (OBM). Small-scale batch fermentations of 14-L working volume were carried out in triplicate using both media. Broth samples were taken from each fermentation at regular intervals from the end of the exponential-growth phase onwards. These were then processed using a Minitan II (acrylic), tangential crossflow-filtration module, fitted with a single 60 cm(2) Durapore hydrophilic 0.2 microm membrane, operated in concentration mode. The OBM fermentations produced higher titers of erythromycin but required longer fermentation times due to increased lag phases and slower maximum-growth rates. The OBM also increased the loading on the membrane; at maximum product titers residual oil concentrations of 3 g. L(-1), antifoam concentrations of 2 g. L(-1) and flour concentrations estimated at approximately 10 g/L(-1) were typical. It was found that both the permeate flux and erythromycin transmission were affected by the choice of medium. The OBM had significantly lower values for both parameters (12.8 Lm(-2) h(-1) and 89.6% respectively) than the SCM (35.9 Lm(-2) h(-1) and 96.7% respectively) when the fermentations were harvested at maximum erythromycin titers. Transmission of erythromycin stayed approximately constant as a function of fermentation time for both media, however, for the OBM the permeate flux decreased with time which correlated with an increase in broth viscosity. The relatively poor microfiltration performance of the OBM medium was, however, offset by

  15. A novel organic nonlinear optical crystal: Creatininium succinate

    SciTech Connect

    Thirumurugan, R.; Anitha, K.

    2015-06-24

    A novel organic material complex of creatininium succinate (CS) has been synthesized and single crystals were grown by the reaction of creatinine and succinic acid from aqueous solution by employing the technique of slow evaporation at room temperature. The structure of the grown crystal has been elucidated using single crystal X-ray diffraction analysis and the structure was refined by least-squares method to R = 0.027 for 1840 reflections. FT-IR spectral investigation has been carried out to identify the various functional groups in the title compound. UV–Vis transmission was carried out which shows the crystal has a good optical transmittance in the visible region with lower cutoff wavelength around 220 nm. Nonlinear optical property of the crystal was confirmed by Kurtz-Perry powder technique.

  16. A novel organic nonlinear optical crystal: Creatininium succinate

    NASA Astrophysics Data System (ADS)

    Thirumurugan, R.; Anitha, K.

    2015-06-01

    A novel organic material complex of creatininium succinate (CS) has been synthesized and single crystals were grown by the reaction of creatinine and succinic acid from aqueous solution by employing the technique of slow evaporation at room temperature. The structure of the grown crystal has been elucidated using single crystal X-ray diffraction analysis and the structure was refined by least-squares method to R = 0.027 for 1840 reflections. FT-IR spectral investigation has been carried out to identify the various functional groups in the title compound. UV-Vis transmission was carried out which shows the crystal has a good optical transmittance in the visible region with lower cutoff wavelength around 220 nm. Nonlinear optical property of the crystal was confirmed by Kurtz-Perry powder technique.

  17. Marked hypertriglyceridemia in a woman receiving metoprolol succinate.

    PubMed

    Kim, Yeunjung; Miller, Michael

    2014-01-01

    β-blockers are commonly used therapies after acute myocardial infarction and in the management of congestive heart failure and hypertension. We report a case of a middle-aged woman with a history of mild hypertension who was placed on metoprolol succinate. Before initiation of the β-blocker, her triglyceride level was in the borderline-high range (150-199 mg/dL). On treatment, her triglyceride levels exceeded 1000 mg/dL. She developed fatigue and mild abdominal discomfort but without biochemical evidence of pancreatitis. After discontinuation of metoprolol succinate, her triglyceride levels receded. This case illustrates an uncommon side effect with a very commonly used therapy in clinical practice. Clinicians should closely evaluate medications and/or other therapies in patients presenting with new-onset hypertriglyceridemia especially when levels are sufficiently elevated to pose increased risk of pancreatitis.

  18. Emerging Concepts in the Flavinylation of Succinate Dehydrogenase

    PubMed Central

    Kim, Hyung J.; Winge, Dennis R.

    2013-01-01

    The Succinate Dehydrogenase (SDH) heterotetrameric complex catalyzes the oxidation of succinate to fumarate in the tricarboxylic acid (TCA) cycle and in the aerobic respiratory chains of eukaryotes and bacteria. Essential in this catalysis, is the covalently-linked cofactor flavin adenine dinucleotide (FAD) in subunit1 (Sdh1) of the SDH enzyme complex. The mechanism of FAD insertion and covalent attachment to Sdh1 is unknown. Our working concept of this flavinylation process has relied mostly on foundational works from the 1990s ago and by applying the principles learned from other enzymes containing a similarly linked FAD. The discovery of the flavinylation factor Sdh5, however, has provided new insight into the possible mechanism associated with Sdh1 flavinylation, bringing into question the autocatalytic mechanism associated with other flavoenzymes. This review focuses on encapsulating prior and recent advances towards understanding the mechanism associated with flavinylation of Sdh1 and how this flavinylation process affects the overall assembly of SDH. PMID:23380393

  19. [Comparative study of the influence of succinate-containing preparations on mitochondrial respiration in rat brain cells].

    PubMed

    Iasnetsov, V V; Prosvirova, E P; Tsublova, E G

    2012-01-01

    It has been established by polarographic measurements that preparations containing succinate, such as cytoflavin (0.85 mM succinate), mexidol, and amtizol succinate (at a concentration of 0.85 mM) but not reamberin (0.045 mM succinate), nearly equally (by 35-45%) increase oxygen consumption in rat brain mitochondria. On the other hand, malonate - inhibitor of the respiratory complex II (succinate dehydrogenase) of mitochondrial chain suppressed the stimulating effect of these drugs.

  20. 21 CFR 573.420 - Ethyl cellulose.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.420 Ethyl cellulose. The food additive ethyl cellulose may be safely used in animal feed in accordance with the following prescribed conditions: (a) The food additive is a cellulose ether containing...

  1. 21 CFR 573.420 - Ethyl cellulose.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.420 Ethyl cellulose. The food additive ethyl cellulose may be safely used in animal feed in accordance with the following prescribed conditions: (a) The food additive is a cellulose ether containing...

  2. 21 CFR 573.420 - Ethyl cellulose.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.420 Ethyl cellulose. The food additive ethyl cellulose may be safely used in animal feed in accordance with the following prescribed conditions: (a) The food additive is a cellulose ether containing...

  3. 21 CFR 573.420 - Ethyl cellulose.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.420 Ethyl cellulose. The food additive ethyl cellulose may be safely used in animal feed in accordance with the following prescribed conditions: (a) The food additive is a cellulose ether containing...

  4. 27 CFR 21.108 - Ethyl ether.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Ethyl ether. 21.108 Section 21.108 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT....108 Ethyl ether. (a) Odor. Characteristic odor. (b) Specific gravity at 15.56 °/15.56 °C. Not...

  5. Formulation and evaluation of sublingual tablets containing Sumatriptan succinate

    PubMed Central

    Prajapati, Shailesh T; Patel, Parth B; Patel, Chhagan N

    2012-01-01

    Objective: Sumatriptan succinate is a selective 5-hydroxytryptamine-1 receptor agonist effective in the acute treatment of migraine headaches, having low bioavailability of about 15% orally due to first-pass metabolism. The purpose of this research was to mask the intensely bitter taste of Sumatriptan succinate and to formulate fast-acting, taste-masked sublingual tablet formulation. Materials and Methods: Taste masking was performed by solid dispersion method with mannitol and ion exchange with Kyron T 114 because it releases the drug in salivary pH. The resultant batches were evaluated for in-vivo taste masking as well compatability study (Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC)). For a better feel in the mouth, menthol and sweetener Na saccharine were added to the tablet formulation. The tablets were prepared by direct compression and evaluated for weight variation, thickness, friability, drug content, hardness, disintegration time, wetting time, in vitro drug release, and in vitro permeation study. Results and Discussion: Optimized batches disintegrated in vitro within 28-34 s. Maximum drug release could be achieved with in 10 min for the solid dispersion batches and 14-15 min for the ion-exchange batches with Kyron T 114. The optimized tablet formulation showed better taste and the formulated sublingual tablets may act as a potential alternate for the Sumatriptan succinate oral tablet. Conclusion: Sumatriptan succinate can be successfully taste-masked by both the solid dispersion method using mannitol by the melting method and Ion exchange resin with Kyron T114. It was also concluded that prepared formulation improve bioavailability by prevention of first pass metabolism. PMID:23373008

  6. Focally perfused succinate potentiates brain metabolism in head injury patients.

    PubMed

    Jalloh, Ibrahim; Helmy, Adel; Howe, Duncan J; Shannon, Richard J; Grice, Peter; Mason, Andrew; Gallagher, Clare N; Stovell, Matthew G; van der Heide, Susan; Murphy, Michael P; Pickard, John D; Menon, David K; Carpenter, T Adrian; Hutchinson, Peter J; Carpenter, Keri Lh

    2016-01-01

    Following traumatic brain injury, complex cerebral energy perturbations occur. Correlating with unfavourable outcome, high brain extracellular lactate/pyruvate ratio suggests hypoxic metabolism and/or mitochondrial dysfunction. We investigated whether focal administration of succinate, a tricarboxylic acid cycle intermediate interacting directly with the mitochondrial electron transport chain, could improve cerebral metabolism. Microdialysis perfused disodium 2,3-(13)C2 succinate (12 mmol/L) for 24 h into nine sedated traumatic brain injury patients' brains, with simultaneous microdialysate collection for ISCUS analysis of energy metabolism biomarkers (nine patients) and nuclear magnetic resonance of (13)C-labelled metabolites (six patients). Metabolites 2,3-(13)C2 malate and 2,3-(13)C2 glutamine indicated tricarboxylic acid cycle metabolism, and 2,3-(13)C2 lactate suggested tricarboxylic acid cycle spinout of pyruvate (by malic enzyme or phosphoenolpyruvate carboxykinase and pyruvate kinase), then lactate dehydrogenase-mediated conversion to lactate. Versus baseline, succinate perfusion significantly decreased lactate/pyruvate ratio (p = 0.015), mean difference -12%, due to increased pyruvate concentration (+17%); lactate changed little (-3%); concentrations decreased for glutamate (-43%) (p = 0.018) and glucose (-15%) (p = 0.038). Lower lactate/pyruvate ratio suggests better redox status: cytosolic NADH recycled to NAD(+) by mitochondrial shuttles (malate-aspartate and/or glycerol 3-phosphate), diminishing lactate dehydrogenase-mediated pyruvate-to-lactate conversion, and lowering glutamate. Glucose decrease suggests improved utilisation. Direct tricarboxylic acid cycle supplementation with 2,3-(13)C2 succinate improved human traumatic brain injury brain chemistry, indicated by biomarkers and (13)C-labelling patterns in metabolites.

  7. [The research progress of succinic acid fermentation strains].

    PubMed

    Wang, Qing-Zhao; Zhao, Xue-Ming

    2007-07-01

    The potential of succinic acid as an important chemical intermediates had been realized and fermentation is one of the best ways to make it possible in economical aspect. Fermentation organism is the key part of the fermentation method. The updated research developments of fermentation organisms and the fermentation characteristics and problems of them were reviewed and analyzed in this paper. Finally,the development future of fermenation organism was forecasted.

  8. Cell-permeable succinate prodrugs bypass mitochondrial complex I deficiency

    PubMed Central

    Ehinger, Johannes K.; Piel, Sarah; Ford, Rhonan; Karlsson, Michael; Sjövall, Fredrik; Frostner, Eleonor Åsander; Morota, Saori; Taylor, Robert W.; Turnbull, Doug M.; Cornell, Clive; Moss, Steven J.; Metzsch, Carsten; Hansson, Magnus J.; Fliri, Hans; Elmér, Eskil

    2016-01-01

    Mitochondrial complex I (CI) deficiency is the most prevalent defect in the respiratory chain in paediatric mitochondrial disease. This heterogeneous group of diseases includes serious or fatal neurological presentations such as Leigh syndrome and there are very limited evidence-based treatment options available. Here we describe that cell membrane-permeable prodrugs of the complex II substrate succinate increase ATP-linked mitochondrial respiration in CI-deficient human blood cells, fibroblasts and heart fibres. Lactate accumulation in platelets due to rotenone-induced CI inhibition is reversed and rotenone-induced increase in lactate:pyruvate ratio in white blood cells is alleviated. Metabolomic analyses demonstrate delivery and metabolism of [13C]succinate. In Leigh syndrome patient fibroblasts, with a recessive NDUFS2 mutation, respiration and spare respiratory capacity are increased by prodrug administration. We conclude that prodrug-delivered succinate bypasses CI and supports electron transport, membrane potential and ATP production. This strategy offers a potential future therapy for metabolic decompensation due to mitochondrial CI dysfunction. PMID:27502960

  9. Atypical features of Thermus thermophilus succinate:quinone reductase.

    PubMed

    Kolaj-Robin, Olga; Noor, Mohamed R; O'Kane, Sarah R; Baymann, Frauke; Soulimane, Tewfik

    2013-01-01

    The Thermus thermophilus succinate:quinone reductase (SQR), serving as the respiratory complex II, has been homologously produced under the control of a constitutive promoter and subsequently purified. The detailed biochemical characterization of the resulting wild type (wt-rcII) and His-tagged (rcII-His(8)-SdhB and rcII-SdhB-His(6)) complex II variants showed the same properties as the native enzyme with respect to the subunit composition, redox cofactor content and sensitivity to the inhibitors malonate, oxaloacetate, 3-nitropropionic acid and nonyl-4-hydroxyquinoline-N-oxide (NQNO). The position of the His-tag determined whether the enzyme retained its native trimeric conformation or whether it was present in a monomeric form. Only the trimer exhibited positive cooperativity at high temperatures. The EPR signal of the [2Fe-2S] cluster was sensitive to the presence of substrate and showed an increased rhombicity in the presence of succinate in the native and in all recombinant forms of the enzyme. The detailed analysis of the shape of this signal as a function of pH, substrate concentration and in the presence of various inhibitors and quinones is presented, leading to a model for the molecular mechanism that underlies the influence of succinate on the rhombicity of the EPR signal of the proximal iron-sulfur cluster.

  10. The Electrospray Ionization - Mass Spectra of Erythromycin A Obtained from a Marine Streptomyces sp. Mutant

    PubMed Central

    El-Bondkly, A. M.; Abd-Alla, Howaida I.; Shaaban, M.; Shaaban, K. A.

    2008-01-01

    In our ongoing search for production improvements of bioactive secondary metabolites from marine Streptomyces through the induction of mutations using UV light, out of 145 isolates, mutant 10/14 was able to produce potent antibacterial metabolites other than the parent strain as established by chromatographic analysis. Up-scaling fermentation of mutant 10/14, followed by working up and isolation delivered five metabolites, phenazine, 1-acetyl-β -carboline, perlolyrin and erythromycin A, along with an oily substance. The latter two compounds were responsible for the antibacterial activity of the strain. In this article, we discuss with the mutation of the marine Streptomyces sp. AH2, bioactivity evaluation, fermentation and isolation of the microbial metabolites. Moreover, we study to first time in detail the 1D and 2D NMR and ESI MS data including ESI MS2 and MS3 patterns combined with HRESI MS of erythromycin A. PMID:20046738

  11. Flow cytometric assessment of susceptibilities of Streptococcus pyogenes to erythromycin and rokitamycin.

    PubMed

    Braga, Pier Carlo; Bovio, Cinzia; Culici, Maria; Dal Sasso, Monica

    2003-01-01

    The effects of erythromycin (a 14-membered ring macrolide) and rokitamycin (a 16-membered ring macrolide) on the viability of the Streptococcus pyogenes M phenotype were studied by means of flow cytometry and fluorescence microscopy by using a combination of two fluorochromes (syto 9 and propidium iodide) that stains live bacteria green and dead bacteria red. In order to apply the flow cytometry, a bacterial sonication procedure was expressly set up to separate single cells from the long, intralaced S. pyogenes chains of up to 30 to 40 cells that have previously prevented the application of flow cytometry to this type of bacteria. The association of flow cytometry using an appropriate sonication procedure, together with a combination of fluorescent probes, offered the possibility of very quickly investigating the different microbiological effects of rokitamycin at 2 microg/ml, which was active on the S. pyogenes M phenotype, and of erythromycin at doses of up to 32 microg/ml, which was not.

  12. Differential modulation of cytokine production by macrolides: interleukin-6 production is increased by spiramycin and erythromycin.

    PubMed Central

    Bailly, S; Pocidalo, J J; Fay, M; Gougerot-Pocidalo, M A

    1991-01-01

    Antibiotics do not act alone but act in conjunction with the host defense system. In particular, it has been shown that some antibiotics can modify cytokine production. We compared the in vitro effects of three macrolides (roxithromycin, spiramycin, and erythromycin) actively concentrated by leukocytes on interleukin-1 alpha, (IL-1 alpha), IL-1 beta, IL-6, and tumor necrosis factor alpha production by human monocytes stimulated with lipopolysaccharide. Our results show that the three macrolides tested have different effects on production of these cytokines. Spiramycin and, to a lesser extent, erythromycin increased total IL-6 production without affecting IL-1 alpha, IL-1 beta, or tumor necrosis factor alpha production, whereas roxithromycin had no effect. To our knowledge, this is the first time that an antibiotic has been shown to increase IL-6 production. PMID:1759822

  13. Random transposon mutagenesis of the Saccharopolyspora erythraea genome reveals additional genes influencing erythromycin biosynthesis

    PubMed Central

    Fedashchin, Andrij; Cernota, William H.; Gonzalez, Melissa C.; Leach, Benjamin I.; Kwan, Noelle; Wesley, Roy K.; Weber, J. Mark

    2015-01-01

    A single cycle of strain improvement was performed in Saccharopolyspora erythraea mutB and 15 genotypes influencing erythromycin production were found. Genotypes generated by transposon mutagenesis appeared in the screen at a frequency of ∼3%. Mutations affecting central metabolism and regulatory genes were found, as well as hydrolases, peptidases, glycosyl transferases and unknown genes. Only one mutant retained high erythromycin production when scaled-up from micro-agar plug fermentations to shake flasks. This mutant had a knockout of the cwh1 gene (SACE_1598), encoding a cell-wall-associated hydrolase. The cwh1 knockout produced visible growth and morphological defects on solid medium. This study demonstrated that random transposon mutagenesis uncovers strain improvement-related genes potentially useful for strain engineering. PMID:26468041

  14. Integration of succinic acid and ethanol production with potential application in a corn or barley biorefinery.

    PubMed

    Nghiem, Nhuan P; Hicks, Kevin B; Johnston, David B

    2010-11-01

    Production of succinic acid from glucose by Escherichia coli strain AFP184 was studied in a batch fermentor. The bases used for pH control included NaOH, KOH, NH(4)OH, and Na(2)CO(3). The yield of succinic acid without and with carbon dioxide supplied by an adjacent ethanol fermentor using either corn or barley as feedstock was examined. The carbon dioxide gas from the ethanol fermentor was sparged directly into the liquid media in the succinic acid fermentor without any pretreatment. Without the CO(2) supplement, the highest succinic acid yield was observed with Na(2)CO(3), followed by NH(4)OH, and lowest with the other two bases. When the CO(2) produced in the ethanol fermentation was sparged into the media in the succinic acid fermentor, no improvement of succinic acid yield was observed with Na(2)CO(3). However, several-fold increases in succinic acid yield were observed with the other bases, with NH(4)OH giving the highest yield increase. The yield of succinic acid with CO(2) supplement from the ethanol fermentor when NH(4)OH was used for pH control was equal to that obtained when Na(2)CO(3) was used, with or without CO(2) supplementation. The benefit of sparging CO(2) from ethanol fermentation on the yield of succinic acid demonstrated the feasibility of integration of succinic acid fermentation with ethanol fermentation in a biorefinery for production of fuels and industrial chemicals.

  15. Menaquinone-dependent succinate dehydrogenase of bacteria catalyzes reversed electron transport driven by the proton potential.

    PubMed

    Schirawski, J; Unden, G

    1998-10-01

    Succinate dehydrogenases from bacteria and archaea using menaquinone (MK) as an electron acceptor (succinate/menaquinone oxidoreductases) contain, or are predicted to contain, two heme-B groups in the membrane-anchoring protein(s), located close to opposite sides of the membrane. All succinate/ubiquinone oxidoreductases, however, contain only one heme-B molecule. In Bacillus subtilis and other bacteria that use MK as the respiratory quinone, the succinate oxidase activity (succinate-->O2), and the succinate/menaquinone oxidoreductase activity were specifically inhibited by uncoupler (CCCP, carbonyl cyanide m-chlorophenylhydrazone) or by agents dissipating the membrane potential (valinomycin). Other parts of the respiratory chains were not affected by the agents. Succinate oxidase or succinate/ubiquinone oxidoreductase from bacteria using ubiquinone as an acceptor were not inhibited. We propose that the endergonic electron transport from succinate (Eo' = +30 mV) to MK (Eo' approximately/= -80 mV) in succinate/menaquinone oxidoreductase includes a reversed electron transport across the cytoplasmic membrane from the inner (negative) to the outer (positive) side via the two heme-B groups. The reversed electron transport is driven by the proton or electrical potential, which provides the driving force for MK reduction.

  16. What causes decreased erythromycin resistance in Streptococcus pyogenes? Dynamics of four clones in a southern European region from 2005 to 2012.

    PubMed

    Montes, Milagrosa; Tamayo, Esther; Mojica, Catalina; García-Arenzana, José M; Esnal, Olatz; Pérez-Trallero, Emilio

    2014-06-01

    To survey antibiotic resistance among Streptococcus pyogenes isolates collected from 2005 to 2012, to characterize those showing erythromycin resistance and to analyse the association of certain emm types with erythromycin resistance or susceptibility. Resistance determinants or mutations conferring erythromycin, clindamycin, tetracycline and fluoroquinolone resistance were analysed. All erythromycin-resistant isolates and a sample of erythromycin-susceptible isolates were emm typed. Multilocus sequence typing was performed for representative emm types. Antimicrobial susceptibility was studied for 12 346 S. pyogenes isolates. Erythromycin, clindamycin and tetracycline resistance showed a decreasing trend. In 2012, 2.8% of isolates were erythromycin resistant versus 7.5% in 2005 and 11.7% in 2006. Although 21 clones were involved, 4 clones accounted for almost 90% of erythromycin-resistant isolates. The emm12/ST36 clone, carrying the mef(A) gene, was the predominant (41.1%) erythromycin-resistant clone, with an incidence peak in 2008, followed by a gradual decline. The M phenotype predominated each year except for 2005, when two of the main erythromycin-resistant clones (emm11/ST403 and emm28/ST52) harboured an erm(B) gene. Erythromycin resistance was significantly higher in adults than in children. Skin isolates showed the highest erythromycin resistance rate; among these, perianal isolates frequently belonged to the emm28/ST52 clone. The emm type was not a predictor of erythromycin resistance; however, most emm11 and emm12 were erythromycin-resistant isolates. Macrolide consumption was similar throughout the study period. Only two isolates with a high level of levofloxacin resistance were detected. Resistance was mainly related to the circulation of emm12/ST36, emm11/ST403, emm28/ST52 and emm4/ST39 clones, all of which declined throughout the study period. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial

  17. Systemic exposure of topical erythromycin in comparison to oral administration and the effect on cytochrome P450 3A4 activity

    PubMed Central

    Carls, Alexandra; Jedamzik, Julia; Witt, Lukas; Hohmann, Nicolas; Burhenne, Juergen; Mikus, Gerd

    2014-01-01

    Aims Erythromycin is a macrolide antibiotic, which is frequently used as a topical formulation for the treatment of acne. It is also known as an inhibitor of the cytochrome P450 (CYP) isoenzyme 3A4. In this study, the systemic availability of topical erythromycin, hence the influence on the activity of CYP3A, is evaluated in comparison to orally administered erythromycin. Methods Sixteen healthy volunteers received consecutively topical (two applications of 800 mg) and oral erythromycin (two dose groups, 250 and 1000 mg, with n = 8) to assess erythromycin pharmacokinetics. A microdose of midazolam (3 μg orally) was used to determine the effect on CYP3A activity. Results After topical administration, erythromycin was detected in the plasma of every participant without causing a statistically significant alteration of CYP3A activity. After oral administration, the dose-normalized erythromycin exposure (AUC∞) was 1335 h ng ml−1 after 250 mg and 3-fold higher after the 1000 mg dose (4051 h ng ml−1; P < 0.01), suggesting nonlinear pharmacokinetics of erythromycin. Both oral doses inhibited CYP3A activity; midazolam clearance was decreased to 61% (250 mg) and 21% (1000 mg). The relationship between erythromycin exposure and CYP3A activity (Hill equation) revealed a 50% reduction of CYP3A activity by an erythromycin AUC∞ of 2106 h ng ml−1. Conclusions Topical erythromycin did not cause clinically relevant CYP3A alterations, although low systemic availability of erythromycin was observed. This supports the assumption that treatment with topical erythromycin is not critical in terms of CYP3A inhibition. Furthermore, substantial nonlinearity of erythromycin pharmacokinetics after two different oral doses was observed, possibly due to autoinhibition. PMID:25139487

  18. Development of pH sensitive polymeric nanoparticles of erythromycin stearate

    PubMed Central

    Bhadra, Sulekha; Prajapati, Atin B.; Bhadra, Dipankar

    2016-01-01

    Context: Bioavailability of conventional tablet of erythromycin stearate is low as it is unstable at acidic pH and also shows a low dissolution rate. Objective: It was proposed to protect it from the acidic condition of the stomach along with an increase in dissolution rate by formulating pH sensitive nanoparticles. Materials and Methods: The nanoparticles were prepared by the solvent evaporation technique using different quantities of Eudragit L100-55 and polyvinyl alcohol (PVA). Size reduction was achieved by high speed homogenization technique using Digital Ultra Turrax homogenizer. The formulation was optimized using 32 factorial design, keeping drug polymer ratio and surfactant concentration as independent variables. Particle size, entrapment efficiency, and drug-release (DR) were studied as dependent variables. Results: Optimized batch containing 1:0.3 erythromycin stearate: Eudragit L100-55 ratio and 1.0% PVA showed 8.24 ± 0.71% DR in pH 1.2 in 1-h and 90.38 ± 5.97% in pH 5.5 and pH 6.8 within 2-h, respectively. Discussion: The optimized batch exhibited lower release in acidic pH and faster release in higher pH compared to the marketed preparation. Conclusion: Thus the present study concludes that pH sensitive nanoparticles of erythromycin stearate increases the dissolution of the drug in intestinal pH and also protect it from acidic pH, which may help in improving the bioavailability of erythromycin. PMID:27134466

  19. High rates of erythromycin and clindamycin resistance among OBGYN isolates of group B Streptococcus.

    PubMed

    DiPersio, Linda P; DiPersio, Joseph R

    2006-01-01

    In vitro susceptibility testing on 200 Streptococcus agalactiae strains isolated during a 4-year period from vaginal/rectal specimens demonstrated a very high resistance rate for both erythromycin (54%) and clindamycin (33%). Methylase genes erm(B) and erm(TR) and efflux genes mef(E) and mef(A) were detected. Pulsed-field gel electrophoresis showed evidence of both clonal spread and multiclonal dissemination of resistant strains. All but 3 of 200 isolates were susceptible to telithromycin.

  20. Recent advances in the medicinal chemistry of novel erythromycin-derivatized antibiotics.

    PubMed

    Ying, Lu; Tang, Datong

    2010-01-01

    Development of novel erythromycin-based antibiotics has been one of the most studied topics in the past three decades. Such tremendous efforts have generated a number of beneficiary drugs such as clarithromycin, azithromycin and telithromycin. However, widespread application of antibiotics in clinical practice has triggered an increasing emergence of bacterial resistance. Therefore, discovery of novel macrolide antibiotics to suppress the resistance is urgent for human healthcare. This review focuses on advances in the area since 2004.

  1. Erythromycin enhances the anti-inflammatory activity of budesonide in COPD rat model.

    PubMed

    Miao, Lijun; Gao, Zengyan; Huang, Fengxiang; Huang, Shifu; Zhang, Ruixia; Ma, Dongbo; Wu, Qiuge; Li, Fang; Chen, Hongjie; Wang, Jing

    2015-01-01

    Glucocorticoids (GCs) have been widely applied to treat patients with chronic obstructive pulmonary disease (COPD). But the effect of GCs was not ideal. This study was to observe whether erythromycin could enhance the anti-inflammatory activity of budesonide in COPD model rats and to explore the mechanism involved. In this study, male Sprague-Dawley rats were divided into five groups: healthy control group (H group), COPD model group (C group), erythromycin group (E group), budesonide group (B group) and erythromycin + budesonide group (E+B group). The rats in groups of C, E, B and E+B were developed into COPD models. Different groups were given different drug interventions. The levels of 8-iso-PGF2α, IL-8, and TNF-α in BALF and serum were measured with ELISA. The protein expression levels of HDAC2, PI3K, and p-AKT in lung tissue were measured with Western-blot and immunohistochemistry. The levels of 8-iso-PGF2α, IL-8, and TNF-α in BALF and serum were lower in E+B group than those in B group and C group (all P<0.001).The protein expression level of HDAC2 was higher and PI3K and p-AKT were lower in E+B group than those in B group and C group (all P<0.001). Moreover, the expression levels of HDAC2 were negatively correlated with the levels of 8-iso-PGF2α, IL-8 and TNF-α both in serum and BALF and the expression levels of PI3K and p-AKT among the five groups, with all P<0.001. We conclude that erythromycin can enhance the anti-inflammatory activity of budesonide in COPD model rats, possibly through inhibiting the PI3K/AKT pathway and enhancing the activity of HDAC2.

  2. Formation and inhibition of ethyl glucuronide and ethyl sulfate.

    PubMed

    Stachel, Nicole; Skopp, Gisela

    2016-08-01

    Ethyl glucuronide (EtG) und ethyl sulfate (EtS) are widely accepted biomarkers in forensic and clinical settings. Even though, levels of EtG and EtS in blood and urine increase with increasing doses of alcohol, a high inter-individual variability in their production has been noticed. Therefore, we investigated the influence of dietary plant phenols on the formation of EtG and EtS and tentatively estimated the magnitude of in vivo inhibitory interactions from our in vitro results. To address these issues, formation of EtS and EtG was investigated using recombinant glucuronosyl- and sulfotransferases as well as human liver microsomes and liver cytosol. After respective kinetics had been established, inhibition experiments using quercetin, kaempferol and resveratrol were performed. These polyphenols are subject to extensive glucuronidation and/or sulfonation. EtG and EtS were determined by LC-MS/MS following solid phase extraction for EtG due to severe matrix effects and by direct injection for EtS. All enzymes investigated were involved in the conjugation of ethanol. Maximal EtG and EtS formation rates were observed with HLM and SULT1A1, respectively. All kinetics could best be described by Michaelis-Menten kinetics. Resveratrol was a competitive inhibitor of UGT1A1, UGT1A9 and HLM; quercetin and kaempferol were inhibitors of all transferases under investigation except UGT2B15. Findings for quercetin with regard to UGT2B7 and SULT2A1 and for kaempferol with regard to SULT1E1 and SULT2A1 suggested a mechanism based inhibition. Competitive inhibition of the glucuronidation and sulfonation of ethanol was estimated as weak to negligible and as moderate to weak, respectively. Beside the known polymorphisms of the transferases involved in EtG and EtS formation, prediction of the inhibitory potential indicates that polyphenols may contribute to the variable formation rate of EtG and EtS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Organic extracts from Indigofera suffruticosa leaves have antimicrobial and synergic actions with erythromycin against Staphylococcus aureus

    PubMed Central

    Bezerra dos Santos, Ana Thereza; Araújo, Tiago Ferreira da Silva; Nascimento da Silva, Luis Cláudio; da Silva, Cleideana Bezerra; de Oliveira, Antonio Fernando Morais; Araújo, Janete Magali; Correia, Maria Tereza dos Santos; Lima, Vera Lúcia de Menezes

    2015-01-01

    A characteristic feature of Staphylococcus aureus is its ability to acquire resistance to antimicrobial agents. There is a need, therefore, for new approaches to combat this pathogen; for example, employing a combination of plant-derived products and antibiotics to overcome bacterial resistance. Indigofera suffruticosa is a plant popularly used to treat infections and has verified antimicrobial action. Here, we investigate the antimicrobial activity of different extracts from I. suffruticosa against S. aureus and their synergistic effects with erythromycin. Leaves of I. suffruticosa were extracted sequentially using diethyl ether, chloroform and acetone and the antimicrobial activity of each extract then tested against nine clinical isolates of S. aureus. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined by microdilution tests, while the fractional inhibitory concentration (FIC) was assessed by checkerboard assay. All organic solvent extracts showed antimicrobial activity against S. aureus strains. The acetone extract was the most potent inhibitor of S. aureus (MIC and MBC of 0.78 and 3.12 mg/mL), followed by the chloroform extract (MIC and MBC of 3.12 and 6.25 mg/mL). Furthermore, acetone or chloroform extracts of I. suffruticosa enhanced the activity of erythromycin against S. aureus (FIC ≤ 0.5). We conclude that organic extracts from leaves of I. suffruticosa, alone or combined with erythromycin, are promising natural products for the development of new anti-S. aureus formulations. PMID:25699022

  4. The joint acute effect of tetracycline, erythromycin and sulfamethoxazole on acetoclastic methanogens.

    PubMed

    Aydın, Sevcan; Ince, Bahar; Ince, Orhan

    2015-01-01

    In this study, we aimed to develop an understanding of the triple effects of sulfamethoxazole-erythromycin-tetracycline (ETS) and the dual effects of sulfamethoxazole-tetracycline (ST), erythromycin-sulfamethoxazole (ES) and erythromycin-tetracycline (ET) on the anaerobic treatment of pharmaceutical industry wastewater throughout a year of operation. Concentrations of the antibiotics in the influent were gradually increased until the metabolic collapse of the anaerobic sequencing batch reactors (SBRs), which corresponded to ETS (40 + 3 + 3 mg/L) and ST (25 + 2.5 mg/L), ET (4 + 4 mg/L) and ES (3 + 40 mg/L). Acetate accumulation in the anaerobic SBRs, acetoclastic activity of the anaerobic sludge taken from different antibiotic feeding stages and also expression of acetyl-coA synthetase from the acetoclastic methanogenic pathway on the mRNA level were assessed. The results indicated that, while acetate accumulation and decrease of acetoclastic activity were observed after stage 3 in the ST and ES reactors, and stage 7 in the ETS and ET reactors, the expression of acetyl-coA synthetase was mostly decreased in the last stages in all SBRs, in which antibiotic mixture feeding was terminated. It might be speculated that acetoclastic methanogens have an important role in acetate degradation by expressing acetyl-coA synthetase.

  5. A Case of Fixed Drug Eruption Due to Doxycycline and Erythromycin Present in Food

    PubMed Central

    Lim, Won-Suk; Kim, Do-Hun; Jin, Sang-Yun; Choi, Yun-Seok; Lee, Seung-Ho; Huh, Hee-Jin; Chae, Seok-Lae

    2013-01-01

    A fixed drug eruption (FDE) is not difficult to diagnose, given its clinical characteristics. However, the causative agent can be difficult to identify, particularly when the patient denies ingestion of any drugs. To the best of our knowledge, we present herein the first reported case of an FDE caused by antibiotics taken in food; doxycycline and erythromycin contained in pork and fish. A 57-year-old female experienced repeated episodes of well-demarcated erythematous patches covering her entire body. She denied taking any medications, but she thought that the lesions appeared after consuming pork and/or fish. An oral provocation test showed positive results for doxycycline and erythromycin, commonly used antibiotics in live-stock farming and in the fishing industry. Because of the antibiotics' thermostability, cooking does not guarantee the elimination of residual drugs. From the patient's history, we concluded that doxycycline and erythromycin contained in the pork and fish that she ate were the cause of the FDE. PMID:24003392

  6. emm Gene distribution among erythromycin-resistant and -susceptible Italian isolates of Streptococcus pyogenes.

    PubMed

    Zampaloni, Claudia; Cappelletti, Paola; Prenna, Manuela; Vitali, Luca Agostino; Ripa, Sandro

    2003-03-01

    The phenotypes and genetic determinants for macrolide resistance were determined for 167 erythromycin-resistant Streptococcus pyogenes strains. A cMLS phenotype was shown in 18% of the erythromycin-resistant strains, while inducible resistance was apparent in 31% and the M phenotype was apparent in 50%. The emm gene type of this set of resistant isolates and that of 48 erythromycin-sensitive isolates were determined. emm2 and emm48 were recorded only in the resistant strains of the M phenotype, while approximately all of the strains harboring the emm22 gene had the cMLS phenotype. More than 80% of the emm89-positive strains had the iMLS phenotype, and the same portion of emm4 strains presented the M phenotype. emm3 is recorded only among sensitive strains. The distribution of frequencies of the genetic determinant for the virulence factor M protein was significantly different both among organisms of different types of resistance and between resistant and sensitive populations of S. pyogenes under study.

  7. emm Gene Distribution among Erythromycin-Resistant and -Susceptible Italian Isolates of Streptococcus pyogenes

    PubMed Central

    Zampaloni, Claudia; Cappelletti, Paola; Prenna, Manuela; Vitali, Luca Agostino; Ripa, Sandro

    2003-01-01

    The phenotypes and genetic determinants for macrolide resistance were determined for 167 erythromycin-resistant Streptococcus pyogenes strains. A cMLS phenotype was shown in 18% of the erythromycin-resistant strains, while inducible resistance was apparent in 31% and the M phenotype was apparent in 50%. The emm gene type of this set of resistant isolates and that of 48 erythromycin-sensitive isolates were determined. emm2 and emm48 were recorded only in the resistant strains of the M phenotype, while approximately all of the strains harboring the emm22 gene had the cMLS phenotype. More than 80% of the emm89-positive strains had the iMLS phenotype, and the same portion of emm4 strains presented the M phenotype. emm3 is recorded only among sensitive strains. The distribution of frequencies of the genetic determinant for the virulence factor M protein was significantly different both among organisms of different types of resistance and between resistant and sensitive populations of S. pyogenes under study. PMID:12624074

  8. Organic extracts from Indigofera suffruticosa leaves have antimicrobial and synergic actions with erythromycin against Staphylococcus aureus.

    PubMed

    Bezerra Dos Santos, Ana Thereza; Araújo, Tiago Ferreira da Silva; Nascimento da Silva, Luis Cláudio; da Silva, Cleideana Bezerra; de Oliveira, Antonio Fernando Morais; Araújo, Janete Magali; Correia, Maria Tereza Dos Santos; Lima, Vera Lúcia de Menezes

    2015-01-01

    A characteristic feature of Staphylococcus aureus is its ability to acquire resistance to antimicrobial agents. There is a need, therefore, for new approaches to combat this pathogen; for example, employing a combination of plant-derived products and antibiotics to overcome bacterial resistance. Indigofera suffruticosa is a plant popularly used to treat infections and has verified antimicrobial action. Here, we investigate the antimicrobial activity of different extracts from I. suffruticosa against S. aureus and their synergistic effects with erythromycin. Leaves of I. suffruticosa were extracted sequentially using diethyl ether, chloroform and acetone and the antimicrobial activity of each extract then tested against nine clinical isolates of S. aureus. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined by microdilution tests, while the fractional inhibitory concentration (FIC) was assessed by checkerboard assay. All organic solvent extracts showed antimicrobial activity against S. aureus strains. The acetone extract was the most potent inhibitor of S. aureus (MIC and MBC of 0.78 and 3.12 mg/mL), followed by the chloroform extract (MIC and MBC of 3.12 and 6.25 mg/mL). Furthermore, acetone or chloroform extracts of I. suffruticosa enhanced the activity of erythromycin against S. aureus (FIC ≤ 0.5). We conclude that organic extracts from leaves of I. suffruticosa, alone or combined with erythromycin, are promising natural products for the development of new anti-S. aureus formulations.

  9. Azithromycin and erythromycin ameliorate the extent of colonic damage induced by acetic acid in rats

    SciTech Connect

    Mahgoub, Afaf . E-mail: afaf_mahgoub@yahoo.com; El-Medany, Azza; Mustafa, Ali; Arafah, Maha; Moursi, Mahmoud

    2005-05-15

    Ulcerative colitis is a common inflammatory bowel disease (IBD) of unknown etiology. Recent studies have revealed the role of some microorganisms in the initiation and perpetuation of IBD. The role of antibiotics in the possible modulation of colon inflammation is still uncertain. In this study, we evaluated the effects of two macrolides, namely azithromycin and erythromycin, at different doses on the extent and severity of ulcerative colitis caused by intracolonic administration of 3% acetic acid in rats. The lesions and the inflammatory response were assessed by histology and measurement of myeloperoxidase (MPO) activity, nitric oxide synthetase (NOS) and tumor necrosis factor alpha (TNF{alpha}) in colonic tissues. Inflammation following acetic acid instillation was characterized by oedema, diffuse inflammatory cell infiltration and necrosis. Increase in MPO, NOS and TNF{alpha} was detected in the colonic tissues. Administration of either azithromycin or erythromycin at different dosage (10, 20 and 40 mg/kg orally, daily for 5 consecutive days) significantly (P < 0.05) reduced the colonic damage, MPO and NOS activities as well as TNF{alpha} level. This reduction was highly significant with azithromycin when given at a dose of 40 mg/kg. It is concluded that azithromycin and erythromycin may have a beneficial therapeutic role in ulcerative colitis.

  10. Intracellular multiplication of Legionnaires' disease bacteria (Legionella pneumophila) in human monocytes is reversibly inhibited by erythromycin and rifampin.

    PubMed Central

    Horwitz, M A; Silverstein, S C

    1983-01-01

    We have previously reported that virulent egg yolk-grown Legionella pneumophila, Philadelphia 1 strain, multiplies intracellularly in human blood monocytes and only intracellularly under tissue culture conditions. In this paper, we have investigated the effect of erythromycin and rifampin on L. pneumophila-monocyte interaction in vitro; erythromycin and rifampin are currently the drugs of choice for the treatment of Legionnaires' disease. The intracellular multiplication of L. pneumophila is inhibited by erythromycin and rifampin, as measured by colony-forming units, whether the antibiotics are added just before or just after infection of monocytes with L. pneumophila, or 2 d after infection when L. pneumophila is in the logarithmic phase of growth in monocytes. Intracellular multiplication of L. pneumophila is inhibited by 1.25 microgram/ml but not less than or equal to 0.125 microgram/ml erythromycin and 0.01 microgram/ml but not less than or equal to 0.001 microgram/ml rifampin. These concentrations of antibiotics are comparable to those that inhibit extracellular multiplication of L. pneumophila under cell-free conditions in artificial medium; the minimal inhibitory concentration is 0.37 microgram/ml for erythromycin and 0.002 microgram/ml for rifampin. Multiplication of L. pneumophila in the logarithmic phase of growth in monocytes is inhibited within 1 h of the addition of antibiotics. Intracellular bacteria inhibited from multiplying by antibiotics are not killed. By electron microscopy, the bacteria appear intact within membrane-bound vacuoles, studded with ribosomelike structures. L. pneumophila multiplying extracellularly on artificial medium is killed readily by relatively low concentrations of erythromycin and rifampin; the minimal bactericidal concentration is 1 microgram/ml for erythromycin and 0.009 microgram/ml for rifampin. In contrast, L. pneumophila multiplying intracellularly is resistant to killing by these concentrations of erythromycin and

  11. A prospective randomized controlled study of erythromycin on gastric and small intestinal distention: implications for MR enterography.

    PubMed

    Bharucha, Adil E; Fidler, Jeff L; Huprich, James E; Ratuapli, Shiva K; Holmes, David R; Riederer, Stephen J; Zinsmeister, Alan R

    2014-11-01

    To assess if erythromycin increases gastric emptying and hence improves small intestinal distention during MR enterography. Gastric, small intestinal, and large intestinal volumes were assessed with MR after neutral oral contrast (1350ml in 45min) and balanced randomization to erythromycin (200mg i.v., age 31±3y, 13 females), or placebo (37±3y, 13 females) in 40 healthy asymptomatic volunteers. Fat-suppressed T2-weighted MR images of the abdomen were acquired on a 1.5T magnet at standard delay times for enterography. Gastric, small, and large intestinal volumes were measured by specialized software. In addition, two radiologists manually measured diameters and percentage distention of jejunal and ileal loops. Treatment effects were evaluated by an ITT analysis based on ANCOVA models. All subjects tolerated erythromycin. MRI scans of the stomach and intestine were obtained at 62±2 (mean±SEM) and 74±2min respectively after starting oral contrast. Gastric volumes were lower (P<0.0001) after erythromycin (260±49ml) than placebo (688±63ml) but jejunal, ileal, and colonic volumes were not significantly different. However, maximum (76-100%) jejunal distention was more frequently observed (P=0.03) after erythromycin (8/20 subjects [40%]) than placebo (2/20 subjects [10%]). The diameter of a representative ileal loop was greater (P=0.001) after erythromycin (18.8±4.3mm) than placebo (17.3±2.8mm) infusion. After ingestion of oral contrast, erythromycin accelerated gastric emptying but effects on small intestinal dimensions were variable. In balance, erythromycin did not substantially enhance small intestinal distention during enterography using current standard delay times. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. RP 59500 prophylaxis of experimental endocarditis due to erythromycin-susceptible and -resistant isogenic pairs of viridans group streptococci.

    PubMed Central

    L'Hériteau, F; Entenza, J M; Lacassin, F; Leport, C; Glauser, M P; Moreillon, P

    1995-01-01

    RP 59500 is a new injectable streptogramin composed of two synergistic components (quinupristin and dalfopristin) which are active against a number of erythromycin-susceptible and -resistant gram-positive bacteria. The following experiments investigate the ability of RP 59500 to prevent experimental endocarditis due to either of two erythromycin-susceptible streptococcal isolates or their constitutively erythromycin-resistant Tn916 delta E transconjugants. RP 59500 had low MICs (0.125 to 0.5 mg/liter) for all four test organisms and was substantially bactericidal in vitro. Rats with catheter-induced aortic vegetations were given single-dose antibiotic prophylaxis 30 to 60 min before bacterial inoculation through a computerized pump system which permitted the simulation of drug kinetics for humans produced by either 7 mg of RP 59500 per kg of body weight or 1 g of vancomycin. Single-dose RP 59500 prophylaxis successfully prevented endocarditis due to both the erythromycin-susceptible parent strains and their erythromycin-resistant derivatives in rats challenged with the minimal inoculum infecting 90% of controls. In addition, RP 59500 also prevented infection in animals challenged with fivefold-larger inocula of the erythromycin-susceptible parent strains. Vancomycin successfully prevented endocarditis due to any of the four test organisms. These results underline the in vivo efficacy of RP 59500 against both erythromycin-susceptible and -resistant streptococci. Such good results against the resistant strains would not be expected with erythromycin or clindamycin, which are the standard macrolidelincosamide-streptogramin antibiotics used for endocarditis prophylaxis in humans. An oral form of RP 59500 which might advantageously replace some of the older prophylactic regimens is currently being developed. PMID:7492079

  13. Josamycin: interpretation of inhibition zones with the Bauer-Kirby agar disk diffusion test as compared with erythromycin.

    PubMed

    Karthein, J; Spohr, M; Traub, W H

    1986-01-01

    A total of 432 clinical isolates of Staphylococcus aureus (128), coagulase-negative staphylococci (123), group A and B beta-hemolytic streptococci (61), group D streptococci (30), Streptococcus penumoniae (29), Haemophilus influenzae (19), Haemophilus parainfluenzae (12), and Legionella pneumophila (30) were examined with the agar dilution and Bauer-Kirby agar disk diffusion tests for susceptibility to josamycin as compared with erythromycin. On a weight-for-weight basis, erythromycin was more active than josamycin against all bacterial species, including L. pneumophila. Josamycin inhibited 18 of 23 S. aureus and 11 of 16 coagulase-negative staphylococcal strains resistant to erythromycin. Utilizing minimal inhibitory concentrations (MIC) breakpoints of less than or equal to 2 micrograms/ml (sensitive), 4 microgram/ml (intermediate) and of greater than or equal to 8 micrograms/ml (resistant), and inhibition zone criteria of greater than or equal to 18 mm diameter (sensitive), 14-17 mm (intermediate), and less than or equal to 13 mm (resistant), and excluding L. pneumophila, there was good correlation between erythromycin MIC and corresponding disk diffusion data for staphylococci and streptococci, but not for Haemophilus species. In comparison, josamycin yielded a significant number of minor discrepant data for group D streptococci and Haemophilus species. It is suggested that erythromycin and josamycin should not be tested against Haemophilus species, and that josamycin should be excluded from test batteries against enterococci. Erythromycin-resistant staphylococci require separate testing with josamycin.

  14. The extinction of topical erythromycin therapy for acne vulgaris and concern for the future of topical clindamycin.

    PubMed

    Austin, Brett A; Fleischer, Alan B

    2017-03-01

    This study aims to evaluate changes in topical antibiotic prescribing trends for acne. We retrospectively reviewed the National Ambulatory Medical Care Survey data from 1993 to 2012 for all visits in which acne vulgaris was the primary diagnosis. Acne vulgaris represented an estimated 94.5 million (92.3, 96.8) visits during the 20-year study period. Bivariate analysis showed that over time erythromycin use declined (p < 0.001) and clindamycin use rose (p = 0.10). Multivariate analysis showed that the likelihood of erythromycin use declined to near zero (p < 0.001), whereas clindamycin utilization increased (p < 0.05). PubMed searches of "erythromycin AND resistance" and "clindamycin AND resistance" demonstrated increasing publication frequency by year, fit with sigmoidal functions (erythromycin: R(2 )=( )0.93 and clindamycin: R(2 )=( )0.94). Yearly publications consistently exceeded 100 papers for erythromycin and clindamycin resistance in 1983 and 2003, respectively, roughly corresponding to the interval between reports of their utility in acne. Our findings suggest topical erythromycin use for acne has essentially ceased. By contrast, clindamycin use is increasing. Current recommendations discourage topical antibiotic monotherapy in favor of combination therapy with benzoyl peroxide and topical retinoids. Our group's previous work demonstrated that this trend is indeed occurring.

  15. Characterization of erythromycin resistance in Campylobacter coli and Campylobacter jejuni isolated from pig offal in New Zealand.

    PubMed

    Harrow, S A; Gilpin, B J; Klena, J D

    2004-01-01

    To determine the level and mechanism(s) of antimicrobial resistance in Campylobacter isolates obtained from human and environmental sources from South Canterbury, New Zealand. A total of 251 Campylobacter isolates were tested for susceptibility to ciprofloxacin, erythromycin, nalidixic acid and tetracycline using disc diffusion assays. Five pig offal isolates were observed to be highly erythromycin resistant, with minimal inhibitory concentrations determined to be >/=256 microg ml(-1). Nucleotide sequencing of the 23S ribosomal DNA (rDNA) in these resistant isolates identified an A --> G change at Escherichia coli position 2059 that has been previously implicated in erythromycin resistance in Campylobacter coli. Macrorestriction profiling using pulsed-field gel electrophoresis showed these isolates were nonclonal. The majority of Campylobacter isolates from South Canterbury remain sensitive to the most clinically relevant antimicrobial agents. Our results support other reports showing that specific variations in the 23S rDNA contribute to erythromycin resistance. This study defines the baseline frequency of antimicrobial resistance associated with Campylobacter isolates from South Canterbury, and discusses the likely molecular mechanisms conferring erythromycin resistance in this organism. Resistance to erythromycin in these isolates is not linked to a dominant Campylobacter clone and has likely arisen independently in different genetic lines exposed to selective antimicrobial pressure.

  16. Electron paramagnetic resonance study of radiation-induced paramagnetic centers in succinic anhydride single crystal

    NASA Astrophysics Data System (ADS)

    Caliskan, Betul; Caliskan, Ali Cengiz; Er, Emine

    2017-09-01

    Succinic anhydride single crystals were exposed to 60Co-gamma irradiation at room temperature. The irradiated single crystals were investigated at 125 K by Electron Paramagnetic Resonance (EPR) Spectroscopy. The investigation of EPR spectra of irradiated single crystals of succinic anhydride showed the presence of two succinic anhydride anion radicals. The anion radicals observed in gamma-irradiated succinic anhydride single crystal were created by the scission of the carbon-oxygen double bond. The structure of EPR spectra demonstrated that the hyperfine splittings arise from the same radical species. The reduction of succinic anhydride was identified which is formed by the addition of an electron to oxygen of the Csbnd O bond. The g values, the hyperfine structure constants and direction cosines of the radiation damage centers observed in succinic anhydride single crystal were obtained.

  17. Adipocyte protein modification by Krebs cycle intermediates and fumarate ester-derived succination.

    PubMed

    Manuel, Allison M; Frizzell, Norma

    2013-11-01

    Protein succination, the non-enzymatic modification of cysteine residues by fumarate, is distinguishable from succinylation, an enzymatic reaction forming an amide bond between lysine residues and succinyl-CoA. Treatment of adipocytes with 30 mM glucose significantly increases protein succination with only a small change in succinylation. Protein succination may be significantly increased intracellularly after treatment with fumaric acid esters, however, the ester must be removed by saponification to permit 2SC-antibody detection of the fumarate adduct.

  18. Recovery of succinic acid produced by fermentation of a metabolically engineered Mannheimia succiniciproducens strain.

    PubMed

    Song, Hyohak; Huh, Yun Suk; Lee, Sang Yup; Hong, Won Hi; Hong, Yeon Ki

    2007-12-01

    There have recently been much advances in the production of succinic acid, an important four-carbon dicarboxylic acid for many industrial applications, by fermentation of several natural and engineered bacterial strains. Mannheimia succiniciproducens MBEL55E isolated from bovine rumen is able to produce succinic acid with high efficiency, but also produces acetic, formic and lactic acids just like other anaerobic succinic acid producers. We recently reported the development of an engineered M. succiniciproducens LPK7 strain which produces succinic acid as a major fermentation product while producing much reduced by-products. Having an improved succinic acid producer developed, it is equally important to develop a cost-effective downstream process for the recovery of succinic acid. In this paper, we report the development of a simpler and more efficient method for the recovery of succinic acid. For the recovery of succinic acid from the fermentation broth of LPK7 strain, a simple process composed of a single reactive extraction, vacuum distillation, and crystallization yielded highly purified succinic acid (greater than 99.5% purity, wt%) with a high yield of 67.05wt%. When the same recovery process or even multiple reactive extraction steps were applied to the fermentation broth of MBEL55E, lower purity and yield of succinic acid were obtained. These results suggest that succinic acid can be purified in a cost-effective manner by using the fermentation broth of engineered LPK7 strain, showing the importance of integrating the strain development, fermentation and downstream process for optimizing the whole processes for succinic acid production.

  19. Glutamine metabolism drives succinate accumulation in plasma and the lung during hemorrhagic shock.

    PubMed

    Slaughter, Anne L; D'Alessandro, Angelo; Moore, Ernest E; Banerjee, Anirban; Silliman, Christopher C; Hansen, Kirk C; Reisz, Julie A; Fragoso, Miguel; Wither, Matthew J; Bacon, Anthony W; Moore, Hunter B; Peltz, Erik D

    2016-12-01

    Metabolomic investigations have consistently reported succinate accumulation in plasma after critical injury. Succinate receptors have been identified on numerous tissues, and succinate has been directly implicated in postischemic inflammation, organ dysfunction, platelet activation, and the generation of reactive oxygen species, which may potentiate morbidity and mortality risk to patients. Metabolic flux (heavy-isotope labeling) studies demonstrate that glycolysis is not the primary source of increased plasma succinate during protracted shock. Glutamine is an alternative parent substrate for ATP generation during anaerobic conditions, a biochemical mechanism that ultimately supports cellular survival but produces succinate as a catabolite. We hypothesize that succinate accumulation during hemorrhagic shock is driven by glutaminolysis. Sprague-Dawley rats were subjected to hemorrhagic shock for 45 minutes (shock, n = 8) and compared with normotensive shams (sham, n = 8). At 15 minutes, animals received intravenous injection of C5-N2-glutamine solution (iLG). Blood, brain, heart, lung, and liver tissues were harvested at defined time points. Labeling distribution in samples was determined by ultrahigh-pressure liquid chromatography-mass spectrometry metabolomic analysis. Repeated-measures analysis of variance with Tukey comparison determined significance of relative fold change in metabolite level from baseline. Hemorrhagic shock instigated succinate accumulation in plasma and lungs tissues (8.5- vs. 1.1-fold increase plasma succinate level from baseline, shock vs. sham, p = 0.001; 3.2-fold higher succinate level in lung tissue, shock vs. sham, p = 0.006). Metabolomic analysis identified labeled glutamine and labeled succinate in plasma (p = 0.002) and lung tissue (p = 0.013), confirming glutamine as the parent substrate. Kinetic analyses in shams showed constant total levels of all metabolites without significant change due to iLG. Glutamine metabolism contributes

  20. Vitamin E Succinate as an Adjuvant for Dendritic Cell Based Vaccines

    DTIC Science & Technology

    2006-07-01

    cancer cells by tocopherols and tocotrienols . Nutr Cancer, 33: 26-32, 1999. 33. Yu, W., Sanders, B. G., and Kline, K. RRR- alpha -tocopheryl succinate...DC vaccines with a chemotherapeutic drug, which may act as an adjuvant for DC vaccines. Vitamin E succinate or alpha tocopheryl succinate (α-TOS) is...residual disease setting, 3) identify the mechanism involved in mediating the anti-tumor response 15. SUBJECT TERMS Chemo-immunotherapy, alpha

  1. Mutagenic Action of Ethyl Methanesulfonate in Maize.

    PubMed

    Neuffer, M G; Ficsor, G

    1963-03-29

    Pollen of corn plants carrying three closely linked genes (alpha beta Sh(2)) on chromosome 3 were treated by ethyl methanesulfonate in order to determine the nature of genetic changes produced. In this genetic material the loss of the beta gene alone represents a discrete genetic change, possibly a point mutation, while the loss of two or more markers represents chromosome aberrations. Ethyl methanesulfonate, x-rays, and ultraviolet light all induced numerous chromosome aberrations, but only ultraviolet light and probably ethyl methanesulfonate induced discrete genetic changes.

  2. Regulation of fructose uptake and catabolism by succinate in Azospirillum brasilense.

    PubMed Central

    Mukherjee, A; Ghosh, S

    1987-01-01

    Fructose uptake and catabolism in Azospirillum brasilense is dependent on three fructose-inducible enzymes (fru-enzymes): (i) enzyme I and (ii) enzyme II of the phosphoenolpyruvate:fructose phosphotransferase system and (iii) 1-phosphofructokinase. In minimal medium containing 3.7 mM succinate and 22 mM fructose as sources of carbon, growth of A. brasilense was diauxic, succinate being utilized in the first phase of growth and fructose in the second phase with a lag period between the two growth phases. None of the fru-enzymes could be detected in cells grown with succinate as the sole source of carbon, but they were detectable toward the end of the first phase of diauxie. All the fru-enzymes were coinduced by fructose and coordinately repressed by succinate. Studies on the effect of succinate on differential rates of syntheses of the fru-enzymes revealed that their induced syntheses in fructose minimal medium were subject to transient as well as permanent (catabolite) repression by succinate. Succinate also caused a similar pattern of transient and permanent repression of the fructose transport system in A. brasilense. However, no inducer (fructose) exclusionlike effect was observed as there was no inhibition of fructose uptake in the presence of succinate with fructose-grown cells even when they were fully induced for succinate uptake activity. PMID:2957360

  3. Fermentative Succinate Production: An Emerging Technology to Replace the Traditional Petrochemical Processes

    PubMed Central

    Cao, Yujin; Zhang, Rubing; Sun, Chao; Cheng, Tao; Liu, Yuhua; Xian, Mo

    2013-01-01

    Succinate is a valuable platform chemical for multiple applications. Confronted with the exhaustion of fossil energy resources, fermentative succinate production from renewable biomass to replace the traditional petrochemical process is receiving an increasing amount of attention. During the past few years, the succinate-producing process using microbial fermentation has been made commercially available by the joint efforts of researchers in different fields. In this review, recent attempts and experiences devoted to reduce the production cost of biobased succinate are summarized, including strain improvement, fermentation engineering, and downstream processing. The key limitations and challenges faced in current microbial production systems are also proposed. PMID:24396827

  4. Effect of sodium succinate on gas exchange in rats with barbiturate-induced coma.

    PubMed

    Shefer, T V; Ivnitskii, Yu Yu; Malakhovskii, V N

    2003-04-01

    Injection of sodium succinate in doses of 5 or 10 mmol/kg (but not 1 mmol/kg) intensified oxygen consumption in rats with sodium thiopental-induced coma. Injection of SDH inhibitor (sodium malonate) inhibited gas exchange and abolished the effect of sodium succinate. The effect of succinate on rat survival was positive, while that of malonate was negative, but manifested only as a trend. The critical role of succinate oxidation in preventing lethal complications of barbiturate-induced coma is proved.

  5. Fermentative succinate production: an emerging technology to replace the traditional petrochemical processes.

    PubMed

    Cao, Yujin; Zhang, Rubing; Sun, Chao; Cheng, Tao; Liu, Yuhua; Xian, Mo

    2013-01-01

    Succinate is a valuable platform chemical for multiple applications. Confronted with the exhaustion of fossil energy resources, fermentative succinate production from renewable biomass to replace the traditional petrochemical process is receiving an increasing amount of attention. During the past few years, the succinate-producing process using microbial fermentation has been made commercially available by the joint efforts of researchers in different fields. In this review, recent attempts and experiences devoted to reduce the production cost of biobased succinate are summarized, including strain improvement, fermentation engineering, and downstream processing. The key limitations and challenges faced in current microbial production systems are also proposed.

  6. Progress of succinic acid production from renewable resources: Metabolic and fermentative strategies.

    PubMed

    Jiang, Min; Ma, Jiangfeng; Wu, Mingke; Liu, Rongming; Liang, Liya; Xin, Fengxue; Zhang, Wenming; Jia, Honghua; Dong, Weiliang

    2017-06-03

    Succinic acid is a four-carbon dicarboxylic acid, which has attracted much interest due to its abroad usage as a precursor of many industrially important chemicals in the food, chemicals, and pharmaceutical industries. Facing the shortage of crude oil supply and demand of sustainable development, biological production of succinic acid from renewable resources has become a topic of worldwide interest. In recent decades, robust producing strain selection, metabolic engineering of model strains, and process optimization for succinic acid production have been developed. This review provides an overview of succinic acid producers and cultivation technology, highlight some of the successful metabolic engineering approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Process for the preparation of ethyl benzene

    DOEpatents

    Smith, Jr., Lawrence A.; Arganbright, Robert P.; Hearn, Dennis

    1995-01-01

    Ethyl benzene is produced in a catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 50.degree. C. to 300.degree. C., using as the catalyst a mole sieve characterized as acidic by feeding ethylene to the catalyst bed while benzene is conveniently added through the reflux to result in a molar excess present in the reactor to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene and diethyl benzene in the bottoms. The bottoms are fractionated, the ethyl benzene recovered and the bottoms are contacted with benzene in the liquid phase in a fixed bed straight pass reactor under conditions to transalkylate the benzene thereby converting most of the diethyl benzene to ethyl benzene which is again separated and recovered.

  8. Process for the preparation of ethyl benzene

    DOEpatents

    Smith, L.A. Jr.; Arganbright, R.P.; Hearn, D.

    1995-12-19

    Ethyl benzene is produced in a catalyst bed under 0.25 to 50 atmospheres of pressure and at temperatures in the range of 50 C to 300 C, using as the catalyst a mole sieve characterized as acidic by feeding ethylene to the catalyst bed while benzene is conveniently added through the reflux to result in a molar excess present in the reactor to that required to react with ethylene, thereby reacting substantially all of the ethylene and recovering benzene as the principal overhead and ethyl benzene and diethyl benzene in the bottoms. The bottoms are fractionated, the ethyl benzene recovered and the bottoms are contacted with benzene in the liquid phase in a fixed bed straight pass reactor under conditions to transalkylate the benzene thereby converting most of the diethyl benzene to ethyl benzene which is again separated and recovered. 2 figs.

  9. Methyl Ethyl Ketoxime; Final Test Rule

    EPA Pesticide Factsheets

    EPA is issuing this final test rule under section 4 of the Toxic Substances Control Act (TSCA), requiring manufacturers and processors of methyl ethyl ketoxime (MEKO, CAS No. 96-29-7) to perform testing for health effects.

  10. [Toxicology of ethyl gasoline 78 and 94].

    PubMed

    Starzyński, Z; Szymańska, S; Jaraczewska, W; Myślak, Z

    1978-01-01

    The authors have described clinical pictures of acute and chronic intoxication, especially toxic effect of ethyl gasoline upon nervous sytem, parenchymatous organs, and irritating effect on skin and mucous membranes.

  11. 77 FR 23625 - Quizalofop Ethyl; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-20

    ... AGENCY 40 CFR Part 180 Quizalofop Ethyl; Pesticide Tolerances AGENCY: Environmental Protection Agency... Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001... are an agricultural producer, food manufacturer, or pesticide manufacturer. Potentially...

  12. Hemo-De as substitute for ethyl acetate in formalin-ethyl acetate concentration technique.

    PubMed Central

    Neimeister, R; Logan, A L; Gerber, B; Egleton, J H; Kleger, B

    1987-01-01

    In comparative studies, Hemo-De (PMP Medical Industries, Inc., Irving, Tex.) was found to be a suitable replacement for ethyl acetate in the Formalin-ethyl acetate concentration technique. With essentially equivalent recovery rates for both procedures, the Formalin-Hemo-De concentration technique is considered to be the preferred technique because Hemo-De is less toxic and less flammable and does not present disposal problems, and its cost is approximately one-fourth that of ethyl acetate. PMID:3818930

  13. Mutagenicity testing of doxylamine succinate, an antinauseant drug.

    PubMed

    Müller, L; Korte, A; Madle, S

    1989-10-01

    Doxylamine succinate (DA), a compound which was formerly used as an antinauseant during pregnancy, showed no substantial mutagenicity in mouse embryos following transplacental exposure. A small dose-dependent induction of chromosomal aberrations was found in mouse embryos on day 11 of gestation. No induction of sister chromatid exchanges (SCE) was found in embryos on day 11 of gestation. A micronucleus test with fetal blood on day 17 of gestation was negative. Additionally, DA was negative in Chinese hamster bone marrow in vivo (micronuclei) and in human lymphocyte cultures in vitro (SCE).

  14. Radiation Protection by the Antioxidant Alpha-Tocopherol Succinate

    DTIC Science & Technology

    2005-01-01

    family of 8 tocols—4 each of α, β, γ, and δ tocopherols and tocotrienols (Figure 1). O CH3 R1 R2 HO CH3 CH3 CH3 CH3 CH3 R1 = R2 = CH3 d- alpha ...CH3 CH3 R1 = R2 = CH3 R1 = R2 = H R1 = H, R2 = CH3 R1 = CH3, R2 = H d- alpha - tocotrienol d-beta- tocotrienol d-gamma- tocotrienol d-delta- tocotrienol ...Radiation Protection by the Antioxidant Alpha -Tocopherol Succinate Vijay K. Singh1, V. Srinivasan1, Raymond Toles1, Patience Karikari1, Thomas

  15. A comparison of two alcohol biomarkers in clinical practice: ethyl glucuronide versus ethyl sulfate.

    PubMed

    Lande, R Gregory; Marin, Barbara

    2013-01-01

    This study compared the characteristics of two direct alcohol biomarkers, ethyl glucuronide and ethyl sulfate. Both biomarkers were analyzed from urine specimens submitted by 58 active duty service members at Walter Reed National Military Medical Center's Addiction Treatment Service. These 58 individuals, as a result of serial testing, submitted a total of 374 urine specimens for laboratory analysis. Of 374 specimens, the paired tests were most often negative (n = 295, 78.9%).The paired tests were both positive less frequently (n = 38, 10.2%). In an interesting development ethyl sulfate produced more positive results than ethyl glucuronide (n = 32, 8.6%).

  16. Ethyl Vanillin Activates TRPA1.

    PubMed

    Wu, Shaw-Wen; Fowler, Daniel K; Shaffer, Forrest J; Lindberg, Jonathon E M; Peters, James H

    2017-09-01

    The nonselective cation channel transient receptor potential ankryn subtype family 1 (TRPA1) is expressed in neurons of dorsal root ganglia and trigeminal ganglia and also in vagal afferent neurons that innervate the lungs and gastrointestinal tract. Many TRPA1 agonists are reactive electrophilic compounds that form covalent adducts with TRPA1. Allyl isothiocyanate (AITC), the common agonist used to identify TRPA1, contains an electrophilic group that covalently binds with cysteine residues of TRPA1 and confers a structural change on the channel. There is scientific motivation to identify additional compounds that can activate TRPA1 with different mechanisms of channel gating. We provide evidence that ethyl vanillin (EVA) is a TRPA1 agonist. Using fluorescent calcium imaging and whole-cell patch-clamp electrophysiology on dissociated rat vagal afferent neurons and TRPA1-transfected COS-7 cells, we discovered that EVA activates cells also activated by AITC. Both agonists display similar current profiles and conductances. Pretreatment with A967079, a selective TRPA1 antagonist, blocks the EVA response as well as the AITC response. Furthermore, EVA does not activate vagal afferent neurons from TRPA1 knockout mice, showing selectivity for TRPA1 in this tissue. Interestingly, EVA appears to be pharmacologically different from AITC as a TRPA1 agonist. When AITC is applied before EVA, the EVA response is occluded. However, they both require intracellular oxidation to activate TRPA1. These findings suggest that EVA activates TRPA1 but via a distinct mechanism that may provide greater ease for study in native systems compared with AITC and may shed light on differential modes of TRPA1 gating by ligand types. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  17. Succinate causes α-SMA production through GPR91 activation in hepatic stellate cells.

    PubMed

    Li, Ying Hui; Woo, Sung Hoon; Choi, Dae Hee; Cho, Eun-Hee

    2015-08-07

    Succinate acts as an extracellular signaling molecule as well as an intermediate in the citric acid cycle. It binds to and activates its specific G protein-coupled receptor 91 (GPR91). GPR91 is present in hepatic stellate cells (HSCs), but its role in hepatic fibrogenesis remains unclear. Cultured HSCs treated with succinate showed increased protein expression of GPR91 and α-smooth muscle actin (α-SMA), markers of fibrogenic response. Succinate also increased mRNA expression of α-SMA, transforming growth factor β (TGF-β), and collagen type I. Transfection of siRNA against GPR91 abrogated succinate-induced increases in α-SMA expression. Malonate, an inhibitor of succinate dehydrogenase (SDH), increased succinate levels in cultured HSCs and increased GPR91 and α-SMA expression. Feeding mice a methionine- and choline-deficient (MCD) diet is a widely used technique to create an animal model of nonalcoholic steatohepatitis (NASH). HSCs cultured in MCD media showed significantly decreased SDH activity and increased succinate concentration and GPR91 and α-SMA expression. Similarly, palmitate treatment significantly decreased SDH activity and increased GPR91 and α-SMA expression. Finally, C57BL6/J mice fed the MCD diet had elevated succinate levels in their plasma. The MCD diet also decreased SDH activity, increased succinate concentration, and increased GPR91 and α-SMA expression in isolated HSCs. Collectively, our results show that succinate plays an important role in HSC activation through GPR91 induction, and suggest that succinate and GPR91 may represent new therapeutic targets for modulating hepatic fibrosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Studies on the mechanism of synthesis of ethyl acetate in Kluyveromyces marxianus DSM 5422.

    PubMed

    Löser, Christian; Urit, Thanet; Keil, Peter; Bley, Thomas

    2015-02-01

    Kluyveromyces marxianus converts whey-borne sugar into ethyl acetate, an environmentally friendly solvent with many applications. K. marxianus DSM 5422 presumably synthesizes ethyl acetate from acetyl-SCoA. Iron limitation as a trigger for this synthesis is explained by a diminished aconitase and succinate dehydrogenase activity (both enzymes depend on iron) causing diversion of acetyl-SCoA from the tricarboxic acid cycle to ester synthesis. Copper limitation as another trigger for ester synthesis in this yeast refers to involvement of the electron transport chain (all ETC complexes depend on iron and complex IV requires copper). This hypothesis was checked by using several ETC inhibitors. Malonate was ineffective but carboxin partially inhibited complex II and initiated ester synthesis. Antimycin A and cyanide as complexes III and IV inhibitors initiated ester synthesis only at moderate levels while higher concentrations disrupted all respiration and caused ethanol formation. A restricted supply of oxygen (the terminal electron acceptor) also initiated some ester synthesis but primarily forced ethanol production. A switch from aerobic to anaerobic conditions nearly stopped ester synthesis and induced ethanol formation. Iron-limited ester formation was compared with anaerobic ethanol production; the ester yield was lower than the ethanol yield but a higher market price, a reduced number of process stages, a faster process, and decreased expenses for product recovery by stripping favor biotechnological ester production.

  19. Influence of Soil Use on Prevalence of Tetracycline, Streptomycin, and Erythromycin Resistance and Associated Resistance Genes

    PubMed Central

    Rzeczycka, Marzenna; Miernik, Antoni; Krawczyk-Balska, Agata; Walsh, Fiona; Duffy, Brion

    2012-01-01

    This study examined differences in antibiotic-resistant soil bacteria and the presence and quantity of resistance genes in soils with a range of management histories. We analyzed four soils from agricultural systems that were amended with manure from animals treated with erythromycin and exposed to streptomycin and/or oxytetracycline, as well as non-manure-amended compost and forest soil. Low concentrations of certain antibiotic resistance genes were detected using multiplex quantitative real-time PCR (qPCR), with tet(B), aad(A), and str(A) each present in only one soil and tet(M) and tet(W) detected in all soils. The most frequently detected resistance genes were tet(B), tet(D), tet(O), tet(T), and tet(W) for tetracycline resistance, str(A), str(B), and aac for streptomycin resistance, and erm(C), erm(V), erm(X), msr(A), ole(B), and vga for erythromycin resistance. Transposon genes specific for Tn916, Tn1549, TnB1230, Tn4451, and Tn5397 were detected in soil bacterial isolates. The MIC ranges of isolated bacteria for tetracycline, streptomycin, and erythromycin were 8 to >256 μg/ml, 6 to >1,024 μg/ml, and 0.094 to >256 μg/ml, respectively. Based on 16S rRNA gene similarity, isolated bacteria showed high sequence identity to genera typical of soil communities. Bacteria with the highest MICs were detected in manure-amended soils or soils from agricultural systems with a history of antibiotic use. Non-manure-amended soils yielded larger proportions of antibiotic-resistant bacteria, but these had lower MICs, carried fewer antibiotic resistance genes, and did not display multidrug resistance (MDR). PMID:22203596

  20. Ribosomal RNA methylation in Staphylococcus aureus and Escherichia coli: effect of the "MLS" (erythromycin resistance) methylase.

    PubMed

    Thakker-Varia, S; Ranzini, A C; Dubin, D T

    1985-09-01

    Classical acquired resistance to erythromycin in Staphylococcus aureus ("MLS," or macrolide-lincosamide-streptogramin, resistance) was shown by Weisblum and colleagues to be a direct consequence of the conversion of one or more adenosine residues of 23S rRNA, within the subsequence(s) GA3G, to N6-dimethyladenosine (m62A). The methylation reaction is effected by a class of methylase, whose genes are typically plasmid- or transposon-associated, and whose synthesis is inducible by erythromycin. Using a recently obtained clinical MLS isolate of S. aureus, we have further defined the methylation locus as YGG X m62A X AAGAC; and have shown that this subsequence occurs once in the 23S RNA and that it is essentially completely methylated in all copies of 23S RNA that accumulate in induced cultures. Similar findings were obtained with laboratory S. aureus strains containing two well-characterized evolutionary variants (ermB, ermC) of MLS methylase genes. Analyses of a strain of E. coli containing the ermC gene indicated that the specificity of the methylase gene was unchanged, but that its expression was muted. Even after prolonged periods of induction, the strain manifested only partial resistance to erythromycin, and only about one-third of the copies of the MLS subsequence were methylated in such "induced" cultures. Since the E. coli 23S RNA sequence is known in its entirety, localization of the MLS subsequence is in this case unambiguous; as inferred by homology arguments applied earlier to the S. aureus data, the subsequence is in a highly conserved region of 23S RNA considered to contribute to the peptidyl transferase center of the ribosome.

  1. Non-isothermal crystallization kinetics and characterization of biodegradable poly(butylene succinate-co-neopentyl glycol succinate) copolyesters.

    PubMed

    Xie, Wen-Jie; Zhou, Xiao-Ming

    2015-01-01

    Both biodegradable aliphatic neat poly(butylene succinate) (PBS) and poly(butylene succinate-co-neopentyl glycol succinate) (P(BS-co-NPGS)) copolyesters with different 1,4-butanediol/neopentyl glycol ratios were synthesized through a two-step process of transesterification and polycondensation using stannous chloride and 4-Methylbenzenesulfonic acid as the co-catalysts. The structure, non-isothermal crystallization behavior, crystalline morphology and crystal structure of neat PBS and P(BS-co-NPGS) copolyesters were characterized by (1)H NMR, differential scanning calorimetry (DSC), polarized optical microscope (POM) and wide angle X-ray diffraction (WAXD), respectively. The Avrami equation modified by Jeziorny and Mo's method was employed to describe the non-isothermal crystallization kinetics of the neat PBS and its copolyesters. The modified Avrami equation could adequately describe the primary stage of non-isothermal crystallization kinetics of the neat PBS and its copolyesters. Mo's method provided a fairly satisfactory description of the non-isothermal crystallization of neat PBS and its copolyesters. Interestingly, the values of 1/t1/2, Zc and F(T) obtained by the modified Avrami equation and Mo's method analysis indicated that the crystallization rate increased first and then decreased with an increase of NPGS content compared that of neat PBS, whereas the crystallization mechanism almost kept unchanged. The results of tensile testing showed that the ductility of PBS was largely improved by incorporating NPGS units. The elongation at break increased remarkably with increasing NPGS content. In particular, the sample with 20% NPGS content showed around 548% elongation at break.

  2. Manufacture and properties of erythromycin beads containing neutron-activated erbium-171

    SciTech Connect

    Parr, A.F.; Digenis, G.A.; Sandefer, E.P.; Ghebre-Sellassie, I.; Iyer, U.; Nesbitt, R.U.; Scheinthal, B.M. )

    1990-03-01

    To evaluate the effects of a neutron activation radiolabeling technique on an enteric-coated multiparticulate formulation of erythromycin, test quantities were produced under industrial pilot scale conditions. The pellets contained the stable isotope erbium oxide (Er-170), which was later converted by neutron activation into the short-lived gamma ray-emitting radionuclide, erbium-171. In vitro studies indicated that the dissolution profile, acid resistance, and enteric-coated surface of the pellets were minimally affected by the irradiation procedure. Antimicrobial potency was also unaffected, as determined by microbiological assay. Neutron activation thus appears to simplify the radiolabeling of complex pharmaceutical dosage forms for in vivo study by external gamma scintigraphy.

  3. An integron cassette encoding erythromycin esterase, ere(A), from Providencia stuartii.

    PubMed

    Plante, Isabelle; Centrón, Daniela; Roy, Paul H

    2003-04-01

    We have mapped the variable region of the two class 1 integrons found in the multiresistant strain Providencia stuartii 1723. Integron 1 contains a new arrangement of gene cassettes, aacA4-aadB-aadA1, conferring resistance to all aminoglycosides used for clinical treatment. Integron 2 contains a variant of the gene cassette ere(A), coding for an erythromycin esterase, whose nucleotide sequence shares 93.7% DNA identity with ere(A) from Escherichia coli BM2195 plasmid pIP1100.

  4. Influence of the test medium on azithromycin and erythromycin regression statistics.

    PubMed

    Barry, A L; Fuchs, P C

    1991-10-01

    Azithromycin and erythromycin disk test results were compared to MIC values obtained in six different media. One hundred isolates were tested in triplicate, and geometric mean MICs were plotted against arithmetic mean zone diameters and regression statistics calculated. The test media evaluated did not markedly influence MIC values, but incubation in 5-7% CO2 resulted in a two- to four-fold decrease in the activity of both drugs. For testing Haemophilus influenzae and other species that need to be tested in 5-7% CO2, interpretive breakpoints for the macrolides and azalides should be modified to compensate for the anticipated decrease in activity.

  5. Stress induced reversible crystal transition in poly(butylene succinate)

    NASA Astrophysics Data System (ADS)

    Liu, Guoming; Zheng, Liuchun; Zhang, Xiuqin; Li, Chuncheng; Wang, Dujin

    2015-03-01

    The plastic deformation mechanism of semi-crystalline polymers is a long-studied topic, which is crucial for establishing structure/property relationships. For polymers with stress induced crystal transition, some open questions still need to be answered, such as on which stage of plastic deformation does the crystal transition take place, and more importantly, what happens on the lamellar structure during crystal transition. In this talk, stress-induced reversible crystal transition in poly(butylene succinate) was systematically investigated by in-situ WAXS and SAXS. A ``lamellar thickening'' phenomenon was observed during stretching, which was shown to mainly originated from the reversible crystal transition. This mechanism was shown to be valid in poly(ethylene succinate). The critical stress for the transition was measured in a series of PBS-based crystalline-amorphous multi-block copolymers. Interestingly, these PBS copolymers exhibited identical critical stress independent of amorphous blocks. The universal critical stress for crystal transition was interpreted through a single-microfibril-stretching mechanism. The work is financially supported by the National Natural Science Foundation of China (Grant No. 51203170).

  6. MAMA-PCR assay for the detection of point mutations associated with high-level erythromycin resistance in Campylobacter jejuni and Campylobacter coli strains.

    PubMed

    Alonso, Rodrigo; Mateo, Estibaliz; Churruca, Estibaliz; Martinez, Irati; Girbau, Cecilia; Fernández-Astorga, Aurora

    2005-10-01

    Twenty Campylobacter jejuni and 16 Campylobacter coli strains isolated from humans and food/animals, including 17 isolates resistant to erythromycin, were analyzed. A combined mismatch amplification mutation assay-PCR technique was developed to detect the mutations A 2074 C and A 2075 G in the 23S rRNA gene associated with erythromycin resistance. All high-level erythromycin-resistant strains examined by DNA sequencing carried the transition mutation A 2075 G, whereas no isolate carried the A 2074 C mutation. No mutations were found among the susceptible and low-level erythromycin-resistant strains.

  7. An erythromycin process improvement using the diethyl methylmalonate-responsive (Dmr) phenotype of the Saccharopolyspora erythraea mutB strain.

    PubMed

    Weber, J Mark; Cernota, William H; Gonzalez, Melissa C; Leach, Benjamin I; Reeves, Andrew R; Wesley, Roy K

    2012-02-01

    The Saccharopolyspora erythraea mutB knockout strain, FL2281, having a block in the methylmalonyl-CoA mutase reaction, was found to carry a diethyl methylmalonate-responsive (Dmr) phenotype in an oil-based fermentation medium. The Dmr phenotype confers the ability to increase erythromycin A (erythromycin) production from 250-300% when the oil-based medium is supplemented with 15 mM levels of this solvent. Lower concentrations of the solvent stimulated proportionately less erythromycin production, while higher concentrations had no additional benefit. Although the mutB strain is phenotypically a low-level erythromycin producer, diethyl methylmalonate supplementation allowed it to produce up to 30% more erythromycin than the wild-type (control) strain-a strain that does not show the Dmr phenotype. The Dmr phenotype represents a new class of strain improvement phenotype. A theory to explain the biochemical mechanism for the Dmr phenotype is proposed. Other phenotypes found to be associated with the mutB knockout were a growth defect and hyper-pigmentation, both of which were restored to normal by exposure to diethyl methylmalonate. Furthermore, mutB fermentations did not significantly metabolize soybean oil in the presence of diethyl methylmalonate. Finally, a novel method is proposed for the isolation of additional mutants with the Dmr phenotype.

  8. Ciprofloxacin plus erythromycin or ambroxol ameliorates endotracheal tube-associated Pseudomonas aeruginosa biofilms in a rat model.

    PubMed

    Cheng, Chen; Du, Lizhong; Yu, Jialin; Lu, Qi; He, Yu; Ran, Tao

    2015-12-01

    Pseudomonas aeruginosa is a multi-drug resistant bacterium, with its biofilm-growing mucoid (alginate-producing) strains being particularly resistant. As atomized drug administration is a common practice in pediatric patients, we compared the effect of inhalational therapy with erythromycin plus ciprofloxacin, with that of ambroxol plus ciprofloxacin, against biofilm producing strains of P. aeruginosa. Both combined treatment regimens were associated with a significant reduction in bacterial counts in endotracheal (ET) tubes and lungs, as compared to that observed with ambroxol and erythromycin monotherapies (P<0.05). Ciprofloxacin plus ambroxol appeared to have a higher efficacy than ciprofloxacin plus erythromycin, both in lowering bacterial counts (P<0.05) and in disrupting the structural integrity of biofilm. Histopathological changes in the lungs were milder in the two combined treatment groups, as compared to that in groups treated with single drugs. Erythromycin or ambroxol in combination with ciprofloxacin could eliminate P. aeruginosa biofilms. When combined with ciprofloxacin, ambroxol outperformed erythromycin in eradicating P. aeruginosa biofilm. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. Fitness and proteome changes accompanying the development of erythromycin resistance in a population of Escherichia coli grown in continuous culture.

    PubMed

    Petráčková, Denisa; Janeček, Jiří; Bezoušková, Silvia; Kalachová, Ladislava; Techniková, Zuzana; Buriánková, Karolína; Halada, Petr; Haladová, Kateřina; Weiser, Jaroslav

    2013-10-01

    We studied the impact of a sublethal concentration of erythromycin on the fitness and proteome of a continuously cultivated population of Escherichia coli. The development of resistance to erythromycin in the population was followed over time by the gradient plate method and minimum inhibitory concentration (MIC) measurements. We measured the growth rate, standardized efficiency of synthesis of radiolabeled proteins, and translation accuracy of the system. The proteome changes were followed over time in two parallel experiments that differed in the presence or absence of erythromycin. A comparison of the proteomes at each time point (43, 68, and 103 h) revealed a group of unique proteins differing in expression. From all 35 proteins differing throughout the cultivation, only three were common to more than one time point. In the final population, a significant proportion of upregulated proteins was localized to the outer or inner cytoplasmic membranes or to the periplasmic space. In a population growing for more than 100 generations in the presence of antibiotic, erythromycin-resistant bacterial clones with improved fitness in comparison to early resistant culture predominated. This phenomenon was accompanied by distinct changes in protein expression during a stepwise, population-based development of erythromycin resistance.

  10. Synthesis and antimicrobial evaluation of dirithromycin (AS-E 136; LY237216), a new macrolide antibiotic derived from erythromycin.

    PubMed Central

    Counter, F T; Ensminger, P W; Preston, D A; Wu, C Y; Greene, J M; Felty-Duckworth, A M; Paschal, J W; Kirst, H A

    1991-01-01

    Dirithromycin is a 9-N-11-O-oxazine derivative which is formed by condensation of 9(S)-erythromycylamine with 2-(2-methoxyethoxy)acetaldehyde. Dirithromycin is hydrolyzed, either under acidic conditions or in vivo, to its major active metabolite, 9(S)-erythromycylamine. The antimicrobial spectrum of dirithromycin is similar to that of erythromycin; both antibiotics are active against gram-positive bacteria, Legionella spp., Helicobacter pylori, and Chlamydia trachomatis. Comparable results were obtained for each antibiotic in MIC and MBC determinations and in the potential development of resistance in vitro. The effects of human serum, bacterial growth media, test methodology, and inoculum size on MICs were similar for each antibiotic. In standard mouse protection studies, dirithromycin was more efficacious than erythromycin against experimental infections after subcutaneous administration of antibiotic. These results were consistent with pharmacokinetic studies in rodents, which showed that dirithromycin gave more persistent concentrations of antibiotic in serum and tissues than were achieved with erythromycin. These studies indicate that dirithromycin possesses antimicrobial activity comparable to that of erythromycin in vitro but is more active than erythromycin in vivo, which may be attributable to the persistence of antimicrobial activity in the tissue(s) of the test animals. PMID:1929252

  11. Impact of POR*28 on the clinical pharmacokinetics of CYP3A phenotyping probes midazolam and erythromycin.

    PubMed

    Elens, Laure; Nieuweboer, Annemieke J M; Clarke, Stephen J; Charles, Kellie A; de Graan, Anne-Joy M; Haufroid, Vincent; van Gelder, Teun; Mathijssen, Ron H J; van Schaik, Ron H N

    2013-03-01

    P450 oxidoreductase (POR) is essential for cytochrome P450 (CYP) activity in humans. The POR*28 allele (A503V) has been shown to impact on in-vitro CYP-mediated metabolism, including CYP3A isoenzymes. The aim of the present study was to determine the in vivo impact of the POR*28 allele on the pharmacokinetics of the classic CYP3A phenotyping probes midazolam and erythromycin. Whereas midazolam is metabolized by both CYP3A4 and CYP3A5, erythromycin is exclusively oxidized by CYP3A4. To assess CYP3A activity, 108 cancer patients received midazolam and 45 others underwent the erythromycin breath test. Patients were genotyped for POR*28, CYP3A4*22 and CYP3A5*3. In patients expressing CYP3A5, POR*28 carriers showed 45% lower midazolam metabolic ratios compared with POR*1/*1 patients (P<0.001). This is in line with a lower CYP3A5 activity toward midazolam for POR*28 carriers. In CYP3A5 nonexpressers, POR*28 had no influence on midazolam pharmacokinetics. For erythromycin, POR*28 carriership did not influence its metabolism. Our data show that the POR*28 allele is associated with a lower in vivo CYP3A5 activity, but has no effects on CYP3A4-mediated erythromycin and midazolam metabolism.

  12. 40 CFR 721.10595 - Octadecen-1-aminium, N-ethyl-N,N-dimethy-, ethyl sulfate (1:1).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Octadecen-1-aminium, N-ethyl-N,N... Significant New Uses for Specific Chemical Substances § 721.10595 Octadecen-1-aminium, N-ethyl-N,N-dimethy... chemical substance identified as octadecen-1-aminium, N-ethyl-N,N-dimethy-, ethyl sulfate (1:1) (PMN P-11...

  13. The effect of the bacterial product, succinic acid, on neutrophil bactericidal activity.

    PubMed

    Abdul-Majid, K B; Kenny, P A; Finlay-Jones, J J

    1997-02-01

    We investigated the effect of succinic acid on neutrophil bactericidal activity in a model of intra-abdominal abscess induced in mice by the peritoneal inoculation of 5 x 10(6) cfu ml-1 E. coli and 5 x 10(8) cfu ml-1 B. fragilis plus 1 mg of bran as faecal fibre analogue. The mean pH of the induced abscesses at week 1 was 6.7, higher than the pH associated with succinic acid inhibitory activity. We therefore determined the effect of succinic acid (0-100 mM) at pH 6.7 on the bactericidal activity of mouse bone marrow-derived neutrophils. Phagocytic killing of Proteus mirabilis by neutrophils was significantly inhibited by 30-100 mM succinic acid at pH 6.7 but there was no significant effect of succinic acid on engulfment of bacteria at this pH. However, significant inhibition of intracellular killing (assayed by adding succinic acid to suspensions of neutrophils which had engulfed bacteria in low serum concentrations but in the absence of succinic acid) was noted at 70 and 100 mM. These results indicate that succinic acid inhibits neutrophil bactericidal activity at a physiological pH, principally through inhibition of intracellular killing mechanisms and therefore contributing to bacterial persistence in this model of abscess formation.

  14. [Environmental factors affecting the succinic acid production by Actinobacillus succinogenes CGMCC 1593].

    PubMed

    Zheng, Pu; Zhou, Wei; Ni, Ye; Jiang, Min; Wei, Ping; Sun, Zhihao

    2008-06-01

    Actinobacillus succinogenes is a promising candidate for the production of bio-based succinic acid. Previously, we isolated a succinic acid-producing strain Actinobacillus succinogenes CGMCC 1593 from bovine rumen. In this paper, the influence of the environmental factors such as gas phase, pH, ORP, on succinic acid production by A. succinogenes CGMCC 1593 was studied. The results showed that CO2 was the optimum gas phase for anaerobic fermentation ofA. succinogenes CGMCC 1593 as well as one of the substrate for the succinic acid synthesis. Using MgCO3 as a pH regulator, the pH was maintained within 7.1-6.2 during the anaerobic fermentation for the cell growth and acid production of A. succinogenes CGMCC 1593. Our results showed that low initial ORP was disadvantageous for the growth of A. succinogenes CGMCC 1593 and an ORP of -270 mV was demonstrated to be beneficial to the succinic acid production. By adding Na2S.9H2O to decrease ORP to -270 mV at the end of exponential growth phase in batch culture of A. succinogenes CGMCC 1593, the succinic acid concentration reached 37 g/L and the yield of succinic acid was 129% at 48 h. This work might provide valuable information for further optimization of succinic acid fermentation by A. succinogenes CGMCC 1593.

  15. 40 CFR 721.10090 - Tertiary amine salt of glycol succinate (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Tertiary amine salt of glycol... Specific Chemical Substances § 721.10090 Tertiary amine salt of glycol succinate (generic). (a) Chemical... as tertiary amine salt of glycol succinate (PMN P-01-595) is subject to reporting under this...

  16. 40 CFR 721.10090 - Tertiary amine salt of glycol succinate (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Tertiary amine salt of glycol... Specific Chemical Substances § 721.10090 Tertiary amine salt of glycol succinate (generic). (a) Chemical... as tertiary amine salt of glycol succinate (PMN P-01-595) is subject to reporting under this...

  17. 40 CFR 721.10090 - Tertiary amine salt of glycol succinate (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Tertiary amine salt of glycol... Specific Chemical Substances § 721.10090 Tertiary amine salt of glycol succinate (generic). (a) Chemical... as tertiary amine salt of glycol succinate (PMN P-01-595) is subject to reporting under this...

  18. 40 CFR 721.10090 - Tertiary amine salt of glycol succinate (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Tertiary amine salt of glycol... Specific Chemical Substances § 721.10090 Tertiary amine salt of glycol succinate (generic). (a) Chemical... as tertiary amine salt of glycol succinate (PMN P-01-595) is subject to reporting under this...

  19. 40 CFR 721.10090 - Tertiary amine salt of glycol succinate (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Tertiary amine salt of glycol... Specific Chemical Substances § 721.10090 Tertiary amine salt of glycol succinate (generic). (a) Chemical... as tertiary amine salt of glycol succinate (PMN P-01-595) is subject to reporting under this...

  20. Study of the role of anaerobic metabolism in succinate production by Enterobacter aerogenes.

    PubMed

    Tajima, Yoshinori; Kaida, Kenichi; Hayakawa, Atsushi; Fukui, Keita; Nishio, Yousuke; Hashiguchi, Kenichi; Fudou, Ryosuke; Matsui, Kazuhiko; Usuda, Yoshihiro; Sode, Koji

    2014-09-01

    Succinate is a core biochemical building block; optimizing succinate production from biomass by microbial fermentation is a focus of basic and applied biotechnology research. Lowering pH in anaerobic succinate fermentation culture is a cost-effective and environmentally friendly approach to reducing the use of sub-raw materials such as alkali, which are needed for neutralization. To evaluate the potential of bacteria-based succinate fermentation under weak acidic (pH <6.2) and anaerobic conditions, we characterized the anaerobic metabolism of Enterobacter aerogenes AJ110637, which rapidly assimilates glucose at pH 5.0. Based on the profile of anaerobic products, we constructed single-gene knockout mutants to eliminate the main anaerobic metabolic pathways involved in NADH re-oxidation. These single-gene knockout studies showed that the ethanol synthesis pathway serves as the dominant NADH re-oxidation pathway in this organism. To generate a metabolically engineered strain for succinate production, we eliminated ethanol formation and introduced a heterogeneous carboxylation enzyme, yielding E. aerogenes strain ΔadhE/PCK. The strain produced succinate from glucose with a 60.5% yield (grams of succinate produced per gram of glucose consumed) at pH <6.2 and anaerobic conditions. Thus, we showed the potential of bacteria-based succinate fermentation under weak acidic conditions.

  1. Metabolic engineering of Mannheimia succiniciproducens for succinic acid production based on elementary mode analysis with clustering.

    PubMed

    Kim, Won Jun; Ahn, Jung Ho; Kim, Hyun Uk; Kim, Tae Yong; Lee, Sang Yup

    2017-02-01

    Mannheimia succiniciproducens, a capnophilic gram-negative rumen bacterium, has been employed for the efficient production of succinic acid. Although M. succiniciproducens metabolism was previously studied using a genome-scale metabolic model, more metabolic characteristics are to be understood. To this end, elementary mode analysis accompanied with clustering ('EMC' analysis) is used to gain further insights on metabolic characteristics of M. succiniciproducens allowing efficient succinic acid production. Elementary modes (EMs) generated from the central carbon metabolic network of M. succiniciproducens are clustered to systematically analyze succinic acid production routes. Based on the results of EMC analysis, zwf gene is identified as a novel overexpression target for the improved succinic acid production. This gene is overexpressed in a previously constructed succinic acid-overproducing M. succiniciproducens LPK7 strain. Heterologous NADPH-dependent mdh is later intuitively selected for overexpression to synergistically improve succinic acid production by utilizing abundant NADPH pool mediated by the overexpressed zwf. The LPK7 strains co-expressing mdh alone and both zwf and mdh genes are subjected to fed-batch fermentation to better examine their succinic acid production performances. Strategies of EMC analysis will be useful for further metabolic engineering of M. succiniciproducens and other microorganisms to improve production of succinic acid and other chemicals of interest. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Synthesis, characterization and nanocomposite formation of poly(glycerol succinate-co-maleate) with cellulose nanowhiskers

    USDA-ARS?s Scientific Manuscript database

    A novel biodegradable polymer based on glycerol, succinic anhydride and maleic anhydride, poly(glycerol succinate-co-maleate), poly(GlySAMA), was synthesized by melt polycondensation and tested as a matrix for composites with cellulose nanowhiskers. This glycerol-based polymer is thermally stable as...

  3. Integration of succinic acid and ethanol production within a corn or barley biorefinery

    USDA-ARS?s Scientific Manuscript database

    Production of succinic acid from glucose by Escherichia coli strain AFP184 was studied in a batch fermentor. The bases used for pH control included NaOH, KOH, NH4OH, and Na2CO3. The yield of succinic acid without and with carbon dioxide supplied by an adjacent ethanol fermentor using either corn or ...

  4. Thermochemical pretreatments for enhancing succinic acid production from industrial hemp (Cannabis sativa L.).

    PubMed

    Gunnarsson, Ingólfur B; Kuglarz, Mariusz; Karakashev, Dimitar; Angelidaki, Irini

    2015-04-01

    The aim of this study was to develop an efficient thermochemical method for treatment of industrial hemp biomass, in order to increase its bioconversion to succinic acid. Industrial hemp was subjected to various thermochemical pretreatments using 0-3% H2SO4, NaOH or H2O2 at 121-180°C prior to enzymatic hydrolysis. The influence of the different pretreatments on hydrolysis and succinic acid production by Actinobacillus succinogenes 130Z was investigated in batch mode, using anaerobic bottles and bioreactors. Enzymatic hydrolysis and fermentation of hemp material pretreated with 3% H2O2 resulted in the highest overall sugar yield (73.5%), maximum succinic acid titer (21.9 g L(-1)), as well as the highest succinic acid yield (83%). Results obtained clearly demonstrated the impact of different pretreatments on the bioconversion efficiency of industrial hemp into succinic acid.

  5. Genetic manipulation of a metabolic enzyme and a transcriptional regulator increasing succinate excretion from unicellular cyanobacterium.

    PubMed

    Osanai, Takashi; Shirai, Tomokazu; Iijima, Hiroko; Nakaya, Yuka; Okamoto, Mami; Kondo, Akihiko; Hirai, Masami Y

    2015-01-01

    Succinate is a building block compound that the U.S. Department of Energy (DOE) has declared as important in biorefineries, and it is widely used as a commodity chemical. Here, we identified the two genes increasing succinate production of the unicellular cyanobacterium Synechocystis sp. PCC 6803. Succinate was excreted under dark, anaerobic conditions, and its production level increased by knocking out ackA, which encodes an acetate kinase, and by overexpressing sigE, which encodes an RNA polymerase sigma factor. Glycogen catabolism and organic acid biosynthesis were enhanced in the mutant lacking ackA and overexpressing sigE, leading to an increase in succinate production reaching five times of the wild-type levels. Our genetic and metabolomic analyses thus demonstrated the effect of genetic manipulation of a metabolic enzyme and a transcriptional regulator on succinate excretion from this cyanobacterium with the data based on metabolomic technique.

  6. Succination of proteins by fumarate: mechanism of inactivation of glyceraldehyde-3-phosphate dehydrogenase in diabetes.

    PubMed

    Blatnik, Matthew; Thorpe, Suzanne R; Baynes, John W

    2008-04-01

    S-(2-succinyl)cysteine (2SC) is a chemical modification of proteins formed by a Michael addition reaction between the Krebs cycle intermediate, fumarate, and thiol groups in protein--a process known as succination of protein. Succination causes irreversible inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in vitro. GAPDH was immunoprecipitated from muscle of diabetic rats, then analyzed by ultra-performance liquid chromatography-electrospray ionization-mass spectroscopy. Succination of GAPDH was increased in muscle of diabetic rats, and the extent of succination correlated strongly with the decrease in specific activity of the enzyme. We propose that 2SC is a biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins may provide the chemical link between glucotoxicity and the pathogenesis of diabetic complications.

  7. Pharmacokinetic considerations of formulation: extended-release metoprolol succinate in the treatment of heart failure.

    PubMed

    Wikstrand, John; Andersson, Bert; Kendall, Martin J; Stanbrook, Hilary; Klibaner, Michael

    2003-02-01

    Extended-release (ER) metoprolol succinate is a controlled-release formulation designed to deliver metoprolol succinate at a near constant rate for approximately 20 h, independent of food intake and gastrointestinal pH. Once-daily dosing of ER metoprolol succinate 12.5-200 mg produces even plasma concentrations over a 24-h period, without the marked peaks and troughs characteristically observed with the immediate-release (IR) formulation. This leads to consistent beta1-blockade over 24 h, while maintaining cardioselectivity at doses up to 200 mg daily. Pharmacokinetic studies have also been performed in heart failure patients and have demonstrated that ER metoprolol succinate is associated with a more pronounced and even beta1-blockade over a 24-h period than the IR formulation. The efficacy and good tolerability of ER metoprolol succinate in heart failure patients has now been demonstrated in a large-scale clinical trial.

  8. Optimization of succinic acid fermentation with Actinobacillus succinogenes by response surface methodology (RSM).

    PubMed

    Zhang, Yun-jian; Li, Qiang; Zhang, Yu-xiu; Wang, Dan; Xing, Jian-min

    2012-02-01

    Succinic acid is considered as an important platform chemical. Succinic acid fermentation with Actinobacillus succinogenes strain BE-1 was optimized by central composite design (CCD) using a response surface methodology (RSM). The optimized production of succinic acid was predicted and the interactive effects between glucose, yeast extract, and magnesium carbonate were investigated. As a result, a model for predicting the concentration of succinic acid production was developed. The accuracy of the model was confirmed by the analysis of variance (ANOVA), and the validity was further proved by verification experiments showing that percentage errors between actual and predicted values varied from 3.02% to 6.38%. In addition, it was observed that the interactive effect between yeast extract and magnesium carbonate was statistically significant. In conclusion, RSM is an effective and useful method for optimizing the medium components and investigating the interactive effects, and can provide valuable information for succinic acid scale-up fermentation using A. succinogenes strain BE-1.

  9. Genetic manipulation of a metabolic enzyme and a transcriptional regulator increasing succinate excretion from unicellular cyanobacterium

    PubMed Central

    Osanai, Takashi; Shirai, Tomokazu; Iijima, Hiroko; Nakaya, Yuka; Okamoto, Mami; Kondo, Akihiko; Hirai, Masami Y.

    2015-01-01

    Succinate is a building block compound that the U.S. Department of Energy (DOE) has declared as important in biorefineries, and it is widely used as a commodity chemical. Here, we identified the two genes increasing succinate production of the unicellular cyanobacterium Synechocystis sp. PCC 6803. Succinate was excreted under dark, anaerobic conditions, and its production level increased by knocking out ackA, which encodes an acetate kinase, and by overexpressing sigE, which encodes an RNA polymerase sigma factor. Glycogen catabolism and organic acid biosynthesis were enhanced in the mutant lacking ackA and overexpressing sigE, leading to an increase in succinate production reaching five times of the wild-type levels. Our genetic and metabolomic analyses thus demonstrated the effect of genetic manipulation of a metabolic enzyme and a transcriptional regulator on succinate excretion from this cyanobacterium with the data based on metabolomic technique. PMID:26500619

  10. Succination of Proteins by Fumarate: Mechanism of Inactivation of Glyceraldehyde-3-Phosphate Dehydrogenase in Diabetes

    PubMed Central

    Blatnik, Matthew; Thorpe, Suzanne R.; Baynes, John W.

    2008-01-01

    S-(2-succinyl)cysteine (2SC) is a chemical modification of proteins formed by a Michael addition reaction between the Krebs cycle intermediate, fumarate, and thiol groups in protein—a process known as succination of protein. Succination causes irreversible inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in vitro. GAPDH was immunoprecipitated from muscle of diabetic rats, then analyzed by ultra-performance liquid chromatography–electrospray ionization–mass spectroscopy. Succination of GAPDH was increased in muscle of diabetic rats, and the extent of succination correlated strongly with the decrease in specific activity of the enzyme. We propose that 2SC is a biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins may provide the chemical link between glucotoxicity and the pathogenesis of diabetic complications. PMID:18448829

  11. GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis

    PubMed Central

    Zhang, Juan; Kneuer, Rainer

    2016-01-01

    When SUCNR1/GPR91-expressing macrophages are activated by inflammatory signals, they change their metabolism and accumulate succinate. In this study, we show that during this activation, macrophages release succinate into the extracellular milieu. They simultaneously up-regulate GPR91, which functions as an autocrine and paracrine sensor for extracellular succinate to enhance IL-1β production. GPR91-deficient mice lack this metabolic sensor and show reduced macrophage activation and production of IL-1β during antigen-induced arthritis. Succinate is abundant in synovial fluids from rheumatoid arthritis (RA) patients, and these fluids elicit IL-1β release from macrophages in a GPR91-dependent manner. Together, we reveal a GPR91/succinate-dependent feed-forward loop of macrophage activation and propose GPR91 antagonists as novel therapeutic principles to treat RA. PMID:27481132

  12. EPR and optical studies of VO2+ doped potassium succinate-succinic acid single crystal - Substitutional incorporation

    NASA Astrophysics Data System (ADS)

    Juliet sheela, K.; Radha Krishnan, S.; Shanmugam, V. M.; Subramanian, P.

    2017-03-01

    EPR and optical absorption studies of VO2+ doped potassium succinate-succinic acid (KSSA) single crystal has been examined at room temperature. EPR spectrum shows that well resolved hyperfine lines. The angular variation of the EPR spectra has shown that two different VO2+ complexes are located in different chemical environments. Among the number of sites, two sites have been followed and reported here. From the EPR analysis, spin Hamiltonian parameters g and A tensors and their directional cosines are evaluated. Both the sites experience rhombic crystal field symmetry around the impurity ion. The VO2+ ion entering the site location of potassium ion has coordination of eight oxygen atoms in a distorted dodecahedral arrangement. The Optical absorption spectrum studied at room temperature shows bands corresponding to C4v symmetry. The crystal field parameter and tetragonal field parameters are calculated. From the Optical and EPR data various molecular orbital coefficients are evaluated and the nature of bonding in the crystal is discussed.

  13. Efficient aerobic succinate production from glucose in minimal medium with Corynebacterium glutamicum

    PubMed Central

    Litsanov, Boris; Kabus, Armin; Brocker, Melanie; Bott, Michael

    2012-01-01

    Summary Corynebacterium glutamicum, an established industrial amino acid producer, has been genetically modified for efficient succinate production from the renewable carbon source glucose under fully aerobic conditions in minimal medium. The initial deletion of the succinate dehydrogenase genes (sdhCAB) led to an accumulation of 4.7 g l−1 (40 mM) succinate as well as high amounts of acetate (125 mM) as by‐product. By deleting genes for all known acetate‐producing pathways (pta‐ackA, pqo and cat) acetate production could be strongly reduced by 83% and succinate production increased up to 7.8 g l−1 (66 mM). Whereas overexpression of the glyoxylate shunt genes (aceA and aceB) or overproduction of the anaplerotic enzyme pyruvate carboxylase (PCx) had only minor effects on succinate production, simultaneous overproduction of pyruvate carboxylase and PEP carboxylase resulted in a strain that produced 9.7 g l−1 (82 mM) succinate with a specific productivity of 1.60 mmol g (cdw)−1 h−1. This value represents the highest productivity among currently described aerobic bacterial succinate producers. Optimization of the production conditions by decoupling succinate production from cell growth using the most advanced producer strain (C. glutamicumΔpqoΔpta‐ackAΔsdhCABΔcat/pAN6‐pycP458Sppc) led to an additional increase of the product yield to 0.45 mol succinate mol−1 glucose and a titre of 10.6 g l−1 (90 mM) succinate. PMID:22018023

  14. Succinate dehydrogenase-deficient GISTs are characterized by IGF1R overexpression.

    PubMed

    Chou, Angela; Chen, Jason; Clarkson, Adele; Samra, Jaswinder S; Clifton-Bligh, Roderick J; Hugh, Thomas J; Gill, Anthony J

    2012-09-01

    Succinate dehydrogenase-deficient gastrointestinal stromal tumors (GISTs) demonstrate unique pathological and clinical features, including the absence of activating mutations of KIT and PDGFRA, and primary resistance to imatinib. They arise exclusively in the stomach and account for 5-7.5% of all adult stomach GISTs and the great majority of these tumors in childhood. Insulin-like growth factor 1 receptor (IGF1R) overexpression has been associated with wild-type and pediatric GISTs. We propose that IGF1R overexpression is a feature of succinate dehydrogenase-deficient GISTs as a group. We assessed succinate dehydrogenase complex subunit B (SDHB) and IGF1R expression by immunohistochemistry in eight known succinate dehydrogenase-deficient GISTs, three GISTs arising in the setting of neurofibromatosis type 1 syndrome and 40 unselected GISTs. Selected KIT and PDGFRA exons were amplified and sequenced from formalin-fixed paraffin-embedded tumor samples. All eight succinate dehydrogenase-deficient tumors were wild-type for KIT and PDGFRA, succinate dehydrogenase B negative and demonstrated IGF1R overexpression. The three neurofibromatosis-related tumors were succinate dehydrogenase B positive and IGF1R negative. Of the 40 unselected upper GISTs, five were wild-type for KIT and PDGFRA in the selected exons. Two of the wild-type GISTs were succinate dehydrogenase B negative and showed IGF1R overexpression and three were succinate dehydrogenase B positive and IGF1R negative. We conclude that IGF1R overexpression is a feature of succinate dehydrogenase deficient GIST as a group, rather than pediatric or wild-type GIST per se. Therefore, IGF1R inhibition represents a potential rational therapeutic approach in this recently recognized subgroup of GIST.

  15. Effect of gene disruptions of the TCA cycle on production of succinic acid in Saccharomyces cerevisiae.

    PubMed

    Arikawa, Y; Kuroyanagi, T; Shimosaka, M; Muratsubaki, H; Enomoto, K; Kodaira, R; Okazaki, M

    1999-01-01

    Succinate is the main taste component produced by yeasts during sake (Japanese rice wine) fermentation. The pathway leading to accumulation of succinate was examined in liquid culture in the presence of a high concentration (15%) of glucose under aerobic and anaerobic conditions using a series of Saccharomyces cerevisiae strains in which various genes that encode the expression of enzymes required in TCA cycle were disrupted. When cultured in YPD medium containing 15% glucose under aerobic conditions, the KGD1 (alpha-ketoglutarate dehydrogenase) gene disrupted mutant produced a lower level of succinate than the wild-type strain, while the SDH1 (succinate dehydrogenase) gene-disrupted mutant produced an increased level of succinate. On the other hand, the FUM1 (fumarase) gene disrupted mutant produced significantly higher levels of fumarate but did not form malate at all. These results indicate that succinate, fumarate and malate are mainly synthesized through the TCA cycle (oxidative direction) even in the presence of glucose at a concentration as high as 15%. When the growth condition was shifted from aerobic to anaerobic, the increased level of succinate in SDH1 disruptants was no longer observed, whereas the decreased level of succinate in the KGD1 diruptant was still observed. A double mutant of the two fumarate reductase isozyme genes (OSM1 and FRDS) showed a succinate productivity of 50% as compared to the parent when cells were incubated in glucose-buffered solution. These results indicate that succinate could be synthesized through two pathways, namely, alpha-ketoglutarate oxidation via the TCA cycle and fumarate reduction under anaerobic conditions.

  16. Evidence of a conjugal erythromycin resistance element in the Lyme disease spirochete Borrelia burgdorferi

    PubMed Central

    Jackson, Charlene R.; Boylan, Julie; Frye, Jonathan G.; Gherardini, Frank C.

    2007-01-01

    We report the identification of isolates of Borrelia burgdorferi strain B31 that exhibit an unusual macrolide–lincosamide (ML) or macrolide–lincosamide–streptogramin A (MLSA) antibiotic resistance pattern. Low-passage isolates were resistant to high levels (>100 μg/mL) of erythromycin, spiramycin and the lincosamides but were sensitive to dalfopristin, an analogue of streptogramin B. Interestingly, the high-passage erythromycin-resistant strain B31 was resistant to quinupristin, an analogue of streptogramin A (25 μg/mL). Biochemical analysis revealed that resistance was not due to antibiotic inactivation or energy-dependent efflux but was instead due to modification of ribosomes in these isolates. Interestingly, we were able to demonstrate high-frequency transfer of the resistance phenotype via conjugation from B. burgdorferi to Bacillus subtilis (10−2–10−4) or Enterococcus faecalis (10−5). An intergeneric conjugal system in B. burgdorferi suggests that horizontal gene transfer may play a role in its evolution and is a potential tool for developing new genetic systems to study the pathogenesis of Lyme disease. PMID:17905571

  17. Effects of Tylosin Use on Erythromycin Resistance in Enterococci Isolated from Swine

    PubMed Central

    Jackson, Charlene R.; Fedorka-Cray, Paula J.; Barrett, John B.; Ladely, Scott R.

    2004-01-01

    The effect of tylosin on erythromycin-resistant enterococci was examined on three farms; farm A used tylosin for growth promotion, farm B used tylosin for treatment of disease, and farm C did not use tylosin for either growth promotion or disease treatment. A total of 1,187 enterococci were isolated from gestation, farrowing, suckling, nursery, and finishing swine from the farms. From a subset of those isolates (n = 662), 59% (124 out of 208), 28% (80 out of 281), and 2% (4 out of 170) were resistant to erythromycin (MIC ≥ 8 μg/ml) from farms A, B, and C, respectively. PCR analysis and Southern blotting revealed that 95% (65 out of 68) of isolates chosen from all three farms for further study were positive for ermB, but all were negative for ermA and ermC. By using Southern blotting, ermB was localized to the chromosome in 56 of the isolates while 9 isolates from farms A and B contained ermB on two similar-sized plasmid bands (12 to 16 kb). Pulsed-field gel electrophoresis revealed that the isolates were genetically diverse and represented a heterogeneous population of enterococci. This study suggests that although there was resistance to a greater number of enterococcal isolates on a farm where tylosin was used as a growth promotant, resistant enterococci also existed on a farm where no antimicrobial agents were used. PMID:15240302

  18. Molecular Identification and Quantification of Tetracycline and Erythromycin Resistance Genes in Spanish and Italian Retail Cheeses

    PubMed Central

    Flórez, Ana Belén; Alegría, Ángel; Delgado, Susana

    2014-01-01

    Large antibiotic resistance gene pools in the microbiota of foods may ultimately pose a risk for human health. This study reports the identification and quantification of tetracycline- and erythromycin-resistant populations, resistance genes, and gene diversity in traditional Spanish and Italian cheeses, via culturing, conventional PCR, real-time quantitative PCR (qPCR), and denaturing gradient gel electrophoresis (DGGE). The numbers of resistant bacteria varied widely among the antibiotics and the different cheese varieties; in some cheeses, all the bacterial populations seemed to be resistant. Up to eight antibiotic resistance genes were sought by gene-specific PCR, six with respect to tetracycline, that is, tet(K), tet(L), tet(M), tet(O), tet(S), and tet(W), and two with respect to erythromycin, that is, erm(B) and erm(F). The most common resistance genes in the analysed cheeses were tet(S), tet(W), tet(M), and erm(B). The copy numbers of these genes, as quantified by qPCR, ranged widely between cheeses (from 4.94 to 10.18log⁡10/g). DGGE analysis revealed distinct banding profiles and two polymorphic nucleotide positions for tet(W)-carrying cheeses, though the similarity of the sequences suggests this tet(W) to have a monophyletic origin. Traditional cheeses would therefore appear to act as reservoirs for large numbers of many types of antibiotic resistance determinants. PMID:25302306

  19. Structure-activity relationships and mechanism of action of macrolides derived from erythromycin as antibacterial agents.

    PubMed

    Liang, Jian-Hua; Han, Xu

    2013-01-01

    Enormous efforts were focused on the 3-descladinosyl erythromycin derivatives which led to 3-keto (ketolides), 3-O-acyl (acylides), 3-O-carbamate (carbamolides), and 3-O-alkyl (alkylides) and cladinosyl-containing erythromycin derivatives such as 4"-O-acyl, 4"-O-carbamate, and 4"-O-alkyl derivatives as recently exemplified by macrolones (macrolide-quinolone hybrids). Ketolides acquire activity against MLSB-resistant pathogens via a featured arylalkyl extension suspended on the macrolide core, which interacts with a base pair formed by A752Ec and U2609Ec located in the nascent peptide release tunnel of the bacterial rRNA. A base pair formed by C2610Ec and G2505Ec probably is another novel binding site for 3-descladinosyl non-ketolides. It is believed that 4"-derived compounds perhaps interfere with the formation of polypeptide because the extension oriented into peptidyl transferase center (PTC) region. Although macrolones are hybrids of macrolides and quinolones, they do not have dual modes of action, and serve only as protein synthesis inhibitors.

  20. Occurrence of erythromycin residues in sheep milk. Validation of an analytical method.

    PubMed

    García-Mayor, M A; Paniagua-González, G; Soledad-Rodríguez, B; Garcinuño-Martínez, R M; Fernández-Hernando, P; Durand-Alegría, J S

    2015-04-01

    The paper describes a new and selective analytical sample treatment for quantitative extraction and preconcentration of erythromycin in presence of other macrolide antibiotics in sheep milk samples. The methodology is based on the use of a molecular imprinted polymer (MIP) employed as solid phase extraction sorbent (MISPE). The synthesized material by bulk polymerization using erythromycin (ERY) as template was evaluated as solid phase extraction sorbent, in a novel sample treatment technique that can be coupled to high-performance liquid chromatography with diode-array detector (HPLC-DAD). MIP selectivity was studied for other macrolide antibiotics with similar structures, such as tylosin (TYL), spiramycin (SPI), josamycin (JOS), roxithromycin (ROX) and ivermectin (IVER) getting recoveries for these interferents lower than 35%, for all cases except for ROX, which recoveries were around 85%. The variables affecting the molecularly imprinted solid-phase extraction (MISPE) procedure were optimized to select the best conditions of selectivity and sensitivity to determine ERY at concentration levels established by EU legislation in sheep milk. Under the selected experimental conditions, quantification limit was 24.1 µg kg(-1). Recoveries were higher than 98%, with RSDs between 0.7% and 2%. The proposed MISPE-HPLC method was validated and successfully applied to ERY analysis in sheep milk samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Combined effect of erythromycin, tetracycline and sulfamethoxazole on performance of anaerobic sequencing batch reactors.

    PubMed

    Aydin, Sevcan; Ince, Bahar; Cetecioglu, Zeynep; Arikan, Osman; Ozbayram, E Gozde; Shahi, Aiyoub; Ince, Orhan

    2015-06-01

    The combined effects of erythromycin-tetracycline-sulfamethoxazole (ETS) and sulfamethoxazole-tetracycline (ST) antibiotics on the performance of anaerobic sequencing batch reactors were studied. A control reactor was fed with wastewater that was free of antibiotics, while two additional reactors were fed with ETS and ST. The way in which the ETS and ST mixtures impact COD removal, VFA production, antibiotic degradation, biogas production and composition were investigated. The effects of the ETS mixtures were different from the ST mixtures, erythromycin can have an antagonistic effect on sulfamethoxazole and tetracycline. The anaerobic pre-treatment of these antibiotics can represent a suitable alternative to the use of chemical treatments for concentrations at 10 mg/L of S and 1 mg/L of T; 2 mg/L of E, 2 mg/L of T and 20 mg/L of S for the ST and ETS reactors respectively, which corresponds to min 70% COD removal efficiency. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Campylobacter pyloridis and associated gastritis: investigator blind, placebo controlled trial of bismuth salicylate and erythromycin ethylsuccinate.

    PubMed Central

    McNulty, C A; Gearty, J C; Crump, B; Davis, M; Donovan, I A; Melikian, V; Lister, D M; Wise, R

    1986-01-01

    An investigator blind trial was performed comparing bismuth salicylate, erythromycin ethylsuccinate, and placebo in the treatment of Campylobacter pyloridis associated gastritis in patients without peptic ulceration. Fifty patients fulfilled the study criteria. There was a strong correlation between the presence of C pyloridis and histologically confirmed gastritis. Clearance of organisms led to improvement of the gastritis. C pyloridis was cleared from 15 patients; of these, 13 had gastritis initially, which resolved in 12. Conversely, gastritis resolved in only four of 32 patients not cleared of organisms (p less than 0.0001). There was significantly greater improvement in endoscopic appearances in the patients cleared of C pyloridis compared with those whose infection persisted (p less than 0.001). In the three treatment groups organisms were cleared from 14 of 18 patients receiving the locally active bismuth salicylate, only one of 15 patients receiving erythromycin ethylsuccinate, and none of 17 patients taking placebo. These findings suggest that the ideal antimicrobial for the successful eradication of C pyloridis associated gastritis should be locally active, stable at low pH, and should penetrate gastric mucus. The resolution of gastritis and improvement in endoscopic appearances associated with clearance of C pyloridis support the view that these organisms may play a part in this condition. Images FIG 2 PMID:3092967

  3. Efficacy and safety of azithromycin versus benzylpenicillin or erythromycin in community-acquired pneumonia.

    PubMed

    Bohte, R; van't Wout, J W; Lobatto, S; Blussé van Oud Alblas, A; Boekhout, M; Nauta, E H; Hermans, J; van den Broek, P J

    1995-03-01

    Azithromycin, a recently introduced antibiotic, offers the potential advantages of short-course administration and lower toxicity compared to other macrolides. Approved for the treatment of mild pneumonia, this drug was investigated in a study of patients hospitalized for community-acquired pneumonia. In an open-labelled randomized study, oral azithromycin was compared with intravenous benzylpenicillin in patients suspected to have pneumococcal pneumonia. Azithromycin was also compared with erythromycin, both administered orally, in all other patients. Three hundred thirty-four patients with community-acquired pneumonia were hospitalized, 108 of whom were randomized; 104 could be evaluated. A need for intravenous therapy was the most common reason for exclusion. In the pneumococcal group, 35 patients received azithromycin and 29 benzylpenicillin. The clinical and radiological success rate achieved with azithromycin (83%) was considerably higher than that achieved with benzylpenicillin (66%), though the difference was not significant. In the non-pneumococcal group, 19 patients received azithromycin and 21 erythromycin; no differences in the success rate were found (79% and 76%, respectively). Eight patients on azithromycin had a blood culture positive for Streptococcus pneumoniae; in three of these patients therapy was changed. None of the five patients with pneumococcal bacteraemia who received benzylpenicillin required a change in therapy. It is concluded that oral azithromycin, administered as short-course therapy, is an appropriate antibiotic for treating patients with community-acquired pneumonia. However, it is not yet certain that azithromycin is a good choice for patients with pneumococcal bacteraemia.

  4. Topical 5% benzoyl peroxide and 3% erythromycin gel: experience with 191 patients with papulopustular acne.

    PubMed

    Rallis, Efstathios; Verros, Constantinos; Katoulis, Alexandros; Katsarou, Alexandra

    2013-01-01

    Acne is the most common skin disease, with a relative prevalence of 85%-100% among young individuals. It affects the cosmetic appearance of the patients provoking severe distress. A number of different topical treatments have been used for the treatment of acne. In this study, we investigated the efficacy and safety of the topical treatment with 5% benzoyl peroxide and 3% erythromycin gel in patients with papulopustular acne. One hundred and ninety-one patients with inflammatory acne completed the study. The patients included 54 males and 137 females, mean age 22.3 ± 8.1 years. Topical gel was applied on the face once daily for 3 months. The mean number of non-inflammatory and inflammatory lesions after 3 months of therapy decreased significantly with respect to baseline, with a mean percentage reduction of the non-inflammatory and inflammatory lesions by 42.2% and 57.5%, respectively. In conclusion, topical 5% benzoyl peroxide and erythromycin 3% as monotherapy is efficient for the treatment of papulopustular acne.

  5. [Ethyl glucuronide: a biomarker of alcohol consumption].

    PubMed

    Kharbouche, H; Sporkert, F; Staub, C; Mangin, P; Augsburger, M

    2009-11-04

    Excessive alcohol consumption represents a major risk factor for morbidity and mortality. It is therefore indispensable to be able to detect at-risk drinking. Ethyl glucuronide (EtG) is a specific marker of alcohol consumption. The determination of ethyl glucuronide in urine or blood can be used to prove recent driving under the influence of alcohol, even if ethanol is no longer detectable. The commercialization of an EtG specific immunological assay now allows to obtain preliminary results rapidly and easily with satisfying sensitivity. Moreover, the detection of ethyl glucuronide in hair offers the opportunity to evaluate an alcohol consumption over a long period. The EtG concentration in hair is in correlation with the amount of ingested alcohol. Thus, the analysis of ethyl glucuronide can be used to monitor abstinence, to detect alcohol relapse and to identify at-risk drinkers. However, a cut off allowing to detect chronic alcohol abuser reliably still does not exist. Therefore, it is recommended to perform the analysis of ethyl glucuronide in complement to the existing blood markers. A study financed by the Swiss Foundation for Alcohol Research is actually conducted by the West Switzerland University Center of Legal Medicine in order to establish an objective cut-off.

  6. [Degradation of thiometon in ethyl acetate].

    PubMed

    Satoh, M; Shimokawa, S; Kobata, M; Tanaka, T; Nakanishi, Y

    2001-04-01

    When performing multiresidue analysis of pesticides, the recovery of thiometon was less than 20% from carrots and eggplants, but about 100% from garlic chives and welsh onions. The recovery of thiometon was found to depend on the lot of ethyl acetate. A 2-year-old lot of ethyl acetate caused degradation of thiometon, but a fresh lot of ethyl acetate did not. Analysis showed that ethyl acetate stored for 2 years contained about 5 microL/mL of acetaldehyde. Thiometon was also degraded by acetone or acetonitrile, when acetaldehyde was added to them, in the same manner as by aged ethyl acetate. The fact that the recovery of thiometon from welsh onions was about 100% indicated that some of the mercaptans in allium vegetables may prevent thiometon degradation. Mercaptans such as L-cysteine and 3-mercaptoproionic acid were confirmed to prevent the degradation of thiometon and disulfoton. These findings show that mercaptans may be useful additives for analyzing thiometon and disulfoton.

  7. Topical nadifloxacin 1% cream vs. topical erythromycin 4% gel in the treatment of mild to moderate acne.

    PubMed

    Tunca, Mustafa; Akar, Ahmet; Ozmen, Ibrahim; Erbil, Hakan

    2010-12-01

    Topical antibiotics are the mainstay of therapy in mild to moderate inflammatory acne. Topical erythromycin is one of the most common prescribed topical antibiotics. Nadifloxacin, another topical antibiotic for acne, was recently introduced into the market in our country. In this study, we compared the efficacies and safety of topical nadifloxacin 1% cream and erythromycin 4% gel in acne. A total of 86 patients with mild to moderate facial acne were randomized into two treatment groups. The efficacies of the drugs were assessed by lesion counts. An acne severity index (ASI) was also calculated. In both groups, there was a significant reduction in lesion counts and ASI scores beginning from the first visit at week 4. This reduction continued throughout the 12-week study period. Both treatments were well tolerated. We conclude that when topically applied, both nadifloxacin 1% cream and erythromycin 4% gel are equally effective and safe treatments for mild to moderate facial acne. © 2010 The International Society of Dermatology.

  8. [Phenotropyl succinate as the means for correction of neuroimmune disturbances under conditions of informational-physical stress].

    PubMed

    Samotrueva, M A; Tiurenkov, I N; Teplyĭ, D L; Serezhnikova, T K; Berestovitskaia, V M; Vasil'eva, O S; Luzhnova, S A

    2011-05-01

    In Wistar rats, psycho-immune-modulating properties of phenotropyl succinate were studied under conditions of informational-physical stress. The effect ofphenotropyl succinate on the organism specific and unspecific resistance was studied. The data obtained indicate the phenotropyl succinate ability to release neuroimmune disturbances developing under conditions of informational-physical stress.

  9. Comparative In Vitro Activities of Linezolid, Quinupristin-Dalfopristin, Moxifloxacin, and Trovafloxacin against Erythromycin-Susceptible and -Resistant Streptococci

    PubMed Central

    Betriu, Carmen; Redondo, Montserrat; Palau, M. Luisa; Sánchez, Ana; Gómez, María; Culebras, Esther; Boloix, Ana; Picazo, Juan J.

    2000-01-01

    The in vitro activities of the new agents linezolid, quinupristin-dalfopristin, moxifloxacin, and trovafloxacin were determined and compared with those of penicillin, clindamycin, and four macrolides against 53 erythromycin-resistant Streptococcus pneumoniae, 117 S. pyogenes (64 erythromycin-susceptible and 53 -resistant), and 101 S. agalactiae (53 erythromycin-susceptible and 48 -resistant) isolates. Differentiation of macrolide resistance phenotypes was performed by the double-disk method. The genetic basis for macrolide resistance in 52 strains was also determined. The M phenotype was found in 84.9, 6.3, and 1.9% of S. pyogenes, S. agalactiae, and S. pneumoniae isolates, respectively. These strains were susceptible to miocamycin and clindamycin. Strains with the inducible phenotype accounted for 27.1% of S. agalactiae isolates and 9.4% each of S. pyogenes and S. pneumoniae isolates. All erythromycin-resistant isolates were also resistant to the 14- and 15-membered macrolides tested. Strains with all three phenotypes were susceptible to ≤2 μg of linezolid per ml. Quinupristin-dalfopristin exhibited good in vitro activity against all strains, irrespective of their resistance to erythromycin (MICs at which 90% of the isolates tested were inhibited [MIC90s], 0.2 to 1 μg/ml). Against the erythromycin-resistant S. pyogenes and S. agalactiae strains, moxifloxacin and trovafloxacin were the most active agents (MIC90s, 0.1 μg/ml). The new antimicrobials evaluated may be alternative agents to treat infections caused by macrolide-resistant as well as macrolide-susceptible streptococci. PMID:10858339

  10. Transition mutations in the 23S rRNA of erythromycin-resistant isolates of Mycoplasma pneumoniae.

    PubMed Central

    Lucier, T S; Heitzman, K; Liu, S K; Hu, P C

    1995-01-01

    Erythromycin is the drug of choice for treatment of Mycoplasma pneumoniae infections due to its susceptibility to low levels of this antibiotic. After exposure of susceptible strains to erythromycin in vitro and in vivo, mutants resistant to erythromycin and other macrolides were isolated. Their phenotypes have been characterized, but the genetic basis for resistance has never been determined. We isolated two resistant mutants (M129-ER1 and M129-ER2) by growing M. pneumoniae M129 on agar containing different amounts of erythromycin. In broth dilution tests both strains displayed resistance to high levels of several macrolide-lincosamide-streptogramin B (MLS) antibiotics. In binding studies, ribosomes isolated from the resistant strains exhibited significantly lower affinity for [14C]erythromycin than did ribosomes from the M129 parent strain. Sequencing of DNA amplified from the region of the 2S rRNA gene encoding domain V revealed an A-to-G transition in the central loop at position 2063 of M129-ER1 and a similar A-to-G transition at position 2064 in M129-ER2. Transitions at homologous locations in the 23S rRNA from other organisms have been shown to result in resistance to MLS antibiotics. Thus, MLS-like resistance can occur in M. pneumoniae as the result of point mutations in the 23S rRNA gene which reduce the affinity of these antibiotics for the ribosome. Since they involve only single-base changes, development of resistance to erythromycin in vivo by these mechanisms could be relatively frequent event. PMID:8593017

  11. The activity of 14-hydroxy clarithromycin, alone and in combination with clarithromycin, against penicillin- and erythromycin-resistant Streptococcus pneumoniae.

    PubMed

    Martin, S J; Garvin, C G; McBurney, C R; Sahloff, E G

    2001-05-01

    There are no data regarding the activity of clarithromycin's active metabolite, 14-hydroxy clarithromycin, against penicillin-intermediate, penicillin-resistant or erythromycin-resistant Streptococcus pneumoniae. Agar dilution MICs were determined for clarithromycin, 14-hydroxy clarithromycin (henceforth called 'metabolite'), azithromycin, erythromycin and clarithromycin/metabolite (2:1 and 1:1 ratio) against 24 penicillin-intermediate and 14 penicillin-resistant strains, including 13 erythromycin-resistant clinical strains and one ATCC strain of S. pneumoniae. The interaction between clarithromycin and its metabolite was determined using an agar chequerboard assay against all isolates, and time-kill tests were performed against five penicillin-intermediate (macrolide-susceptible) and five penicillin-resistant (two macrolide-resistant) strains of S. pneumoniae using all antibiotics alone at simulated peak serum concentrations, and clarithromycin/metabolite in a 2:1 ratio (physiological). MICs were as follows: clarithromycin, 0.008-->64 mg/L; metabolite, 0.015-->64 mg/L; erythromycin, 0.015-->64 mg/L; azithromycin, 0.125-->64 mg/L; clarithromycin/metabolite (1:1 and 2:1 combinations), 0.001-->64 mg/L. The MIC of the clarithromycin/metabolite combination was one or more tube dilution lower than the MIC of clarithromycin in 28 of the isolates tested. In chequerboard testing, 13 strains (seven erythromycin susceptible and six erythromycin resistant) demonstrated synergy, 18 additivity and seven indifference. In time-kill testing, bacterial eradication below detection limits occurred with clarithromycin and metabolite in seven of 10 organisms. The combination of parent and metabolite was more rapidly bactericidal than clarithromycin alone in six of the seven isolates (P = 0.026). The metabolite has potent activity against S. pneumoniae and enhances the activity of the parent compound against this organism. The metabolite's activity must be considered in evaluating

  12. Pre-endoscopic erythromycin administration in upper gastrointestinal bleeding: an updated meta-analysis and systematic review

    PubMed Central

    Rahman, Rubayat; Nguyen, Douglas L.; Sohail, Umair; Almashhrawi, Ashraf A.; Ashraf, Imran; Puli, Srinivas R.; Bechtold, Matthew L.

    2016-01-01

    Background In patients suffering from upper gastrointestinal bleeding (UGIB), adequate visualization is essential during endoscopy. Prior to endoscopy, erythromycin administration has been shown to enhance visualization in these patients; however, guidelines have not fully adopted this practice. Thus, we performed a comprehensive, up-to-date meta-analysis on the issue of erythromycin administration in this patient population. Methods After searching multiple databases (November 2015), randomized controlled trials on adult subjects comparing administration of erythromycin before endoscopy in UGIB patients to no erythromycin or placebo were included. Pooled estimates of adequacy of gastric mucosa visualized, need for second endoscopy, duration of procedure, length of hospital stay, units of blood transfused, and need for emergent surgery using odds ratio (OR) or mean difference (MD) were calculated. Heterogeneity and publication bias were assessed. Results Eight studies (n=598) were found to meet the inclusion criteria. Erythromycin administration showed statistically significant improvement in adequate gastric mucosa visualization (OR 4.14; 95% CI: 2.01-8.53, P<0.01) while reduced the need for a second-look endoscopy (OR 0.51; 95% CI: 0.34-0.77, P<0.01) and length of hospital stay (MD -1.75; 95% CI: -2.43 to -1.06, P<0.01). Duration of procedure (P=0.2), units of blood transfused (P=0.08), and need for emergent surgery (P=0.88) showed no significant differences. Conclusion Pre-endoscopic erythromycin administration in UGIB patients significantly improves gastric mucosa visualization while reducing length of hospital stay and the need for second-look endoscopy. PMID:27366031

  13. Effects of penicillin and erythromycin on adherence of invasive and noninvasive isolates of Streptococcus pyogenes to laminin

    PubMed Central

    Šmitran, Aleksandra; Vuković, Dragana; Gajić, Ina; Marinković, Jelena; Ranin, Lazar

    2015-01-01

    This study investigated the possible relationship between the invasiveness of group A Streptococcus (GAS) strains and their abilities to adhere to laminin and assessed the effects of subinhibitory concentrations of penicillin and erythromycin on the ability of GAS to adhere to laminin. The adherence of noninvasive and highly invasive isolates of GAS to laminin was significantly higher than the adherence displayed by isolates of low invasiveness. Antibiotic treatment caused significant reductions in adherence to laminin in all three groups of strains. Penicillin was more successful in reducing the adherence abilities of the tested GAS strains than erythromycin. PMID:26270594

  14. Succinic acid production from lignocellulosic hydrolysate by Basfia succiniciproducens

    DOE PAGES

    Salvachúa, Davinia; Smith, Holly; St. John, Peter C.; ...

    2016-05-09

    The production of chemicals alongside fuels will be essential to enhance the feasibility of lignocellulosic biorefineries. Succinic acid (SA), a naturally occurring C4-diacid, is a primary intermediate of the tricarboxylic acid cycle and a promising building block chemical that has received significant industrial attention. Basfia succiniciproducens is a relatively unexplored SA-producing bacterium with advantageous features such as broad substrate utilization, genetic tractability, and facultative anaerobic metabolism. Here B. succiniciproducens is evaluated in high xylose-content hydrolysates from corn stover and different synthetic media in batch fermentation. SA titers in hydrolysate at an initial sugar concentration of 60 g/L reached up tomore » 30 g/L, with metabolic yields of 0.69 g/g, and an overall productivity of 0.43 g/L/h. These results demonstrate that B. succiniciproducens may be an attractive platform organism for bio-SA production from biomass hydrolysates.« less

  15. Succinic acid production from lignocellulosic hydrolysate by Basfia succiniciproducens

    SciTech Connect

    Salvachúa, Davinia; Smith, Holly; St. John, Peter C.; Mohagheghi, Ali; Peterson, Darren J.; Black, Brenna A.; Dowe, Nancy; Beckham, Gregg T.

    2016-05-09

    The production of chemicals alongside fuels will be essential to enhance the feasibility of lignocellulosic biorefineries. Succinic acid (SA), a naturally occurring C4-diacid, is a primary intermediate of the tricarboxylic acid cycle and a promising building block chemical that has received significant industrial attention. Basfia succiniciproducens is a relatively unexplored SA-producing bacterium with advantageous features such as broad substrate utilization, genetic tractability, and facultative anaerobic metabolism. Here B. succiniciproducens is evaluated in high xylose-content hydrolysates from corn stover and different synthetic media in batch fermentation. SA titers in hydrolysate at an initial sugar concentration of 60 g/L reached up to 30 g/L, with metabolic yields of 0.69 g/g, and an overall productivity of 0.43 g/L/h. These results demonstrate that B. succiniciproducens may be an attractive platform organism for bio-SA production from biomass hydrolysates.

  16. Desvenlafaxine succinate for the treatment of major depressive disorder.

    PubMed

    Lohoff, Falk W; Rickels, Karl

    2008-08-01

    Major depressive disorder (MDD) remains one of the most common psychiatric disorders with high morbidity and mortality. Effective treatment is limited and response/remission to antidepressant pharmacotherapy remains poor and unpredictable. The development of new antidepressants is thus of great importance to the field. Desvenlafaxine succinate (DVS) is the active metabolite of the serotonin and noradrenaline re-uptake inhibitor venlafaxine and was recently FDA approved for the treatment of MDD. DVS showed efficacy in clinical trials in MDD with doses ranging from 50 - 400 mg. Advantages compared to other antidepressants include once daily dosing at effective doses, no CYP450 metabolism and low drug-drug interactions. Concerns include side effect profile and moderate efficacy. DVS might be a useful addition to the arsenal of antidepressants available to the clinician. Additional studies, in particular head-to-head comparison to other antidepressants and long-term treatment studies, will be necessary to comprehensively evaluate DVS safety and efficacy for clinical practice.

  17. Succinic acid production from lignocellulosic hydrolysate by Basfia succiniciproducens

    SciTech Connect

    Salvachúa, Davinia; Smith, Holly; St. John, Peter C.; Mohagheghi, Ali; Peterson, Darren J.; Black, Brenna A.; Dowe, Nancy; Beckham, Gregg T.

    2016-05-09

    The production of chemicals alongside fuels will be essential to enhance the feasibility of lignocellulosic biorefineries. Succinic acid (SA), a naturally occurring C4-diacid, is a primary intermediate of the tricarboxylic acid cycle and a promising building block chemical that has received significant industrial attention. Basfia succiniciproducens is a relatively unexplored SA-producing bacterium with advantageous features such as broad substrate utilization, genetic tractability, and facultative anaerobic metabolism. Here B. succiniciproducens is evaluated in high xylose-content hydrolysates from corn stover and different synthetic media in batch fermentation. SA titers in hydrolysate at an initial sugar concentration of 60 g/L reached up to 30 g/L, with metabolic yields of 0.69 g/g, and an overall productivity of 0.43 g/L/h. These results demonstrate that B. succiniciproducens may be an attractive platform organism for bio-SA production from biomass hydrolysates.

  18. Succinic acid production from lignocellulosic hydrolysate by Basfia succiniciproducens.

    PubMed

    Salvachúa, Davinia; Smith, Holly; St John, Peter C; Mohagheghi, Ali; Peterson, Darren J; Black, Brenna A; Dowe, Nancy; Beckham, Gregg T

    2016-08-01

    The production of chemicals alongside fuels will be essential to enhance the feasibility of lignocellulosic biorefineries. Succinic acid (SA), a naturally occurring C4-diacid, is a primary intermediate of the tricarboxylic acid cycle and a promising building block chemical that has received significant industrial attention. Basfia succiniciproducens is a relatively unexplored SA-producing bacterium with advantageous features such as broad substrate utilization, genetic tractability, and facultative anaerobic metabolism. Here B. succiniciproducens is evaluated in high xylose-content hydrolysates from corn stover and different synthetic media in batch fermentation. SA titers in hydrolysate at an initial sugar concentration of 60g/L reached up to 30g/L, with metabolic yields of 0.69g/g, and an overall productivity of 0.43g/L/h. These results demonstrate that B. succiniciproducens may be an attractive platform organism for bio-SA production from biomass hydrolysates.

  19. Biologically produced succinic acid: A new route to chemical intermediates

    SciTech Connect

    Not Available

    1995-01-01

    The US Department of Energy (DOE) Alternative Feedstocks (AF) program is forging new links between the agricultural community and the chemicals industry through support of research and development (R & D) that uses `green` feedstocks to produce chemicals. The program promotes cost-effective industrial use of renewable biomass as feedstocks to manufacture high-volume chemical building blocks. Industrial commercialization of such processes would stimulate the agricultural sector by increasing the demand of agricultural and forestry commodities. New alternatives for American industry may lie in the nation`s forests and fields. The national laboratory consortium has undertaken a joint R&D project with the Michigan Biotechnology Institute to demonstrate the feasibility of producing a chemical intermediate, succinic acid, and various derivatives, from renewable agricultural resources.

  20. 40 CFR 721.10244 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, 2-[bis(2- chloroethoxy)phosphinyl]ethyl...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphonic acid, P- ethyl]-, 2- ethyl... New Uses for Specific Chemical Substances § 721.10244 Phosphonic acid, P- ethyl]-, 2- ethyl 2... substance identified as phosphonic acid, P- ethyl]-, 2- ethyl 2-chloroethyl ester (PMN P-09-195; CAS No...

  1. 40 CFR 721.10244 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, 2-[bis(2- chloroethoxy)phosphinyl]ethyl...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphonic acid, P- ethyl]-, 2- ethyl... New Uses for Specific Chemical Substances § 721.10244 Phosphonic acid, P- ethyl]-, 2- ethyl 2... substance identified as phosphonic acid, P- ethyl]-, 2- ethyl 2-chloroethyl ester (PMN P-09-195; CAS No...

  2. 40 CFR 721.10244 - Phosphonic acid, P-[2-[bis(2-hydroxyethyl)amino]ethyl]-, 2-[bis(2- chloroethoxy)phosphinyl]ethyl...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphonic acid, P- ethyl]-, 2- ethyl... New Uses for Specific Chemical Substances § 721.10244 Phosphonic acid, P- ethyl]-, 2- ethyl 2... substance identified as phosphonic acid, P- ethyl]-, 2- ethyl 2-chloroethyl ester (PMN P-09-195; CAS No...

  3. Purification and characterization of Plasmodium falciparum succinate dehydrogenase.

    PubMed

    Suraveratum, N; Krungkrai, S R; Leangaramgul, P; Prapunwattana, P; Krungkrai, J

    2000-02-05

    Succinate dehydrogenase (SDH), a Krebs cycle enzyme and complex II of the mitochondrial electron transport system was purified to near homogeneity from the human malarial parasite Plasmodium falciparum cultivated in vitro by FPLC on Mono Q, Mono S and Superose 6 gel filtration columns. The malarial SDH activity was found to be extremely labile. Based on Superose 6 FPLC, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and nondenaturing-PAGE analyses, it was demonstrated that the malarial enzyme had an apparent native molecular mass of 90 +/- 8 kDa and contained two major subunits with molecular masses of 55 +/- 6 and 35 +/- 4 kDa (n = 8). The enzymatic reaction required both succinate and coenzyme Q (CoQ) for its maximal catalysis with Km values of 3 and 0.2 microM, and k(cat) values of 0.11 and 0.06 min(-1), respectively. Catalytic efficiency of the malarial SDH for both substrates were found to be relatively low (approximately 600-5000 M(-1) s(-1)). Fumarate, malonate and oxaloacetate were found to inhibit the malarial enzyme with Ki values of 81, 13 and 12 microM, respectively. The malarial enzyme activity was also inhibited by substrate analog of CoQ, 5-hydroxy-2-methyl-1,4-naphthoquinone, with a 50% inhibitory concentration of 5 microM. The quinone had antimalarial activity against the in vitro growth of P. falciparum with a 50% inhibitory concentration of 0.27 microM and was found to completely inhibit oxygen uptake of the parasite at a concentration of 0.88 microM. A known inhibitor of mammalian mitochondrial SDH, 2-thenoyltrifluoroacetone. had no inhibitory effect on both the malarial SDH activity and the oxygen uptake of the parasite at a concentration of 50 microM. Many properties observed in the malarial SDH were found to be different from the host mammalian enzyme.

  4. Mutation from guanine to adenine in 25S rRNA at the position equivalent to E. coli A2058 does not confer erythromycin sensitivity in Sacchromyces cerevisae

    PubMed Central

    Bommakanti, Ananth S.; Lindahl, Lasse; Zengel, Janice M.

    2008-01-01

    The macrolide erythromycin binds to the large subunit of the prokaryotic ribosome near the peptidyltransferase center (PTC) and inhibits elongation of new peptide chains beyond a few amino acids. Nucleotides A2058 and A2059 (E. coli numbering) in 23S rRNA play a crucial role in the binding of erythromycin, and mutation of nucleotide A2058 confers erythromycin resistance in both Gram-positive and Gram-negative bacteria. There are high levels of sequence and structural similarity in the PTC of prokaryotic and eukaryotic ribosomes. However, eukaryotic ribosomes are resistant to erythromycin and the presence of a G at the position equivalent to E. coli nucleotide A2058 is believed to be the reason. To test this hypothesis, we introduced a G to A mutation at this position of the yeast Saccharomyces cerevisiae 25S rRNA and analyzed sensitivity toward erythromycin. Neither growth studies nor erythromycin binding assays on mutated yeast ribosomes indicated any erythromycin sensitivity in mutated yeast strains. These results suggest that the identity of nucleotide 2058 is not the only determinant responsible for the difference in erythromycin sensitivity between yeast and prokaryotes. PMID:18218702

  5. Mutation from guanine to adenine in 25S rRNA at the position equivalent to E. coli A2058 does not confer erythromycin sensitivity in Sacchromyces cerevisae.

    PubMed

    Bommakanti, Ananth S; Lindahl, Lasse; Zengel, Janice M

    2008-03-01

    The macrolide erythromycin binds to the large subunit of the prokaryotic ribosome near the peptidyltransferase center (PTC) and inhibits elongation of new peptide chains beyond a few amino acids. Nucleotides A2058 and A2059 (E. coli numbering) in 23S rRNA play a crucial role in the binding of erythromycin, and mutation of nucleotide A2058 confers erythromycin resistance in both gram-positive and gram-negative bacteria. There are high levels of sequence and structural similarity in the PTC of prokaryotic and eukaryotic ribosomes. However, eukaryotic ribosomes are resistant to erythromycin and the presence of a G at the position equivalent to E. coli nucleotide A2058 is believed to be the reason. To test this hypothesis, we introduced a G to A mutation at this position of the yeast Saccharomyces cerevisiae 25S rRNA and analyzed sensitivity toward erythromycin. Neither growth studies nor erythromycin binding assays on mutated yeast ribosomes indicated any erythromycin sensitivity in mutated yeast strains. These results suggest that the identity of nucleotide 2058 is not the only determinant responsible for the difference in erythromycin sensitivity between yeast and prokaryotes.

  6. Erythromycin-induced ribosome stall in the ermA leader: a barricade to 5'-to-3' nucleolytic cleavage of the ermA transcript.

    PubMed

    Sandler, P; Weisblum, B

    1989-12-01

    The Staphylococcus aureus ermA gene, whose product confers resistance to the macrolide-lincosamide-streptogramin B family of antibiotics, is induced at the level of translation by nanomolar concentrations of erythromycin. Erythromycin also specifically stabilizes ermA transcripts, and the induced stabilization requires in-phase translation of at least one of two small leader peptides in the 5' leader region of the transcript. Erythromycin-induced mRNA stabilization was tested in three constructions in which the ermA transcript was elongated by making insertions at the ermA transcription start. Whereas mRNA downstream of the leader peptide is stabilized by erythromycin, mRNA upstream is not. In the presence of erythromycin, specific mRNA decay intermediates in both the extended ermA genes and the wild-type ermA gene were detected by both Northern blotting and S1 nuclease mapping. The 5' ends of the intermediates map to the sequences that encode each of the two ermA leader peptides, suggesting that the intermediates are produced by stalled erythromycin-bound ribosomes acting as barricades to degradation by 5'-to-3' RNases. In addition, whereas erythromycin was found previously to stabilize ermA transcripts only physically, an ermC-cat-86 hybrid transcript was stabilized both physically and functionally by erythromycin.

  7. Erythromycin-induced ribosome stall in the ermA leader: a barricade to 5'-to-3' nucleolytic cleavage of the ermA transcript.

    PubMed Central

    Sandler, P; Weisblum, B

    1989-01-01

    The Staphylococcus aureus ermA gene, whose product confers resistance to the macrolide-lincosamide-streptogramin B family of antibiotics, is induced at the level of translation by nanomolar concentrations of erythromycin. Erythromycin also specifically stabilizes ermA transcripts, and the induced stabilization requires in-phase translation of at least one of two small leader peptides in the 5' leader region of the transcript. Erythromycin-induced mRNA stabilization was tested in three constructions in which the ermA transcript was elongated by making insertions at the ermA transcription start. Whereas mRNA downstream of the leader peptide is stabilized by erythromycin, mRNA upstream is not. In the presence of erythromycin, specific mRNA decay intermediates in both the extended ermA genes and the wild-type ermA gene were detected by both Northern blotting and S1 nuclease mapping. The 5' ends of the intermediates map to the sequences that encode each of the two ermA leader peptides, suggesting that the intermediates are produced by stalled erythromycin-bound ribosomes acting as barricades to degradation by 5'-to-3' RNases. In addition, whereas erythromycin was found previously to stabilize ermA transcripts only physically, an ermC-cat-86 hybrid transcript was stabilized both physically and functionally by erythromycin. Images PMID:2592348

  8. Arrangement and number of clustered regularly interspaced short palindromic repeat spacers are associated with erythromycin susceptibility in emm12, emm75 and emm92 of group A streptococcus.

    PubMed

    Zheng, P-X; Chiang-Ni, C; Wang, S-Y; Tsai, P-J; Kuo, C-F; Chuang, W-J; Lin, Y-S; Liu, C-C; Wu, J-J

    2014-06-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) are composed of numerous repeat-spacer units and are considered a prokaryotic defence system against foreign nucleic acids. Since antibiotic-resistant genes are frequently encoded in foreign nucleic acids, the aim of this study was to test whether erythromycin susceptibility in group A streptococcus (Streptococcus pyogenes) is associated with characteristics of CRISPR elements. Erythromycin susceptibility of 330 isolates collected between 1997 and 2003 was analysed. Among 29 emm types, emm12, emm75 and emm92 showed significant changes in erythromycin-resistance rates. By sequencing the spacers from two CRISPR loci, spacer contents in emm12, emm75 and emm92 strains were associated with erythromycin susceptibility. Strains with fewer spacers were more resistant to erythromycin. Moreover, in emm4 strains, which showed no significant change in their annual erythromycin-resistance rate, CRISPR type and number of spacers were not correlated with erythromycin susceptibility. These results highlight a novel association between CRISPR spacer content and erythromycin susceptibility in group A streptococcus. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  9. The Succinate Receptor as a Novel Therapeutic Target for Oxidative and Metabolic Stress-Related Conditions

    PubMed Central

    Ariza, Ana Carolina; Deen, Peter Meinardus T.; Robben, Joris Hubertus

    2012-01-01

    The succinate receptor (also known as GPR91) is a G protein-coupled receptor that is closely related to the family of P2Y purinoreceptors. It is expressed in a variety of tissues, including blood cells, adipose tissue, the liver, retina, and kidney. In these tissues, this receptor and its ligand succinate have recently emerged as novel mediators in local stress situations, including ischemia, hypoxia, toxicity, and hyperglycemia. Amongst others, the succinate receptor is involved in recruitment of immune cells to transplanted tissues. Moreover, it was shown to play a key role in the development of diabetic retinopathy. However, most prominently, the role of locally increased succinate levels and succinate receptor activation in the kidney, stimulating the systemic and local renin–angiotensin system, starts to unfold: the succinate receptor is a key mediator in the development of hypertension and possibly fibrosis in diabetes mellitus and metabolic syndrome. This makes the succinate receptor a promising drug target to counteract or prevent cardiovascular and fibrotic defects in these expanding disorders. Recent development of SUCNR1-specific antagonists opens novel possibilities for research in models for these disorders and may eventually provide novel opportunities for the treatment of patients. PMID:22649411

  10. Mitochondrial stress causes increased succination of proteins in adipocytes in response to glucotoxicity.

    PubMed

    Frizzell, Norma; Thomas, Sonia A; Carson, James A; Baynes, John W

    2012-07-15

    2SC [S-(2-succino)-cysteine] is a chemical modification formed by a Michael addition reaction of fumarate with cysteine residues in proteins. Formation of 2SC, termed 'succination' of proteins, increases in adipocytes grown in high-glucose medium and in adipose tissues of Type 2 diabetic mice. However, the metabolic mechanisms leading to increased fumarate and succination of protein in the adipocyte are unknown. Treatment of 3T3 cells with high glucose (30 mM compared with 5 mM) caused a significant increase in cellular ATP/ADP, NADH/NAD+ and Δψm (mitochondrial membrane potential). There was also a significant increase in the cellular fumarate concentration and succination of proteins, which may be attributed to the increase in NADH/NAD+ and subsequent inhibition of tricarboxylic acid cycle NAD+-dependent dehydrogenases. Chemical uncouplers, which dissipated Δψm and reduced the NADH/NAD+ ratio, also decreased the fumarate concentration and protein succination. High glucose plus metformin, an inhibitor of complex I in the electron transport chain, caused an increase in fumarate and succination of protein. Thus excess fuel supply (glucotoxicity) appears to create a pseudohypoxic environment (high NADH/NAD+ without hypoxia), which drives the increase in succination of protein. We propose that increased succination of proteins is an early marker of glucotoxicity and mitochondrial stress in adipose tissue in diabetes.

  11. Succinic acid production from Bacteroides fragilis: process optimization and scale up in a bioreactor.

    PubMed

    Isar, Jasmine; Agarwal, Lata; Saran, Saurabh; Saxena, Rajendra Kumar

    2006-01-01

    We report the effect of different physiological and nutritional parameters on succinic acid production from Bacteroides fragilis. This strain initially produced 0.70gL(-1) of succinic acid in 60h. However, when process optimization was employed, 5.4gL(-1) of succinic acid was produced in medium consisting of glucose (1.5%); tryptone (2.5%); Na(2)CO(3) (1.5%), at pH 7.0, when inoculated with 4% inoculum and incubated at 37 degrees C, 100rpm for 48h. A marked enhancement in succinic acid production was observed when the optimized conditions were employed in a 10L bioreactor. A total of 12.5gL(-1) of succinic acid was produced in 30h. This is approximately 12-fold increase in succinic acid production when compared to the initial un-optimized medium production. This enhancement in succinic acid production may be due to the control of CO(2) supply and the impeller speed. This is also resulted in the reduction of the production time. The present study provides useful information to the industrialists seeking environmentally benign technology for the production of bulk biomolecules through manipulation of various chemical parameters.

  12. Production of Succinic Acid from Citric Acid and Related Acids by Lactobacillus Strains

    PubMed Central

    Kaneuchi, Choji; Seki, Masako; Komagata, Kazuo

    1988-01-01

    A number of Lactobacillus strains produced succinic acid in de Man-Rogosa-Sharpe broth to various extents. Among 86 fresh isolates from fermented cane molasses in Thailand, 30 strains (35%) produced succinic acid; namely, 23 of 39 Lactobacillus reuteri strains, 6 of 18 L. cellobiosus strains, and 1 of 6 unidentified strains. All of 10 L. casei subsp. casei strains, 5 L. casei subsp. rhamnosus strains, 6 L. mali strains, and 2 L. buchneri strains did not produce succinic acid. Among 58 known strains including 48 type strains of different Lactobacillus species, the strains of L. acidophilus, L. crispatus, L. jensenii, and L. parvus produced succinic acid to the same extent as the most active fresh isolates, and those of L. alimentarius, L. collinoides, L. farciminis, L. fructivorans (1 of 2 strains tested), L. malefermentans, and L. reuteri were also positive, to lesser extents. Diammonium citrate in de Man-Rogosa-Sharpe broth was determined as a precursor of the succinic acid produced. Production rates were about 70% on a molar basis with two fresh strains tested. Succinic acid was also produced from fumaric and malic acids but not from dl-isocitric, α-ketoglutaric, and pyruvic acids. The present study is considered to provide the first evidence on the production of succinic acid, an important flavoring substance in dairy products and fermented beverages, from citrate by lactobacilli. PMID:16347795

  13. Succinic Acid Production from Cheese Whey using Actinobacillus succinogenes 130 Z

    NASA Astrophysics Data System (ADS)

    Wan, Caixia; Li, Yebo; Shahbazi, Abolghasem; Xiu, Shuangning

    Actinobacillus succinogenes 130 Z was used to produce succinic acid from cheese whey in this study. At the presence of external CO2 supply, the effects of initial cheese whey concentration, pH, and inoculum size on the succinic acid production were studied. The by-product formation during the fermentation process was also analyzed. The highest succinic acid yield of 0.57 was obtained at initial cheese whey concentration of 50 g/L, while the highest succinic acid productivity of 0.58 g h-1 L-1 was obtained at initial cheese whey concentration of 100 g/L. Increase in pH and inoculum size caused higher succinic acid yield and productivity. At the preferred fermentation condition of pH 6.8, inoculum size of 5% and initial cheese whey concentration of 50 g/L, succinic acid yield of 0.57, and productivity of 0.44 g h-1 L-1 were obtained. Acetic acid and formic acid were the main by-products throughout the fermentation run of 48 h. It is feasible to produce succinic acid using lactose from cheese whey as carbon resource by A. succinogenes 130 Z.

  14. Activating Phosphoenolpyruvate Carboxylase and Phosphoenolpyruvate Carboxykinase in Combination for Improvement of Succinate Production

    PubMed Central

    Tan, Zaigao; Zhu, Xinna; Chen, Jing; Li, Qingyan

    2013-01-01

    Phosphoenolpyruvate (PEP) carboxylation is an important step in the production of succinate by Escherichia coli. Two enzymes, PEP carboxylase (PPC) and PEP carboxykinase (PCK), are responsible for PEP carboxylation. PPC has high substrate affinity and catalytic velocity but wastes the high energy of PEP. PCK has low substrate affinity and catalytic velocity but can conserve the high energy of PEP for ATP formation. In this work, the expression of both the ppc and pck genes was modulated, with multiple regulatory parts of different strengths, in order to investigate the relationship between PPC or PCK activity and succinate production. There was a positive correlation between PCK activity and succinate production. In contrast, there was a positive correlation between PPC activity and succinate production only when PPC activity was within a certain range; excessive PPC activity decreased the rates of both cell growth and succinate formation. These two enzymes were also activated in combination in order to recruit the advantages of each for the improvement of succinate production. It was demonstrated that PPC and PCK had a synergistic effect in improving succinate production. PMID:23747698

  15. ATP-Based Ratio Regulation of Glucose and Xylose Improved Succinate Production

    PubMed Central

    Zhang, Fengyu; Li, Jiaojiao; Liu, Huaiwei; Liang, Quanfeng; Qi, Qingsheng

    2016-01-01

    We previously engineered E. coli YL104H to efficiently produce succinate from glucose. Furthermore, the present study proved that YL104H could also co-utilize xylose and glucose for succinate production. However, anaerobic succinate accumulation using xylose as the sole carbon source failed, probably because of an insufficient supply of energy. By analyzing the ATP generation under anaerobic conditions in the presence of glucose or xylose, we indicated that succinate production was affected by the intracellular ATP level, which can be simply regulated by the substrate ratio of xylose to glucose. This finding was confirmed by succinate production using an artificial mixture containing different xylose to glucose ratios. Using xylose mother liquor, a waste containing both glucose and xylose derived from xylitol production, a final succinate titer of 61.66 g/L with an overall productivity of 0.95 g/L/h was achieved, indicating that the regulation of the intracellular ATP level may be a useful and efficient strategy for succinate production and can be extended to other anaerobic processes. PMID:27315279

  16. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions.

    PubMed

    Ariza, Ana Carolina; Deen, Peter Meinardus T; Robben, Joris Hubertus

    2012-01-01

    The succinate receptor (also known as GPR91) is a G protein-coupled receptor that is closely related to the family of P2Y purinoreceptors. It is expressed in a variety of tissues, including blood cells, adipose tissue, the liver, retina, and kidney. In these tissues, this receptor and its ligand succinate have recently emerged as novel mediators in local stress situations, including ischemia, hypoxia, toxicity, and hyperglycemia. Amongst others, the succinate receptor is involved in recruitment of immune cells to transplanted tissues. Moreover, it was shown to play a key role in the development of diabetic retinopathy. However, most prominently, the role of locally increased succinate levels and succinate receptor activation in the kidney, stimulating the systemic and local renin-angiotensin system, starts to unfold: the succinate receptor is a key mediator in the development of hypertension and possibly fibrosis in diabetes mellitus and metabolic syndrome. This makes the succinate receptor a promising drug target to counteract or prevent cardiovascular and fibrotic defects in these expanding disorders. Recent development of SUCNR1-specific antagonists opens novel possibilities for research in models for these disorders and may eventually provide novel opportunities for the treatment of patients.

  17. Enhanced succinic acid production from corncob hydrolysate by microbial electrolysis cells.

    PubMed

    Zhao, Yan; Cao, Weijia; Wang, Zhen; Zhang, Bowen; Chen, Kequan; Ouyang, Pingkai

    2016-02-01

    In this study, Actinobacillus succinogenes NJ113 microbial electrolysis cells (MECs) were used to enhance the reducing power responsible for succinic acid production from corncob hydrolysate. During corncob hydrolysate fermentation, electric MECs resulted in a 1.31-fold increase in succinic acid production and a 1.33-fold increase in the reducing power compared with those in non-electric MECs. When the hydrolysate was detoxified by combining Ca(OH)2, NaOH, and activated carbon, succinic acid production increased from 3.47 to 6.95 g/l. Using a constant potential of -1.8 V further increased succinic acid production to 7.18 g/l. A total of 18.09 g/l of succinic acid and a yield of 0.60 g/g total sugar were obtained after a 60-h fermentation when NaOH was used as a pH regulator. The improved succinic acid yield from corncob hydrolysate fermentation using A. succinogenes NJ113 in electric MECs demonstrates the great potential of using biomass as a feedstock to cost-effectively produce succinate.

  18. Inhibition of succinic acid production in metabolically engineered Escherichia coli by neutralizing agent, organic acids, and osmolarity.

    PubMed

    Andersson, Christian; Helmerius, Jonas; Hodge, David; Berglund, Kris A; Rova, Ulrika

    2009-01-01

    The economical viability of biochemical succinic acid production is a result of many processing parameters including final succinic acid concentration, recovery of succinate, and the volumetric productivity. Maintaining volumetric productivities >2.5 g L(-1) h(-1) is important if production of succinic acid from renewable resources should be competitive. In this work, the effects of organic acids, osmolarity, and neutralizing agent (NH4OH, KOH, NaOH, K2CO3, and Na2CO3), and Na2CO3) on the fermentative succinic acid production by Escherichia coli AFP184 were investigated. The highest concentration of succinic acid, 77 g L(-1), was obtained with Na2CO3. In general, irrespective of the base used, succinic acid productivity per viable cell was significantly reduced as the concentration of the produced acid increased. Increased osmolarity resulting from base addition during succinate production only marginally affected the productivity per viable cell. Addition of the osmoprotectant glycine betaine to cultures resulted in an increased aerobic growth rate and anaerobic glucose consumption rate, but decreased succinic acid yield. When using NH4OH productivity completely ceased at a succinic acid concentration of approximately 40 g L(-1). Volumetric productivities remained at 2.5 g L(-1) h(-1) for up to 10 h longer when K- or Na-bases where used instead of NH4OH. The decrease in cellular succinic acid productivity observed during the anaerobic phase was found to be due to increased organic acid concentrations rather than medium osmolarity.

  19. Study of the interaction of cadmium with membrane-bound succinate dehydrogenase.

    PubMed

    Jay, D; Zamorano, R; Muñoz, E; Gleason, R; Boldu, J L

    1991-04-01

    Cadmium ions inhibit membrane-bound succinate dehydrogenase with a second-order rate constant of 10.42 mM-1 s-1 at pH 7.35 and 25 degrees C. Succinate and malonate protect the enzyme against cadmium ion inhibition. The protection pattern exerted by succinate and malonate suggests that the group modified by cadmium is located at the active site. The pH curve of inactivation by Cd2+ indicates the involvement of an amino acid residue with pKa of 7.23.

  20. Six Month Oral Toxicity Study of WR238605 Succinate in Rats. Volume 1

    DTIC Science & Technology

    1996-02-02

    Test Article: WR238605 Succinate Contract No.: DAMD17-92-C-2001 Study Director Barry S. Levine, D.Sc, D.A.B.T. In-Life Phase Completed On...AND DRAFT REPORT FROM THE ANALYTICAL LABORATORY INSPECT ON 9/19/95, TO STUDY DIR 9/20/95, TO MGMT 9/21/95 PHASES: TEST ARTICLE ANALYSIS INSPECT ON 1...MONTH ORAL TOXICITY STUDY OF WR238605 SUCCINATE IN RATS Test Article.: WR238605 Succinate Sponsor: US Army Medical Materiel Development

  1. Comparative fluxome and metabolome analysis for overproduction of succinate in Escherichia coli.

    PubMed

    Taymaz-Nikerel, Hilal; De Mey, Marjan; Baart, Gino J E; Maertens, Jo; Foulquié-Moreno, Maria Remedios; Charlier, Daniel; Heijnen, Joseph J; van Gulik, Walter M

    2016-04-01

    An aerobic succinate-producing Escherichia coli mutant was compared to its wild-type by quantitatively analyzing both the metabolome and fluxome, during glucose-limited steady-state and succinate excess dynamic conditions, in order to identify targets for further strain engineering towards more efficient succinate production. The mutant had four functional mutations under the conditions investigated: increased expression of a succinate exporter (DcuC), deletion of a succinate importer (Dct), deletion of succinate dehydrogenase (SUCDH) and expression of a PEP carboxylase (PPC) with increased capacity due to a point mutation. The steady-state and dynamic patterns of the intracellular metabolite levels and fluxes in response to changes were used to locate the quantitative differences in the physiology/metabolism of the mutant strain. Unexpectedly the mutant had a higher energy efficiency, indicated by a much lower rate of oxygen consumption, under glucose-limited conditions, caused by the deletion of the transcription factors IclR and ArcA. Furthermore the mutant had a much lower uptake capacity for succinate (26-fold) and oxygen (17-fold under succinate excess) compared to the wild-type strain. The mutant strain produced 7.9 mmol.CmolX(-1).h(-1) succinate during chemostat cultivation, showing that the choice of the applied genetic modifications was a successful strategy. Furthermore, the applied genetic modifications resulted in multiple large changes in metabolite levels (FBP, pyruvate, 6PG, NAD(+) /NADH ratio, α-ketogluarate) corresponding to large changes in fluxes. Compared to the wild-type a considerable flux shift occurred from the tricarboxylic acid (TCA) cycle to the oxidative part of the pentose phosphate pathway, including an inversion of the pyruvate kinase flux. The mutant responded very differently to excess of succinate, with a remarkable possible reversal of the TCA cycle. The mutant and the wild-type both showed homeostatic behaviour with respect

  2. Succinate production from CO₂-grown microalgal biomass as carbon source using engineered Corynebacterium glutamicum through consolidated bioprocessing.

    PubMed

    Lee, Jungseok; Sim, Sang Jun; Bott, Michael; Um, Youngsoon; Oh, Min-Kyu; Woo, Han Min

    2014-07-24

    The potential for production of chemicals from microalgal biomass has been considered as an alternative route for CO₂ mitigation and establishment of biorefineries. This study presents the development of consolidated bioprocessing for succinate production from microalgal biomass using engineered Corynebacterium glutamicum. Starch-degrading and succinate-producing C. glutamicum strains produced succinate (0.16 g succinate/g total carbon source) from a mixture of starch and glucose as a model microalgal biomass. Subsequently, the engineered C. glutamicum strains were able to produce succinate (0.28 g succinate/g of total sugars including starch) from pretreated microalgal biomass of CO₂-grown Chlamydomonas reinhardtii. For the first time, this work shows succinate production from CO₂ via sequential fermentations of CO₂-grown microalgae and engineered C. glutamicum. Therefore, consolidated bioprocessing based on microalgal biomass could be useful to promote variety of biorefineries.

  3. 21 CFR 573.420 - Ethyl cellulose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethyl cellulose. 573.420 Section 573.420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive...

  4. Ethyl p-nitrophenyl phenylphosphorothioate (EPN)

    Integrated Risk Information System (IRIS)

    Ethyl p - nitrophenyl phenylphosphorothioate ( EPN ) ; CASRN 2104 - 64 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Ha

  5. Manufacturing Ethyl Acetate From Fermentation Ethanol

    NASA Technical Reports Server (NTRS)

    Rohatgi, Naresh K.; Ingham, John D.

    1991-01-01

    Conceptual process uses dilute product of fermentation instead of concentrated ethanol. Low-concentration ethanol, extracted by vacuum from fermentation tank, and acetic acid constitutes feedstock for catalytic reaction. Product of reaction goes through steps that increases ethyl acetate content to 93 percent by weight. To conserve energy, heat exchangers recycle waste heat to preheat process streams at various points.

  6. 21 CFR 184.1295 - Ethyl formate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... chapter; and 0.01 percent in all other food categories. (e) Prior sanctions for ethyl formate different... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DIRECT FOOD... the animal kingdom. (b) The ingredient meets the specifications of the “Food Chemicals Codex,” 3d Ed...

  7. Manufacturing Ethyl Acetate From Fermentation Ethanol

    NASA Technical Reports Server (NTRS)

    Rohatgi, Naresh K.; Ingham, John D.

    1991-01-01

    Conceptual process uses dilute product of fermentation instead of concentrated ethanol. Low-concentration ethanol, extracted by vacuum from fermentation tank, and acetic acid constitutes feedstock for catalytic reaction. Product of reaction goes through steps that increases ethyl acetate content to 93 percent by weight. To conserve energy, heat exchangers recycle waste heat to preheat process streams at various points.

  8. 21 CFR 173.228 - Ethyl acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Ethyl acetate. 173.228 Section 173.228 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SECONDARY DIRECT FOOD ADDITIVES PERMITTED IN FOOD FOR HUMAN CONSUMPTION Solvents, Lubricants, Release Agents and Related...

  9. Nucleotide sequence of the gene ereA encoding the erythromycin esterase in Escherichia coli.

    PubMed

    Ounissi, H; Courvalin, P

    1985-01-01

    We have cloned and determined the nucleotide sequence of the gene ereA of plasmid pIP1100 which confers high-level resistance to erythromycin (Em) in Escherichia coli. The gene was defined by initiation and termination codons and by in vitro insertion-inactivation into an open reading frame (ORF) of 1032 bp corresponding to a product with an Mr of 37 765. However, the enzyme, an Em esterase, displayed an apparent Mr of 43 000 upon electrophoresis of a minicell extract on the SDS-polyacrylamide gels. The G + C content (50.5%) of the gene ereA and the preferential codon usage in its ORF suggest that this resistance determinant should be indigenous to E. coli.

  10. Life-Threatening Invasive Helcococcus kunzii Infections in Intravenous-Drug Users and ermA-Mediated Erythromycin Resistance

    PubMed Central

    Woo, Patrick C. Y.; Tse, Herman; Wong, Samson S. Y.; Tse, Cindy W. S.; Fung, Ami M. Y.; Tam, Dorothy M. W.; Lau, Susanna K. P.; Yuen, Kwok-yung

    2005-01-01

    We report the first two cases of life-threatening invasive Helcococcus kunzii infection, with primary bacteremia and empyema thoracis, respectively. Gram smears of both H. kunzii isolates showed a mixture of gram-positive and gram-negative cocci. The isolate from the first patient, resistant to erythromycin and clindamycin, possessed an ermA gene. PMID:16333132

  11. Life-threatening invasive Helcococcus kunzii infections in intravenous-drug users and ermA-mediated erythromycin resistance.

    PubMed

    Woo, Patrick C Y; Tse, Herman; Wong, Samson S Y; Tse, Cindy W S; Fung, Ami M Y; Tam, Dorothy M W; Lau, Susanna K P; Yuen, Kwok-yung

    2005-12-01

    We report the first two cases of life-threatening invasive Helcococcus kunzii infection, with primary bacteremia and empyema thoracis, respectively. Gram smears of both H. kunzii isolates showed a mixture of gram-positive and gram-negative cocci. The isolate from the first patient, resistant to erythromycin and clindamycin, possessed an ermA gene.

  12. Correlation between genetic features of the mef(A)-msr(D) locus and erythromycin resistance in Streptococcus pyogenes.

    PubMed

    Vitali, Luca Agostino; Di Luca, Maria Chiara; Prenna, Manuela; Petrelli, Dezemona

    2016-01-01

    We investigated the correlation between the genetic variation within mef(A)-msr(D) determinants of efflux-mediated erythromycin resistance in Streptococcus pyogenes and the level of erythromycin resistance. Twenty-eight mef(A)-positive strains were selected according to erythromycin MIC (4-32 μg/mL), and their mef(A)-msr(D) regions were sequenced. Strains were classified according to the bacteriophage carrying mef(A)-msr(D). A new Φm46.1 genetic variant was found in 8 strains out of 28 and named VP_00501.1. Degree of allelic variation was higher in mef(A) than in msr(D). Hotspots for recombination were mapped within the locus that could have shaped the apparent mosaic structure of the region. There was a general correlation between mef(A)-msr(D) sequence and erythromycin resistance level. However, lysogenic conversion of susceptible strains by mef(A)-msr(D)-carrying Φm46.1 indicated that key determinants may not all reside within the mef(A)-msr(D) locus and that horizontal gene transfer could contribute to changes in the level of antibiotic resistance in S. pyogenes.

  13. Draft Genome Sequence of an Erythromycin-Resistant Propionibacterium acnes Isolate Recovered from Folliculitis of the Scalp

    PubMed Central

    Aubin, Guillaume Ghislain; Kambarev, Stanimir; Guillouzouic, Aurélie; Khammari, Amir; Dréno, Brigitte

    2017-01-01

    ABSTRACT Propionibacterium acnes is now well-known and recognized for its implication in the pathogenesis of acne vulgaris. Here, we report the draft genome sequence of an erythromycin-resistant P. acnes strain isolated from a case of folliculitis of the scalp belonging to phylotype IA1 and sequence type 18 (ST18). PMID:28126936

  14. Risk of adverse effects in pneumonic foals treated with erythromycin versus other antibiotics: 143 cases (1986-1996).

    PubMed

    Stratton-Phelps, M; Wilson, W D; Gardner, I A

    2000-07-01

    To determine whether foals with pneumonia that were treated with erythromycin, alone or in combination with rifampin or gentamicin, had a higher risk of developing adverse effects, compared with foals treated with trimethoprim-sulfamethoxazole (TMS), penicillin G procaine (PGP), or a combination of TMS and PGP (control foals). Retrospective study. 143 foals < 240 days old. Information on age, sex, breed, primary drug treatment, total days of treatment with the primary drug, and whether the foal developed diarrhea, hyperthermia, or respiratory distress was obtained from the medical records. Relative risk (RR) and attributable risk (AR) were calculated to compare risk of adverse reactions between foals treated with erythromycin and control foals. Only 3 (4.3%) control foals developed diarrhea; none developed hyperthermia or respiratory distress. Foals treated with erythromycin had an 8-fold risk (RR, 8.3) of developing diarrhea, compared with control foals, and increased risks of hyperthermia (AR, 25%) and respiratory distress (AR, 15%). Results suggest that use of erythromycin to treat foals with pneumonia was associated with an increased risk of diarrhea, hyperthermia, and respiratory distress, compared with use of TMS or PGP.

  15. Effect of compression force on the crystal properties of erythromycin acistrate tablets.

    PubMed

    Riippi, M; Tanninen, V; Yliruusi, J

    2000-11-01

    The crystal properties of compressed and powdered erythromycin acistrate tablets were studied by the X-ray powder diffraction (XRPD) method. Detailed analysis of X-ray powder diffraction line profiles was performed. Diffraction peak intensities and full width at half maximum (FWHM) values of the peaks corresponding to three different crystal lattice directions were determined. Crystallite size was calculated by Scherrer's equation using the data of integral breadth of the peaks. The preferred orientation of the crystallites is also discussed. According to the results, the crystallite size increased on the tablet surface after a small compression force (4 kN) in all crystal lattice directions studied. Even small compression forces caused recrystallization. With higher compression forces (8-18 kN) the crystallite size and the FWHM values remained rather constant. After the compression force of 18 kN the peaks in different crystal lattice directions behaved differently. In the lattice directions of diffraction maxima 2 and 3, the effect was the same with the small (4 kN) and the high compression force (22 kN). Further recrystallization occurred with 22 kN. However, in the crystal lattice direction of diffraction maximum 1 at the compression force of 8 kN the crystallite broke and crystallinity decreased. These were not seen in the powdered tablet samples. It could be concluded that the effect of compression force on the crystal properties of erythromycin acistrate tablets was seen on the tablet surface but not in the powdered tablets. Compression force also affected the preferred orientation of crystallites on the tablet surface and especially in the lattice direction of diffraction maximum 3. This was not seen in the powdered tablets.

  16. Prevalence of erm gene classes in erythromycin-resistant Staphylococcus aureus strains isolated between 1959 and 1988.

    PubMed Central

    Westh, H; Hougaard, D M; Vuust, J; Rosdahl, V T

    1995-01-01

    The epidemiology of the two common erythromycin resistance methylase (erm) genes ermA and ermC was analyzed by Southern blotting in 428 erythromycin-resistant Staphylococcus aureus strains isolated from blood between 1959 and 1988 in Denmark. ermA and/or ermC was present in 98% of the erythromycin-resistant strains tested. ermA was found only as a chromosomal insert and was solely responsible for erythromycin resistance in these strains until about 1971. ermA was the only erm gene found in 337 strains and was a single insert in 61% of these strains, two inserts were seen in 37%, and three inserts were found in 2%. Thirteen different ermA EcoRI restriction fragment length polymorphisms were identified. ermA was not found in strains of phage type patterns group II and type 95, which are very common today. ermC was found on a plasmid in 77 strains. ermC was first seen in 1971 and spread rapidly in the S. aureus population, with a 5- to 10-fold increase every 5 years, and in 1984 to 1988, it was responsible for erythromycin resistance in 72% of the strains. The predominant plasmid carrying ermC was 2.5 kb, while four plasmids were smaller and three were larger. ermC has been found in all phage type patterns. Eight strains contained combinations of ermA and ermC, and no erm gene was detected in six strains. PMID:7726500

  17. Treatment of experimental endocarditis due to erythromycin-susceptible or -resistant methicillin-resistant Staphylococcus aureus with RP 59500.

    PubMed

    Entenza, J M; Drugeon, H; Glauser, M P; Moreillon, P

    1995-07-01

    RP 59500 is a new injectable streptogramin composed of two synergistic components (quinupristin and dalfopristin) which are active against erythromycin-susceptible and -resistant gram-positive pathogens. The present experiments compared the therapeutic efficacy of RP 59500 with that of vancomycin against experimental endocarditis due to either of two erythromycin-susceptible or two constitutively erythromycin-resistant isolates of methicillin-resistant Staphylococcus aureus. RP 59500 had low MICs for the four test organisms as well as for 24 additional isolates (the MIC at which 90% of the isolates were inhibited was < 1 mg/liter) which were mostly inducibly (47%) or constitutively (39%) erythromycin resistant. Aortic endocarditis in rats was produced with catheter-induced vegetations. Three-day therapy was initiated 12 h after infection, and the drugs were delivered via a computerized pump, which permitted the mimicking of the drug kinetics produced in human serum by twice-daily intravenous injections of 7 mg of RP 59500 per kg of body weight or 1 g of vancomycin. Both antibiotics reduced vegetation bacterial titers to below detection levels in ca. 70% of animals infected with the erythromycin-susceptible isolates (P < 0.05 compared with titers in controls). Vancomycin was also effective against the constitutively resistant strains, but RP 59500 failed against these isolates. Further experiments proved that RP 59500 failures were related to the very short life span of dalfopristin in serum (< or = 2 h, compared with > or = 6 h for quinupristin), since successful treatment was restored by artificially prolonging the dalfopristin levels for 6 h. Thus, RP 59500 is a promising alternative to vancomycin against methicillin-resistant S. aureus infections, provided that pharmacokinetic parameters are adjusted to afford prolonged levels of both of its constituents in serum. This observation is also relevant to humans, in whom the life span of dalfopristin in serum is also

  18. Separation of ethyl acetate and ethanol from methyl ethyl ketone and water, and ethyl acetate from ethanol and water by extractive distillation

    SciTech Connect

    Ratanapupech, P.

    1983-01-01

    A number of extractive distillation agents were investigated to separate ethyl acetate and ethanol from methyl ethyl ketone and water in an ethyl acetate-ethanol-methyl ethyl ketone-water mixture, and ethyl acetate from ethanol and water in an ethyl acetate-ethanol-water mixture by means of extractive distillation. A measure of separation is the relative volatility, which was calculated by the Fenske equation. The results showed that it is possible to separate the components from these two mixtures by extractive distillation with a distillation column containing relatively few theoretical plates. It was found that the proper extractive distillation agent completely eliminated azeotrope formation among the components in the mixtures investigated. Packed columns can be used in extractive distillation even though they are not quite as efficient as perforated plate columns. For the separation of ethyl acetate and ethanol from methyl ethyl ketone and water one of the more attractive extractive agents is comprised of 25.0 wt.% hydroquinone, 25.0 wt.% ortho-tertbutylphenol, 25.0 wt.% catechol and 25.0 wt.% dimethylformamide, and the relative volatilities of ethnaol to methyl ethyl ketone obtained was 1.51 and ethyl acetate to methyl ethyl ketone was 1.69. For the separation of ethyl acetate from ethanol and water a typical attractive extractive agent is comprised of 33.33 wt.% glycerol, 33.33 wt.% ethylene glycol and 33.33 wt.% triethylene glycol, and the relative volatility of ethyl acetate to ethanol obtained was 3.93.

  19. 40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... combined residues of the herbicide quizalofop (2- propanoic acid) and quizalofop ethyl (ethyl-2- propanoate...) Tolerances are established for the combined residues of the herbicide quizalofop (2- propanoic acid... herbicide quizalofop-p ethyl ester , and its acid metabolite quizalofop-p , and the S enantiomers of...

  20. 21 CFR 177.1320 - Ethylene-ethyl acrylate copolymers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Ethylene-ethyl acrylate copolymers. 177.1320... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1320 Ethylene-ethyl acrylate copolymers. Ethylene-ethyl acrylate copolymers may be safely used to produce packaging materials,...

  1. 21 CFR 177.1320 - Ethylene-ethyl acrylate copolymers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Ethylene-ethyl acrylate copolymers. 177.1320... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1320 Ethylene-ethyl acrylate copolymers. Ethylene-ethyl acrylate copolymers may be safely used to produce packaging materials,...

  2. 21 CFR 177.1320 - Ethylene-ethyl acrylate copolymers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Ethylene-ethyl acrylate copolymers. 177.1320... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1320 Ethylene-ethyl acrylate copolymers. Ethylene-ethyl acrylate copolymers may be safely used to produce packaging materials,...

  3. 40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... residues of the herbicide quizalofop ethyl, including its metabolites and degradates, in or on the....05 (2) Tolerances are established for residues of the herbicide quizalofop ethyl, including its... with regional registration are established for residues of the herbicide quizalofop ethyl, including...

  4. 40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... residues of the herbicide quizalofop ethyl, including its metabolites and degradates, in or on the....05 (2) Tolerances are established for residues of the herbicide quizalofop ethyl, including its... with regional registration are established for residues of the herbicide quizalofop ethyl, including...

  5. 40 CFR 180.441 - Quizalofop ethyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... residues of the herbicide quizalofop ethyl, including its metabolites and degradates, in or on the....05 (2) Tolerances are established for residues of the herbicide quizalofop ethyl, including its... with regional registration are established for residues of the herbicide quizalofop ethyl, including...

  6. Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance

    PubMed Central

    Ferreyra, Jessica A.; Wu, Katherine J.; Hryckowian, Andrew J.; Bouley, Donna M.; Weimer, Bart C.; Sonnenburg, Justin L.

    2016-01-01

    Summary Clostridium difficile is a leading cause of antibiotic-associated diarrhea. The mechanisms underlying C. difficile expansion after microbiota disturbance are just emerging. We assessed the gene expression profile of C. difficile within the intestine of gnotobiotic mice to identify genes regulated in response to either dietary or microbiota compositional changes. In the presence of the gut symbiont Bacteroides thetaiotaomicron, C. difficile induces a pathway that metabolizes the microbiota fermentation end-product succinate to butyrate. The low concentration of succinate in the microbiota of conventional mice is transiently elevated upon antibiotic treatment or chemically-induced intestinal motility disturbance, and C. difficile exploits this succinate spike to expand in the perturbed intestine. A C. difficile mutant compromised in succinate utilization is at a competitive disadvantage during these perturbations. Understanding the metabolic mechanisms involved in microbiota-C. difficile interactions may help to identify approaches for the treatment and prevention of C. difficile-associated diseases. PMID:25498344

  7. Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages.

    PubMed

    Mills, Evanna L; Kelly, Beth; Logan, Angela; Costa, Ana S H; Varma, Mukund; Bryant, Clare E; Tourlomousis, Panagiotis; Däbritz, J Henry M; Gottlieb, Eyal; Latorre, Isabel; Corr, Sinéad C; McManus, Gavin; Ryan, Dylan; Jacobs, Howard T; Szibor, Marten; Xavier, Ramnik J; Braun, Thomas; Frezza, Christian; Murphy, Michael P; O'Neill, Luke A

    2016-10-06

    Activated macrophages undergo metabolic reprogramming, which drives their pro-inflammatory phenotype, but the mechanistic basis for this remains obscure. Here, we demonstrate that upon lipopolysaccharide (LPS) stimulation, macrophages shift from producing ATP by oxidative phosphorylation to glycolysis while also increasing succinate levels. We show that increased mitochondrial oxidation of succinate via succinate dehydrogenase (SDH) and an elevation of mitochondrial membrane potential combine to drive mitochondrial reactive oxygen species (ROS) production. RNA sequencing reveals that this combination induces a pro-inflammatory gene expression profile, while an inhibitor of succinate oxidation, dimethyl malonate (DMM), promotes an anti-inflammatory outcome. Blocking ROS production with rotenone by uncoupling mitochondria or by expressing the alternative oxidase (AOX) inhibits this inflammatory phenotype, with AOX protecting mice from LPS lethality. The metabolic alterations that occur upon activation of macrophages therefore repurpose mitochondria from ATP synthesis to ROS production in order to promote a pro-inflammatory state.

  8. Quinone reduction by Rhodothermus marinus succinate:menaquinone oxidoreductase is not stimulated by the membrane potential

    SciTech Connect

    Fernandes, Andreia S.; Konstantinov, Alexander A.; Teixeira, Miguel; Pereira, Manuela M. . E-mail: mpereira@itqb.unl.pt

    2005-05-06

    Succinate:quinone oxidoreductase (SQR), a di-haem enzyme purified from Rhodothermus marinus, reveals an HQNO-sensitive succinate:quinone oxidoreductase activity with several menaquinone analogues as electron acceptors that decreases with lowering the redox midpoint potential of the quinones. A turnover with the low-potential 2,3-dimethyl-1,4-naphthoquinone that is the closest analogue of menaquinone, although low, can be detected in liposome-reconstituted SQR. Reduction of the quinone is not stimulated by an imposed K{sup +}-diffusion membrane potential of a physiological sign (positive inside the vesicles). Nor does the imposed membrane potential increase the reduction level of the haems in R. marinus SQR poised with the succinate/fumarate redox couple. The data do not support a widely discussed hypothesis on the electrogenic transmembrane electron transfer from succinate to menaquinone catalysed by di-haem SQRs. The role of the membrane potential in regulation of the SQR activity is discussed.

  9. Succinic Semialdehyde Promotes Prosurvival Capability of Agrobacterium tumefaciens

    PubMed Central

    Wang, Chao; Tang, Desong; Gao, Yong-Gui

    2016-01-01

    ABSTRACT Succinic semialdehyde (SSA), an important metabolite of γ-aminobutyric acid (GABA), is a ligand of the repressor AttJ regulating the expression of the attJ-attKLM gene cluster in the plant pathogen Agrobacterium tumefaciens. While the response of A. tumefaciens to GABA and the function of attKLM have been extensively studied, genetic and physiological responses of A. tumefaciens to SSA remain unknown. In combination with microarray and genetic approaches, this study sets out to explore new roles of the SSA-AttJKLM regulatory mechanism during bacterial infection. The results showed that SSA plays a key role in regulation of several bacterial activities, including C4-dicarboxylate utilization, nitrate assimilation, and resistance to oxidative stress. Interestingly, while the SSA relies heavily on the functional AttKLM in mediating nitrate assimilation and oxidative stress resistance, the compound could regulate utilization of C4-dicarboxylates independent of AttJKLM. We further provide evidence that SSA controls C4-dicarboxylate utilization through induction of an SSA importer and that disruption of attKLM attenuates the tumorigenicity of A. tumefaciens. Taken together, these findings indicate that SSA could be a potent plant signal which, together with AttKLM, plays a vital role in promoting the bacterial prosurvival abilities during infection. IMPORTANCE Agrobacterium tumefaciens is a plant pathogen causing crown gall diseases and has been well known as a powerful tool for plant genetic engineering. During the long history of microbe-host interaction, A. tumefaciens has evolved the capabilities of recognition and response to plant-derived chemical metabolites. Succinic semialdehyde (SSA) is one such metabolite. Previous results have demonstrated that SSA functions to activate a quorum-quenching mechanism and thus to decrease the level of quorum-sensing signals, thereby avoiding the elicitation of a plant defense. Here, we studied the effect of SSA on gene

  10. Industrial systems biology of Saccharomyces cerevisiae enables novel succinic acid cell factory.

    PubMed

    Otero, José Manuel; Cimini, Donatella; Patil, Kiran R; Poulsen, Simon G; Olsson, Lisbeth; Nielsen, Jens

    2013-01-01

    Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust commerically compatible scaffold to be exploitted for diverse chemical production. Succinic acid is a highly sought after added-value chemical for which there is no native pre-disposition for production and accmulation in S. cerevisiae. The genome-scale metabolic network reconstruction of S. cerevisiae enabled in silico gene deletion predictions using an evolutionary programming method to couple biomass and succinate production. Glycine and serine, both essential amino acids required for biomass formation, are formed from both glycolytic and TCA cycle intermediates. Succinate formation results from the isocitrate lyase catalyzed conversion of isocitrate, and from the α-keto-glutarate dehydrogenase catalyzed conversion of α-keto-glutarate. Succinate is subsequently depleted by the succinate dehydrogenase complex. The metabolic engineering strategy identified included deletion of the primary succinate consuming reaction, Sdh3p, and interruption of glycolysis derived serine by deletion of 3-phosphoglycerate dehydrogenase, Ser3p/Ser33p. Pursuing these targets, a multi-gene deletion strain was constructed, and directed evolution with selection used to identify a succinate producing mutant. Physiological characterization coupled with integrated data analysis of transcriptome data in the metabolically engineered strain were used to identify 2(nd)-round metabolic engineering targets. The resulting strain represents a 30-fold improvement in succinate titer, and a 43-fold improvement in succinate yield on biomass, with only a 2.8-fold decrease in the specific growth rate compared to the reference strain. Intuitive genetic targets for either over-expression or interruption of succinate producing or consuming pathways, respectively, do not lead to increased succinate. Rather, we demonstrate how

  11. Industrial Systems Biology of Saccharomyces cerevisiae Enables Novel Succinic Acid Cell Factory

    PubMed Central

    Otero, José Manuel; Cimini, Donatella; Patil, Kiran R.; Poulsen, Simon G.; Olsson, Lisbeth; Nielsen, Jens

    2013-01-01

    Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust commerically compatible scaffold to be exploitted for diverse chemical production. Succinic acid is a highly sought after added-value chemical for which there is no native pre-disposition for production and accmulation in S. cerevisiae. The genome-scale metabolic network reconstruction of S. cerevisiae enabled in silico gene deletion predictions using an evolutionary programming method to couple biomass and succinate production. Glycine and serine, both essential amino acids required for biomass formation, are formed from both glycolytic and TCA cycle intermediates. Succinate formation results from the isocitrate lyase catalyzed conversion of isocitrate, and from the α-keto-glutarate dehydrogenase catalyzed conversion of α-keto-glutarate. Succinate is subsequently depleted by the succinate dehydrogenase complex. The metabolic engineering strategy identified included deletion of the primary succinate consuming reaction, Sdh3p, and interruption of glycolysis derived serine by deletion of 3-phosphoglycerate dehydrogenase, Ser3p/Ser33p. Pursuing these targets, a multi-gene deletion strain was constructed, and directed evolution with selection used to identify a succinate producing mutant. Physiological characterization coupled with integrated data analysis of transcriptome data in the metabolically engineered strain were used to identify 2nd-round metabolic engineering targets. The resulting strain represents a 30-fold improvement in succinate titer, and a 43-fold improvement in succinate yield on biomass, with only a 2.8-fold decrease in the specific growth rate compared to the reference strain. Intuitive genetic targets for either over-expression or interruption of succinate producing or consuming pathways, respectively, do not lead to increased succinate. Rather, we demonstrate how

  12. Succinate reverses in-vitro platelet inhibition by acetylsalicylic acid and P2Y receptor antagonists.

    PubMed

    Spath, Brigitte; Hansen, Arne; Bokemeyer, Carsten; Langer, Florian

    2012-01-01

    High on-treatment platelet reactivity has been associated with adverse cardiovascular events in patients receiving anti-platelet agents, but the molecular mechanisms underlying this phenomenon remain incompletely understood. Succinate, a citric acid cycle intermediate, is released into the circulation under conditions of mitochondrial dysfunction due to hypoxic organ damage, including sepsis, stroke, and myocardial infarction. Because the G protein-coupled receptor (GPCR) for succinate, SUCNR1 (GPR91), is present on human platelets, we hypothesized that succinate-mediated platelet stimulation may counteract the pharmacological effects of cyclooxygenase-1 and ADP receptor antagonists. To test this hypothesis in a controlled in-vitro study, washed platelets from healthy donors were treated with acetylsalicylic acid (ASA) or small-molecule P2Y(1) or P2Y(12) inhibitors and subsequently analyzed by light transmittance aggregometry using arachidonic acid (AA), ADP and succinate as platelet agonists. Aggregation in response to succinate alone was highly variable with only 29% of donors showing a (mostly delayed) platelet response. In contrast, succinate reproducibly and concentration-dependently (10-1000 µM) enhanced platelet aggregation in response to low concentrations of exogenous ADP. Furthermore, while succinate alone had no effect in the presence of platelet inhibitors, responsiveness of platelets to ADP after pretreatment with P2Y(1) or P2Y(12) antagonists was fully restored, when platelets were co-stimulated with 100 µM succinate. Similarly, succinate completely (at 1000 µM) or partially (at 100 µM) reversed the inhibitory effect of ASA on AA-induced platelet aggregation. In contrast, succinate failed to restore platelet responsiveness in the presence of both ASA and the P2Y(12) antagonist, suggesting that concomitant signaling via different GPCRs was required. Essentially identical results were obtained, when flow cytometric analysis of surface CD62P

  13. Targeted optimization of central carbon metabolism for engineering succinate production in Escherichia coli.

    PubMed

    Zhao, Ying; Wang, Chang-Song; Li, Fei-Fei; Liu, Zhen-Ning; Zhao, Guang-Rong

    2016-06-24

    Succinate is a kind of industrially important C4 platform chemical for synthesis of high value added products. Due to the economical and environmental advantages, considerable efforts on metabolic engineering and synthetic biology have been invested for bio-based production of succinate. Precursor phosphoenolpyruvate (PEP) is consumed for transport and phosphorylation of glucose, and large amounts of byproducts are produced, which are the crucial obstacles preventing the improvement of succinate production. In this study, instead of deleting genes involved in the formation of lactate, acetate and formate, we optimized the central carbon metabolism by targeting at metabolic node PEP to improve succinate production and decrease accumulation of byproducts in engineered E. coli. By deleting ptsG, ppc, pykA, maeA and maeB, we constructed the initial succinate-producing strain to achieve succinate yield of 0.22 mol/mol glucose, which was 2.1-fold higher than that of the parent strain. Then, by targeting at both reductive TCA arm and PEP carboxylation, we deleted sdh and co-overexpressed pck and ecaA, which led to a significant improvement in succinate yield of 1.13 mol/mol glucose. After fine-tuning of pykF expression by anti-pykF sRNA, yields of lactate and acetate were decreased by 43.48 and 38.09 %, respectively. The anaerobic stoichiometric model on metabolic network showed that the carbon fraction to succinate of engineered strains was significantly increased at the expense of decreased fluxes to lactate and acetate. In batch fermentation, the optimized strain BKS15 produced succinate with specific productivity of 5.89 mmol gDCW(-1) h(-1). This report successfully optimizes succinate production by targeting at PEP of the central carbon metabolism. Co-overexpressing pck-ecaA, deleting sdh and finely tuning pykF expression are efficient strategies for improving succinate production and minimizing accumulation of lactate and acetate in metabolically engineered E

  14. The Hydroxyl Radical Reaction Rate Constant and Products of Dimethyl Succinate

    DTIC Science & Technology

    2008-03-01

    AFRL-RX-TY-TR-2008-4522 THE HYDROXYL RADICAL REACTION RATE CONSTANT AND PRODUCTS OF DIMETHYL SUCCINATE Sheryl E. Calidonna and...the gas-phase hydroxyl radical reaction with dimethyl succinate. Additional reports and publications resulting from this work unit are not described...herein but are listed below for reference. Baxley, J.Steven and J.R. Wells, “The Hydroxyl Radical Rate Constant and Atmospheric Transforamtion

  15. Evidence for succinate production by reduction of fumarate during hypoxia in isolated adult rat heart cells.

    PubMed

    Hohl, C; Oestreich, R; Rösen, P; Wiesner, R; Grieshaber, M

    1987-12-01

    It has been demonstrated that perfusion of myocardium with glutamic acid or tricarboxylic acid cycle intermediates during hypoxia or ischemia, improves cardiac function, increases ATP levels, and stimulates succinate production. In this study isolated adult rat heart cells were used to investigate the mechanism of anaerobic succinate formation and examine beneficial effects attributed to ATP generated by this pathway. Myocytes incubated for 60 min under hypoxic conditions showed a slight loss of ATP from an initial value of 21 +/- 1 nmol/mg protein, a decline of CP from 42 to 17 nmol/mg protein and a fourfold increase in lactic acid production to 1.8 +/- 0.2 mumol/mg protein/h. These metabolite contents were not altered by the addition of malate and 2-oxoglutarate to the incubation medium nor were differences in cell viability observed; however, succinate release was substantially accelerated to 241 +/- 53 nmol/mg protein. Incubation of cells with [U-14C]malate or [2-U-14C]oxoglutarate indicates that succinate is formed directly from malate but not from 2-oxoglutarate. Moreover, anaerobic succinate formation was rotenone sensitive. We conclude that malate reduction to succinate occurs via the reverse action of succinate dehydrogenase in a coupled reaction where NADH is oxidized (and FAD reduced) and ADP is phosphorylated. Furthermore, by transaminating with aspartate to produce oxaloacetate, 2-oxoglutarate stimulates cytosolic malic dehydrogenase activity, whereby malate is formed and NADH is oxidized. In the form of malate, reducing equivalents and substrate are transported into the mitochondria where they are utilized for succinate synthesis.

  16. Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis.

    PubMed

    Tretter, Laszlo; Patocs, Attila; Chinopoulos, Christos

    2016-08-01

    Succinate is an important metabolite at the cross-road of several metabolic pathways, also involved in the formation and elimination of reactive oxygen species. However, it is becoming increasingly apparent that its realm extends to epigenetics, tumorigenesis, signal transduction, endo- and paracrine modulation and inflammation. Here we review the pathways encompassing succinate as a metabolite or a signal and how these may interact in normal and pathological conditions.(1).

  17. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... residues of the herbicide, flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl ester], in or on the following...) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl ester...

  18. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... residues of the herbicide, flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl ester], in or on the following...) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl ester...

  19. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... residues of the herbicide, flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl ester], in or on the following...) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl ester...

  20. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... residues of the herbicide, flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl ester], in or on the following...) Tolerances are established for residues of the herbicide flufenpyr-ethyl; acetic acid, -phenoxy]-ethyl ester...

  1. Urine ethyl glucuronide and ethyl sulphate using liquid chromatography-tandem mass spectrometry in a routine clinical laboratory.

    PubMed

    Armer, Jane M; Allcock, Rebecca L

    2017-01-01

    Background Detection of alcohol consumption in clients undergoing treatment for alcohol dependence can be difficult. The ethanol metabolites ethyl glucuronide and ethyl sulphate are detectable for longer in urine than either breath ethanol or urine ethanol. Our aim was to develop a liquid chromatography-tandem mass spectrometry method for urine ethyl glucuronide and ethyl sulphate for use in a routine clinical laboratory and define clinical cut-offs in a large population who had not consumed alcohol for at least two weeks. Methods Urine samples were diluted in 0.05% formic acid in HPLC grade water and then directly injected onto a Waters Acquity ultra high performance liquid chromatography coupled to a Waters TQ Detector. Eighty participants were recruited who had not consumed alcohol for at least two weeks to define cut-offs for urine ethyl glucuronide and ethyl sulphate. Samples and alcohol diaries were also collected from 12 alcohol-dependent clients attending a treatment programme. Results The assay was validated with a lower limit of quantitation of 0.20 mg/L for ethyl glucuronide and 0.04 mg/L for ethyl sulphate. Accuracy, precision, linearity and recovery were acceptable. Cut-offs were established for ethyl glucuronide, ethyl sulphate and ethyl sulphate/creatinine ratio (≤0.26 mg/L, ≤0.22 mg/L and ≤0.033 mg/mmol, respectively) in a non-drinking population. The validated cut-offs correctly identified clients in alcohol treatment who were continuing to drink alcohol. Conclusions A simple liquid chromatography-tandem mass spectrometry method for urine ethyl glucuronide and ethyl sulphate has been validated and cut-offs defined using 80 participants who had not consumed alcohol for at least two weeks. This is the largest study to date to define cut-offs for ethyl glucuronide, ethyl sulphate and ethyl sulphate/creatinine ratio.

  2. Novel Characteristics of Succinate Coenzyme A (Succinate-CoA) Ligases: Conversion of Malate to Malyl-CoA and CoA-Thioester Formation of Succinate Analogues In Vitro

    PubMed Central

    Nolte, Johannes Christoph; Schürmann, Marc; Schepers, Catherine-Louise; Vogel, Elvira; Wübbeler, Jan Hendrik

    2014-01-01

    Three succinate coenzyme A (succinate-CoA) ligases (SucCD) from Escherichia coli, Advenella mimigardefordensis DPN7T, and Alcanivorax borkumensis SK2 were characterized regarding their substrate specificity concerning succinate analogues. Previous studies had suggested that SucCD enzymes might be promiscuous toward succinate analogues, such as itaconate and 3-sulfinopropionate (3SP). The latter is an intermediate of the degradation pathway of 3,3′-dithiodipropionate (DTDP), a precursor for the biotechnical production of polythioesters (PTEs) in bacteria. The sucCD genes were expressed in E. coli BL21(DE3)/pLysS. The SucCD enzymes of E. coli and A. mimigardefordensis DPN7T were purified in the native state using stepwise purification protocols, while SucCD from A. borkumensis SK2 was equipped with a C-terminal hexahistidine tag at the SucD subunit. Besides the preference for the physiological substrates succinate, itaconate, ATP, and CoA, high enzyme activity was additionally determined for both enantiomeric forms of malate, amounting to 10 to 21% of the activity with succinate. Km values ranged from 2.5 to 3.6 mM for l-malate and from 3.6 to 4.2 mM for d-malate for the SucCD enzymes investigated in this study. As l-malate-CoA ligase is present in the serine cycle for assimilation of C1 compounds in methylotrophs, structural comparison of these two enzymes as members of the same subsubclass suggested a strong resemblance of SucCD to l-malate-CoA ligase and gave rise to the speculation that malate-CoA ligases and succinate-CoA ligases have the same evolutionary origin. Although enzyme activities were very low for the additional substrates investigated, liquid chromatography/electrospray ionization-mass spectrometry analyses proved the ability of SucCD enzymes to form CoA-thioesters of adipate, glutarate, and fumarate. Since all SucCD enzymes were able to activate 3SP to 3SP-CoA, we consequently demonstrated that the activation of 3SP is not a unique characteristic

  3. Localization of the succinate receptor in the distal nephron and its signaling in polarized MDCK cells.

    PubMed

    Robben, Joris H; Fenton, Robert A; Vargas, Sarah L; Schweer, Horst; Peti-Peterdi, Janos; Deen, Peter M T; Milligan, Graeme

    2009-12-01

    When the succinate receptor (SUCNR1) is activated in the afferent arterioles of the glomerulus it increases renin release and induces hypertension. To study its location in other nephron segments and its role in kidney function, we performed immunohistochemical analysis and found that SUCNR1 is located in the luminal membrane of macula densa cells of the juxtaglomerular apparatus in close proximity to renin-producing granular cells, the cortical thick ascending limb, and cortical and inner medullary collecting duct cells. In order to study its signaling, SUCNR1 was stably expressed in Madin-Darby Canine Kidney (MDCK) cells, where it localized to the apical membrane. Activation of the cells by succinate caused Gq and Gi-mediated intracellular calcium mobilization, transient phosphorylation of extracellular regulated kinase (ERK)1/2 and the release of arachidonic acid along with prostaglandins E2 and I2. Signaling was desensitized without receptor internalization but rapidly resensitized upon succinate removal. Immunohistochemical evidence of phosphorylated ERK1/2 was found in cortical collecting duct cells of wild type but not SUCNR1 knockout streptozotocin-induced diabetic mice, indicating in vivo relevance. Since urinary succinate concentrations in health and disease are in the activation range of the SUCNR1, this receptor can sense succinate in the luminal fluid. Our study suggests that changes in the luminal succinate concentration may regulate several aspects of renal function.

  4. [Optimization of succinic acid fermentation with Actinobacillus succinogenes by response surface methodology].

    PubMed

    Shen, Naikun; Qin, Yan; Wang, Qingyan; Xie, Nengzhong; Mi, Huizhi; Zhu, Qixia; Liao, Siming; Huang, Ribo

    2013-10-01

    Succinic acid is an important C4 platform chemical in the synthesis of many commodity and special chemicals. In the present work, different compounds were evaluated for succinic acid production by Actinobacillus succinogenes GXAS 137. Important parameters were screened by the single factor experiment and Plackeet-Burman design. Subsequently, the highest production of succinic acid was approached by the path of steepest ascent. Then, the optimum values of the parameters were obtained by Box-Behnken design. The results show that the important parameters were glucose, yeast extract and MgCO3 concentrations. The optimum condition was as follows (g/L): glucose 70.00, yeast extract 9.20 and MgCO3 58.10. Succinic acid yield reached 47.64 g/L at the optimal condition. Succinic acid increased by 29.14% than that before the optimization (36.89 g/L). Response surface methodology was proven to be a powerful tool to optimize succinic acid production.

  5. Immobilization of Actinobacillus succinogenes by adhesion or entrapment for the production of succinic acid.

    PubMed

    Corona-González, Rosa Isela; Miramontes-Murillo, Ricardo; Arriola-Guevara, Enrique; Guatemala-Morales, Guadalupe; Toriz, Guillermo; Pelayo-Ortiz, Carlos

    2014-07-01

    The production of succinic acid was studied with entrapped and adsorbed Actinobacillus succinogenes. The adsorption of fermentation products (organic acids in the concentration range of 1-20 g/L) on different supports was evaluated. It was found that succinic acid was adsorbed in small quantities on diatomite and zeolite (12.6 mg/g support). The highest production of succinic acid was achieved with A. succinogenes entrapped in agar beads. Batch fermentations with immobilized cells were carried out with glucose concentrations ranging from 20 to 80 g/L. Succinic acid (43.4 g/L) was obtained from 78.3g/L glucose, and a high productivity (2.83 g/Lh) was obtained with a glucose concentration of 37.6g/L. For repeated batch fermentations (5 cycles in 72 h) with immobilized cells in agar, the total glucose consumed was 147.55 g/L, while the production of succinic acid was 107 g/L. Immobilized cells reduced significantly the fermentation time, yield, productivity and final concentration of succinic acid. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. The photo-oxidation of succinate by chromatophores of Rhodospirillum rubrum

    PubMed Central

    Evans, M. C. W.

    1965-01-01

    1. The stoicheiometry of the photo-oxidation of succinate by chromatophores has been investigated with [2,3-14C2]succinate. It was found that there is a stoicheiometric relationship between the amount of succinate oxidized and the NAD reduced, and that fumarate is the only product of succinate oxidation. 2. The possibility of a direct hydrogen transfer from succinate to NAD in this reaction was investigated with tritiated substrates. With tritiated succinate less than 3% of the activity expected if direct hydrogen transfer occurred was recovered in the NADH2, and this was due to contamination with the substrate. In experiments with tritiated water, NADH2 was labelled, and had half the specific activity of the water, as expected if water was the source of protons. It was also found that chromatophores catalyse an exchange reaction between NADH2 and water. 3. It is concluded that the exchange reaction makes it impossible to interpret these results as indicating either a hydrogen-transfer or an electron-transfer mechanism for the photoreduction reaction. PMID:14342500

  7. Biotechnological route for sustainable succinate production utilizing oil palm frond and kenaf as potential carbon sources.

    PubMed

    Luthfi, Abdullah Amru Indera; Manaf, Shareena Fairuz Abdul; Illias, Rosli Md; Harun, Shuhaida; Mohammad, Abdul Wahab; Jahim, Jamaliah Md

    2017-04-01

    Due to the world's dwindling energy supplies, greater thrust has been placed on the utilization of renewable resources for global succinate production. Exploration of such biotechnological route could be seen as an act of counterbalance to the continued fossil fuel dominance. Malaysia being a tropical country stands out among many other nations for its plenty of resources in the form of lignocellulosic biomass. To date, oil palm frond (OPF) contributes to the largest fraction of agricultural residues in Malaysia, while kenaf, a newly introduced fiber crop with relatively high growth rate, holds great potential for developing sustainable succinate production, apart from OPF. Utilization of non-food, inexhaustible, and low-cost derived biomass in the form of OPF and kenaf for bio-based succinate production remains largely untapped. Owing to the richness of carbohydrates in OPF and kenaf, bio-succinate commercialization using these sources appears as an attractive proposition for future sustainable developments. The aim of this paper was to review some research efforts in developing a biorefinery system based on OPF and kenaf as processing inputs. It presents the importance of the current progress in bio-succinate commercialization, in addition to describing the potential use of different succinate production hosts and various pretreatments-saccharifications under development for OPF and kenaf. Evaluations on the feasibility of OPF and kenaf as fermentation substrates are also discussed.

  8. Production of succinic acid from oil palm empty fruit bunch cellulose using Actinobacillus succinogenes

    NASA Astrophysics Data System (ADS)

    Pasma, Satriani Aga; Daik, Rusli; Maskat, Mohamad Yusof

    2013-11-01

    Succinic acid is a common metabolite in plants, animals and microorganisms. It has been used widely in agricultural, food and pharmaceutical industries. Enzymatic hydrolysate glucose from oil palm empty fruit bunch (OPEFB) cellulose was used as a substrate for succinic acid production using Actinobacillus succinogenes. Using cellulose extraction from OPEFB can enhance the production of glucose as a main substrate for succinic acid production. The highest concentration of glucose produced from enzymatic hydrolysis is 167 mg/mL and the sugar recovery is 0.73 g/g of OPEFB. By optimizing the culture medium for succinic acid fermentation with enzymatic hydrolysate of OPEFB cellulose, the nitrogen sources could be reduced to just only 2.5 g yeast extract and 2.5 g corn step liquor. Batch fermentation was carried out using enzymatic hydrolysate of OPEFB cellulose with yeast extract, corn steep liquor and the salts mixture, 23.5 g/L succinic acid was obtained with consumption of 72 g/L glucose in enzymatic hydrolysate of OPEFB cellulose at 38 hours and 37°C. This study suggests that enzymatic hydrolysate of OPEFB cellulose maybe an alternative substrate for the efficient production of succinic acid by Actinobacillus succinogenes.

  9. A statistical method for enhancing the production of succinic acid from Escherichia coli under anaerobic conditions.

    PubMed

    Isar, Jasmine; Agarwal, Lata; Saran, Saurabh; Saxena, Rajendra Kumar

    2006-09-01

    The most influential parameters for succinic acid production obtained through one at a time method were sucrose, tryptone, magnesium carbonate, inoculum size and incubation period. These resulted in the production of 7.0 g L(-1) of succinic acid in 60 h from Escherichia coli W3110 under anaerobic conditions. Based on these results, a statistical method, face centered central composite design (FCCCD) falling under response surface method (RSM) was employed for further enhancing the succinic acid production and to monitor the interactive effect of these parameters, which resulted in a twofold increase in yield (14.3 g L(-1) in 48 h). The analysis of variance (ANOVA) showed the adequacy of the model and the verification experiments confirmed its validity. On subsequent scale-up in a 10-L bioreactor using conditions optimized through RSM, 24.2 g L(-1) of succinic acid was obtained in 30 h. This clearly indicated that the model stood valid even on large-scale. Thus, the statistical optimization strategy led to a 3.5-fold increase in the yield of succinic acid. This is the first report on the use of FCCCD to improve succinic acid production from E. coli.

  10. Methodological problems in the histochemical demonstration of succinate semialdehyde dehydrogenase activity.

    PubMed

    Bernocchi, G; Barni, S

    1983-12-01

    Methodological aspects of the histochemical technique for the demonstration of succinate semialdehyde dehydrogenase activity (EC 1.2.1.24) (indicative of the degradative step of gamma-aminobutyric acid catabolism) have been analysed in rat Purkinje neurons, where gamma-aminobutyric acid has been shown to be a neurotransmitter, and in hepatocytes, where it is metabolized. During a histochemical incubation for the enzyme, artefacts of succinate dehydrogenase activity and the 'nothing dehydrogenase' reaction are produced. Inhibition of these artefacts by the addition of two inhibitors, malonate and p-hydroxybenzaldehyde, revealed specific reaction products. Formazan granules, which can be ascribed only to specific succinate semialdehyde dehydrogenase activity, are obtained by adding malonate to the incubation medium in order to inhibit both succinate dehydrogenase activity and nothing dehydrogenase. The formation of these granules is completely inhibited by p-hydroxybenzaldehyde, an inhibitor of succinate semialdehyde dehydrogenase activity. Different levels of succinate semialdehyde dehydrogenase activity were noted in Purkinje neurons. This activity was also found in hepatocytes, mostly in the portal area, but with a lesser degree of intensity and specificity. Indeed, non-specific formazan granules were still produced, because of the 'nothing dehydrogenase' reaction, even in the presence of malonate. Thus, a malonate-insensitive 'nothing dehydrogenase' reaction seems to be present in neural and hepatic tissues.

  11. The role of succinate in the respiratory chain of Trypanosoma brucei procyclic trypomastigotes.

    PubMed

    Turrens, J F

    1989-04-15

    Trypanosoma brucei procyclic trypomastigotes were made permeable by using digitonin (0-70 micrograms/mg of protein). This procedure allowed exposure of coupled mitochondria to different substrates. Only succinate and glycerol phosphate (but not NADH-dependent substrates) were capable of stimulating oxygen consumption. Fluorescence studies on intact cells indicated that addition of succinate stimulates NAD(P)H oxidation, contrary to what happens in mammalian mitochondria. Addition of malonate, an inhibitor of succinate dehydrogenase, stimulated NAD(P)H reduction. Malonate also inhibited intact-cell respiration and motility, both of which were restored by further addition of succinate. Experiments carried out with isolated mitochondrial membranes showed that, although the electron transfer from succinate to cytochrome c was inhibitable by antimycin, NADH-cytochrome c reductase was antimycin-insensitive. We postulate that the NADH-ubiquinone segment of the respiratory chain is replaced by NADH-fumarate reductase, which reoxidizes the mitochondrial NADH and in turn generates succinate for the respiratory chain. This hypothesis is further supported by the inhibitory effect on cell growth and respiration of 3-methoxyphenylacetic acid, an inhibitor of the NADH-fumarate reductase of T. brucei.

  12. Interaction of the membrane-bound succinate dehydrogenase with substrate and competitive inhibitors.

    PubMed

    Kotlyar, A B; Vinogradov, A D

    1984-01-18

    The protective effect of dicarboxylates on the active-site-directed inhibition of the membrane-bound succinate dehydrogenase by N-ethylmaleimide, steady-state kinetics methods for Ki and Ks determinations, and equilibrium studies were employed to quantitate the relative affinities of succinate, fumarate, malonate and oxaloacetate to the reduced and oxidized species of the enzyme. A more than 10-fold difference in the relative affinities of the reduced and oxidized succinate dehydrogenase to succinate, fumarate and oxaloacetate is found, whereas the reactivity of the active-site sulphydryl group does not depend on the redox state of the enzyme. The redox-state-dependent changes in the affinity of the membrane-bound succinate dehydrogenase to oxaloacetate can be quantitatively accounted for by a 10-fold increase in the rate of dissociation of the enzyme-inhibitor complex which occurs upon reduction of the enzyme. The data obtained give no support for either the existence of a sulphydryl group other than the active-site one important for the catalysis or for the presence of a separate dicarboxylate-specific regulatory site in the succinate dehydrogenase molecule.

  13. Whey fermentation by anaerobiospirillum succiniciproducens for production of a succinate-based animal feed additive

    PubMed

    Samuelov; Datta; Jain; Zeikus

    1999-05-01

    Anaerobic fermentation processes for the production of a succinate-rich animal feed supplement from raw whey were investigated with batch, continuous, and variable-volume fed-batch cultures with Anaerobiospirillum succiniciproducens. The highest succinate yield, 90%, was obtained in a variable-volume fed-batch process in comparison to 80% yield in a batch cultivation mode. In continuous culture, succinate productivity was 3 g/liter/h, and the yield was 60%. Under conditions of excess CO2, more than 90% of the whey-lactose was consumed, with an end product ratio of 4 succinate to 1 acetate. Under conditions of limited CO2, lactose was only partially consumed and lactate was the major end product, with lower levels of ethanol, succinate, and acetate. When the succinic acid in this fermentation product was added to rumen fluid, it was completely consumed by a mixed rumen population and was 90% decarboxylated to propionate on a molar basis. The whey fermentation product formed under excess CO2, which contained mainly organic acids and cells, could potentially be used as an animal feed supplement.

  14. Whey fermentation by Anaerobiospirillum succiniciproducens for production of a succinate-based animal feed additive

    SciTech Connect

    Samuelov, N.S.; Datta, R.; Jain, M.K. |; Zeikus, J.G. |

    1999-05-01

    Anaerobic fermentation processes for the production of a succinate-rich animal feed supplement from raw whey were investigated with batch, continuous, and variable-volume fed-batch cultures with Anaerobiospirillum succiniciproducens. The highest succinate yield, 90%, was obtained in a variable-volume fed-batch process in comparison to 80% yield in a batch cultivation mode. In continuous culture, succinate productivity was 3 g/liter/h, and the yield was 60%. Under conditions of excess CO{sub 2}, more than 90% of the whey-lactose was consumed, with an end product ratio of 4 succinate to 1 acetate. Under conditions of limited CO{sub 2}, lactose was only partially consumed and lactate was the major end product, with lower levels of ethanol, succinate, and acetate. When the succinic acid in this fermentation product was added to rumen fluid, it was completely consumed by a mixed rumen population and was 90% decarboxylated to propionate on a molar basis. The whey fermentation product formed under excess CO{sub 2}, which contained mainly organic acids and cells, could potentially be used as an animal feed supplement.

  15. Ginsenoside Rg5 Inhibits Succinate-Associated Lipolysis in Adipose Tissue and Prevents Muscle Insulin Resistance

    PubMed Central

    Xiao, Na; Yang, Le-Le; Yang, Yi-Lin; Liu, Li-Wei; Li, Jia; Liu, Baolin; Liu, Kang; Qi, Lian-Wen; Li, Ping

    2017-01-01

    Endoplasmic reticulum (ER) stress, inflammation, and lipolysis occur simultaneously in adipose dysfunction and contribute to insulin resistance. This study was designed to investigate whether ginsenoside Rg5 could ameliorate adipose dysfunction and prevent muscle insulin resistance. Short-term high-fat diet (HFD) feeding induced hypoxia with ER stress in adipose tissue, leading to succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activity. Rg5 treatment reduced cellular energy charge, suppressed ER stress and then prevented succinate accumulation in adipose tissue. Succinate promoted IL-1β production through NLRP3 inflammasome activation and then increased cAMP accumulation by impairing PDE3B expression, leading to increased lipolysis. Ginsenoside Rg5 treatment suppressed NLRP3 inflammasome activation, preserved PDE3B expression and then reduced cAMP accumulation, contributing to inhibition of lipolysis. Adipose lipolysis increased FFAs trafficking from adipose tissue to muscle. Rg5 reduced diacylglycerol (DAG) and ceramides accumulation, inhibited protein kinase Cθ translocation, and prevented insulin resistance in muscle. In conclusion, succinate accumulation in hypoxic adipose tissue acts as a metabolic signaling to link ER stress, inflammation and cAMP/PKA activation, contributing to lipolysis and insulin resistance. These findings establish a previously unrecognized role of ginsenosides in the regulation of lipid and glucose homeostasis and suggest that adipose succinate-associated NLRP3 inflammasome activation might be targeted therapeutically to prevent lipolysis and insulin resistance. PMID:28261091

  16. Absorbance correction method for estimation of telmisartan and metoprolol succinate in combined tablet dosage forms

    PubMed Central

    Patel, Komal; Patel, Amit; Dave, Jayant; Patel, Chaganbhai

    2012-01-01

    Aim and Background: The present manuscript describes simple, sensitive, rapid, accurate, precise and economical spectrophotometric method for the simultaneous determination of telmisartan and metoprolol succinate in combined tablet dosage form. Materials and Methods: The method is based on the absorbance correction equations for analysis of both the drugs using methanol as solvent. Telmisartan has absorbance maxima at 296 nm and metoprolol succinate has absorbance maxima at 223 nm in methanol. The linearity was obtained in the concentration range of 2-16 μg/ ml and 3-24 μg/ml for telmisartan and metoprolol succinate, respectively. The concentrations of the drugs were determined by using absorbance correction method at both the wavelengths. The method was successfully applied to pharmaceutical dosage form because no interference from the tablet excipients was found. The suitability of this method for the quantitative determination of telmisartan and metoprolol succinate was proved by validation. The proposed method was found to be simple and sensitive for the quality control application of telmisartan and metoprolol succinate in pharmaceutical dosage form. Result: The result of analysis has been validated statistically and by recovery studies. Recoveries were found in the range of 98.08-100.55% of telmisartan and 98.41-101.87% of metoprolol succinate. PMID:23781489

  17. New reactive extraction systems for separation of bio-succinic acid.

    PubMed

    Kurzrock, Tanja; Weuster-Botz, Dirk

    2011-09-01

    Biotechnologically produced succinic acid has the potential to displace maleic acid and its uses and to become an important feedstock for the chemical industry. In addition to optimized production strains and fermentation processes, an efficient separation of succinic acid from the aqueous fermentation broth is indispensable to compete with the current petrochemical production processes. In this context, high molecular weight amines are known to be effective extractants for organic acids. For this reason, as a first step of isolation and purification, the reactive extraction of succinic acid was studied by mixing aqueous succinic acid solutions with 448 different amine-solvent mixtures as extraction agents (mixer-settler studies). The extraction agents consist either of one amine and one solvent (208 reactive extraction systems) or two amines and two solvents (240 reactive extraction systems). Maximum extraction yields of succinic acid from an aqueous solution with 423 mM succinic acid at pH 2.0 were obtained with more than 95% yield with trihexylamine solved in 1-octanol or with dihexylamine and diisooctylamine solved in 1-octanol and 1-hexanol. Applying these optimized reactive extraction systems with Escherichia coli fermentation broth resulted in extraction yields of 78-85% due to the increased ionic strength of the fermentation supernatant and the co-extraction of other organic acids (e.g., lactic acid and acetic acid), which represent typical fermentation byproducts.

  18. Effect of succinate sodium on the metmyoglobin reduction and color stability of beef patties.

    PubMed

    Zhu, Jinyuan; Liu, Fang; Li, Xingmin; Dai, Ruitong

    2009-07-08

    In two experiments, the effect of succinate sodium on the metmyoglobin (MetMb) reduction and color stability of beef patties was investigated. In experiment 1, the ground-beef strip loins (longissimus dorsi muscle) were blended with different concentrations of succinate. Enhancing patties with 6 mM succinate significantly increased the MetMb-reducing ability and subsequent color stability during storage. In experiment 2, MetMb and different concentrations of succinate, lactate, and reduced nicotinamide adenine dinucleotide (NADH) were incubated with mitochondria, and their effect on meat MetMb reduction was investigated. Increasing the concentration of NADH and lactate increased MetMb reduction, but only succinate of 16 and 24 mM significantly decreased the relative MetMb percentage compared to other systems. This indicate that there are no significant differences between aerobic and anaerobic MetMb-reducing activities. In comparison to the systems of NADH-MetMb reduction (including the systems of lactate-MetMb reduction), the succinate-MetMb reduction systems are more stable and less affected by oxygen. More identification work is needed to obtain the more complete pathways on MetMb reduction.

  19. Succinic acid production by Actinobacillus succinogenes using hydrolysates of spent yeast cells and corn fiber.

    PubMed

    Chen, Ke-Quan; Li, Jian; Ma, Jiang-Feng; Jiang, Min; Wei, Ping; Liu, Zhong-Min; Ying, Han-Jie

    2011-01-01

    The enzymatic hydrolysate of spent yeast cells was evaluated as a nitrogen source for succinic acid production by Actinobacillus succinogenes NJ113, using corn fiber hydrolysate as a carbon source. When spent yeast cell hydrolysate was used directly as a nitrogen source, a maximum succinic acid concentration of 35.5 g/l was obtained from a glucose concentration of 50 g/l, with a glucose utilization of 95.2%. Supplementation with individual vitamins showed that biotin was the most likely factor to be limiting for succinic acid production with spent yeast cell hydrolysate. After supplementing spent yeast cell hydrolysate and 90 g/l of glucose with 150 μg/l of biotin, cell growth increased 32.5%, glucose utilization increased 37.6%, and succinic acid concentration was enhanced 49.0%. As a result, when biotin-supplemented spent yeast cell hydrolysate was used with corn fiber hydrolysate, a succinic acid yield of 67.7% was obtained from 70.3 g/l of total sugar concentration, with a productivity of 0.63 g/(l h). Our results suggest that biotin-supplemented spent yeast cell hydrolysate may be an alternative nitrogen source for the efficient production of succinic acid by A. succinogenes NJ113, using renewable resources.

  20. Improving succinic acid production by Actinobacillus succinogenes from raw industrial carob pods.

    PubMed

    Carvalho, Margarida; Roca, Christophe; Reis, Maria A M

    2016-10-01

    Carob pods are an inexpensive by-product of locust bean gum industry that can be used as renewable feedstock for bio-based succinic acid. Here, for the first time, unprocessed raw carob pods were used to extract a highly enriched sugar solution, afterwards used as substrate to produce succinic acid using Actinobacillus succinogenes. Batch fermentations containing 30g/L sugars resulted in a production rate of 1.67gSA/L.h and a yield of 0.39gSA/g sugars. Taking advantage of A. succinogenes' metabolism, uncoupling cell growth from succinic acid production, a fed-batch mode was implemented to increase succinic acid yield and reduce by-products formation. This strategy resulted in a succinic acid yield of 0.94gSA/g sugars, the highest yield reported in the literature for fed-batch and continuous experiments, while maintaining by-products at residual values. Results demonstrate that raw carob pods are a highly efficient feedstock for bio-based succinic acid production.

  1. Thermal and thermomechanical properties of poly(butylene succinate) nanocomposites.

    PubMed

    Makhatha, Mamookho E; Ray, Suprakas Sinha; Hato, Joseph; Luyt, Adriaan S

    2008-04-01

    This article describes the thermal and thermomechanical properties of poly(butylene succinate) (PBS) and its nanocomposites. PBS nanocomposites with three different weight ratios of organically modified synthetic fluorine mica (OMSFM) have been prepared by melt-mixing in a batch mixer at 140 degrees C. The structure and morphology of the nanocomposites were characterized by X-ray diffraction (XRD) analyses and transmission electron microscopy (TEM) observations that reveal the homogeneous dispersion of the intercalated silicate layers into the PBS matrix. The thermal properties of pure PBS and the nanocomposite samples were studied by both conventional and temperature modulated differential scanning calorimetry (DSC) analyses, which show multiple melting behavior of the PBS matrix. The investigation of the thermomechanical properties was performed by dynamic mechanical analysis. Results reveal significant improvement in the storage modulus of neat PBS upon addition of OMSFM. The tensile modulus of neat PBS is also increased substantially with the addition of OMSFM, however, the strength at yield and elongation at break of neat PBS systematically decreases with the loading of OMSFM. The thermal stability of the nanocomposites compared to that of the pure polymer sample was examined under both pyrolytic and thermo-oxidative environments. It is shown that the thermal stability of PBS is increased moderately in the presence of 3 wt% of OMSFM, but there is no significant effect on further silicate loading in the oxidative environment. In the nitrogen environment, however, the thermal stability systematically decreases with increasing clay loading.

  2. Radioprotective properties of tocopherol succinate against ionizing radiation in mice

    PubMed Central

    Singh, Vijay K.; Singh, Pankaj K.; Wise, Stephen Y.; Posarac, Ana; Fatanmi, Oluseyi O.

    2013-01-01

    Threats of nuclear and other radiologic exposures have been increasing but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. In prior publications we have demonstrated the efficacy of tocopherol succinate (TS) as a promising radiation countermeasure with the potential to protect against lethal doses of ionizing radiation exposure. The aim of this study was to gain further insight regarding how TS protects mice against a lethal dose of radiation. CD2F1 mice were injected subcutaneously with 400 mg/kg of TS, and 24 h later exposed to 60Co γ–radiation. Intestinal tissues or spleen/thymus were harvested after irradiation and analyzed for CD68-positive inflammatory cells and apoptotic cells by immunostaining of jejunal cross-sections. Comet assay was used to analyze DNA damage in various tissues. Phospho-histone H3(pH3) and the proliferating cell nuclear antigen (PCNA) were used as mitotic markers for immunostaining jejunal cross-sections. We observed that injecting TS significantly decreased the number of CD68-positive cells, DNA damage and apoptotic cells (BAX, caspase 3 and cleaved poly(ADP-ribose) polymerase-positive cells) as judged by various apoptotic pathway markers. TS treatment also increased proliferating cells in irradiated mice. Results of this study further support our contention that TS protects mice against lethal doses of ionizing radiation by inhibiting radiation-induced apoptosis and DNA damage while enhancing cell proliferation. PMID:23038797

  3. Mixed food waste as renewable feedstock in succinic acid fermentation.

    PubMed

    Sun, Zheng; Li, Mingji; Qi, Qingsheng; Gao, Cuijuan; Lin, Carol Sze Ki

    2014-11-01

    Mixed food waste, which was directly collected from restaurants without pretreatments, was used as a valuable feedstock in succinic acid (SA) fermentation in the present study. Commercial enzymes and crude enzymes produced from Aspergillus awamori and Aspergillus oryzae were separately used in hydrolysis of food waste, and their resultant hydrolysates were evaluated. For hydrolysis using the fungal mixture comprising A. awamori and A. oryzae, a nutrient-complete food waste hydrolysate was generated, which contained 31.9 g L(-1) glucose and 280 mg L(-1) free amino nitrogen. Approximately 80-90 % of the solid food waste was also diminished. In a 2.5 L fermentor, 29.9 g L(-1) SA was produced with an overall yield of 0.224 g g(-1) substrate using food waste hydrolysate and recombinant Escherichia coli. This is comparable to many similar studies using various wastes or by-products as substrates. Results of this study demonstrated the enormous potential of food waste as renewable resource in the production of bio-based chemicals and materials via microbial bioconversion.

  4. Succinic semialdehyde dehydrogenase deficiency: lessons from mice and men.

    PubMed

    Pearl, P L; Gibson, K M; Cortez, M A; Wu, Y; Carter Snead, O; Knerr, I; Forester, K; Pettiford, J M; Jakobs, C; Theodore, W H

    2009-06-01

    Succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder of GABA degradation with subsequent elevations in brain GABA and GHB, is a neurometabolic disorder with intellectual disability, epilepsy, hypotonia, ataxia, sleep disorders, and psychiatric disturbances. Neuroimaging reveals increased T2-weighted MRI signal usually affecting the globus pallidus, cerebellar dentate nucleus, and subthalamic nucleus, and often cerebral and cerebellar atrophy. EEG abnormalities are usually generalized spike-wave, consistent with a predilection for generalized epilepsy. The murine phenotype is characterized by failure-to-thrive, progressive ataxia, and a transition from generalized absence to tonic-clonic to ultimately fatal convulsive status epilepticus. Binding and electrophysiological studies demonstrate use-dependent downregulation of GABA(A) and (B) receptors in the mutant mouse. Translational human studies similarly reveal downregulation of GABAergic activity in patients, utilizing flumazenil-PET and transcranial magnetic stimulation for GABA(A) and (B) activity, respectively. Sleep studies reveal decreased stage REM with prolonged REM latencies and diminished percentage of stage REM. An ad libitum ketogenic diet was reported as effective in the mouse model, with unclear applicability to the human condition. Acute application of SGS-742, a GABA(B) antagonist, leads to improvement in epileptiform activity on electrocorticography. Promising mouse data using compounds available for clinical use, including taurine and SGS-742, form the framework for human trials.

  5. Incidence and Geographic Distribution of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency.

    PubMed

    Attri, Savita Verma; Singhi, Pratibha; Wiwattanadittakul, Natrujee; Goswami, Jyotindra N; Sankhyan, Naveen; Salomons, Gajja S; Roullett, Jean-Baptiste; Hodgeman, Ryan; Parviz, Mahsa; Gibson, K Michael; Pearl, Phillip L

    2016-11-05

    The incidence of succinic semialdehyde dehydrogenase (SSADH) deficiency, an autosomal recessive inherited disorder of GABA degradation, is unknown. Upon a recent diagnosis of a new family of affected fraternal twins from the Punjabi ethnic group of India, case ascertainment from the literature and our database was done to determine the number of confirmed cases along with their geographic distribution. The probands presented with global developmental delay, infantile onset epilepsy, and a persistent neurodevelopmental disorder upon diagnosis at 10 years of age with intellectual disability, expressive aphasia, and behavioral problems most prominent for hyperactivity. Gamma-hydroxybutyric aciduria and homozygous ALDH5A1 c.608C>T; p.Pro203Leu mutations were confirmed. Identification of all available individual cases with clinical details available including geographic or ethnic origin revealed 182 patients from 40 countries, with the largest number of patients reported from the USA (24%), Turkey (10%), China (7%), Saudi Arabia (6%), and Germany (5%). This study provides an accounting of all published cases of confirmed SSADH deficiency and provides data useful in planning further studies of this rare inborn error of metabolism.

  6. Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood

    PubMed Central

    Lewis, Evan Cole; De Meulemeester, Christine; Chakraborty, Pranesh; Gibson, K. Michael; Torres, Carlos; Guberman, Alan; Salomons, Gajja S.; Jakobs, Cornelis; Ali-Ridha, Andre; Parviz, Mahsa; Pearl, Phillip L.

    2015-01-01

    Objective: The natural history of succinic semialdehyde dehydrogenase (SSADH) deficiency in adulthood is unknown; we elucidate the clinical manifestations of the disease later in life. Methods: A 63-year-old man with long-standing intellectual disability was diagnosed with SSADH deficiency following hospitalization for progressive decline, escalating seizures, and prolonged periods of altered consciousness. We present a detailed review of his clinical course and reviewed our SSADH deficiency database adult cohort to derive natural history information. Results: Of 95 patients in the database for whom age at diagnosis is recorded, there are 40 individuals currently aged 18 years or older. Only 3 patients were diagnosed after age 18 years. Of 25 adults for whom data are available after age 18, 60% have a history of epilepsy. Predominant seizure types are generalized tonic-clonic, absence, and myoclonic. EEGs showed background slowing or generalized epileptiform discharges in two-thirds of adults for whom EEG data were collected. History of psychiatric symptoms was prominent, with frequent anxiety, sleep disturbances, and obsessive-compulsive disorder. Conclusions: We identified patients older than 18 years with SSADH deficiency in our database following identification and review of a patient diagnosed in the seventh decade of life. The illness had a progressive course with escalating seizures in the index case, with fatality at age 63. Diagnosis in adulthood is rare. Epilepsy is more common in the adult than the pediatric SSADH deficiency cohort; neuropsychiatric morbidity remains prominent. PMID:26268900

  7. Membrane fouling mechanism in ultrafiltration of succinic acid fermentation broth.

    PubMed

    Wang, Caixia; Li, Qiang; Tang, Huang; Yan, Daojiang; Zhou, Wei; Xing, Jianmin; Wan, Yinhua

    2012-07-01

    The membrane fouling mechanism was studied in treating succinic acid fermentation broth during dead-end ultrafiltration. Different membranes were used and two models were applied to analyze the fouling mechanism. Resistance-in-series model was applied to determine the main factor that caused the operation resistance. Results indicated that most membranes tended to be fouled by cake layer or concentration polarization. Hermia's model, which is composed of four individual sub-models, was used to analyze the predominant fouling mechanism. Results showed that the fouling of RC 10 kDa and PES 30 kDa was controlled by the complete blocking mechanism, while PES 100 kDa was controlled by the intermediate blocking and PES 10 kDa was controlled by cake layer. This conclusion was also proved by SEM photos. Membrane characteristics were monitored before and after ultrafiltration by AFM and goniometer. Both contact angle and roughness of most membranes increased after ultrafiltration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Production of ethyl alcohol from bananas

    SciTech Connect

    Jones, R.L.; Towns, T.

    1983-12-01

    The production of ethyl alcohol from waste bananas presents many special problems. During cooking, matting of the latex fibers from the banana peel recongeal when cooled and left untreated. This problem has been addressed by Alfaro by the use of CaC1/sub 2/. Separation of solids prior to distillation of the mashes in an economical fashion and use of the by product are also of concern to banana processors.

  9. Synthesis of Ethyl Salicylate Using Household Chemicals

    NASA Astrophysics Data System (ADS)

    Solomon, Sally; Hur, Chinhyu; Lee, Alan; Smith, Kurt

    1996-02-01

    Ethyl salicylate is synthesized, isolated, and characterized in a three-step process using simple equipment and household chemicals. First, acetylsalicylic acid is extracted from aspirin tablets with isopropyl alcohol, then hydrolyzed to salicylic acid with muriatic acid, and finally, the salicylic acid is esterified using ethanol and a boric acid catalyst. The experiment can be directed towards high school or university level students who have sufficient background in organic chemistry to recognize the structures and reactions that are involved.

  10. Inhibitory and bactericidal activities of levofloxacin, ofloxacin, erythromycin, and rifampin used singly and in combination against Legionella pneumophila.

    PubMed Central

    Baltch, A L; Smith, R P; Ritz, W

    1995-01-01

    The susceptibilities of 56 Legionella pneumophila isolates (43 clinical and 15 environmental isolates) to levofloxacin, ofloxacin, erythromycin, and rifampin were studied with buffered charcoal yeast extract (BCYE) agar (inoculum, 10(4) CFU per spot), and the susceptibilities of five isolates were studied with buffered yeast extract (BYE) broth (inoculum, 10(5) CFU/ml). The MICs inhibiting 90% of strains tested on BCYE agar were 0.125, 0.25, 1.0, and < or = 0.004 micrograms/ml for levofloxacin, ofloxacin, erythromycin, and rifampin, respectively. The MICs by the BYE broth dilution method were 1 to 3, 2, 1 to 2, and 1 tube lower than those by the agar dilution method for levofloxacin, ofloxacin, erythromycin, and rifampin, respectively. The MBCs were 1 to 2 tubes higher than the broth dilution MICs for levofloxacin, 1 to 3 tubes higher than the broth dilution MICs for ofloxacin, 1 to 3 tubes higher than the broth dilution MICs for erythromycin, and the same as the broth dilution MICs for rifampin. In kinetic time-kill curve studies, at drug concentrations of 1.0 and 2.0 times the MIC, the most active drugs were levofloxacin and rifampin. At 72 h, concentrations of levofloxacin and rifampin of 2.0 times the MIC demonstrated a bactericidal effect against L. pneumophila. In contrast, at concentrations of 1.0 and 2.0 times the MICs regrowth was observed with ofloxacin and only a gradual decrease in the numbers of CFU per milliliter was observed with erythromycin. Only a minor inhibitory effect was observed with 0.25 or 0.5 time the MICs of all drugs at 24 to 48 h, with regrowth occurring at 72 h. In contrast to erythromycin or ofloxacin plus rifampin at 0.25 time the MICs, only levofloxacin plus rifampin demonstrated synergy. Thus, levofloxacin demonstrated the best inhibitory and bactericidal effects against L. pneumophila when it was studied alone or in a combination with rifampin. PMID:7486896

  11. 40 CFR 721.3152 - Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates (salts). 721.3152 Section 721... Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates... ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

  12. 40 CFR 721.3152 - Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates (salts). 721.3152 Section 721... Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates... ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

  13. 40 CFR 721.3152 - Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates (salts). 721.3152 Section 721... Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates... ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

  14. Chemical and thermochemical aspects of the ozonolysis of ethyl oleate: decomposition enthalpy of ethyl oleate ozonide.

    PubMed

    Cataldo, Franco

    2013-01-01

    Neat ethyl oleate was ozonized in a bubble reactor and the progress of the ozonolysis was followed by infrared (FT-IR) spectroscopy and by the differential scanning calorimetry (DSC). The ozonolysis was conducted till a molar ratio O3/C=C≈1 when the exothermal reaction spontaneously went to completion. A specific thermochemical calculation on ethyl oleate ozonation has been made to determine the theoretical heat of the ozonization reaction using the group increment approach. A linear relationship was found both in the integrated absorptivity of the ozonide infrared band at 1110 cm(-1) and the ozonolysis time as well as the thermal decomposition enthalpy of the ozonides and peroxides formed as a result of the ozonation. The DSC decomposition temperature of ozonated ethyl oleate occurs with an exothermal peak at about 150-155 °C with a decomposition enthalpy of 243.0 kJ/mol at molar ratio O3/C=C≈1. It is shown that the decomposition enthalpy of ozonized ethyl oleate is a constant value (≈243 kJ/mol) at any stage of the O3/C=C once an adequate normalization of the decomposition enthalpy for the amount of the adsorbed ozone is taken into consideration. The decomposition enthalpy of ozonized ethyl oleate was also calculated using a simplified thermochemical model, obtaining a result in reasonable agreement with the experimental value.

  15. Determination of Characteristics of Erythromycin Resistant Streptococcus pneumoniae with Preferred PCV Usage in Iran.

    PubMed

    Talebi, Malihe; Azadegan, Azadeh; Sadeghi, Javad; Ahmadi, Ali; Ghanei, Mostafa; Katouli, Mohammad; Owlia, Parviz; Pourshafie, Mohammad R

    2016-01-01

    Amongst 100 Streptococcus pneumoniae isolated from clinical cases and nasopharynx of healthy individuals, 60 erythromycin resistant strains were isolated and characterized using MLST, PFGE, transposon analysis and Quellung reaction. Most of the S. pneumoniae erythromycin resistant (80%) were found to be attributable to the ermB-edncoded ribosome methylase activity which differs from the dominant mechanism of macrolide resistance seen in North America. The most predominant transposons were; Tn1545/6003 (27%), Tn6002 (22%), Tn2009 (20%), Tn2010 (17%). Number of the clinical isolates carrying Tn2010 was more significant than the normal flora. The serotypes found were; 14 (33%), 3 (22%), 23F (15%), 19F (15%), 19A (7%), 6A (3%), 9V (3%) and 6B (2%). The most prevalent serotypes among the clinical (n = 28) and normal flora (n = 32) isolates were serotypes 14 (46%) and 3 (31%), respectively. The most prevalent vaccine serotypes amongst the clinical isolates and the healthy individuals were pneumococcal conjugate vaccines (PCV) 13 and PCV10, respectively. PFGE revealed 34 pulsotypes with 9 common and 25 single types. Significant number of the normal isolates belonged to CT5 and CT6. On the other hand, significant number of clinical isolates belonged to CT8 as compared to the normal flora isolates. MLST showed 2 dominant sequence types. ST3130 (23%) and ST180 (22%) were the most predominant sequence types in the clinical and normal isolates, respectively. There was no significant difference in other sequence types between clinical and normal flora isolates. Three polyclonal complexes including Sweden15A -25, Spain23F-1 and Spain9V-3 constituted 58% of the isolates. Our results suggest that the genetic diversity and transposon distribution were high among S. pneumoniae, particularly in the isolates containing erm(B) and double antibiotic resistant genes (erm/mef). The results presented here could influence the change in the current vaccination practices in Iran which

  16. Determination of Characteristics of Erythromycin Resistant Streptococcus pneumoniae with Preferred PCV Usage in Iran

    PubMed Central

    Talebi, Malihe; Azadegan, Azadeh; Sadeghi, Javad; Ahmadi, Ali; Katouli, Mohammad

    2016-01-01

    Amongst 100 Streptococcus pneumoniae isolated from clinical cases and nasopharynx of healthy individuals, 60 erythromycin resistant strains were isolated and characterized using MLST, PFGE, transposon analysis and Quellung reaction. Most of the S. pneumoniae erythromycin resistant (80%) were found to be attributable to the ermB-edncoded ribosome methylase activity which differs from the dominant mechanism of macrolide resistance seen in North America. The most predominant transposons were; Tn1545/6003 (27%), Tn6002 (22%), Tn2009 (20%), Tn2010 (17%). Number of the clinical isolates carrying Tn2010 was more significant than the normal flora. The serotypes found were; 14 (33%), 3 (22%), 23F (15%), 19F (15%), 19A (7%), 6A (3%), 9V (3%) and 6B (2%). The most prevalent serotypes among the clinical (n = 28) and normal flora (n = 32) isolates were serotypes 14 (46%) and 3 (31%), respectively. The most prevalent vaccine serotypes amongst the clinical isolates and the healthy individuals were pneumococcal conjugate vaccines (PCV) 13 and PCV10, respectively. PFGE revealed 34 pulsotypes with 9 common and 25 single types. Significant number of the normal isolates belonged to CT5 and CT6. On the other hand, significant number of clinical isolates belonged to CT8 as compared to the normal flora isolates. MLST showed 2 dominant sequence types. ST3130 (23%) and ST180 (22%) were the most predominant sequence types in the clinical and normal isolates, respectively. There was no significant difference in other sequence types between clinical and normal flora isolates. Three polyclonal complexes including Sweden15A -25, Spain23F-1 and Spain9V-3 constituted 58% of the isolates. Our results suggest that the genetic diversity and transposon distribution were high among S. pneumoniae, particularly in the isolates containing erm(B) and double antibiotic resistant genes (erm/mef). The results presented here could influence the change in the current vaccination practices in Iran which

  17. Conversion of succinic acid to 1,4-butanediol via dimethyl succinate over rhenium nano-catalyst supported on copper-containing mesoporous carbon.

    PubMed

    Hong, Ung Gi; Kim, Jeong Kwon; Lee, Joongwon; Lee, Jong Kwon; Yi, Jongheop; Song, In Kyu

    2014-11-01

    Copper-containing mesoporous carbons (XCu-MC) with different copper content (X = 8.0, 12.7, 15.9, 23.3, and 26.8 wt%) were prepared by a single-step surfactant-templating method. Rhenium nano-catalysts supported on copper-containing mesoporous carbons (Re/XCu-MC) were then prepared by an incipient wetness method. Re/XCu-MC (X = 8.0, 12.7, 15.9, 23.3, and 26.8 wt%) catalysts were characterized by nitrogen adsorption-desorption isotherm, HR-TEM, FT-IR, and H2- TPR analyses. Liquid-phase hydrogenation of succinic acid to 1,4-butanediol (BDO) via dimethyl succinate (DMS) was carried out over Re/XCu-MC catalysts in a batch reactor. The effect of copper content on the physicochemical properties and catalytic activities of Re/XCu-MC catalysts in the hydrogenation of succinic acid to BDO was investigated. Re/XCu-MC catalysts retained different physicochemical properties depending on copper content. In the hydrogenation of succinic acid to BDO, yield for BDO showed a volcano-shaped trend with respect to copper content. Thus, an optimal copper content was required to achieve maximum catalytic performance of Re/XCu-MC. It was also observed that yield for BDO increased with increasing the amount of hydrogen consumption by copper in the Re/XCu-MC catalysts.

  18. Sources of propionate for the biogenesis of ethyl-braced insect juvenile hormones: role of isoleucine and valine

    SciTech Connect

    Brindle, P.A.; Baker, F.C.; Tsai, L.W.; Reuter, C.C.; Schooley, D.A.

    1987-11-01

    Corpora allata from adult female Manduca sexta biosynthesis the sesquiterpenoid juvenile hormone (JH) III and the unusual ethyl-branched homologue JH II in vitro. The authors maintained corpora allata in medium 199 using (methyl-/sup 3/H)methionine as the source of the JH methyl ester moiety and as a mass marker. This allowed measurement of the relative contributions of /sup 14/C-labeled precursors to the biogenesis of JH II and III carbon skeletons. They showed efficient incorporation of a propionate equivalent, from isoleucine or valine catabolism, into the ethyl-branched portion of JH II, using double-label liquid scintillation counting of isolated JHs and gas chromatography/mass spectrometry with selected ion monitoring of JH deuteromethoxyhydrin derivatives. Methionine was a poor source of propionate for JH II biosynthesis, while glucose, succinate, threonine, and ..beta..-alanine did not contribute propionate at all. Leucine, isoleucine, and glucose incorporated into JH III and the acetate-derivative portion of JH II.

  19. 3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase

    PubMed Central

    Alston, Theodore A.; Mela, Leena; Bright, Harold J.

    1977-01-01

    We have shown that 3-nitropropionate, an isoelectronic analogue of succinate, is a suicide inactivator of succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1] as follows. (i) When rat liver mitochondria oxidize succinate in the presence of 3-nitropropionate carbanion, the rate of O2 consumption decreases exponentially to a zero value. This pattern is duplicated by subsequent additions of mitochondria. The dependence of the apparent first-order rate constant for enzyme inhibition, as well as the number of enzyme turnovers completed before inhibition, on the concentrations of 3-nitropropionate carbanion and succinate are those expected for an active site-directed and irreversible inhibitor. (ii) The inactivated enzyme is not resuscitated by centrifugation and washing of the mitochondria, in contrast to malonate-treated enzyme, and malonate protects against irreversible, inhibition. (iii) The inhibitor species is 3-nitropropionate carbanion and no external nucleophile is required for inhibition. (iv) The respiratory rates, respiratory control ratios, and ADP/O ratios obtained with NAD-linked substrates are unaffected by 3-nitropropionate carbanion. These results show that 3-nitropropionate carbanion is a highly specific, time-dependent, and irreversible inhibitor of succinate dehydrogenase. By analogy with the reaction of nitroethane with D-amino acid oxidase, the data are consistent with the hypothesis that the carbanionic inhibitor forms a covalent N-5 adduct with the active site flavin. However, the precise mechanism of inactivation, as well as mechanistic extrapolations to the oxidation of succinate, must await the elucidation of the structure of the modified enzyme. We can now explain the toxicity of plants such as Indigofera endecaphylla for mammals and fowl as being due to the irreversible blockage of the Krebs cycle by 3-nitropropionate carbanion. PMID:269430

  20. 3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase.

    PubMed

    Alston, T A; Mela, L; Bright, H J

    1977-09-01

    We have shown that 3-nitropropionate, an isoelectronic analogue of succinate, is a suicide inactivator of succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1] as follows. (i) When rat liver mitochondria oxidize succinate in the presence of 3-nitropropionate carbanion, the rate of O(2) consumption decreases exponentially to a zero value. This pattern is duplicated by subsequent additions of mitochondria. The dependence of the apparent first-order rate constant for enzyme inhibition, as well as the number of enzyme turnovers completed before inhibition, on the concentrations of 3-nitropropionate carbanion and succinate are those expected for an active site-directed and irreversible inhibitor. (ii) The inactivated enzyme is not resuscitated by centrifugation and washing of the mitochondria, in contrast to malonate-treated enzyme, and malonate protects against irreversible, inhibition. (iii) The inhibitor species is 3-nitropropionate carbanion and no external nucleophile is required for inhibition. (iv) The respiratory rates, respiratory control ratios, and ADP/O ratios obtained with NAD-linked substrates are unaffected by 3-nitropropionate carbanion. These results show that 3-nitropropionate carbanion is a highly specific, time-dependent, and irreversible inhibitor of succinate dehydrogenase. By analogy with the reaction of nitroethane with D-amino acid oxidase, the data are consistent with the hypothesis that the carbanionic inhibitor forms a covalent N-5 adduct with the active site flavin. However, the precise mechanism of inactivation, as well as mechanistic extrapolations to the oxidation of succinate, must await the elucidation of the structure of the modified enzyme. We can now explain the toxicity of plants such as Indigofera endecaphylla for mammals and fowl as being due to the irreversible blockage of the Krebs cycle by 3-nitropropionate carbanion.