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Sample records for erythromycin ethyl succinate

  1. 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 ...

  2. [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. PMID:26215417

  3. 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.

  4. Induction of erythromycin resistance in Staphyloccus aureus by erythromycin derivatives.

    PubMed

    Pestka, S; Vince, R; LeMahieu, R; Weiss, F; Fern, L; Unowsky, J

    1976-01-01

    The ability of 53 erythromycin analogues to induce resistance to erythromycin in Staphlococcus aureus was evaluated. Only derivatives with antibacterial activity induced resistance, although some antibacterial compounds did not induce resistance. No derivatives without antibacterial activity but with ability to induce resistance were found.

  5. 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

  6. 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. PMID:24703267

  7. 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.

  8. 21 CFR 520.823 - Erythromycin phosphate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... (a) Specifications. Erythromycin phosphate is the phosphate salt of the antibiotic substance produced by the growth of Streptomyces erythreus or the same antibiotic substance produced by any other...

  9. 21 CFR 520.823 - Erythromycin phosphate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... (a) Specifications. Erythromycin phosphate is the phosphate salt of the antibiotic substance produced by the growth of Streptomyces erythreus or the same antibiotic substance produced by any other...

  10. 21 CFR 520.823 - Erythromycin phosphate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... (a) Specifications. Erythromycin phosphate is the phosphate salt of the antibiotic substance produced by the growth of Streptomyces erythreus or the same antibiotic substance produced by any other...

  11. 21 CFR 520.823 - Erythromycin phosphate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... (a) Specifications. Erythromycin phosphate is the phosphate salt of the antibiotic substance produced by the growth of Streptomyces erythreus or the same antibiotic substance produced by any other...

  12. 21 CFR 520.823 - Erythromycin phosphate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... (a) Specifications. Erythromycin phosphate is the phosphate salt of the antibiotic substance produced by the growth of Streptomyces erythreus or the same antibiotic substance produced by any other...

  13. 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.

  14. 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...

  15. 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...

  16. Icosapent Ethyl

    MedlinePlus

    ... pharmacist if you are allergic to icosapent ethyl; fish, including shellfish (clams, scallops, shrimp, lobster, crayfish, crab, ... and ticlopidine (Ticlid); aspirin or aspirin-containing products; beta-blockers such as atenolol (Tenormin), labetalol (Normodyne), metoprolol ( ...

  17. Succinic anhydrides from epoxides

    SciTech Connect

    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.

  18. Succinic anhydrides from epoxides

    SciTech Connect

    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.

  19. 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

  20. 21 CFR 558.248 - Erythromycin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... in Animal Feeds § 558.248 Erythromycin. (a) Approvals. Type A medicated articles: (1) 2.2 percent to... periods of stress Feed for 2 d before stress and 3 to 6 d after stress; withdraw 24 h before slaughter... stress Feed for 2 d before stress and 3 to 6 d after stress (vi) 185 1. Chickens; as an aid in...

  1. 21 CFR 558.248 - Erythromycin thiocyanate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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...

  2. 21 CFR 526.820 - Erythromycin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... vehicle is triglyceride of saturated fatty acids from coconut oil. (4) The drug may or may not be sterile... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Erythromycin. 526.820 Section 526.820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL...

  3. Erythromycin induces expression of the chloramphenicol acetyltransferase gene cat-86.

    PubMed Central

    Rogers, E J; Lovett, P S

    1990-01-01

    The plasmid gene cat-86 specifies chloramphenicol-inducible chloramphenicol acetyltransferase in Bacillus subtilis. This gene, like the erythromycin-inducible erm genes, is regulated by translational attenuation. Here we show that cat-86 is also inducibly regulated by erythromycin. cat-86 does not confer resistance to erythromycin. PMID:2115875

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Metabolism of propionyl erythromycin lauryl sulfate. I. Fate of the propionyl erythromycin moiety in the rat.

    PubMed

    Murphy, P J; Williams, T L; McMahon, R E; Marshall, F J

    1975-01-01

    The absorption, excretion, and metabolism of propionyl erythromycin (PE) has been studied in the rat. The major routes of metabolism of PE are ester hydrolysis and N-demethylation. The rates of these two reactions have been examined in vivo using radiolabeled PE. The plasma half-life of the ester is 5.5 hr. The correlation of blood levels of radioactivity with 14CO2 production indicates that the ester is continually hydrolyzed after absorption. The half-life of the dimethyl-amino moiety of the desosamine sugar is estimated at 1.5 hr. This relatively short half-life compared to that of the ester is supported by the fact that at 3.5 hr after dosing there is twice as much desmethyl-PE in plasma as PE. After oral administration of either 14C-PE or 14C-erythromycin, 70% of the radioactivity is absorbed in 6 hr. The major route of excretion is via bile. Approximatley 40% of the absorbed dose is excreted in bile in the first 6 hr after dosing. Tissue levels of radioactivity after administration of 14C-erythromycin or 14C-PE indicate that PE or a metabolite accumulates in the tissue during chronic dosing, whereas erythromycin-related levels are similar after single or multiple doses.

  11. Oral erythromycin treatment for childhood blepharokeratitis.

    PubMed

    Meisler, D M; Raizman, M B; Traboulsi, E I

    2000-12-01

    Blepharokeratitis is a chronic external ocular and adnexal inflammatory condition marked by erythematous and edematous lid margins, lid margin crusting and scaling, meibomian gland inflammation and inspissation, and conjunctival hyperemia. The associated keratitis usually involves the inferior cornea and is characterized by punctate epithelial keratopathy and marginal stromal infiltrates. The inflammation sometimes leads to corneal thinning, scarring, and vascularization. The standard therapy for adult blepharokeratitis includes lid hygiene, topical cortico-steroid preparations, and topical antibiotics. Oral tetracycline and its analogues, doxycycline and minocycline, are used in adults to treat associated meibomian gland dysfunction. Whereas blepharitis is common in children, blepharokeratitis is rare and is often associated with severe ocular and psychosocial morbidity. Treatment of youths may be problematic because of poor compliance with lid hygiene and therapy that includes drops and ointment.(1) Furthermore, the use of tetracycline and its analogues is contraindicated in children aged less than 8 years because it may cause dental enamel abnormalities. Isolated case reports have suggested that erythromycin may be a reasonable alternative to tetracycline in childhood blepharokeratitis.(2,3) We report on the successful treatment of this condition with oral erythromycin in 5 children.

  12. 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

  13. Effects of erythromycin in chronic idiopathic intestinal pseudo-obstruction.

    PubMed

    Minami, T; Nishibayashi, H; Shinomura, Y; Matsuzawa, Y

    1996-12-01

    The prokinetic effects of erythromycin, a macrolide antibiotic, on the gastrointestinal tract as a motilin receptor agonist and its potential value for the treatment of gastrointestinal motility disorders have recently attracted interest. The effects of erythromycin on the clinical symptoms and gastrointestinal motility of patients with chronic idiopathic pseudo-obstruction have not been investigated extensively. We presented a case of chronic idiopathic intestinal pseudo-obstruction, in a 67-year-old man in whom oral erythromycin (900 mg/day) dramatically improved postprandial abdominal distention, nausea, and vomiting. Other agents with prokinetic effects on intestinal motility, i.e., cisapride, domperidone, metoclopramide, and trimebutine maleate did not have a favorable effect. Gastric emptying, measured by the sulfamethizole method; and intestinal transit, evaluated using radio-opaque markers, were markedly improved by treatment with erythromycin. Our experience suggests that the prokinetic effects of erythromycin may be of therapeutic value in chronic idiopathic intestinal pseudo-obstruction. PMID:9027652

  14. 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

  15. [Effect of erythromycin on neutrophil adhesion molecules].

    PubMed

    Kusano, S; Mukae, H; Morikawa, T; Asai, T; Sawa, H; Morikawa, N; Oda, H; Sakito, O; Shukuwa, C; Senju, R

    1993-01-01

    The mechanisms of erythromycin (EM) in chronic lower respiratory tract diseases including diffuse panbronchiolitis (DPB) has been reported. In this study we investigated the effect of EM on peripheral neutrophil adhesion molecules such as LFA-1 and Mac-1 obtained from six healthy subjects. Pretreatment of neutrophils with each concentration (10 ng/ml approximately 100 micrograms/ml) of EM resulted in no significant reduction in the expression of LFA-1 alpha, beta and Mac-1. Moreover, EM had no capability of reducing these expressions even when neutrophils were pretreated with 1 microgram/ml of EM at time from 0 to 60 min. These findings indicate that EM does not directly reduce the expression of LFA-1 alpha, beta and Mac-1 on peripheral neutrophil obtained from healthy subjects. PMID:8450276

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. Erythromycin ethosomal systems: physicochemical characterization and enhanced antibacterial activity.

    PubMed

    Godin, Biana; Touitou, Elka

    2005-07-01

    The rationale behind this work was that a permeation enhancing carrier could facilitate the transport of antibacterial molecules through the two biological barriers: stratum corneum of the skin and bacterial membrane/cell wall. To this end, erythromycin ethosomes (EE) were designed and characterized, and their antibacterial efficiency was evaluated in vitro and in vivo. TEM, CLSM, DLS, DSC and ultracentrifugation tests indicate that EE are small unilamellar soft vesicles encapsulating 78.6% erythromycin. The compositions were stable for at least one year at room temperature. In live/dead viability/cytotoxicity tests, EE systems were nontoxic to cultured 3T3 dermal fibroblasts. Susceptibility studies conducted on three bacterial strains (B. subtilis ATCC 6633, S. aureus ATCC 29213 and S. aureus clinically resistant to erythromycin) showed significantly larger inhibition zones for EE as compared to erythromycin in hydroethanolic solutions. Moreover, EE reduced erythromycin MIC as compared to control solution: from 2.5 to 1.25 microg/ml for S. aureus ATCC 29213 and from 12.5 to 5.0 microg/ml for clinically isolated resistant S. aureus strain. Ethosomal erythromycin applied to the skin of ICR mice inoculated with 10(7)cfu S. aurues ATCC 29213 resulted in complete inhibition of infection. On the contrary, when hydroethanolic solution of erythromycin was applied, deep dermal and subcutaneous abscesses developed within five days after challenge. On day seven, a similar number of S. aureus colonies (1.06x10(7) vs. 0.90x10(7) cfu/g tissue) were isolated from the untreated wounds or treated with hydroethanolic erythromycin. For these animals, histopathological examination showed necrosis, destroyed skin structures and dense infiltrates of neutrophils and macrophages. These findings show that ethosomes are efficient carriers for erythromycin delivery to bacteria localized within the deep skin strata for eradication of staphylococcal infections.

  2. Cyclosporin-erythromycin interaction in renal transplant patients.

    PubMed Central

    Gupta, S K; Bakran, A; Johnson, R W; Rowland, M

    1989-01-01

    1. The interaction between cyclosporin (CyA) and erythromycin was studied in renal transplant patients following oral and intravenous administration of CyA. 2. Blood and plasma CyA concentrations and blood concentrations of metabolite 17 were measured by h.p.l.c. 3. Erythromycin produced almost a two-fold increase in bioavailability, from 36% to 60%; with a small (13%) decrease in clearance of CyA. 4. The metabolite 17 data further support the postulate that erythromycin increases the absorption of CyA rather than inhibits its metabolism, as generally believed. PMID:2655690

  3. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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 gallons... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ethyl alcohol containing ethyl acetate....

  4. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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 gallons... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ethyl alcohol containing ethyl acetate....

  5. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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 gallons... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ethyl alcohol containing ethyl acetate....

  6. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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 gallons... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethyl alcohol containing ethyl acetate....

  7. 21 CFR 584.200 - Ethyl alcohol containing ethyl acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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 gallons... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ethyl alcohol containing ethyl acetate....

  8. Bis(melaminium) succinate succinic acid monosolvate dihydrate

    PubMed Central

    Froschauer, Barbara; Weil, Matthias

    2012-01-01

    The asymmetric unit of the solvated title salt, 2C3H7N6 +·C4H4O4 2−·C4H6O4·2H2O, contains one essentially planar melaminium (2,4,6-triamino-1,3,5-triazin-1-ium) cation (r.m.s. deviation of the non-H atoms = 0.0097 Å), one-half of a succinate anion, one-half of a succinic acid solvent mol­ecule and one water molecule of crystallization; full mol­ecules are generated by inversion symmetry. Supra­molecular layers parallel to (12-1) are formed through extensive inter­molecular hydrogen bonding of the types O—H⋯O, N—H⋯N and N—H⋯O between the components. PMID:22904985

  9. 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

  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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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.

  16. 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.

  17. A 4% erythromycin and zinc combination (Zineryt) versus 2% erythromycin (Eryderm) in acne vulgaris: a randomized, double-blind comparative study.

    PubMed

    Habbema, L; Koopmans, B; Menke, H E; Doornweerd, S; De Boulle, K

    1989-10-01

    A double-blind, randomized multi-centre study was performed to evaluate the efficacy of a 4% erythromycin and zinc combination (Zineryt) versus 2% erythromycin (Eryderm). One-hundred and twenty-two patients suffering from acne vulgaris were treated with either Zineryt lotion or 2% erythromycin lotion. Acne grading and lesion counts for comedones, papules, pustules, nodules and macules were performed at each visit at 0, 1, 2, 4, 8 and 12 weeks. Treatment with Zineryt lotion was found to be more effective than with 2% erythromycin as regards the reduction in number of the acne lesions and the severity grade of the acne.

  18. 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.

  19. Downstream processing of biotechnological produced succinic acid.

    PubMed

    Cheng, Ke-Ke; Zhao, Xue-Bing; Zeng, Jing; Wu, Ru-Chun; Xu, Yun-Zhen; Liu, De-Hua; Zhang, Jian-An

    2012-08-01

    Succinic acid is a promising chemical which has a wide range of applications and can be biologically produced. The separation of succinic acid from fermentation broth makes more than 50 % of the total costs in their microbial production. This review summarizes the present state of methods studied for the recovery and purification of biologically produced succinate. Previous studies on the separation of succinic acid primarily include direct crystallization, precipitation, membrane separation, extraction, chromatography, and in situ separation. No single method has proved to be simple and efficient, and improvements are especially needed with regard to yield, purity, and energy consumption. It is argued that separation technologies coupled with upstream technology, in situ product removal, and biorefining strategy deserve more attentions in the future. PMID:22707056

  20. 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. PMID:19898782

  1. Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis.

    PubMed

    De Vadder, Filipe; Kovatcheva-Datchary, Petia; Zitoun, Carine; Duchampt, Adeline; Bäckhed, Fredrik; Mithieux, Gilles

    2016-07-12

    Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose homeostasis. Accordingly, dietary succinate improved glucose and insulin tolerance in wild-type mice, but those effects were absent in mice deficient in IGN. Conventional mice colonized with the succinate producer Prevotella copri exhibited metabolic benefits, which could be related to succinate-activated IGN. Thus, microbiota-produced succinate is a previously unsuspected bacterial metabolite improving glycemic control through activation of IGN. PMID:27411015

  2. 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.

  3. 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

  4. Chlorimuron-ethyl

    Integrated Risk Information System (IRIS)

    Chlorimuron - ethyl ; CASRN 90982 - 32 - 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 Assessments for Noncarcinog

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Influence of erythromycin on establishment of feeding in preterm infants: observations from a randomised controlled trial

    PubMed Central

    Stenson, B.; Middlemist, L.; Lyon, A.

    1998-01-01

    AIM—To determine the effect of erythromycin on the establishment of enteral feeding in ventilated infants <31 weeks gestation.
METHODS—Erythromycin was randomly allocated as an antimicrobial treatment for the first 7 days of life in 76 infants: 35 received erythromycin and 41 acted as controls. Feed toleration, time taken to establish full enteral feeding, vomiting, prescription of glycerine suppositories and occurrence of necrotising enterocolitis were recorded.
RESULTS—There were no significant differences between the groups for any of the outcomes. The infants treated with erythromycin reached full feeding at a median (quartile) age of 8 (5-12) days compared with 9 (6-14) days for controls.
CONCLUSIONS—Intravenous erythromycin in antimicrobial doses is unlikely to benefit the introduction of feeding in preterm infants.

 PMID:10194995

  11. Effect of loxiglumide and atropine on erythromycin-induced reduction in gallbladder volume in human subjects.

    PubMed

    Jebbink, M C; Masclee, A A; van der Kleij, F G; Schipper, J; Rovati, L C; Jansen, J B; Lamers, C B

    1992-10-01

    This study was undertaken to investigate the effect of erythromycin, a motilin agonist with prokinetic activity, on fasting gallbladder volume. To evaluate the mechanism of action of erythromycin on gallbladder motility, erythromycin (3.5 mg/kg.20 min, intravenously) was infused on three separate occasions: during cholinergic blockage with atropine (0.005 mg/kg.hr), during cholecystokinin receptor blockade with loxiglumide (10 mg/kg.hr) and during saline solution infusion (control). Atropine, loxiglumide and saline solution infusions were started 3 hr before administration of erythromycin and were continued for 3 hr thereafter. Gallbladder volumes (measured by ultrasonography), plasma cholecystokinin levels (radioimmunoassay) and plasma pancreatic polypeptide levels (radioimmunoassay) were determined at regular intervals for 6 hr in six healthy volunteers. During the 3-hr infusion before administration of erythromycin, both loxiglumide and atropine significantly increased gallbladder volumes--from 18 +/- 2 to 37 +/- 3 cm3 (p less than 0.05) and from 17 +/- 3 to 24 +/- 2 cm3 (p less than 0.05), respectively--whereas saline solution did not significantly affect gallbladder volume. During control saline solution infusion, erythromycin induced prolonged gallbladder contraction that was significant (p less than 0.05) between 60 and 180 min and reached a maximum of 45% +/- 8% at 150 min. Plasma cholecystokinin levels were not affected by erythromycin. Erythromycin induced a significant (p less than 0.05) increase in plasma pancreatic polypeptide levels, from 12 +/- 1 pmol/L to 34 +/- 3 pmol/L. Loxiglumide did not prevent the erythromycin-induced reduction in gallbladder volume. Atropine markedly reduced the effect of erythromycin, causing slight but significant (p less than 0.05) gallbladder volume reductions (18% +/- 4%) between 150 and 180 min.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. 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

  13. 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. PMID:27371794

  14. Succinate dehydrogenase-deficient gastrointestinal stromal tumors

    PubMed Central

    Wang, Ya-Mei; Gu, Meng-Li; Ji, Feng

    2015-01-01

    Most gastrointestinal stromal tumors (GISTs) are characterized by KIT or platelet-derived growth factor alpha (PDGFRA) activating mutations. However, there are still 10%-15% of GISTs lacking KIT and PDGFRA mutations, called wild-type GISTs (WT GISTs). Among these so-called WT GISTs, a small subset is associated with succinate dehydrogenase (SDH) deficiency, known as SDH-deficient GISTs. In addition, GISTs that occur in Carney triad and Carney-Stratakis syndrome represent specific examples of SDH-deficient GISTs. SDH-deficient GISTs locate exclusively in the stomach, showing predilection for children and young adults with female preponderance. The tumor generally pursues an indolent course and exhibits primary resistance to imatinib therapy in most cases. Loss of succinate dehydrogenase subunit B expression and overexpression of insulin-like growth factor 1 receptor (IGF1R) are common features of SDH-deficient GISTs. In WT GISTs without succinate dehydrogenase activity, upregulation of hypoxia-inducible factor 1α may lead to increased growth signaling through IGF1R and vascular endothelial growth factor receptor (VEGFR). As a result, IGF1R and VEGFR are promising to be the novel therapeutic targets of GISTs. This review will update the current knowledge on characteristics of SDH-deficient GISTs and further discuss the possible mechanisms of tumorigenesis and clinical management of SDH-deficient GISTs. PMID:25741136

  15. Benzoyl peroxide versus topical erythromycin in the treatment of acne vulgaris.

    PubMed

    Burke, B; Eady, E A; Cunliffe, W J

    1983-02-01

    In a double-blind clinical study in ninety-four subjects a 1.5% (w/v) erythromycin lotion was as effective as 5% (w/v) benzoyl peroxide gel in significantly reducing the number of small inflamed lesions and the overall acne severity. However, benzoyl peroxide also significantly reduced the number of non-inflamed lesions whereas erythromycin had no effect on these lesions. This study supports the view that, although topical erythromycin is of value in the treatment of mild or moderate acne vulgaris, long established, safe and effective remedies should not be replaced by topical antibiotics until more comparative studies and investigations on bacterial resistance have been completed.

  16. 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.

  17. 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.

  18. 75 FR 21300 - North American Bioproducts Corp.; Filing of Food Additive Petition (Animal Use); Erythromycin...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ... erythromycin thiocyanate as an antimicrobial processing aid in fuel- ethanol fermentations with respect to its... thiocyanate as an antimicrobial processing aid in fuel- ethanol fermentations with respect to its...

  19. [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. PMID:26841533

  20. 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. PMID:15054284

  1. 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.

  2. 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.

  3. Effects of erythromycin in combination with penicillin, ampicillin, or gentamicin on the growth of Listeria monocytogenes.

    PubMed Central

    Penn, R L; Ward, T T; Steigbigel, R T

    1982-01-01

    Since the optimal antimicrobial therapy for infections caused by Listeria monocytogenes, particularly in patients allergic to penicillin, is uncertain, we investigated the in vitro effects of erythromycin, alone and in combination with other antibiotics, on listeriae. Seven strains of listeriae were inhibited but not killed by erythromycin, penicillin G, or ampicillin when tested by a microtiter broth dilution method. Susceptibility to gentamicin decreased when tryptose phosphate broth was substituted for Mueller-Hinton broth, but was independent of their calcium and magnesium concentrations. Quantitative killing studies performed with erythromycin combined with either penicillin G or ampicillin yielded antagonism for all strains, in contrast to microtiter checkerboard determinations, which did not indicate antagonism in all instances. Antagonism occurred with strains in both the stationary and log phases of growth and was slightly reversed by a 120-min preincubation of the listeriae with penicillin before the addition of erythromycin. Erythromycin and gentamicin were antagonistic in quantitative killing studies. Based on these in vitro findings, we conclude that the addition of gentamicin to erythromycin offers no advantage in the treatment of listeriosis in the penicillin-allergic patient. PMID:6821458

  4. 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. PMID:27447798

  5. 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. PMID:27222285

  6. Materials and methods for efficient succinate and malate production

    DOEpatents

    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.

  7. Inhibition of mitochondrial aconitase by succination in fumarate hydratase deficiency.

    PubMed

    Ternette, Nicola; Yang, Ming; Laroyia, Mahima; Kitagawa, Mitsuhiro; O'Flaherty, Linda; Wolhulter, Kathryn; Igarashi, Kaori; Saito, Kaori; Kato, Keiko; Fischer, Roman; Berquand, Alexandre; Kessler, Benedikt M; Lappin, Terry; Frizzell, Norma; Soga, Tomoyoshi; Adam, Julie; Pollard, Patrick J

    2013-03-28

    The gene encoding the Krebs cycle enzyme fumarate hydratase (FH) is mutated in hereditary leiomyomatosis and renal cell cancer (HLRCC). Loss of FH activity causes accumulation of intracellular fumarate, which can directly modify cysteine residues to form 2-succinocysteine through succination. We undertook a proteomic-based screen in cells and renal cysts from Fh1 (murine FH)-deficient mice and identified 94 protein succination targets. Notably, we identified the succination of three cysteine residues in mitochondrial Aconitase2 (ACO2) crucial for iron-sulfur cluster binding. We show that fumarate exerts a dose-dependent inhibition of ACO2 activity, which correlates with increased succination as determined by mass spectrometry, possibly by interfering with iron chelation. Importantly, we show that aconitase activity is impaired in FH-deficient cells. Our data provide evidence that succination, resulting from FH deficiency, targets and potentially alters the function of multiple proteins and may contribute to the dysregulated metabolism observed in HLRCC. PMID:23499446

  8. EPA dashes ethyl`s hopes for MMT

    SciTech Connect

    Heller, K.

    1992-01-15

    Up until the Environmental Protection Agency (EPA; Washington) decided to deny Ethyl`s (Richmond, VA) petition to sell manganese-based gasoline additive MMT, many on Wall Street were bullish. Bets were that MMT sales could create an up to $200 million/year sales windfall for Ethyl with $60 million/year income, and push its near $26/share price up by at least 50 cts. But EPA ruled January 8 against MMT in unleaded gas due to its potential to increase hydrocarbon emissions. What kept analysts hoping is that octane enhancer MMT`s environmental impacts are mixed. An Ethyl spokesman says that MMT cut tailpipe emissions of nitrogen oxide by 20% and carbon monoxide by 7%. Ethyl also points out that MMT could save as much as 85,000 barrels/day of imported oil because of lower energy requirements in blending. And the product has sold for 13 years in Canada with no reported ill health effects. But, points out Smith, Barney (New York) analyst James Wilbur, Canada is not the congested Los Angeles basin, where the unknown effects of small amounts of heavy metal manganese would show up a lot faster if every car burnt MMT. For now, the financial effect of the decision is negligible, although at some point Ethyl may have to take a write-down on its Orangeburg, NC plant.

  9. Ethyl`s MMT ready to hit the road

    SciTech Connect

    Stringer, J.

    1996-01-03

    After spending two decades and about $30 million on the fight to sell the fuel octane booster methylcyclopentadienyl manganese tricarbonyl (MMT), Ethyl has started marketing the product. Ethyl president and chief operating officer Thomas Gottwald says he expects a profit from MMT from the outset. {open_quotes}MMT is a gangbuster new product,{close_quotes} says Paul Raman, an analyst with S.G. Warburg (New York), {open_quotes}and it will be very profitable for Ethyl.{close_quotes} Ethyl`s effort to bring MMT to market faced pressure from EPA and automakers. EPA says MMT should not be marketed until more research is done on health effects of the manganese-based additive. US automakers oppose MMT, fearing it will damage catalytic converters. Last October Ethyl won a federal appeals court decision compelling EPA to approve MMT use. Gottwald says the MMT fight has been well worth it: {open_quotes}We fought with our eye on the bottom line.{close_quotes}

  10. [Streptococcus pyogenes: penicillin and erythromycin susceptibility in the cities of Neuquen and Cipolletti].

    PubMed

    Soriano, S V; Brasili, S; Saiz, M; Carranza, C; Vidal, P; Calderón, J; Lopardo, H A

    2000-01-01

    Penicillin resistance has not yet been detected in Streptococcus pyogenes. However macrolide-resistant streptococci have emerged in several countries. Only low rates of erythromycin-resistant S. pyogenes were reported in Argentina, with the exception of a 11.1% observed in Mendoza. The aim of the present study was to determine the susceptibility to penicillin and to erythromycin of 251 consecutive clinically-significant isolates of S. pyogenes obtained from four centers of Cipolletti and Neuquén during the period April-December 1998. The double disk test with erythromycin and clindamycin disks was employed as a screening method to detect ERY-resistant streptococci and to determine the phenotype of macrolide resistance. Disk diffusion was also employed for determining penicillin susceptibility. Macrolide-resistant isolates were also tested for penicillin, ceftriaxone, erythromycin, clindamycin and azithromycin susceptibility by the agar dilution method. Additionally they were also tested for erythromycin susceptibility by E-test (AB Biodisk, Solna, Sweden). All streptococci studied were susceptible to penicillin and thirty of them (12.0%) were resistant to erythromycin. All these resistant isolates were also resistant to azithromycin but susceptible to ceftriaxone and clindamycin. They showed the phenotype M (probably efflux-mediated mechanism) and the MICs of erythromycin ranged between 8 and 16 micrograms/ml. According to these results we conclude that in spite of universal susceptibility to penicillin in S. pyogenes, macrolide resistance is a matter of concern in Neuquén and Cipolletti. At least in those cities it appears to be necessary to routinely perform macrolide susceptibility tests in beta-hemolytic streptococci.

  11. 21 CFR 173.228 - Ethyl acetate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the specifications of the Food Chemicals Codex, 1 (Ethyl Acetate; p. 372, 3d Ed., 1981), which are... 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....

  12. 21 CFR 173.228 - Ethyl acetate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the specifications of the Food Chemicals Codex, 1 (Ethyl Acetate; p. 372, 3d Ed., 1981), which are... 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....

  13. Randomised controlled study of oral erythromycin for treatment of gastrointestinal dysmotility in preterm infants

    PubMed Central

    Ng, P; So, K; Fung, K; Lee, C; Fok, T; Wong, E; Wong, W; Cheung, K; Cheng, A

    2001-01-01

    AIM—To evaluate the effectiveness of oral erythromycin as a prokinetic agent for the treatment of moderately severe gastrointestinal dysmotility in preterm very low birthweight infants.
METHODS—A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 56 preterm infants (< 1500 g) consecutively admitted to the neonatal unit. The infants were randomly allocated by minimisation to receive oral erythromycin (12.5 mg/kg, every six hours for 14 days) or an equivalent volume of placebo solution (normal saline) if they received less than half the total daily fluid intake or less than 75 ml/kg/day of milk feeds by the enteral route on day 14 of life. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were compared between the two groups. Potential adverse effects of oral erythromycin and complications associated with parenteral nutrition were assessed as secondary outcomes.
RESULTS—Twenty seven and 29 infants received oral erythromycin and placebo solution respectively. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were significantly shorter in the group receiving oral erythromycin than in those receiving the placebo (p < 0.05, p < 0.05 and p < 0.0001 respectively). There was also a trend suggesting that more infants with prolonged feed intolerance developed cholestatic jaundice in the placebo than in the oral erythromycin group (10v 5 infants). None of the infants receiving oral erythromycin developed cardiac dysrhythmia, pyloric stenosis, or septicaemia caused by multiresistant organisms.
CONCLUSIONS—Oral erythromycin is effective in facilitating enteral feeding in preterm very low birthweight infants with moderately severe gastrointestinal dysmotility. Treated infants can achieve full enteral feeding 10 days earlier, and this may result in a substantial saving on

  14. Data on the mechanisms underlying succinate-induced aortic contraction.

    PubMed

    Gonzaga, Natália A; Simplicio, Janaina A; Leite, Letícia N; Vale, Gabriel T; Carballido, José M; Alves-Filho, José C; Tirapelli, Carlos R

    2016-12-01

    We describe the mechanisms underlying the vascular contraction induced by succinate. The data presented here are related to the article entitled "Pharmacological characterization of the mechanisms underlying the vascular effects of succinate" (L.N. Leite, N.A. Gonzaga, J.A. Simplicio, G.T. Vale, J.M. Carballido, J.C. Alves-Filho, C.R. Tirapelli, 2016) [1]. Succinate acts as a signaling molecule by binding to a G-protein-coupled receptor termed GPR91, "Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors" (W. He, F.J. Miao, D.C. Lin, R.T. Schwandner, Z. Wang, J. Gao, J.L. Chen, H. Tian, L. Ling, 2004) [2]. Here we include data on the contractile effect of succinate in the aorta. Succinate contracted both endothelium-intact and endothelium-denuded aortic rings isolated from male Wistar rats or C57BL/6 mice. Succinate was less effective at inducing contraction in arteries isolated from GPR91-deficient mice, when compared to its vascular effect in aortas from wild type mice. SB203508 (p38MAK inhibitor), SP600125 (JNK inhibitor) and Y27632 (Rho-kinase inhibitor) reduced succinate-induced contraction in both endothelium-intact and endothelium-denuded rat aortic rings, while PD98059 (ERK1/2 inhibitor) did not affect succinate-induced contraction. The contractile response induced by succinate on endothelium-intact and endothelium-denuded rat aortic rings was reduced by indomethacin (non-selective cyclooxygenase inhibitor), H7 (protein kinase C inhibitor), verapamil (Ca(2+) channel blocker) and tiron (superoxide anion scavenger). PMID:27656674

  15. Data on the mechanisms underlying succinate-induced aortic contraction.

    PubMed

    Gonzaga, Natália A; Simplicio, Janaina A; Leite, Letícia N; Vale, Gabriel T; Carballido, José M; Alves-Filho, José C; Tirapelli, Carlos R

    2016-12-01

    We describe the mechanisms underlying the vascular contraction induced by succinate. The data presented here are related to the article entitled "Pharmacological characterization of the mechanisms underlying the vascular effects of succinate" (L.N. Leite, N.A. Gonzaga, J.A. Simplicio, G.T. Vale, J.M. Carballido, J.C. Alves-Filho, C.R. Tirapelli, 2016) [1]. Succinate acts as a signaling molecule by binding to a G-protein-coupled receptor termed GPR91, "Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors" (W. He, F.J. Miao, D.C. Lin, R.T. Schwandner, Z. Wang, J. Gao, J.L. Chen, H. Tian, L. Ling, 2004) [2]. Here we include data on the contractile effect of succinate in the aorta. Succinate contracted both endothelium-intact and endothelium-denuded aortic rings isolated from male Wistar rats or C57BL/6 mice. Succinate was less effective at inducing contraction in arteries isolated from GPR91-deficient mice, when compared to its vascular effect in aortas from wild type mice. SB203508 (p38MAK inhibitor), SP600125 (JNK inhibitor) and Y27632 (Rho-kinase inhibitor) reduced succinate-induced contraction in both endothelium-intact and endothelium-denuded rat aortic rings, while PD98059 (ERK1/2 inhibitor) did not affect succinate-induced contraction. The contractile response induced by succinate on endothelium-intact and endothelium-denuded rat aortic rings was reduced by indomethacin (non-selective cyclooxygenase inhibitor), H7 (protein kinase C inhibitor), verapamil (Ca(2+) channel blocker) and tiron (superoxide anion scavenger).

  16. A double-blind controlled evaluation of the sebosuppressive activity of topical erythromycin-zinc complex.

    PubMed

    Piérard-Franchimont, C; Goffin, V; Visser, J N; Jacoby, H; Piérard, G E

    1995-01-01

    In a double-blind randomised study, 14 volunteers applied 4% erythromycin plus 1.2% zinc (Zineryt lotion) and 4% erythromycin lotions, each on half of the forehead twice daily for 3 months. The sebum output was evaluated at 3-week intervals using the photometric and the lipid-sensitive film methods. Evaluations of casual level (CL) and sebum excretion rate (SER) were made with a Sebumeter, and total area of lipid spots (TAS) was measured on Sebutapes. Compared to baseline values, the formulation of the erythromycin-zinc complex induced significant reductions in SER after 6 and 9 weeks, and in CL and TAS at 3, 6, 9 and 12 weeks. The mean reduction in TAS was over 20% for four successive 1-h samplings on completion of the study. Significant reductions in CL, SER and TAS were observed for the erythromycin-zinc formulation compared to the control lotion at 6 and 9 weeks, and also at 3 weeks for SER and TAS, and at 12 weeks for CL and TAS. This study indicates that sebum output is significantly reduced by the erythromycin-zinc complex. This reduction is theoretically beneficial for the acneic patient.

  17. 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.

  18. Accumulation and depletion kinetics of erythromycin in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Vendrell, Daniel; Serarols, Lidia; Balcázar, José Luis; de Blas, Ignacio; Gironés, Olivia; Múzquiz, José Luis; Ruiz-Zarzuela, Imanol

    2012-06-01

    Erythromycin is an antimicrobial agent recommended for the control and treatment of diseases caused by gram-positive bacteria. Few studies, however, have determined the metabolic and pharmacokinetic aspects of this antimicrobial agent in fish. The aim of the present study, therefore, was to determine the accumulation and depletion time of erythromycin after administration of medicated feed containing 52 mg kg(-1) body weight day(-1) for 8 days in rainbow trout (Oncorhynchus mykiss). Results were analyzed following the European Agency for Evaluation of Medicinal Products guidelines. We measured a withdrawal time of 187°C-day (°C-day=water temperature×days), lower than the value (500°C-day) recommended by Council Directive 2004/28/EC for veterinary medicinal products. Our results provide data to establish therapeutic regimens for the use of erythromycin in aquaculture. PMID:22436556

  19. 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

  20. Development of an enhanced separation of erythromycin and its related substances by liquid chromatography.

    PubMed

    Deubel, A; Holzgrabe, U

    2007-01-17

    A new HPLC-UV method for the determination of the impurity profile of erythromycin is developed. In contrast to the liquid chromatography described in the European Pharmacopoeia the analysis could be performed at a temperature of 25 degrees C. Erythromycin samples were analysed on an endcapped RP phase with cyanopropyl groups on the surface using gradient elution with 32 mM potassium phosphate buffer pH 8.0 and acetonitrile/methanol (75:25). The aforementioned method shows clear improvements compared to the actual method of the European Pharmacopoeia, which is less selective and sensitive.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Novel membrane-based biotechnological alternative process for succinic acid production and chemical synthesis of bio-based poly (butylene succinate).

    PubMed

    Wang, Caixia; Ming, Wei; Yan, Daojiang; Zhang, Congcong; Yang, Maohua; Liu, Yilan; Zhang, Yu; Guo, Baohua; Wan, Yinhua; Xing, Jianmin

    2014-03-01

    Succinic acid was produced in a novel membrane-based fermentation and separation integrated system. With this integrated system, product inhibition was alleviated by removing acids and replenishing fresh broth. High cell density maintain for a longer time from 75 to 130h and succinic acid concentration increased from 53 to 73g/L. In the developed separation process, succinic acid was crystallized at a recovery of 85-90%. The purity of the obtained succinic acid crystals reached 99.4% as found by HPLC and (1)H NMR analysis. A crystallization experiment indicated that among by-products glucose had a negative effect on succinic acid crystallization. Poly (butylene succinate) (PBS) was synthesized using the purified succinic acid and (1)H NMR analysis confirmed that the composition of the synthesized PBS is in agreement with that from petro-based succinic acid.

  6. Novel membrane-based biotechnological alternative process for succinic acid production and chemical synthesis of bio-based poly (butylene succinate).

    PubMed

    Wang, Caixia; Ming, Wei; Yan, Daojiang; Zhang, Congcong; Yang, Maohua; Liu, Yilan; Zhang, Yu; Guo, Baohua; Wan, Yinhua; Xing, Jianmin

    2014-03-01

    Succinic acid was produced in a novel membrane-based fermentation and separation integrated system. With this integrated system, product inhibition was alleviated by removing acids and replenishing fresh broth. High cell density maintain for a longer time from 75 to 130h and succinic acid concentration increased from 53 to 73g/L. In the developed separation process, succinic acid was crystallized at a recovery of 85-90%. The purity of the obtained succinic acid crystals reached 99.4% as found by HPLC and (1)H NMR analysis. A crystallization experiment indicated that among by-products glucose had a negative effect on succinic acid crystallization. Poly (butylene succinate) (PBS) was synthesized using the purified succinic acid and (1)H NMR analysis confirmed that the composition of the synthesized PBS is in agreement with that from petro-based succinic acid. PMID:24472699

  7. [Recycle of spent cells from anaerobic succinate fermentation].

    PubMed

    Bai, Xuefei; Chen, Kequan; Ye, Guizi; Huang, Xiumei; Li, Jian; Jiang, Min

    2010-09-01

    Spent cells recovered from anaerobic fermentation by Actinobacillus succinogenes were used as nitrogen source for succinic acid production. Three methods were investigated for cell wall-breaking. The results showed that enzymatic hydrolysis was more effective for higher succinic acid yield. When the enzymatic hydrolysate of spent cells was added to reach a total nitrogen concentration 1.11 g/L (equivalent to 10 g/L yeast extract), the succinic acid concentration was 42.0 g/L, but it increased slightly when enhancing the level of enzymatic hydrolysate. However, when 5 g/L yeast extract was supplemented with the enzymatic hydrolysate of spent cells, the succinic acid concentration reached 75.5 g/L after 36 hours and, the succinic acid productivity was 2.10 g/(L x h), which increased by 66.7% compared with the fermentation using 10 g/L yeast extract. Therefore, enzymatic hydrolysate of spent cells could replace 50% yeast extract in the original medium for succinic acid production.

  8. Economical succinic acid production from cane molasses by Actinobacillus succinogenes.

    PubMed

    Liu, Yu-Peng; Zheng, Pu; Sun, Zhi-Hao; Ni, Ye; Dong, Jin-Jun; Zhu, Lei-Lei

    2008-04-01

    In this work, production of succinic acid by Actinobacillus succinogenes CGMCC1593 using cane molasses as a low cost carbon source was developed. In anaerobic bottles fermentation, succinic acid concentration of 50.6+/-0.9 g l(-1) was attained at 60 h using an optimum medium containing molasses pretreated with sulfuric acid, resulting in a succinic acid yield of 79.5+/-1.1% and sugar utilization of 97.1+/-0.6%. When batch fermentation was carried out in a 5-l stirred bioreactor with pretreated molasses, 46.4 g l(-1) of succinic acid was attained at 48 h and faster cells growth was also observed. Fed batch fermentation was performed to minimize the substrate (sugar) inhibition effect, giving 55.2 g l(-1) of succinic acid and 1.15 g l(-1)h(-1) of productivity at 48 h. The present study suggests that the inexpensive cane molasses could be utilized for the economical and efficient production of succinic acid by A. succinogenes.

  9. 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

  10. The Succinated Proteome of FH-Mutant Tumours.

    PubMed

    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

  11. 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.

  12. Investigation of the chemical stability of an erythromycin-tretinoin lotion by the use of an optimization system.

    PubMed

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

    2000-03-20

    A combination of 2% erythromycin and 0.05% tretinoin in an alcohol-isopropanol lotion was prepared. Two parameters were investigated for their influence on the stability of erythromycin and/or tretinoin, namely pH and the concentration of butylhydroxytoluene (BHT) as antioxidant. To investigate these two parameters, an optimization technique was used with two factors (pH and concentration of BHT) at two levels. Accelerated stability analysis was performed at 45 degrees C in the dark to exclude isomerization of tretinoin. To analyse erythromycin and tretinoin in the combination preparation, a TLC method, previously developed in the laboratory, was used. The degradation of erythromycin seemed to be much faster than the tretinoin degradation. Optimal stability is shown in the pH range of 8.2-8.6 for erythromycin and 7.2-8.2 for tretinoin while the concentration of BHT had no significant influence.

  13. 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

  14. 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.

  15. Intravenous infusion of erythromycin inhibits CXC chemokine production, but augments neutrophil degranulation in whole blood stimulated with Streptococcus pneumoniae.

    PubMed

    Schultz, M J; Speelman, P; Hack, C E; Buurman, W A; van Deventer, S J; van Der Poll, T

    2000-08-01

    Macrolides may influence the inflammatory response to an infection by mechanisms that are unrelated to their antimicrobial effect. Indeed, erythromycin and other macrolides inhibit cytokine production and induce degranulation of neutrophils in vitro. CXC chemokines are small chemotactic cytokines that specifically influence neutrophil functions. To determine the effect of a clinically relevant dose of erythromycin on the production of CXC chemokines and neutrophil degranulation, six healthy humans received a 30 min iv infusion of erythromycin (1000 mg). Whole blood obtained before and at various times after the infusion was stimulated ex vivo with heat-killed Streptococcus pneumoniae. Ex vivo production of the CXC chemokines interleukin 8 (IL-8) and epithelial cell-derived neutrophil attractant 78 (ENA-78), in whole blood obtained after erythromycin infusion, was lower than that in blood drawn before erythromycin infusion (maximum inhibition post-infusion: 32.9 +/- 6.5% and 35.2 +/- 12.6% decrease in production, respectively, expressed as percentage change relative to production before infusion of erythromycin, both P < 0.05). In contrast, infusion of erythromycin was associated with an enhanced capacity of whole blood to release the neutrophil degranulation products bactericidal/permeability increasing protein (BPI), human neutrophil elastase (HNE) and human lactoferrin (HLF) upon stimulation with S. pneumoniae. Effects of erythromycin were greatest 4 h after infusion was stopped, when BPI, HNE and HLF concentrations were increased by +107.6 +/- 33.5%, +134.7 +/- 34.8% and +205.9 +/- 55.9 %, respectively (expressed as percentage change relative to production before infusion of erythromycin) (all P < 0. 05). These results indicate the ability of erythromycin to reduce CXC chemokine production and to enhance neutrophil degranulation in human blood.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Erythromycin prophylaxis for Legionnaire's disease in immunosuppressed patients in a contaminated hospital environment.

    PubMed

    Vereerstraeten, P; Stolear, J C; Schoutens-Serruys, E; Maes, N; Thys, J P; Liesnard, C; Rost, F; Kinnaert, P; Toussaint, C

    1986-01-01

    Between January 1 and June 30, 1983, immunosuppressive drugs were administered in 20 renal transplant recipients undergoing 23 rejection episodes and in 3 patients with renal failure secondary to systemic disease. Legionella pneumophila, serogroup 1, pneumonia was diagnosed on 12/26 (47%) occasions. In an attempt to decrease this high rate, a program of erythromycin prophylaxis was instituted for every new patient who received immunosuppressive chemotherapy until eradication of the organism from the water supply could be realized. From July 1, 1983 to April 30, 1984, erythromycin prophylaxis (1.5-3 g/day by mouth) was administered during 39 episodes of high-dose immunosuppression (20 kidney graft recipients and 4 patients with systemic diseases); no cases of Legionnaire's disease were recorded. During the same period, erythromycin prophylaxis was withheld from 9 other high-dose immunosuppression episodes (7 kidney graft recipients and one patient with sarcoidosis); 5 cases of Legionnaire's disease occurred (56%) in this group. We conclude that erythromycin effectively protects immunocompromised patients in an environment contaminated with L pneumophila.

  2. Direct Detection of Erythromycin-Resistant Bordetella pertussis in Clinical Specimens by PCR.

    PubMed

    Wang, Zengguo; Han, Ruijun; Liu, Ying; Du, Quanli; Liu, Jifeng; Ma, Chaofeng; Li, Hengxin; He, Qiushui; Yan, Yongping

    2015-11-01

    Resistance of Bordetella pertussis to erythromycin has been increasingly reported. We developed an allele-specific PCR method for rapid detection of erythromycin-resistant B. pertussis directly from nasopharyngeal (NP) swab samples submitted for diagnostic PCR. Based on the proven association of erythromycin resistance with the A2047G mutation in the 23S rRNA of B. pertussis, four primers, two of which were designed to be specific for either the wild-type or the mutant allele, were used in two different versions of the allele-specific PCR assay. The methods were verified with results obtained by PCR-based sequencing of 16 recent B. pertussis isolates and 100 NP swab samples submitted for diagnostic PCR. The detection limits of the two PCR assays ranged from 10 to 100 fg per reaction for both erythromycin-susceptible and -resistant B. pertussis. Two amplified fragments of each PCR, of 286 and 112 bp, respectively, were obtained from a mutant allele of the isolates and/or NP swab samples containing B. pertussis DNAs. For the wild-type allele, only a 286-bp fragment was visible when the allele-specific PCR assay 1 was performed. No amplification was found when a number of non-Bordetella bacterial pathogens and NP swab samples that did not contain the DNAs of B. pertussis were examined. This assay can serve as an alternative for PCR-based sequencing, especially for local laboratories in resource-poor countries.

  3. 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. PMID:26118901

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

    PubMed

    Harrell, Erin A; Miller, Eric S

    2016-01-01

    ITALIC! Aeromicrobium erythreumNRRL 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 ( ITALIC! ery) biosynthetic gene sequences provide resources for metabolic and combinatorial engineering of polyketides. PMID:27103725

  5. 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

  6. Fabrication of surface plasmon resonance nanosensor for the selective determination of erythromycin via molecular imprinted nanoparticles.

    PubMed

    Sari, Esma; Üzek, Recep; Duman, Memed; Denizli, Adil

    2016-04-01

    The main objective of this study was to develop a novel surface plasmon resonance (SPR) nanosensor method based on a more rapid and selective determination of erythromycin (ERY) in the aqueous solution. This study is a combination of three techniques, which are miniemulsion polymerization, molecular imprinting and surface plasmon resonance techniques. In the first part, nanoparticles prepared with methacryl groups of functional monomer at surface acted as reactive sites for erythromycin as a template molecule. The molecularly imprinted nanoparticles were characterized by FTIR, SEM and zetasizer. After immobilization of nanoparticles on gold surface of SPR chip, nanosensor was characterized with contact angle measurements. This nanosensor was then used for selective determination of erythromycin. The linearity range and detection limit were obtained as 0.99 (r(2)) and 0.29 ppm, respectively. Association kinetic analysis, Scatchard, Langmuir, Freundlich and Freundlich-Langmuir isotherms were applied data. The selectivity of the SPR nanosensor was determined by using competitor agents (kanamycin sulfate, neomycin sulfate, spiramycin). The non-imprinted nanosensor was also used to evaluate the selectivity of ERY imprinted nanosensor. Finally, the nanosensor was tested for repeatability and it gave satisfactory response. These results demonstrate a method which is of low cost, rapid and provide reliable results in order to be used in detection of erythromycin from aqueous solution.

  7. Direct Detection of Erythromycin-Resistant Bordetella pertussis in Clinical Specimens by PCR

    PubMed Central

    Wang, Zengguo; Han, Ruijun; Liu, Ying; Du, Quanli; Liu, Jifeng; Ma, Chaofeng; Li, Hengxin

    2015-01-01

    Resistance of Bordetella pertussis to erythromycin has been increasingly reported. We developed an allele-specific PCR method for rapid detection of erythromycin-resistant B. pertussis directly from nasopharyngeal (NP) swab samples submitted for diagnostic PCR. Based on the proven association of erythromycin resistance with the A2047G mutation in the 23S rRNA of B. pertussis, four primers, two of which were designed to be specific for either the wild-type or the mutant allele, were used in two different versions of the allele-specific PCR assay. The methods were verified with results obtained by PCR-based sequencing of 16 recent B. pertussis isolates and 100 NP swab samples submitted for diagnostic PCR. The detection limits of the two PCR assays ranged from 10 to 100 fg per reaction for both erythromycin-susceptible and -resistant B. pertussis. Two amplified fragments of each PCR, of 286 and 112 bp, respectively, were obtained from a mutant allele of the isolates and/or NP swab samples containing B. pertussis DNAs. For the wild-type allele, only a 286-bp fragment was visible when the allele-specific PCR assay 1 was performed. No amplification was found when a number of non-Bordetella bacterial pathogens and NP swab samples that did not contain the DNAs of B. pertussis were examined. This assay can serve as an alternative for PCR-based sequencing, especially for local laboratories in resource-poor countries. PMID:26224847

  8. Erythromycin hepatotoxicity. A rare cause of a false-positive technetium-99m DISIDA study

    SciTech Connect

    Swayne, L.C.; Kolc, J.

    1986-01-01

    An unusual cause of a cholescintigraphic, false-positive, erythromycin-induced hepatotoxicity is presented. This occurred in the presence of preservation of hepatic uptake and the normal appearance of gut activity. Serial scintigraphy and serum chemistries documented underlying gallbladder normalcy.

  9. 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.

  10. Erythromycin resistance genes in group A streptococci in Finland. The Finnish Study Group for Antimicrobial Resistance.

    PubMed

    Kataja, J; Huovinen, P; Skurnik, M; Seppälä, H

    1999-01-01

    Streptococcus pyogenes isolates (group A streptococcus) of different erythromycin resistance phenotypes were collected from all over Finland in 1994 and 1995 and studied; they were evaluated for their susceptibilities to 14 antimicrobial agents (396 isolates) and the presence of different erythromycin resistance genes (45 isolates). The erythromycin-resistant isolates with the macrolide-resistant but lincosamide- and streptogramin B-susceptible phenotype (M phenotype) were further studied for their plasmid contents and the transferability of resistance genes. Resistance to antimicrobial agents other than macrolides, clindamycin, tetracycline, and chloramphenicol was not found. When compared to our previous study performed in 1990, the rate of resistance to tetracycline increased from 10 to 93% among isolates with the inducible resistance (IR) phenotype of macrolide, lincosamide, and streptogramin B (MLSB) resistance. Tetracycline resistance was also found among 75% of the MLSB-resistant isolates with the constitutive resistance (CR) phenotype. Resistance to chloramphenicol was found for the first time in S. pyogenes in Finland; 3% of the isolates with the IR phenotype were resistant. All the chloramphenicol-resistant isolates were also resistant to tetracycline. Detection of erythromycin resistance genes by PCR indicated that, with the exception of one isolate with the CR phenotype, all M-phenotype isolates had the macrolide efflux (mefA) gene and all the MLSB-resistant isolates had the erythromycin resistance methylase (ermTR) gene; the isolate with the CR phenotype contained the ermB gene. No plasmid DNA could be isolated from the M-phenotype isolates, but the mefA gene was transferred by conjugation.

  11. 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.

  12. High prevalence of erythromycin-resistant Bordetella pertussis in Xi'an, China.

    PubMed

    Wang, Z; Cui, Z; Li, Y; Hou, T; Liu, X; Xi, Y; Liu, Y; Li, H; He, Q

    2014-11-01

    Resistance of Bordetella pertussis, the causative agent of pertussis, to erythromycin is rare. Recently, several Chinese isolates were found to be erythromycin resistant. This study aimed to investigate the occurrence of pertussis in children suffering persistent cough and the prevalence of B. pertussis resistance to erythromycin in Xi'an, China. Three hundred and thirteen patients with suspected pertussis admitted to Xi'an Children's Hospital from January 2012 through to December 2013 were included and their nasopharyngeal (NP) swabs were taken for culture and PCRs (targeting IS481 and ptx-Pr). PCR-based sequencing was used to identify the A2047G mutation of B. pertussis 23S rRNA directly from the NP samples. Sixteen (5.1%) and 168 (53.7%) patients were positive for culture and IS481 PCR. Of the 168 samples positive for IS481 PCR, 122 (72.6%) and 100 (59.5%) were positive for ptx-Pr and 23S rRNA PCRs, respectively. All culture-positive samples were also positive for the three PCRs. Fourteen (87.5%) of the 16 B. pertussis isolates were found to be resistant to erythromycin (MICs>256 mg/L). All the 14 isolates were confirmed to have a homogeneous A2047G mutation of 23S rRNA. Of the 100 samples positive for 23S rRNA PCR, 85 (85.0%) were found to have the A2047G mutation by sequencing. Our results indicate that in Xi'an, China, pertussis remains endemic in young children, and the circulating B. pertussis strains are mostly erythromycin resistant.

  13. 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. PMID:25957255

  14. 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.

  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. Succinate esters: odd-even effects in melting points.

    PubMed

    Joseph, Sumy; Sathishkumar, Ranganathan

    2014-10-01

    Dialkyl succinates show a pattern of alternating behavior in their melting points, as the number of C atoms in the alkane side chain increases, unlike in the dialkyl oxalates [Joseph et al. (2011). Acta Cryst. B67, 525-534]. Dialkyl succinates with odd numbers of C atoms in the alkyl side chain show higher melting points than the immediately adjacent analogues with even numbers. The crystal structures and their molecular packing have been analyzed for a series of dialkyl succinates with 1-4 C atoms in the alkyl side chain. The energy difference (ΔE) between the optimized and observed molecular conformations, density, Kitaigorodskii packing index (KPI) and C-H...O interactions are considered to rationalize this behavior. In contrast to the dialkyl oxalates where a larger number of moderately strong C-H...O interactions were characteristic of oxalates with elevated melting points, here the molecular packing and the density play a major role in raising the melting point. On moving from oxalate to succinate esters the introduction of the C2 spacer adds two activated H atoms to the asymmetric unit, resulting in the formation of stronger C-H...O hydrogen bonds in all succinates. As a result the crystallinity of long-chain alkyl substituted esters improves enormously in the presence of hydrogen bonds from activated donors.

  18. 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.

  19. Antioxidant and antitumor activity of trolox, trolox succinate, and α-tocopheryl succinate conjugates with nitroxides.

    PubMed

    Zakharova, Ol'ga D; Frolova, Tat'yana S; Yushkova, Yuliya V; Chernyak, Elena I; Pokrovsky, Andrei G; Pokrovsky, Mikhail A; Morozov, Sergei V; Sinitsina, Ol'ga I; Grigor'ev, Igor A; Nevinsky, Georgy A

    2016-10-21

    A possible ability of twelve new derivatives of known antioxidants trolox (TroH), trolox succinate (TroS), α-tocopheryl succinate (α-TOS) containing nitroxyl radicals (1-12) to protect bacterial cells from spontaneous and peroxide-induced mutagenesis and their cytotoxicity against six different tumor cells as well as two normal cells were investigated and compared with that for TroH, TroS, α-TOH, and α-TOS for the first time. In contrast to TroH and TroS, all nitroxide derivatives 1-12 demonstrated not only antioxidant properties, but also suppress the growth of human tumor cells: myeloma, mammary adenocarcinoma, hepatocarcinoma, T cells leukemia, histiocytic lymphoma, and T-cellular leucosis. The IC50 values (24 - ≥ 300 μM) depend significantly on the compounds and type of tumor cells. Some compounds were capable to inhibit the growth of normal mouse (LMTK) and hamster (AG17) fibroblast cells and demonstrate very different ratios in inhibition of various tumor and normal cell lines. Some nitroxide conjugates showed pronounced selectivity in suppressing the growth of several cancer cells. Overall, several compounds may be promising in parallel as antioxidants and as specific inhibitors of some tumor cells growth. Among considered spin labeled conjugates the most perspective derivatives as antioxidants and as antitumor agents are the compounds containing pyrrolidine nitroxides. In contrast to spin labeled TroH, TroS and α-TOS conjugates 1-12 succinyl derivatives 13-15 were inactive in inhibiting the growth of any tumor cells. It means that for suppressing the cancer cells the compounds should contain in their structures fragments of TroH, TroS or α-TOS. PMID:27344490

  20. 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

  1. 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

  2. Increased erythromycin production by alginate as a medium ingredient or immobilization support in cultures of Saccharopolyspora erythraea.

    PubMed

    Hamedi, J; Khodagholi, F; Hassani-Nasab, A

    2005-05-01

    Erythromycin production by Saccharopolyspora erythraea immobilized in 2% (w/v) calcium alginate or grown in medium containing 20 g sodium alginate/l inoculated with free cells was almost twice more than that of the control. S. erythraea did not consume alginate, agar, dextran, silicon antifoaming agent or cyclodextrin as a carbon source, although, all of these increased the production of erythromycin. Highest titer of erythromycin (2.3 times more than that of the control) was achieved in medium containing 1 g agar/l.

  3. 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.

  4. 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.

  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. 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.

  7. 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

  8. 2-Amino-5-bromo­pyridinium hydrogen succinate

    PubMed Central

    Hemamalini, Madhukar; Fun, Hoong-Kun

    2010-01-01

    In the title compound, C5H6BrN2 +·C4H5O4 −, the pyridine N atom of the 2-amino-5-bromo­pyridine mol­ecule is protonated. The protonated N atom and the amino group are linked via N—H⋯O hydrogen bonds to the carboxyl­ate O atoms of the singly deprotonated succinate anion. The hydrogen succinate anions are linked via O—H⋯O hydrogen bonds. A weak inter­molecular C—H⋯O hydrogen bond is also observed. PMID:21580432

  9. 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. PMID:27176670

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

    PubMed

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

    2015-11-01

    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

  11. Orally administered erythromycin in rainbow trout (Oncorhynchus mykiss): residues in edible tissues and withdrawal time.

    PubMed

    Esposito, Annarita; Fabrizi, Laura; Lucchetti, Dario; Marvasi, Luigi; Coni, Ettore; Guandalini, Emilio

    2007-03-01

    Aquaculture production has notably increased in the last decades, mainly thanks to intensive farming. Together with market globalization, this gives rise to the spreading of several fish diseases, thus increasing the demand for veterinary drugs for aquatic species. Nonetheless, very few chemicals are registered for use in aquaculture, and fish farmers are often forced to resort to off-label use of drugs authorized for other food-producing animal species. Rainbow trout is the major farmed fish species in Italy and the second one in Europe. Erythromycin is the antibiotic of choice against gram-positive cocci, the major concern for trout farming, but it is not yet registered for aquaculture use in most European countries. The aim of this study was to follow the depletion of erythromycin in rainbow trout (Oncorhynchus mykiss), after its administration at 100 mg kg(-1) trout body weight day(-1) for 21 days through medicated feed (water temperature, 11.5 degrees C). Erythromycin residues in fish muscle plus skin in natural proportion were determined by a validated liquid chromatography-electrospray ionization-tandem mass spectrometry method. Interpolation of our data, following European Agency for the Evaluation of Medicinal Products guidelines, gives a withdrawal time of 255 degrees C-days ( degrees C-day = water temperature x days), thus showing that the general value (500 degrees C-day) recommended by the Council Directive (EEC) no. 82/2001 for off-label drug use in aquaculture would be too conservative in this case, with excessive costs for the farmers. Our study provides preliminary data for a more prudent use of erythromycin in rainbow trout, suggesting a possible withdrawal time after treatment. PMID:17194823

  12. Effects of erythromycin, tetracycline and ibuprofen on the growth of Synechocystis sp. and Lemna minor.

    PubMed

    Pomati, Francesco; Netting, Andrew G; Calamari, Davide; Neilan, Brett A

    2004-05-12

    Pharmaceutically active substances have recently been recognised as an emerging environmental problem. Human and veterinarian therapeutic agents can contaminate aquatic ecosystems via sewage discharges (human and animal excretion), improper disposal or industrial waste. Very little is known on the effects of pharmaceutical pollutants on aquatic photosynthetic organisms. In this study the effects of erythromycin, tetracycline and ibuprofen on the growth of the cyanobacterium Synechocystis sp. PCC6803 and the duckweed Lemna minor FBR006 were studied at concentrations of 1-1000 microg l(-1). At dosage of 1 mg l(-1), erythromycin affected the growth of both Synechocystis and Lemna with a maximum inhibition of 70 and 20%, respectively. Tetracycline had inhibitory effects (20-22% reduction in growth) on Synechocystis at intermediate dosages. The same aminoglycoside antibiotic promoted growth in Lemna by 26% at 10 microg l(-1), while frond development was reduced at 1 mg l(-1) (tetracycline). The anti-inflammatory ibuprofen strongly stimulated the growth of Synechocystis at all concentrations tested (72% increase at 10 microg l(-1)) although inhibited Lemna in a linear dose-dependent manner with a 25% reduction over control levels at a dosage of 1 mg l(-1). The 7 days effective concentration (EC(50)) calculated for Lemna were 5.6, 1 and 4 g l(-1), respectively, for erythromycin, tetracycline and ibuprofen. Moreover, exposure to the three pharmaceuticals resulted in the production of the stress hormone, abscisic acid (ABA), in Lemna. Erythromycin and tetracycline were more effective in promoting ABA synthesis compared to ibuprofen. The effects shown by the three therapeutic drugs on Synechocystis and Lemna growth may have potential implications in the assessments of residual environmental risks associated with the presence of pharmaceuticals in freshwater ecosystems. Promotion of ABA synthesis in Lemna by the two antibiotics and by copper suggests that the plant hormone

  13. Randomised trial of erythromycin on the development of chronic lung disease in preterm infants

    PubMed Central

    Lyon, A; McColm, J; Middlemist, L; Fergusson, S; McIntosh, N; Ross, P

    1998-01-01

    AIMS—To determine if erythromycin given from birth reduces the inflammatory response and the incidence and severity of chronic lung disease.
METHODS—Seventy five infants less than 30 weeks of gestation and ventilated from birth for lung disease were randomly assigned to receive erythromycin intravenously for 7 days or to no treatment. Ureaplasma urealyticum was detected in tracheal secretions by culture and polymerase chain reaction. Differential cell counts were obtained from bronchoalveolar lavage fluid collected daily for 5 days and concentrations of the cytokines interluekins IL-1β and IL-8, and tumour necrosis factor α (TNF-α) were measured. Chronic lung disease (CLD) was defined as oxygen dependency at 36 weeks of gestation.
RESULTS—Nine infants (13%) were positive for U urealyticum. The inflammatory cytokines in the lungs increased over the first 5 days of life in all babies, but no association was found between their concentrations and the development of CLD. Those treated with erythromycin showed no significant differences from the non- treated group in the differential cell counts or concentrations of the cytokines. The two groups had a similar incidence of CLD. Babies infected with U urealyticum did not have a more pronounced cytokine response than those without infection. Chorioamnionitis was associated with significantly higher concentrations of IL-1β and IL-8 on admission: these babies had less severe acute lung disease and developed significantly less CLD.
CONCLUSIONS—U urealyticum in the trachea was not associated with an increased inflammatory response in preterm infants. Erythromycin did not reduce the incidence or severity of CLD.

 PMID:9536833

  14. 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

  15. Densitometric thin layer chromatographic analysis of tretinoin and erythromycin in lotions for topical use in acne treatment.

    PubMed

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

    1999-07-01

    A TLC-method was developed to analyse tretinoin and erythromycin in a lotion in the presence of several excipients. Erythromycin was separated on a silica gel plate and a mobile phase with dichloromethane, methanol and ammonia 25% (60:6:1 (v/v/v)), tretinoin on a C(18) RP plate with acetonitrile and water (50:25 (v/v)) as mobile phase, adding 1 ml acetic acid for the separation of the excipients and erythromycin. The derivatization for both was done with a dipping reagent, consisting of anisaldehyde, sulphuric acid and acetic acid (respectively 1, 2 and 10% (v/v/v)) and dissolved in chloroform/alcohol 94% v/v (60:30 (v/v)) for erythromycin and alcohol 94%/water (50:40 (v/v)) for tretinoin. These TLC-systems were quantitatively evaluated in terms of stability of the colour, precision, accuracy and calibration, proving the utility in the analysis of the lotion.

  16. Improvement of erythromycin production by Saccharopolyspora erythraea in molasses based medium through cultivation medium optimization.

    PubMed

    El-Enshasy, H A; Mohamed, N A; Farid, M A; El-Diwany, A I

    2008-07-01

    In the present work, erythromycin production was carried out in submerged culture using Saccharopolyspora erythraea. Different experiments were conducted to optimize the cultivation medium through the change of carbon and nitrogen sources to cheaper one in order to reduce the cost of medium and to utilize sugar cane molasses as one of major sugar industry by-products in Egypt. It was found that the addition of sugar cane molasses a sole carbon source at a concentration of 60 g/l accompanied by corn steep liquor (as organic N-source) in combination with ammonium sulphate (as inorganic N-source) gave the maximal erythromycin production. The antibiotic production in this medium reached about 600 mg/l which is about 33% higher than the value obtained in glucose based medium. On the other hand, the addition of n-propanol in concentration of 1% (v/v) increased the antibiotic production reaching about 720 mg/l after 144 h. Concluding, the new medium formulation based on cheap carbon source, sugar cane molasses, was a good alternative solution for the production of erythromycin economically.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. Nucleation kinetics of urea succinic acid -ferroelectric single crystal

    NASA Astrophysics Data System (ADS)

    Dhivya, R.; Vizhi, R. Ezhil; Babu, D. Rajan

    2015-06-01

    Single crystals of Urea Succinic Acid (USA) were grown by slow cooling technique. The crystalline system was confirmed by powder X-ray diffraction. The metastable zonewidth were carried out for various temperatures i.e., 35°, 40°, 45° and 50°C. The induction period is experimentally determined and various nucleation parameters have been estimated.

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. Pharmacological characterization of the mechanisms underlying the vascular effects of succinate.

    PubMed

    Leite, Letícia N; Gonzaga, Natália A; Simplicio, Janaina A; do Vale, Gabriel T; Carballido, José M; Alves-Filho, José C; Tirapelli, Carlos R

    2016-10-15

    We investigated the mechanisms underlying the vascular effects of succinate. Vascular reactivity experiments were performed in aortic rings isolated from male Wistar rats and C57BL/6 wild type (WT) or GPR91(-/-) mice. Nitrate/nitrite (NOx) was measured colorimetrically whereas 6-keto-prostaglandin F1α (stable product of prostacyclin) was measured by enzyme immunoassay (EIA). Phosphorylation of endothelial nitric oxide synthase (eNOS) was assessed by western immunoblotting. Functional assays revealed that the direct effect of succinate in the vasculature is biphasic. At lower concentrations succinate induced relaxation while at higher concentrations succinate induced vascular contraction. Succinate concentration dependently relaxed rat aortic rings with intact endothelium. Endothelial removal reduced, but not abolished succinate-induced relaxation. Similarly, succinate relaxed endothelium-intact and endothelium-denuded aortas isolated from both C57BL/6 and GPR91(-/-) mice. Pre-incubation of endothelium-intact, but not endothelium-denuded rat aortic rings with l-NAME, indomethacin and tetraethylammonium (TEA) reduced succinate-induced relaxation. In endothelium-intact rings, succinate-induced relaxation was attenuated by ODQ, haemoglobin, Rp-8-Br-Pet-cGMPS, thapsigargin, wortmannin and SC-560. Blockade of K(+) channels with 4-aminopyridine, apamin and charybdotoxin reduced succinate-induced relaxation. Succinate increased the concentration of NOx and 6-keto-prostaglandin F1α as well as eNOS phosphorylation at ser(1177) residue. CaCl2-induced contraction of endothelium-intact or endothelium-denuded aortas was not affected by succinate. The major finding of our study is that it first demonstrates a direct effect of succinate in the vasculature. Succinate displays a biphasic and concentration-dependent effect. The vascular relaxation induced by succinate is partially mediated by endothelial GPR91 receptors via the NO-cGMP pathway, a vasodilator cyclooxygenase (COX

  8. Susceptibility to tetracycline and erythromycin of Lactobacillus paracasei strains isolated from traditional Italian fermented foods.

    PubMed

    Comunian, Roberta; Daga, Elisabetta; Dupré, Ilaria; Paba, Antonio; Devirgiliis, Chiara; Piccioni, Valeria; Perozzi, Giuditta; Zonenschain, Daniela; Rebecchi, Annalisa; Morelli, Lorenzo; De Lorentiis, Angela; Giraffa, Giorgio

    2010-03-31

    The aim of this study was to evaluate the susceptibility of 197 isolates of Lactobacillus paracasei, isolated from Italian fermented products coming from different geographical areas, to tetracycline and erythromycin, two antimicrobials widely used in clinical and animal therapy. Isolation media were supplemented with antibiotics according to the microbiological breakpoints (BPs) defined by European Food Safety Authority (EFSA). Isolates were identified at the species level and were typed by rep-PCR using the (GTG)(5) primer. A total of 121 genotypically different strains were detected and their phenotypic antimicrobial resistance to tetracycline and erythromycin was determined as the minimum inhibitory concentration (MIC) using the broth microdilution method. The presence of the genes ermB, ermC and tetL, tetM, tetS, tetW, in the phenotypically resistant isolates was investigated by PCR. Tetracycline induction of tetM expression on representative resistant strains, grown in medium either lacking or containing the antibiotic, was also analyzed by RT-PCR. Among the 121 tested strains, 77.7% were susceptible to tetracycline (MICerythromycin (MICerythromycin (MIC>or=1024 microg/ml) (Erm(R)). The tetM and ermB genes were the most frequently detected in the Tet(R) and/or Erm(R) strains. The tetM expression was induced by antibiotic addition to the growth medium. Our study confirmed that L. paracasei is quite sensitive to tetracycline and erythromycin, but the high level of resistance of Erm(R) strains suggested that acquired resistance took place. Further investigations are required to analyze whether the genes identified in L. paracasei isolates might be horizontally transferred to other species. Since "commensal" bacteria, which L. paracasei belongs to

  9. Antimicrobial properties of erythromycin and colistin impregnated bone cement. An in vitro analysis.

    PubMed

    Ruzaimi, M Y; Shahril, Y; Masbah, O; Salasawati, H

    2006-02-01

    Deep surgical site infection is a devastating consequence of total joint arthroplasty. The use of antibiotic impregnated bone cement is a well-accepted adjunct for treatment of established infection and prevention of deep orthopaedic infection. It allows local delivery of the antibiotic at the cement-bone interface and sustained release of antibiotic provides adequate antibiotic coverage after the wound closure. Preclinical testing, randomised and clinical trials indicate that the use of antibiotic-impregnated bone cement is a potentially effective strategy in reducing the risk of deep surgical site infection following total joint arthroplasty. The purpose of this study was to assess antibacterial activity of erythromycin and colistin impregnated bone cement against strains of organisms' representative of orthopaedic infections including Gram-positive and Gram-negative aerobic organisms: Staphylococcus aureus, coagulase-negative Staphylococci, Enterococcus sp., Proteus sp., Klebsiella sp., Pseudomonas sp., and Escherichia coli. Pre-blended Simplex P bone cement with the addition of erythromycin and colistin (Howemedica Inc) was mixed thoroughly with 20ml liquid under sterile conditions to produce uniform cylindrical discs with a diameter of 14mm and thickness of 2mm. 24-48 hour agar cultures of Staphylococcus aureus, coagulase-negative Staphylococci, Enterococcus sp.,Proteus sp., Klebsiella sp.,Pseudomonas sp., and Escherichia coli were used for the agar diffusion tests. The agar plates were streaked for confluent growth followed by application of erythromycin and colistin impregnated bone cement disc to each agar plate. The plates were incubated at 30 degrees C and examined at 24, 48, 72 hours, and four and five days after the preparation of the impregnated cement. The susceptibility of Staphylococcus aureus to the control discs was most clearly demonstrated showing a distinct zone of inhibition. The zone observed around coagulase-negative Staphylococci

  10. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are available from the National Academy Press, Box... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Ethyl alcohol. 184.1293 Section 184.1293 Food and....1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH. (b) The ingredient meets...

  11. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Ethyl alcohol. 184.1293 Section 184.1293 Food and... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  12. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethyl alcohol. 184.1293 Section 184.1293 Food and... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  13. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Ethyl alcohol. 184.1293 Section 184.1293 Food and... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  14. 21 CFR 184.1293 - Ethyl alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. Copies are... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Ethyl alcohol. 184.1293 Section 184.1293 Food and... Substances Affirmed as GRAS § 184.1293 Ethyl alcohol. (a) Ethyl alcohol (ethanol) is the chemical C2H5OH....

  15. 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.

  16. Succinic semialdehyde reductase Gox1801 from Gluconobacter oxydans in comparison to other succinic semialdehyde-reducing enzymes.

    PubMed

    Meyer, Maria; Schweiger, Paul; Deppenmeier, Uwe

    2015-05-01

    Gluconobacter oxydans is an industrially important bacterium that possesses many uncharacterized oxidoreductases, which might be exploited for novel biotechnological applications. In this study, gene gox1801 was homologously overexpressed in G. oxydans and it was found that the relative expression of gox1801 was 13-fold higher than that in the control strain. Gox1801 was predicted to belong to the 3-hydroxyisobutyrate dehydrogenase-type proteins. The purified enzyme had a native molecular mass of 134 kDa and forms a homotetramer. Analysis of the enzymatic activity revealed that Gox1801 is a succinic semialdehyde reductase that used NADH and NADPH as electron donors. Lower activities were observed with glyoxal, methylglyoxal, and phenylglyoxal. The enzyme was compared to the succinic semialdehyde reductase GsSSAR from Geobacter sulfurreducens and the γ-hydroxybutyrate dehydrogenase YihU from Escherichia coli K-12. The comparison revealed that Gox1801 is the first enzyme from an aerobic bacterium reducing succinic semialdehyde with high catalytic efficiency. As a novel succinic semialdehyde reductase, Gox1801 has the potential to be used in the biotechnological production of γ-hydroxybutyrate. PMID:25425279

  17. 27 CFR 21.108 - Ethyl ether.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Ethyl ether. 21.108 Section 21.108 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21.108 Ethyl ether. (a) Odor. Characteristic odor....

  18. 27 CFR 21.108 - Ethyl ether.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Ethyl ether. 21.108 Section 21.108 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21.108 Ethyl ether. (a) Odor. Characteristic odor....

  19. 27 CFR 21.108 - Ethyl ether.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Ethyl ether. 21.108 Section 21.108 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21.108 Ethyl ether. (a) Odor. Characteristic odor....

  20. 21 CFR 573.420 - Ethyl cellulose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 27 CFR 21.108 - Ethyl ether.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 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...

  6. 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...

  7. Removal of 1-ethyl-3-methylimidazolium cations with bacterial biosorbents from aqueous media.

    PubMed

    Won, Sung Wook; Choi, Sun Beom; Mao, Juan; Yun, Yeoung-Sang

    2013-01-15

    This study aims to determine whether biosorption can be used for the removal of ionic liquids (ILs), especially their cationic parts, from aqueous media. As a model IL, 1-ethyl-3-methylimidazolium acetate ([EMIM]OAc) was used. Five types of bacterial biosorbents were prepared from fermentation wastes through chemical modification of the bacterial surface. Screening study was performed to compare the cationic [EMIM] biosorption capacity among the bacterial biosorbents, indicating that the succinated Escherichia coli biomass (SB-E) was the best biosorbent for removing [EMIM] cations. The [EMIM] biosorption performance of SB-E was evaluated in detail through various experiments. The optimal pH range for [EMIM] biosorption was from 7 to 10, and biosorption equilibrium was reached within 10 min. The maximum uptake of SB-E was also estimated to be 72.6 mg/g. Moreover, [EMIM] cations were easily desorbed from [EMIM]-sorbed SB-E by adding acetic acid. PMID:23246948

  8. High-resolution melting analysis for the detection of two erythromycin-resistant Bordetella pertussis strains carried by healthy schoolchildren in China.

    PubMed

    Zhang, Q; Li, M; Wang, L; Xin, T; He, Q

    2013-06-01

    Two erythromycin-resistant strains of Bordetella pertussis were isolated from nasopharyngeal specimens of two asymptomatic schoolchildren in China. High-resolution melting and sequencing analyses confirmed the homogeneous A2047G mutation in 23S rRNA genes of the two isolates. High-resolution melting (HRM) analysis is a useful assay for the rapid detection of erythromycin-resistant B. pertussis. The appearance of erythromycin-resistant B. pertussis strains in China is alarming.

  9. Variation in erythromycin and clindamycin susceptibilities of Streptococcus pneumoniae by four test methods.

    PubMed Central

    Fasola, E L; Bajaksouzian, S; Appelbaum, P C; Jacobs, M R

    1997-01-01

    Susceptibilities of 124 strains of Streptococcus pneumoniae to erythromycin and clindamycin were determined by the National Committee for the Clinical Laboratory Standards (NCCLS) broth microdilution method, with incubation for 20 to 24 h in ambient air and with modifications of this method by incubation for up to 48 h in air and CO2. Strains were also tested by agar dilution, E-test, and disk diffusion; good correlation was obtained with these methods, with clear separation into bimodal populations of susceptible and resistant stains. The broth microdilution method, however, using incubation in air for 24 h (NCCLS method), misclassified 4 of 92 erythromycin-resistant strains (1 as susceptible and 3 as intermediate) and 25 of 58 clindamycin-resistant strains (all as susceptible). With the exception of one strain with clindamycin, susceptible and resistant strains were correctly classified by the microdilution method with incubation in CO2 for 24 h or in ambient air for 48 h. Disk diffusion, agar dilution, and E-test methods with incubation in 5% CO2 are therefore reliable methods for susceptibility testing of pneumococci against these agents. However, the NCCLS microdilution method, which specifies incubation for 20 to 24 h in ambient air, produced significant very major errors (43%) clindamycin. Modification of the microdilution method by incubation in 5% CO2 or by extension of incubation time in ambient air to 48 h corrected these errors. Disk diffusion, however, was shown to be a simple, convenient, and reliable method for susceptibility testing of pneumococci to erythromycin and clindamycin and is suggested as the method of choice for these agents. PMID:8980768

  10. 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.

  11. 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.

  12. Constituents of Fagraea fragrans with Antimycobacterial Activity in Combination with Erythromycin.

    PubMed

    Madmanang, Suwaibah; Cheyeng, Naseebah; Heembenmad, Sareefah; Mahabusarakam, Wilawan; Saising, Jongkon; Seeger, Markus; Chusri, Sasitorn; Chakthong, Suda

    2016-04-22

    Seven new compounds constituted by three secoiridoids (1-3), two isocoumarins (4 and 5), an iridoid (6), and an aromatic derivative (7) in addition to 24 known compounds were isolated from the stem bark of Fagraea fragrans. The structures of the new compounds were determined on the basis of spectroscopic data analysis. The isolated compounds showed no antibacterial activity against Staphylococcus aureus and Escherichia coli. However, 5-formylisochromen-1-one (4), (-)-mellein (8), and swermacrolactone C (9) exhibited potent antimycobacterial activities against Mycobacterium smegmatis when used in combination with the antibiotic drug erythromycin.

  13. [Dermatologic preparations with erythromycin--the correlation of the pharmaceutical form-therapeutic effect].

    PubMed

    Cojocaru, I; Irimia, O; Constantin, T

    1997-01-01

    Erythromycin associated with progesterone and A vitamin has been included in three dermatological pharmaceutical forms: a lotion, a L/H emulsion and a L/H nonionogenic ointment. Aspect of these preparations has been noticed for a 90 days period. pH and electrical conductance were also determined during this interval. All the formulations mentioned above revealed insignificant variations of these parameters proving an appreciable physico-chemical stability. Clinical investigative studies in juvenile acne, showed efficiency, particularly for the emulsion form.

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

    PubMed

    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 [(13)C]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

  15. 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

  16. 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.

  17. 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. PMID:22048617

  18. Clinical efficacy and safety of a topical combination of retinaldehyde 0.1% with erythromycin 4% in acne vulgaris.

    PubMed

    Morel, P; Vienne, M P; Beylot, C; Bonérandi, J J; Dréno, B; Lehucher-Ceyrac, D; Slimani, S; Dupuy, P

    1999-09-01

    The objective of this randomized, controlled, multicentre study was to assess the efficacy and safety of a topically applied retinaldehyde 0.1% gel in combination with a topical erythromycin 4% lotion for the treatment of acne vulgaris. Treatment consisted of applying either retinaldehyde or its vehicle every morning and erythromycin every evening for 8 weeks. Efficacy parameters were sequential lesion counts for papules and pustules, and a 6-point semiquantitative scale for comedones and microcysts. Safety parameters were local tolerance and adverse events. Of 74 recruited patients, 73 were appraisable for efficacy and safety. In both treatment groups, papules and pustules were reduced significantly at the end of treatment (P < 0.001), and no statistical difference was observed between the groups. Comedones and microcysts were significantly improved with retinaldehyde combined with erythromycin (P = 0.005), but not with erythromycin alone. However, no statistical difference between the groups could be demonstrated (test power, 50%). Local tolerance of the combined treatment group was very satisfactory, as only a few patients experienced local irritation. In conclusion, retinaldehyde combined with erythromycin appears to be a valuable topical therapy in polymorphic acne.

  19. Proteomic response of methicillin-resistant S. aureus to a synergistic antibacterial drug combination: a novel erythromycin derivative and oxacillin

    PubMed Central

    Liu, Xiaofen; Pai, Pei-Jin; Zhang, Weipeng; Hu, Yingwei; Dong, Xiaojing; Qian, Pei-yuan; Chen, Daijie; Lam, Henry

    2016-01-01

    The use of antibacterial drug combinations with synergistic effects is increasingly seen as a critical strategy to combat multi-drug resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). In this work, the proteome responses in MRSA under the stress of a sub-inhibitory dose of a synergistic drug combination of a novel erythromycin derivative, SIPI-8294, and oxacillin, were studied by label-free quantitative proteomics. Several control treatment groups were designed to isolate proteome responses potentially related to the synergy: (1) the non-synergistic drug combination of erythromycin and oxacillin, (2) SIPI-8294 only, (3) oxacillin only and (4) erythromycin only. Results showed that 200 proteins were differentially expressed in SIPI-8294/oxacillin-treated cells. Among these proteins, the level of penicillin binding protein 2a, the protein mainly responsible for oxacillin resistance in MRSA, was four times lower in the SIPI-8294/oxacillin group than in the erythromycin/oxacillin group, suggesting that SIPI-8294 may interfere with this known oxacillin resistance mechanism. Moreover, hierarchical clustering analysis of differentially expressed proteins under different treatments revealed that SIPI-8294/oxacillin elicits very different responses than the individual drugs or the non-synergistic erythromycin/oxacillin combination. Bioinformatic analysis indicated that the synergistic effect can be further traced to a disruption in oxidation-reduction homeostasis and cell wall biosynthesis. PMID:26806358

  20. 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

  1. Ineffectiveness of erythromycin for treatment of Haemophilus vaginalis-associated vaginitis: possible relationship to acidity of vaginal secretions.

    PubMed Central

    Durfee, M A; Forsyth, P S; Hale, J A; Holmes, K K

    1979-01-01

    To assess the efficacy of oral erythromycin in the treatment of nonspecific vaginitis (NSV), conducted a nonrandom, unblinded pilot study among 17 women with symptoms and signs of NSV. At the completion of treatment, 10 of 13 patients had persistent symptoms, 9 of 13 had persistent abnormal discharge, and 11 of 13 had persistently positive cultures for Haemophilus vaginalis. Ten patients with persistent or relapsing NSV and four who did not complete erythromycin treatment were retreated with oral metronidazole, and 14 of 14 showed clinical improvement and eradication of H. vaginalis. The susceptibility of 27 clinical isolates of H. vaginalis to erythromycin was determined at pH 5.5, 6.0, 6.5, and 7.0. The minimal inhibitory concentration of erythromycin for H. vaginalis was approximately 10-fold higher at pH 5.5 than at pH 7.0. Erythromycin is not effective for the treatment of H. vaginalis-associated NSV; this may be partly attributable to the reduced activity of this drug in acidic vaginal secretions. PMID:43114

  2. Pharmacokinetics and residue depletion of erythromycin in gilthead sea bream Sparus aurata L. after oral administration.

    PubMed

    Di Salvo, A; Pellegrino, R M; Cagnardi, P; della Rocca, G

    2014-09-01

    Erythromycin (ERY) is an antibiotic effective against Streptococcus iniae, a microorganism responsible for significant losses in aquaculture. No data are available on the pharmacokinetics and residue depletion of ERY in sea bream. The aim of this study was thus to evaluate the pharmacokinetics of ERY in this species after a single oral administration at 75 mg kg(-1) b.w. and to assess its residue depletion from tissues after prolonged treatment for 10 days. ERY was rapidly absorbed in sea bream (Cmax  = 10.04 μg g(-1) and Tmax =1 h), with a half-life of 9.35 h and an AUC0-24 of 56.81 (h μg mL(-1) ). The data obtained and the evaluation of pharmacokinetic/pharmacodynamic parameters allowed us to hypothesize that dosage used in this study should be effective against S. iniae. A rapid reduction in erythromycin concentrations was observed in tissues, with the drug being detectable only during the first day post-treatment. In Europe, the use of ERY in aquaculture is allowed by off-label prescription with a withdrawal time of 500 °C day(-1) . The absence of ERY residues in tissues already at 24 h post-treatment suggests that ERY in sea bream should not pose human food safety issues.

  3. Effects of tylosin use on erythromycin resistance in enterococci isolated from swine.

    PubMed

    Jackson, Charlene R; Fedorka-Cray, Paula J; Barrett, John B; Ladely, Scott R

    2004-07-01

    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 microg/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

  4. In vitro activity of azithromycin compared with that of erythromycin against Actinobacillus actinomycetemcomitans.

    PubMed Central

    Pajukanta, R; Asikainen, S; Saarela, M; Alaluusua, S; Jousimies-Somer, H

    1992-01-01

    The in vitro susceptibility of Actinobacillus actinomycetemcomitans to azithromycin, a new macrolide antibiotic of a new class known as azalides, was compared with that of erythromycin by the agar dilution method on Mueller-Hinton Haemophilus test medium. Eighty-two A. actinomycetemcomitans strains, 79 recent clinical isolates obtained from 40 periodontally healthy or diseased subjects, and 3 type strains were included in the study. Erythromycin showed poor in vitro activity against A. actinomycetemcomitans. Azithromycin, however, was highly effective against A. actinomycetemcomitans: all strains were inhibited at 2.0 micrograms/ml. Azithromycin exhibited the best in vitro activity against the serotype a subpopulation of A. actinomycetemcomitans: 100% of the strains were inhibited at 1.0 micrograms/ml. The lowest MICs were, however, recorded by serotype b strains. Since azithromycin has favorable pharmacokinetic properties, including excellent distribution into tissues, it could be expected to pass into gingival crevicular fluid at levels sufficient to inhibit A. actinomycetemcomitans in vivo. Therefore, it is a good candidate for future clinical trials in A. actinomycetemcomitans-associated periodontitis. PMID:1329617

  5. Molecular identification and quantification of tetracycline and erythromycin resistance genes in Spanish and Italian retail cheeses.

    PubMed

    Belén Flórez, Ana; Alegría, Ángel; Rossi, Franca; Delgado, Susana; Felis, Giovanna E; Torriani, Sandra; Mayo, Baltasar

    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 10.18log10/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

  6. The Effect of Cationic Polyamidoamine Dendrimers on Physicochemical Characteristics of Hydrogels with Erythromycin.

    PubMed

    Wróblewska, Magdalena; Winnicka, Katarzyna

    2015-08-27

    Polyamidoamine dendrimers (PAMAM) represent a new class of hyperbranched, monodisperse, three-dimensional polymers with unique properties, which make them very promising carriers of antimicrobial agents. The present study aimed to evaluate the influence of PAMAM-NH₂ dendrimers generation two (G2) or three (G3) on physicochemical characteristics and structure of hydrogels with a model antibacterial lipophilic drug-erythromycin-commonly used in topical applications. From the obtained rheograms, it can be concluded that tested hydrogels were non-Newtonian thixotropic systems with shear-thinning behaviour. The dissolution tests revealed that erythromycin was definitely faster released from formulations containing PAMAM-NH₂ in concentration and generation dependent manner. However, the addition of PAMAM-NH₂ to hydrogels evoked only slight improvement of their antibacterial activity. It was also shown that the structure of hydrogels changed in the presence of PAMAM-NH₂ becoming less compact, diversified and more porous. Designed hydrogels with PAMAM-NH₂ G2 or G3 were stable stored up to three months at 40 ± 2 °C and 75% ± 5% RH.

  7. 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.

  8. 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

  9. Structures of Gate Loop Variants of the AcrB Drug Efflux Pump Bound by Erythromycin Substrate

    PubMed Central

    Ababou, Abdessamad; Koronakis, Vassilis

    2016-01-01

    Gram-negative bacteria such as E. coli use tripartite efflux pumps such as AcrAB-TolC to expel antibiotics and noxious compounds. A key feature of the inner membrane transporter component, AcrB, is a short stretch of residues known as the gate/switch loop that divides the proximal and distal substrate binding pockets. Amino acid substitutions of the gate loop are known to decrease antibiotic resistance conferred by AcrB. Here we present two new AcrB gate loop variants, the first stripped of its bulky side chains, and a second in which the gate loop is removed entirely. By determining the crystal structures of the variant AcrB proteins in the presence and absence of erythromycin and assessing their ability to confer erythromycin tolerance, we demonstrate that the gate loop is important for AcrB export activity but is not required for erythromycin binding. PMID:27403665

  10. 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

  11. 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.

  12. 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. PMID:17765349

  13. Effects of penicillin and erythromycin on adherence of invasive and noninvasive isolates of Streptococcus pyogenes to laminin.

    PubMed

    Šmitran, Aleksandra; Vuković, Dragana; Gajić, Ina; Marinković, Jelena; Ranin, Lazar

    2015-08-01

    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.

  14. 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

  15. 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

  16. Collaborative regulation of CO2 transport and fixation during succinate production in Escherichia coli

    PubMed Central

    Zhu, Li-Wen; Zhang, Lei; Wei, Li-Na; Li, Hong-Mei; Yuan, Zhan-Peng; Chen, Tao; Tang, Ya-Ling; Liang, Xin-Hua; Tang, Ya-Jie

    2015-01-01

    In Escherichia coli, succinic acid is synthesized by CO2 fixation-based carboxylation of C3 metabolites. A two-step process is involved in CO2 integration: CO2 uptake into the cell and CO2 fixation by carboxylation enzymes. The phosphoenolpyruvate (PEP) carboxylase (PPC) and carboxykinase (PCK) are two important carboxylation enzymes within the succinate synthetic pathway, while SbtA and BicA are two important bicarbonate transporters. In this study, we employed a dual expression system, in which genes regulating both CO2 uptake and fixation were co-overexpressed, or overexpressed individually to improve succinate biosynthesis. Active CO2 uptake was observed by the expression of SbtA or/and BicA, but the succinate biosynthesis was decreased. The succinate production was significantly increased only when a CO2 fixation gene (ppc or pck) and a CO2 transport gene (sbtA or bicA) were co-expressed. Co-expression of pck and sbtA provided the best succinate production among all the strains. The highest succinate production of 73.4 g L−1 was 13.3%, 66.4% or 15.0% higher than that obtained with the expression of PCK, SbtA alone, or with empty plasmids, respectively. We believe that combined regulation of CO2 transport and fixation is critical for succinate production. Imbalanced gene expression may disturb the cellular metabolism and succinate production. PMID:26626308

  17. Collaborative regulation of CO2 transport and fixation during succinate production in Escherichia coli.

    PubMed

    Zhu, Li-Wen; Zhang, Lei; Wei, Li-Na; Li, Hong-Mei; Yuan, Zhan-Peng; Chen, Tao; Tang, Ya-Ling; Liang, Xin-Hua; Tang, Ya-Jie

    2015-01-01

    In Escherichia coli, succinic acid is synthesized by CO2 fixation-based carboxylation of C3 metabolites. A two-step process is involved in CO2 integration: CO2 uptake into the cell and CO2 fixation by carboxylation enzymes. The phosphoenolpyruvate (PEP) carboxylase (PPC) and carboxykinase (PCK) are two important carboxylation enzymes within the succinate synthetic pathway, while SbtA and BicA are two important bicarbonate transporters. In this study, we employed a dual expression system, in which genes regulating both CO2 uptake and fixation were co-overexpressed, or overexpressed individually to improve succinate biosynthesis. Active CO2 uptake was observed by the expression of SbtA or/and BicA, but the succinate biosynthesis was decreased. The succinate production was significantly increased only when a CO2 fixation gene (ppc or pck) and a CO2 transport gene (sbtA or bicA) were co-expressed. Co-expression of pck and sbtA provided the best succinate production among all the strains. The highest succinate production of 73.4 g L(-1) was 13.3%, 66.4% or 15.0% higher than that obtained with the expression of PCK, SbtA alone, or with empty plasmids, respectively. We believe that combined regulation of CO2 transport and fixation is critical for succinate production. Imbalanced gene expression may disturb the cellular metabolism and succinate production. PMID:26626308

  18. 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.

  19. 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.

  20. 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.

  1. Recovery and separation of erythromycin from industrial wastewater by imprinted magnetic nanoparticles that exploit β-cyclodextrin as the functional monomer.

    PubMed

    Zhang, Yuxin; Li, Jinyang; Wang, FeiFei; Wu, Gang; Qv, Xue; Hong, Hua; Liu, Changsheng

    2016-01-01

    A type of surface imprinting over magnetic Fe3 O4 nanoparticles utilizing erythromycin-A as a template for use in the separation and recovery of erythromycin was developed and investigated. As the intermolecular forces play a key role in the performance of imprinted materials, differential scanning calorimetry, and (1) H NMR spectroscopy was employed to evaluate the interactions between erythromycin and the functional monomer β-cyclodextrin. To synthesize the surface imprinted polymers, magnetic Fe3 O4 nanoparticles, the core materials, were modified with a free radical initiator to initialize polymerization in a "grafting from" manner. Then using acryloyl-modified β-cyclodextrin as the functional monomer and ethyleneglycol dimethacrylate as the cross-linker, thin erythromycin-imprinted films were fabricated by the radical-induced graft copolymerization of monomers on the surface of the Fe3 O4 nanoparticles. Selectivity experiments showed that the erythromycin-A-imprinted materials had recognition ability toward erythromycin derivatives. Finally, these magnetic molecularly imprinted particles were successfully used for the separation and enrichment of erythromycin from the mother liquor. The recovery, detected by high-performance liquid chromatography and differential pulse voltammetry, approached 97%. The combination of the specific selectivity of the imprinted material and the magnetic separation provided a powerful tool that is simple, flexible, and selective for the separation and recovery of erythromycin. PMID:26805958

  2. 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. PMID:25487884

  3. 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.

  4. 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.

  5. Treatment of community-acquired pneumonia: a randomized comparison of sparfloxacin, amoxycillin-clavulanic acid and erythromycin.

    PubMed

    Lode, H; Garau, J; Grassi, C; Hosie, J; Huchon, G; Legakis, N; Segev, S; Wijnands, G

    1995-12-01

    The treatment of community-acquired pneumonia is empirical in most cases and must cover a wide range of potential pathogens, such as Streptococcus pneumoniae, including penicillin-resistant strains, Haemophilus influenzae and intracellular microorganisms. The objective of this double-blind, randomized, parallel group study was to compare the efficacy and safety of sparfloxacin (400 mg loading dose, followed by 200 mg o.d.) with that of oral amoxycillin-clavulanic acid (500/125 mg t.i.d.) or oral erythromycin (1 g b.i.d.), during 7-14 days in 808 patients with confirmed community-acquired pneumonia. The overall success rates for sparfloxacin (87%), amoxycillin-clavulanic acid (80%) and erythromycin (85%) were similar in evaluable patients, and the equivalence hypothesis used for the statistical analysis showed at least an equivalent efficacy for the three antibiotics tested. The analysis of microbiologically documented infections (40% of the patients) showed that overall success rates were similar for S. pneumoniae and H. influenzae infections. Treatment withdrawal was necessary in 3.5, 2.5 and 7.7% of the patients treated with sparfloxacin, amoxycillin-clavulanic acid and erythromycin, respectively. This study indicates that sparfloxacin was at least as effective as amoxycillin-clavulanic acid or erythromycin in the treatment of mild-to-moderate community-acquired pneumonia and that the adverse effects were similar in the three groups.

  6. Sensitive determination of erythromycin in human plasma by LC-MS/MS.

    PubMed

    Li, Y X; Neufeld, K; Chastain, J; Curtis, A; Velagaleti, P

    1998-02-01

    A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of erythromycin in human plasma (EDTA as anticoagulant) was developed and validated. The concentration ranges were 0.5-50 and 50-5000 ng ml-1. The procedure involved alkalization of 0.5 ml of plasma, one step liquid-liquid extraction, dryness of the extract and reconstitution in 80:20 water:acetonitrile. An Inertsil ODS-2 5 microns, 3.0 x 50 mm column (Metachem) with a C8 guard column and isocratic mobile phase were used for liquid chromatography. The mobile phase consisted of 1:1 acetonitrile:water with 2 mM NH4OAc and 0.1% HOAc. A flow rate of 0.7 ml min-1 was used. The analysis time on LC-MS/MS for one sample was approximately 2 min. A Turbo-Ionspray source was interfaced between the HPLC and triple quadrupole mass spectrometer (Sciex API III Plus). MS/MS analysis used Multi-Reaction Monitoring (MRM) mode. The lowest limit of quantitation (LOQ) was 0.5 ng ml-1 with all Quality Control (QC) sample recoveries varying between 88 and 105%. Nine intraday and interday calibration curves were generated yielding correlation coefficients ranging from 0.995 to 1.000. Average recovery for erythromycin at 1 ng ml-1 was 105% (+/- 4.5%). Average recovery for the internal standard was 83-103%. Short-term and long-term stability in the freezer (-20 degrees C), bench stability, and stability after 3 freeze/thaw cycles at -20 and -80 degrees C were conducted. The samples were found to be stable under all conditions. The method developed and validated proved useful for clinical pharmacokinetic study sample analysis with high throughput due to its high sensitivity and very short analysis time. PMID:9547699

  7. 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.

  8. Continuous succinic acid production from xylose by Actinobacillus succinogenes.

    PubMed

    Bradfield, Michael F A; Nicol, Willie

    2016-02-01

    Continuous, anaerobic fermentations of D-xylose were performed by Actinobacillus succinogenes 130Z in a custom, biofilm reactor at dilution rates of 0.05, 0.10 and 0.30 h(-1). Succinic acid yields on xylose (0.55-0.68 g g(-1)), titres (10.9-29.4 g L(-1)) and productivities (1.5-3.4 g L(-1) h(-1)) were lower than those of a previous study on glucose, but product ratios (succinic acid/acetic acid = 3.0-5.0 g g(-1)) and carbohydrate consumption rates were similar. Also, mass balance closures on xylose were up to 18.2 % lower than those on glucose. A modified HPLC method revealed pyruvic acid excretion at appreciable concentrations (1.2-1.9 g L(-1)) which improved the mass balance closure by up to 16.8 %. Furthermore, redox balances based on the accounted xylose consumed and the excreted metabolites, indicated an overproduction of reducing power. The oxidative pentose phosphate pathway was shown to be a plausible source of the additional reducing power. PMID:26610345

  9. 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).

  10. Synthesis, characterization and nanocomposite formation of poly(glycerol succinate-co-maleate) with cellulose nanowhiskers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  11. Integration of succinic acid and ethanol production within a corn or barley biorefinery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  12. Structural basis for the binding of succinate to succinyl-CoA synthetase.

    PubMed

    Huang, Ji; Fraser, Marie E

    2016-08-01

    Succinyl-CoA synthetase catalyzes the only step in the citric acid cycle that provides substrate-level phosphorylation. Although the binding sites for the substrates CoA, phosphate, and the nucleotides ADP and ATP or GDP and GTP have been identified, the binding site for succinate has not. To determine this binding site, pig GTP-specific succinyl-CoA synthetase was crystallized in the presence of succinate, magnesium ions and CoA, and the structure of the complex was determined by X-ray crystallography to 2.2 Å resolution. Succinate binds in the carboxy-terminal domain of the β-subunit. The succinate-binding site is near both the active-site histidine residue that is phosphorylated in the reaction and the free thiol of CoA. The carboxy-terminal domain rearranges when succinate binds, burying this active site. However, succinate is not in position for transfer of the phosphoryl group from phosphohistidine. Here, it is proposed that when the active-site histidine residue has been phosphorylated by GTP, the phosphohistidine displaces phosphate and triggers the movement of the carboxylate of succinate into position to be phosphorylated. The structure shows why succinyl-CoA synthetase is specific for succinate and does not react appreciably with citrate nor with the other C4-dicarboxylic acids of the citric acid cycle, fumarate and oxaloacetate, but shows some activity with L-malate.

  13. The effect of biotin on the production of succinic acid by Anaerobiospirillum succiniciproducens

    SciTech Connect

    Nghiem, N.P.; Davison, B.H.; Thompson, J.E.

    1995-07-01

    Succinic acid is an intermediate of the tricarboxylic acid (TCA) cycle, and therefore, is found in almost all plant and animal cells, albeit at very low concentrations. It has a very wide usage range, which includes applications in agriculture, food, medicine, plastics, cosmetics, textiles, plating and waste-gas scrubbing. Succinic acid currently is produced commercially by chemical processes. A fermentation process for its production is of great interest because in such process, renewable resources such as corn-derived glucose can be used as starting material. There is not a current biological process for the commercial production of succinic acid. Extensive efforts have been devoted to the isolation and screening of succinic acid-producing microorganisms. The anaerobic bacterium, Anaerobiospirillum succiniciproducens, is considered among the best direct succinic acid producers. A number of patents concerning the production of succinic acid by this organism have been issued. Our first attempt to develop a biological process for the production of succinic acid by A. succiniciproducens involved fermentation media improvement, in particular the use of supplemented nutrients. In this note, we show that higher yield of succinic acid could be achieved by supplementing the fermentation media with biotin, as a potential nutrient supplement representative.

  14. Structural basis for the binding of succinate to succinyl-CoA synthetase.

    PubMed

    Huang, Ji; Fraser, Marie E

    2016-08-01

    Succinyl-CoA synthetase catalyzes the only step in the citric acid cycle that provides substrate-level phosphorylation. Although the binding sites for the substrates CoA, phosphate, and the nucleotides ADP and ATP or GDP and GTP have been identified, the binding site for succinate has not. To determine this binding site, pig GTP-specific succinyl-CoA synthetase was crystallized in the presence of succinate, magnesium ions and CoA, and the structure of the complex was determined by X-ray crystallography to 2.2 Å resolution. Succinate binds in the carboxy-terminal domain of the β-subunit. The succinate-binding site is near both the active-site histidine residue that is phosphorylated in the reaction and the free thiol of CoA. The carboxy-terminal domain rearranges when succinate binds, burying this active site. However, succinate is not in position for transfer of the phosphoryl group from phosphohistidine. Here, it is proposed that when the active-site histidine residue has been phosphorylated by GTP, the phosphohistidine displaces phosphate and triggers the movement of the carboxylate of succinate into position to be phosphorylated. The structure shows why succinyl-CoA synthetase is specific for succinate and does not react appreciably with citrate nor with the other C4-dicarboxylic acids of the citric acid cycle, fumarate and oxaloacetate, but shows some activity with L-malate. PMID:27487822

  15. 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.

  16. 21 CFR 172.765 - Succistearin (stearoyl propylene glycol hydrogen succinate).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Succistearin (stearoyl propylene glycol hydrogen... Other Specific Usage Additives § 172.765 Succistearin (stearoyl propylene glycol hydrogen succinate). The food additive succistearin (stearoyl propylene glycol hydrogen succinate) may be safely used...

  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, 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...

  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. 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...

  1. 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...

  2. Simultaneous saccharification and fermentation of cassava to succinic acid by Escherichia coli NZN111.

    PubMed

    Chen, Cuixia; Ding, Shaopeng; Wang, Dezheng; Li, Zhimin; Ye, Qin

    2014-07-01

    In this study, the production of succinic acid from cassava starch and raw cassava instead of glucose by Escherichia coli NZN111 was investigated. During the two-stage fermentation, simultaneous saccharification and fermentation (SSF) was applied in the anaerobic stage. The results showed that both the productivity and specific productivity in the process conducted at 40°C were higher than those in the cultivation conducted at 37°C. The yield of succinic acid based on the amount of added starch reached the highest level 0.86 g/g and cassava starch was almost totally hydrolyzed in the SSF process. With the improved cell density, 127.13 g/L of succinic acid was obtained. When the liquefied crude cassava powder was used directly in SSF, 106.17 g/L of succinic acid was formed. The result showed that crude cassava powder could be another cheap raw material for succinic acid formation.

  3. Succinic semialdehyde as a substrate for the formation of gamma-aminobutyric acid.

    PubMed

    van Bemmelen, F J; Schouten, M J; Fekkes, D; Bruinvels, J

    1985-11-01

    The conversion of succinic semialdehyde into gamma-aminobutyric acid (GABA) by GABA-transaminase was measured in rat brain homogenate in the presence of different concentrations of the cosubstrate glutamate. The calculated kinetic parameters of succinic semialdehyde for GABA-transaminase were a limiting Km value of 168 microM and a limiting Vmax value of 38 mumol g-1 h-1. Combination with previously obtained data for the conversion of GABA into succinic semialdehyde revealed a kEq value of 0.04, indicating that equilibrium of GABA-transaminase is biased toward the formation of GABA. The increased formation of GABA in the presence of succinic semialdehyde was not due to an increased conversion of glutamate into GABA by glutamic acid decarboxylase. Therefore these results indicate that succinic semialdehyde can act as a precursor for GABA synthesis.

  4. 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.

  5. 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.

  6. GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis.

    PubMed

    Littlewood-Evans, Amanda; Sarret, Sophie; Apfel, Verena; Loesle, Perrine; Dawson, Janet; Zhang, Juan; Muller, Alban; Tigani, Bruno; Kneuer, Rainer; Patel, Saijel; Valeaux, Stephanie; Gommermann, Nina; Rubic-Schneider, Tina; Junt, Tobias; Carballido, José M

    2016-08-22

    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.

  7. Succinic acid production from corn stover by simultaneous saccharification and fermentation using Actinobacillus succinogenes.

    PubMed

    Zheng, Pu; Fang, Lin; Xu, Yan; Dong, Jin-Jun; Ni, Ye; Sun, Zhi-Hao

    2010-10-01

    Simultaneous saccharification and fermentation (SSF) technique was applied for succinic acid production by Actinobacillus succinogenes in a 5-l stirred bioreactor with corn stover as the raw material. The process parameters of SSF, including corn stover pretreatment condition, substrate concentration, enzyme loading and fermentation temperature were investigated. Results indicated that pretreating corn stover with diluted alkaline was beneficial for the succinic acid production, and succinic acid yield could be significantly increased when adding the cellulase supplemented with cellobiase. The maximal succinic acid concentration and yield could reach 47.4 g/l and 0.72 g/g-substrate, respectively. The corresponding operation conditions were summarized as follows: SSF operation at 38 °C for 48 h, diluted alkaline pretreated corn stover as substrate with concentration of 70 g/l, enzyme loading of 20FPU cellulase and 10 U cellobiase per gram substrate. This result suggested an industrial potential of succinic acid production by using SSF and corn stover.

  8. Aerobic production of succinate from arabinose by metabolically engineered Corynebacterium glutamicum.

    PubMed

    Chen, Tao; Zhu, Nianqing; Xia, Huihua

    2014-01-01

    Arabinose is considered as an ideal feedstock for the microbial production of value-added chemicals due to its abundance in hemicellulosic wastes. In this study, the araBAD operon from Escherichia coli was introduced into succinate-producing Corynebacterium glutamicum, which enabled aerobic production of succinate using arabinose as sole carbon source. The engineered strain ZX1 (pXaraBAD, pEacsAgltA) produced 74.4 mM succinate with a yield of 0.58 mol (mol arabinose)(-1), which represented 69.9% of the theoretically maximal yield. Moreover, this strain produced 110.2 mM succinate using combined substrates of glucose and arabinose. To date, this is the highest succinate production under aerobic conditions in minimal medium.

  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. 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

  11. Alternative splicing isoform in succinate dehydrogenase complex, subunit C causes downregulation of succinate-coenzyme Q oxidoreductase activity in mitochondria.

    PubMed

    Satoh, Nana; Yokoyama, Chikako; Itamura, Noriaki; Miyajima-Nakano, Yoshiharu; Hisatomi, Hisashi

    2015-01-01

    Mitochondrial succinate dehydrogenase (SDH) is localized to the inner mitochondrial membrane and is responsible for the redox of succinic acid. SDH is a tetrameric iron-sulfur flavoprotein of the tricarboxylic acid cycle and respiratory chain. The SDH complex, subunit C (SDHC) transcript has deletion-type alternative splicing sites. Generally, alternative splicing produces variant proteins and expression patterns, as products of different genes. In certain cases, specific alternative splicing variants (ASVs) have been associated with human disease. Due to a frameshift mutation causing loss of the heme binding region, the SDHC Δ5 isoform (lacking exon 5) exhibits no SDHC activity. To investigate whether the SDHC splicing variants can function as dominant-negative inhibitors, SDHC ASVs were overexpressed in HCT-15 human colorectal cancer cells. Using real-time reverse transcription-polymerase chain reaction, a dominant-negative effect of the Δ5 isoform on SDHC mRNA was shown. In addition, Δ5 overexpression increased the levels of reactive oxygen species. Furthermore, in the Δ5 isoform-overexpressing cells, SDH activity was reduced. SDHC activation is a significant event during the electron transport chain, and the function of the SDHC Δ5 variant may be significant for the differentiation of tumor cells. PMID:25435987

  12. 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...

  13. 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...

  14. 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...

  15. In vitro activity of A-56268 (TE-031), a new macrolide, compared with that of erythromycin and clindamycin against selected gram-positive and gram-negative organisms.

    PubMed Central

    Benson, C A; Segreti, J; Beaudette, F E; Hines, D W; Goodman, L J; Kaplan, R L; Trenholme, G M

    1987-01-01

    The in vitro activity of A-56268 was determined and compared with that of erythromycin and clindamycin against a limited spectrum of 401 gram-positive and gram-negative organisms. A-56268 was quite active against erythromycin-susceptible Staphylococcus aureus, Neisseria gonorrhoeae, Listeria monocytogenes, Streptococcus pneumoniae, Streptococcus pyogenes, and group B streptococci and was moderately active against Campylobacter fetus subsp. fetus. A-56268 was consistently bactericidal only for S. pneumoniae. The activity of A-56268 was comparable to that of erythromycin against most organisms tested. PMID:2952063

  16. Protein-mediated assembly of succinate dehydrogenase and its cofactors.

    PubMed

    Van Vranken, Jonathan G; Na, Un; Winge, Dennis R; Rutter, Jared

    2015-01-01

    Succinate dehydrogenase (or complex II; SDH) is a heterotetrameric protein complex that links the tribarboxylic acid cycle with the electron transport chain. SDH is composed of four nuclear-encoded subunits that must translocate independently to the mitochondria and assemble into a mature protein complex embedded in the inner mitochondrial membrane. Recently, it has become clear that failure to assemble functional SDH complexes can result in cancer and neurodegenerative syndromes. The effort to thoroughly elucidate the SDH assembly pathway has resulted in the discovery of four subunit-specific assembly factors that aid in the maturation of individual subunits and support the assembly of the intact complex. This review will focus on these assembly factors and assess the contribution of each factor to the assembly of SDH. Finally, we propose a model of the SDH assembly pathway that incorporates all extant data.

  17. Enhanced performance of alkylated graphene reinforced polybutylene succinate nanocomposite

    NASA Astrophysics Data System (ADS)

    Abidin, A. S. Zainal; Yusoh, K.; Jamari, S. S.; Abdullah, A. H.; Ismail, Z.

    2016-07-01

    Polybutylene succinate (PBS) was being grafted with octadecylamine-functionalized graphene oxide (GO-ODA) to produce novel PBS/GO-ODA nanocomposites by solution blending technique. Alkylated graphene oxide has superhydrophobic surface thus improved the affinity of the filler with low polar polymer such as PBS. The structure and compatibility of the filler and nanocomposites were being characterized using Fourier transform infrared spectroscopy (FTIR), Universal tensile machine (UTM) and thermogravimetric analysis (TGA). Enhancement of tensile strength and Young's modulus by 30% and 165% respectively was achieved with cooperation of 0.5% GO-ODA loading. The functionalization of GO-ODA in PBS matrix leads to the improvement in the nanocomposites properties.

  18. 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.

  19. 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. PMID:27179951

  20. 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.

  1. Setaria cervi: enzymes of glycolysis and PEP-succinate pathway.

    PubMed

    Anwar, N; Ansari, A A; Ghatak, S; Krishna Murti, C R

    1977-04-15

    Setaria cervi, the filarial parasite inhabiting the Indian water buffalo (Bubalus bubalis Linn.) contained almost all the enzymes involved in glycogen degradation. Significant activities of glycogen phosphorylase, glucokinase, phosphoglucomutase, phosphoglucose isomerase, phosphofructokinase, FDP-aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphopyruvate hydratase, pyruvate kinase, lactate dehydrogenase glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were detected in cell-free extracts of whole worms. The presence of PEP-carboxykinase, malate dehydrogenase, fumarase and fumarate reductase revealed the functioning of the PEP-succinate pathway in addition to phosphorylating glycolysis and pentose phosphate pathway in the parasite. Excepting fumarate reductase all other enzymes were localized in the particulate-free cytosol fraction, although small amounts of glycogen phosphorylase, aldolase and lactate dehydrogenase were also detected in the mitochondrial fraction.

  2. 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.

  3. [Effects of furfural and 5-hydroxymethylfurfural on succinic acid production by Escherichia coli].

    PubMed

    Wang, Dan; Wang, Honghui; Wang, Jing; Wang, Nan; Zhang, Jie; Xing, Jianmin

    2013-10-01

    Succinic acid production by fermentation from biomass, especially the lignocellulosic hydrolysate, is an alternative to chemical synthesis. Many studies report the inhibition of cell growth and succinic acid production from lignocellulosic hydrolysate, hardly is known about the actual kinetic and mechanism of the inhibition of individual factors. In this study, we studied inhibition effects of furfurals and 5-hydroxymethylfurfural (5-HMF) on cell growth and succinic acid production of engineered E. coli. Cell growth and succinic acid titer were severely inhibited by furfural and HMF with both concentrations higher than 0.8 g/L. Cell growth was totally inhibited when the concentration of furfural was above 6.4 g/L, or the concentration of HMF was above 12.8 g/L. At the concentration of maximum toleration, which was 3.2 g/L, furfural decreased the cell mass by 77.8% and the succinic acid titer by 36.1%. HMF decreased the cell mass by 13.6% and the succinic acid titer by 18.3%. Activity measurements of key enzymes revealed that phosphoenolpyruvate carboxylase, malate dehydrogenase, fumarate reductase all were inhibited by furfural and HMF. This study gave a quantitative view to the succinic acid production under the inhibition of lignocellulose degradation products and will help overcome the difficulties of the lignocellulosic hydrolysate fermentation.

  4. 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.

  5. 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. PMID:26708482

  6. 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

  7. 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

  8. Elastic electron scattering by ethyl vinyl ether

    NASA Astrophysics Data System (ADS)

    Khakoo, M. A.; Hong, L.; Kim, B.; Winstead, C.; McKoy, V.

    2010-02-01

    We report measured and calculated results for elastic scattering of low-energy electrons by ethyl vinyl ether (ethoxyethene), a prototype system for studying indirect dissociative attachment processes that may play a role in DNA damage. The integral cross section displays the expected π* shape resonance. The agreement between the calculated and measured cross sections is generally good.

  9. 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.

  10. 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

  11. Succinic acid production by Actinobacillus succinogenes from batch fermentation of mixed sugars.

    PubMed

    Almqvist, Henrik; Pateraki, Chrysanthi; Alexandri, Maria; Koutinas, Apostolis; Lidén, Gunnar

    2016-08-01

    Succinic acid production from the monosaccharides xylose, arabinose, glucose, mannose and galactose was studied using the bacterium Actinobacillus succinogenes. In Duran bottle cultures, containing 10 g/L of each of sugar, succinic acid was produced from all sugars except for galactose. The highest succinate yield, 0.56 g/g, was obtained with glucose, whereas the succinate yield was 0.42, 0.38 and 0.44 g/g for xylose, mannose and arabinose, respectively. The specific succinate productivity was 0.7 g/g h for glucose, but below 0.2 g/g h for the other sugars. Batch bioreactor fermentations were carried out using a sugar mixture of the five sugars giving a total concentration of 50 g/L, mimicking the distribution of sugars in spent sulfite liquor (SSL) from Eucalyptus which is rich in xylose. In this mixture, an almost complete conversion of all sugars (except galactose) was achieved resulting in a final succinate concentration of 21.8-26.8 g/L and a total yield of 0.59-0.68 g/g. There was evidence of co-consumption of glucose and xylose, whereas mannose was consumed after glucose. The main by-products were acetate 0.14-0.20 g/g and formate 0.08-0.13 g/g. NADH balance calculations suggested that NADH required for succinate production was not met solely from formate and acetate production, but other means of NADH production was necessary. Results from mixed sugar fermentations were verified using SSL as substrate resulting in a succinate yield of 0.60 g/g. In addition, it was found that CO2 sparging could replace carbonate supply in the form of MgCO3 without affecting the succinate yield. PMID:27255975

  12. 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.

  13. 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.

  14. Rapid monomerization of poly(butylene succinate)-co-(butylene adipate) by Leptothrix sp.

    PubMed

    Nakajima-Kambe, Toshiaki; Toyoshima, Kieko; Saito, Chika; Takaguchi, Hitoshi; Akutsu-Shigeno, Yukie; Sato, Megumi; Miyama, Kazuyuki; Nomura, Nobuhiko; Uchiyama, Hiroo

    2009-12-01

    For rapid monomerization of biodegradable plastics, various microorganisms were screened and TB-71 was selected as the best strain. TB-71 degraded solid poly(butylene succinate)-co-(butylene adipate) (PBSA), poly(ethylene succinate), and poly(epsilon-caprolactone) but not poly(butylene succinate), poly(2-hydroxybutylate-co-valerate) or poly(lactic acid). Esterase activity was observed in the culture broth during PBSA degradation, which was specifically induced by PBSA. Analysis of the degradation products revealed that PBSA was degraded to monomers. PMID:19914585

  15. Rapid monomerization of poly(butylene succinate)-co-(butylene adipate) by Leptothrix sp.

    PubMed

    Nakajima-Kambe, Toshiaki; Toyoshima, Kieko; Saito, Chika; Takaguchi, Hitoshi; Akutsu-Shigeno, Yukie; Sato, Megumi; Miyama, Kazuyuki; Nomura, Nobuhiko; Uchiyama, Hiroo

    2009-12-01

    For rapid monomerization of biodegradable plastics, various microorganisms were screened and TB-71 was selected as the best strain. TB-71 degraded solid poly(butylene succinate)-co-(butylene adipate) (PBSA), poly(ethylene succinate), and poly(epsilon-caprolactone) but not poly(butylene succinate), poly(2-hydroxybutylate-co-valerate) or poly(lactic acid). Esterase activity was observed in the culture broth during PBSA degradation, which was specifically induced by PBSA. Analysis of the degradation products revealed that PBSA was degraded to monomers.

  16. 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

  17. Prevalence of mef and ermB genes in invasive pediatric erythromycin-resistant Streptococcus pneumoniae isolates from Argentina.

    PubMed

    Corso, A; Faccone, D; Gagetti, P; Pace, J; Regueira, M; Pace, Julio

    2009-01-01

    During the period 1993-2001, a total of 1,499 pneumococci isolates were recovered through the Argentinean surveillance of Streptococcus pneumoniae causing invasive disease in children under 6 years of age, 3.5% of which were erythromycin resistant. Among the 50 erythromycin-resistant strains available, 58% (n=29) harbored mefA/E genes (15 mefA, 30%; and 14 mefE, 28%), 34% (n=17) ermB, and 6% (n=3) both mefA/E plus ermB genes, while one isolate was negative for all the acquired genes studied. The England14-9 (42%), Poland6B-20 (20%) and Spain9V-3 (16%) clones were responsible for the emergence of pneumococcal macrolide resistance in pediatric population from Argentina.

  18. Micronucleus test and comet assay for the evaluation of zebrafish genomic damage induced by erythromycin and lincomycin.

    PubMed

    Rocco, Lucia; Peluso, Carmela; Stingo, Vincenzo

    2012-10-01

    An enormous quantity of pharmacologically active principles are currently being introduced into the environment, with consequent escalation of environmental problems, but only a small number of studies are focusing on an assessment of their genotoxic effects. The aim of this article is to assess the genotoxic effects of erythromycin, lincomycin, and of a combination of these two antibiotics on the genome of the zebrafish. The genotoxicity of the two antibiotics was assessed by applying the micronucleus test to erythrocytes and performing a Comet assay on erythrocytes and hepatocytes. The fish were exposed to antibiotics at different concentrations and times of exposure, under standard laboratory conditions. Depending on the different experimental conditions, erythromycin and lincomycin induced a significant increase in DNA migration (tail moment) and a significant increase in micronuleus frequency. We also conducted an analysis on the activation of repair mechanisms when the genotoxic agent was removed. Only a few of the cells displayed a decrease in damage under these test conditions.

  19. Erythromycin and azithromycin transport into Haemophilus influenzae ATCC 19418 under conditions of depressed proton motive force (delta mu H)

    SciTech Connect

    Capobianco, J.O.; Goldman, R.C. )

    1990-09-01

    The effect of collapsing the electrochemical proton gradient (delta mu H) on ({sup 3}H)erythromycin and ({sup 14}C)azithromycin transport in Haemophilus influenzae ATCC 19418 was studied. The proton gradient and membrane potential were determined from the distribution of (2-{sup 14}C)dimethadione and rubidium-86, respectively. delta mu H was reduced from 124 to 3 mV in EDTA-valinomycin-treated cells at 22{degrees}C with 150 mM KCl and 0.1 mM carbonyl cyanide m-chlorophenylhydrazone. During the collapse of delta mu H, macrolide uptake increased. Erythromycin efflux studies strongly suggested that this increase was not due to an energy-dependent efflux pump but was likely due to increased outer membrane permeability. These data indicated that macrolide entry was not a delta mu H-driven active transport process but rather a passive diffusion process.

  20. Evidence for functional interaction between domains II and V of 23S ribosomal RNA from an erythromycin-resistant mutant.

    PubMed Central

    Douthwaite, S; Prince, J B; Noller, H F

    1985-01-01

    A mutation affording low levels of erythromycin resistance has been obtained by in vitro hydroxylamine mutagenesis of a cloned ribosomal RNA operon from Escherichia coli. The site of the mutational event responsible for antibiotic resistance was localized to the gene region encoding domain II of 23S rRNA by replacement of restriction fragments in the wild-type plasmid by corresponding fragments from the mutant plasmid. DNA sequencing showed that positions 1219-1230 of the 23S rRNA gene are deleted in the mutant. Since all previously characterized rRNA mutations conferring resistance to erythromycin show changes exclusively in domain V, our present findings provide direct evidence for functional interaction between domains II and V of 23S rRNA. Images PMID:3909142

  1. The Effect of Cationic Polyamidoamine Dendrimers on Physicochemical Characteristics of Hydrogels with Erythromycin

    PubMed Central

    Wróblewska, Magdalena; Winnicka, Katarzyna

    2015-01-01

    Polyamidoamine dendrimers (PAMAM) represent a new class of hyperbranched, monodisperse, three-dimensional polymers with unique properties, which make them very promising carriers of antimicrobial agents. The present study aimed to evaluate the influence of PAMAM-NH2 dendrimers generation two (G2) or three (G3) on physicochemical characteristics and structure of hydrogels with a model antibacterial lipophilic drug—erythromycin—commonly used in topical applications. From the obtained rheograms, it can be concluded that tested hydrogels were non-Newtonian thixotropic systems with shear-thinning behaviour. The dissolution tests revealed that erythromycin was definitely faster released from formulations containing PAMAM-NH2 in concentration and generation dependent manner. However, the addition of PAMAM-NH2 to hydrogels evoked only slight improvement of their antibacterial activity. It was also shown that the structure of hydrogels changed in the presence of PAMAM-NH2 becoming less compact, diversified and more porous. Designed hydrogels with PAMAM-NH2 G2 or G3 were stable stored up to three months at 40 ± 2 °C and 75% ± 5% RH. PMID:26343637

  2. Distribution of specific tetracycline and erythromycin resistance genes in environmental samples assessed by macroarray detection.

    PubMed

    Patterson, Andrea J; Colangeli, Roberto; Spigaglia, Patrizia; Scott, Karen P

    2007-03-01

    A macroarray system was developed to screen environmental samples for the presence of specific tetracycline (Tc(R)) and erythromycin (erm(R)) resistance genes. The macroarray was loaded with polymerase chain reaction (PCR) amplicons of 23 Tc(R) genes and 10 erm(R) genes. Total bacterial genomic DNA was extracted from soil and animal faecal samples collected from different European countries. Macroarray hybridization was performed under stringent conditions and the results were analysed by fluorescence scanning. Pig herds in Norway, reared without antibiotic use, had a significantly lower incidence of antibiotic resistant bacteria than those reared in other European countries, and organic herds contained lower numbers of resistant bacteria than intensively farmed animals. The relative proportions of the different genes were constant across the different countries. Ribosome protection type Tc(R) genes were the most common resistance genes in animal faecal samples, with the tet(W) gene the most abundant, followed by tet(O) and tet(Q). Different resistance genes were present in soil samples, where erm(V) and erm(E) were the most prevalent followed by the efflux type Tc(R) genes. The macroarray proved a powerful tool to screen DNA extracted from environmental samples to identify the most abundant Tc(R) and erm(R) genes within those tested, avoiding the need for culturing and biased PCR amplification steps.

  3. Development of Novel Erythromycin Derivatives with Inhibitory Activity against Proliferation of Tumor Cells

    PubMed Central

    Wu, Lan; Bao, Kai; Song, Rui; Wang, Defa; Zhang, Lei; Wang, Weiyun; Zhang, Weige; Bin, Wen

    2016-01-01

    In our continuing structure-activity relationship study of a new class of erythromycin A (EM-A) derivatives with antiproliferative activity, a new series of de(N-methyl) EM-A dimers jointed by a four-atom linker, -CH2CH = CHCH2-, were prepared and their antiproliferative activity against three human tumor cell lines was evaluated by MTT assay. The most active EM-A dimer, compound 1b, that carrying C6 methoxyl groups was further investigated and showed potent antiproliferative activity in six other human tumor cell lines. Flow cytometry analysis of 1b treated HeLa and MCF-7 cells indicated that the four-atom EM-A dimers induced the SubG1 phase cell cycle arrest and cell apoptosis, in time- and dose-dependent manners. Further experiments including morphologic observation, DNA agarose gel electrophoresis, mitochondrial potential alternation and western blot analysis revealed that the antiproliferative mechanism may involve the induction of apoptosis in activating the mitochondrial pathway, and regulation of apoptotic proteins. PMID:27447724

  4. Enantioseparation of basic chiral drugs on a carbamoylated erythromycin-zirconia hybrid monolith using capillary electrochromatography.

    PubMed

    Dixit, Shuchi; Park, Jung Hag

    2015-10-16

    An organic-inorganic hybrid monolithic column was prepared within the confines of a capillary via a single-step in situ sol-gel approach using zirconium tetrabutoxide as a precursor to compose the inorganic backbone and 3-triethoxysilylpropyl carbamoylated derivative of erythromycin (TEOSPC-ERY) as a co-precursor to introduce the organic chiral selector moiety in the zirconia backbone. The resulting carbamoylated ERY-zirconia hybrid monolith (ERY-ZHM) showed homogeneous morphology with well-defined through pores and was tightly connected with the inner wall of the capillary. The column was employed for capillary electrochromatographic enantioseparation of six basic chiral drugs in mobile phases (MPs) consisting of acetonitrile (ACN) and triethylammonium acetate (TEAA) buffer. The effects of composition of MP and applied voltage on chiral separation were investigated by using propranolol as a representative analyte. The highest resolution (Rs=3.33) was obtained with a MP consisting of 10/90 (v/v) ACN/TEAA buffer (10mM, pH 7), 10 kV applied voltage and 25°C capillary temperature. The relative standard deviations for resolution values regarding run to run, day to day, column to column and batch to batch repeatability were 0.41%, 0.89%, 1.80% and 2.26% (for n=3), respectively, indicating satisfactory stability of columns and reproducibility of column preparation process.

  5. Mitigative Effect of Erythromycin on PMMA Challenged Preosteoblastic MC3T3-E1 Cells

    PubMed Central

    Shen, Yi; Wang, Weili; Li, Xiaomiao; Markel, David C.; Ren, Weiping

    2014-01-01

    Background. Aseptic loosening (AL) is a major complication of total joint replacement. Recent approaches to limiting AL have focused on inhibiting periprosthetic inflammation and osteoclastogenesis. Questions/Purposes. The purpose of this study was to determine the effects of erythromycin (EM) on polymethylmethacrylate (PMMA) particle-challenged MC3T3 osteoblast precursor cells. Methods. MC3T3 cells were pretreated with EM (0–10 μg/mL) and then stimulated with PMMA (1 mg/mL). Cell viability was evaluated by both a lactate dehydrogenase (LDH) release assay and cell counts. Cell differentiation was determined by activity of alkaline phosphatase (ALP). Gene expression was measured via real-time quantitative RT-PCR. Results. We found that exposure to PMMA particles reduced cellular viability and osteogenetic potential in MC3T3 cell line. EM treatment mitigated the effects of PMMA particles on the proliferation, viability and differentiation of MC3T3 cells. PMMA decreased the gene expression of Runx2, osterix and osteocalcin, which can be partially restored by EM treatment. Furthermore, EM suppressed PMMA- induced increase of NF-κB gene expression. Conclusions. These data demonstrate that EM mitigates the effects of PMMA on MC3T3 cell viability and differentiation, in part through downregulation of NF-κB pathway. EM appeared to represent an anabolic agent on MC3T3 cells challenged with PMMA particles. PMID:25110723

  6. From Erythromycin to Azithromycin and New Potential Ribosome-Binding Antimicrobials

    PubMed Central

    Jelić, Dubravko; Antolović, Roberto

    2016-01-01

    Macrolides, as a class of natural or semisynthetic products, express their antibacterial activity primarily by reversible binding to the bacterial 50S ribosomal subunits and by blocking nascent proteins’ progression through their exit tunnel in bacterial protein biosynthesis. Generally considered to be bacteriostatic, they may also be bactericidal at higher doses. The discovery of azithromycin from the class of macrolides, as one of the most important new drugs of the 20th century, is presented as an example of a rational medicinal chemistry approach to drug design, applying classical structure-activity relationship that will illustrate an impressive drug discovery success story. However, the microorganisms have developed several mechanisms to acquire resistance to antibiotics, including macrolide antibiotics. The primary mechanism for acquiring bacterial resistance to macrolides is a mutation of one or more nucleotides from the binding site. Although azithromycin is reported to show different, two-step process of the inhibition of ribosome function of some species, more detailed elaboration of that specific mode of action is needed. New macrocyclic derivatives, which could be more potent and less prone to escape bacterial resistance mechanisms, are also continuously evaluated. A novel class of antibiotic compounds—macrolones, which are derived from macrolides and comprise macrocyclic moiety, linker, and either free or esterified quinolone 3-carboxylic group, show excellent antibacterial potency towards key erythromycin-resistant Gram-positive and Gram-negative bacterial strains, with possibly decreased potential of bacterial resistance to macrolides. PMID:27598215

  7. An erythromycin derivative, EM-523, induces motilin-like gastrointestinal motility in dogs.

    PubMed

    Inatomi, N; Satoh, H; Maki, Y; Hashimoto, N; Itoh, Z; Omura, S

    1989-11-01

    The effect of an erythromycin derivative, EM-523, on gastrointestinal motility was investigated in conscious dogs and compared with that of motilin cisapride, trimebutine and metoclopramide. In the fasting state, EM-523 given i.v. or i.d. at 3 micrograms/kg or more induced contractions in the stomach that migrated along the small intestine. The pattern of the contractions was very similar to that induced by motilin. In the digestive state, EM-523 increased the amplitude of gastric contractions. Cisapride and metoclopramide increased gastrointestinal motility both in the fasting and digestive states; however, their contractile pattern was different from that of EM-523. Trimebutine did not induce gastric motility in the fasting state but rather decreased gastric motility in the digestive state. The contractions induced by EM-523 and motilin were inhibited by atropine but were not affected by naloxone, suggesting that the cholinergic pathway is important in the exertion of their action. These results indicate that EM-523 mimics motilin in stimulating gastrointestinal motility and that this agent may be useful treat gastrointestinal disorders such as gastric stasis, gastroesophageal reflux, and postoperative ileus, and so forth. PMID:2810120

  8. Selective removal of erythromycin by magnetic imprinted polymers synthesized from chitosan-stabilized Pickering emulsion.

    PubMed

    Ou, Hongxiang; Chen, Qunhui; Pan, Jianming; Zhang, Yunlei; Huang, Yong; Qi, Xueyong

    2015-05-30

    Magnetic imprinted polymers (MIPs) were synthesized by Pickering emulsion polymerization and used to adsorb erythromycin (ERY) from aqueous solution. The oil-in-water Pickering emulsion was stabilized by chitosan nanoparticles with hydrophobic Fe3O4 nanoparticles as magnetic carrier. The imprinting system was fabricated by radical polymerization with functional and crosslinked monomer in the oil phase. Batches of static and dynamic adsorption experiments were conducted to analyze the adsorption performance on ERY. Isotherm data of MIPs well fitted the Freundlich model (from 15 °C to 35 °C), which indicated heterogeneous adsorption for ERY. The ERY adsorption capacity of MIPs was about 52.32 μmol/g at 15 °C. The adsorption kinetics was well described by the pseudo-first-order model, which suggested that physical interactions were primarily responsible for ERY adsorption. The Thomas model used in the fixed-bed adsorption design provided a better fit to the experimental data. Meanwhile, ERY exhibited higher affinity during adsorption on the MIPs compared with the adsorption capacity of azithromycin and chloramphenicol. The MIPs also exhibited excellent regeneration capacity with only about 5.04% adsorption efficiency loss in at least three repeated adsorption-desorption cycles. PMID:25704432

  9. From Erythromycin to Azithromycin and New Potential Ribosome-Binding Antimicrobials.

    PubMed

    Jelić, Dubravko; Antolović, Roberto

    2016-01-01

    Macrolides, as a class of natural or semisynthetic products, express their antibacterial activity primarily by reversible binding to the bacterial 50S ribosomal subunits and by blocking nascent proteins' progression through their exit tunnel in bacterial protein biosynthesis. Generally considered to be bacteriostatic, they may also be bactericidal at higher doses. The discovery of azithromycin from the class of macrolides, as one of the most important new drugs of the 20th century, is presented as an example of a rational medicinal chemistry approach to drug design, applying classical structure-activity relationship that will illustrate an impressive drug discovery success story. However, the microorganisms have developed several mechanisms to acquire resistance to antibiotics, including macrolide antibiotics. The primary mechanism for acquiring bacterial resistance to macrolides is a mutation of one or more nucleotides from the binding site. Although azithromycin is reported to show different, two-step process of the inhibition of ribosome function of some species, more detailed elaboration of that specific mode of action is needed. New macrocyclic derivatives, which could be more potent and less prone to escape bacterial resistance mechanisms, are also continuously evaluated. A novel class of antibiotic compounds-macrolones, which are derived from macrolides and comprise macrocyclic moiety, linker, and either free or esterified quinolone 3-carboxylic group, show excellent antibacterial potency towards key erythromycin-resistant Gram-positive and Gram-negative bacterial strains, with possibly decreased potential of bacterial resistance to macrolides.

  10. From Erythromycin to Azithromycin and New Potential Ribosome-Binding Antimicrobials.

    PubMed

    Jelić, Dubravko; Antolović, Roberto

    2016-01-01

    Macrolides, as a class of natural or semisynthetic products, express their antibacterial activity primarily by reversible binding to the bacterial 50S ribosomal subunits and by blocking nascent proteins' progression through their exit tunnel in bacterial protein biosynthesis. Generally considered to be bacteriostatic, they may also be bactericidal at higher doses. The discovery of azithromycin from the class of macrolides, as one of the most important new drugs of the 20th century, is presented as an example of a rational medicinal chemistry approach to drug design, applying classical structure-activity relationship that will illustrate an impressive drug discovery success story. However, the microorganisms have developed several mechanisms to acquire resistance to antibiotics, including macrolide antibiotics. The primary mechanism for acquiring bacterial resistance to macrolides is a mutation of one or more nucleotides from the binding site. Although azithromycin is reported to show different, two-step process of the inhibition of ribosome function of some species, more detailed elaboration of that specific mode of action is needed. New macrocyclic derivatives, which could be more potent and less prone to escape bacterial resistance mechanisms, are also continuously evaluated. A novel class of antibiotic compounds-macrolones, which are derived from macrolides and comprise macrocyclic moiety, linker, and either free or esterified quinolone 3-carboxylic group, show excellent antibacterial potency towards key erythromycin-resistant Gram-positive and Gram-negative bacterial strains, with possibly decreased potential of bacterial resistance to macrolides. PMID:27598215

  11. Systems perspectives on erythromycin biosynthesis by comparative genomic and transcriptomic analyses of S. erythraea E3 and NRRL23338 strains

    PubMed Central

    2013-01-01

    Background S. erythraea is a Gram-positive filamentous bacterium used for the industrial-scale production of erythromycin A which is of high clinical importance. In this work, we sequenced the whole genome of a high-producing strain (E3) obtained by random mutagenesis and screening from the wild-type strain NRRL23338, and examined time-series expression profiles of both E3 and NRRL23338. Based on the genomic data and transcriptpmic data of these two strains, we carried out comparative analysis of high-producing strain and wild-type strain at both the genomic level and the transcriptomic level. Results We observed a large number of genetic variants including 60 insertions, 46 deletions and 584 single nucleotide variations (SNV) in E3 in comparison with NRRL23338, and the analysis of time series transcriptomic data indicated that the genes involved in erythromycin biosynthesis and feeder pathways were significantly up-regulated during the 60 hours time-course. According to our data, BldD, a previously identified ery cluster regulator, did not show any positive correlations with the expression of ery cluster, suggesting the existence of alternative regulation mechanisms of erythromycin synthesis in S. erythraea. Several potential regulators were then proposed by integration analysis of genomic and transcriptomic data. Conclusion This is a demonstration of the functional comparative genomics between an industrial S. erythraea strain and the wild-type strain. These findings help to understand the global regulation mechanisms of erythromycin biosynthesis in S. erythraea, providing useful clues for genetic and metabolic engineering in the future. PMID:23902230

  12. The [14C-N-methyl]-erythromycin breath test dosimetry complies with the French regulations for radiation safety.

    PubMed

    Salvat, Cécile; Mouly, Stéphane; Rizzo-Padoin, Nathalie; Knellwolf, Anne-Laure; Simoneau, Guy; Duet, Michèle; Nataf, Valérie; Bailliart, Olivier; Bergmann, Jean-François

    2003-06-01

    The [14C-N-methyl]-erythromycin breath test (14C-ERMBT) is one of the most valuable probes for liver cytochrome P450-3A4 activity in humans. In order to extend the use of this test in France, we herein provide safety data regarding either patient dosimetry or worker exposure to [14C-N-methyl]-erythromycin. In order to determine the maximum radiation exposure for patient and nuclear medicine technician following one intravenous 14C-ERMBT [111 kiloBequerel (kBq)], we have used the dosimetric data gathered in animal studies and extrapolated to humans using a weight-based method, approximate data provided by the French Society of Radioprotection and erythromycin pharmacokinetics in humans, considering always the worst conditions for the patient and worker exposure determination. The radioactivity administered to a patient after one 14C-ERMBT was equal to 108.8 kBq (i.e. 98% of the total radioactivity in the 14C-erythromycin vial) leading to a patient effective dose of 20 microsievert (microSv) and a maximum effective dose after 14CO2 inhalation by the exposed worker of 16 microSv compared with a mean individual annual effective dose from natural and artificial radioactivity exposure of 3500 microSv in France. The 14C-ERMBT is safe and complies with the European regulations regarding the administration of 14C-labelled compounds in humans. It can therefore be used in clinical research in France without any particular safety requirement.

  13. Control of inducer accumulation plays a key role in succinate-mediated catabolite repression in Sinorhizobium meliloti.

    PubMed

    Bringhurst, Ryan M; Gage, Daniel J

    2002-10-01

    The symbiotic, nitrogen-fixing bacterium Sinorhizobium meliloti favors succinate and related dicarboxylic acids as carbon sources. As a preferred carbon source, succinate can exert catabolite repression upon genes needed for the utilization of many secondary carbon sources, including the alpha-galactosides raffinose and stachyose. We isolated lacR mutants in a genetic screen designed to find S. meliloti mutants that had abnormal succinate-mediated catabolite repression of the melA-agp genes, which are required for the utilization of raffinose and other alpha-galactosides. The loss of catabolite repression in lacR mutants was seen in cells grown in minimal medium containing succinate and raffinose and grown in succinate and lactose. For succinate and lactose, the loss of catabolite repression could be attributed to the constitutive expression of beta-galactoside utilization genes in lacR mutants. However, the inactivation of lacR did not cause the constitutive expression of alpha-galactoside utilization genes but caused the aberrant expression of these genes only when succinate was present. To explain the loss of diauxie in succinate and raffinose, we propose a model in which lacR mutants overproduce beta-galactoside transporters, thereby overwhelming the inducer exclusion mechanisms of succinate-mediated catabolite repression. Thus, some raffinose could be transported by the overproduced beta-galactoside transporters and cause the induction of alpha-galactoside utilization genes in the presence of both succinate and raffinose. This model is supported by the restoration of diauxie in a lacF lacR double mutant (lacF encodes a beta-galactoside transport protein) grown in medium containing succinate and raffinose. Biochemical support for the idea that succinate-mediated repression operates by preventing inducer accumulation also comes from uptake assays, which showed that cells grown in raffinose and exposed to succinate have a decreased rate of raffinose transport

  14. 21 CFR 172.872 - Methyl ethyl cellulose.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Methyl ethyl cellulose. 172.872 Section 172.872... Methyl ethyl cellulose. The food additive methyl ethyl cellulose may be safely used in food in accordance with the following prescribed conditions. (a) The additive is a cellulose ether having the...

  15. 21 CFR 177.1320 - Ethylene-ethyl acrylate copolymers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... prescribed for polyethylene in § 177.1520. (1) Specifications—(i) Infrared identification. Ethylene-ethyl acrylate copolymers can be identified by their characteristic infrared spectra. (ii) Quantitative determination of ethyl acrylate content. The ethyl acrylate can be determined by the infrared spectra. Prepare...

  16. 21 CFR 177.1320 - Ethylene-ethyl acrylate copolymers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... prescribed for polyethylene in § 177.1520. (1) Specifications—(i) Infrared identification. Ethylene-ethyl acrylate copolymers can be identified by their characteristic infrared spectra. (ii) Quantitative determination of ethyl acrylate content. The ethyl acrylate can be determined by the infrared spectra. Prepare...

  17. Effects of erythromycin on the phenotypic and genotypic biofilm expression in two clinical Staphylococcus capitis subspecies and a functional analysis of Ica proteins in S. capitis.

    PubMed

    Cui, Bintao; Smooker, Peter M; Rouch, Duncan A; Deighton, Margaret A

    2015-06-01

    The ica operon encoding polysaccharide intercellular adhesion, which facilitates biofilm formation in staphylococci, has been extensively studied in Staphylococcus epidermidis and Staphylococcus aureus. Based on in silico analysis, we suggest the following functional model for Ica proteins in S. capitis. IcaA is responsible for polysaccharide synthesis. IcaA and IcaD complete transferring the growing sugar chain to the cell surface; IcaB is a deacetylase, with the same function as IcaB of S. epidermidis. IcaC mainly modifies the synthesized glucan by acetylation. We also examined the effects of subinhibitory concentrations of erythromycin on phenotypic biofilm expression and transcription of biofilm-related genes, using isolates representing the two subspecies of Staphylococcus capitis and different biofilm and resistance phenotypes. On induction with erythromycin, biofilm density was strongly elevated in two erythromycin-resistant S. capitis, but not in three susceptible isolates. In the representative erythromycin-resistant S. capitis subsp. urealyticus, there were significant upregulations of the icaA gene and its positive regulator sarA on transition to the stationary phase without erythromycin induction. There were also significant increases in the transcription levels of icaA, rsbU and sigB corresponding to a very strong biofilm phenotype in the stationary phase on erythromycin stress. In contrast, the representative erythromycin-susceptible S. capitis subsp. capitis displayed upregulation only of altE on entry into the stationary phase with erythromycin induction, but this change was not associated with enhancement of biofilm production. These findings suggest that the two subspecies of S. capitis adopt different pathogenesis and survival strategies to adapt to a hostile environment.

  18. 21 CFR 172.765 - Succistearin (stearoyl propylene glycol hydrogen succinate).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... additive is the reaction product of succinic anhydride, fully hydrogenated vegetable oil (predominantly C16... additive is used or intended for use as an emulsifier in or with shortenings and edible oils intended...

  19. 21 CFR 172.765 - Succistearin (stearoyl propylene glycol hydrogen succinate).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... additive is the reaction product of succinic anhydride, fully hydrogenated vegetable oil (predominantly C16... additive is used or intended for use as an emulsifier in or with shortenings and edible oils intended...

  20. 21 CFR 172.765 - Succistearin (stearoyl propylene glycol hydrogen succinate).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... additive is the reaction product of succinic anhydride, fully hydrogenated vegetable oil (predominantly C16... additive is used or intended for use as an emulsifier in or with shortenings and edible oils intended...

  1. 21 CFR 172.765 - Succistearin (stearoyl propylene glycol hydrogen succinate).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... additive is the reaction product of succinic anhydride, fully hydrogenated vegetable oil (predominantly C16... additive is used or intended for use as an emulsifier in or with shortenings and edible oils intended...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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

  7. Differential labeling of the subunits of respiratory complex III with (3H)succinic anhydride, (14C)succinic anhydride, and p-diazobenzene-(35S)sulfonate

    SciTech Connect

    Ho, S.H.; Rieske, J.S.

    1985-12-01

    Exposure of antimycin-treated Complex III (ubiquinol-cytochrome c reductase) purified from bovine heart mitochondria to (3H)succinic anhydride plus (35S)p-diazobenzenesulfonate (DABS) resulted in somewhat uniform relative labeling of the eight measured subunits of the complex by (3H)succinic anhydride. In contrast, relative labeling by (35S)DABS was similar to (3H)succinic anhydride for the subunits of high molecular mass, i.e., core proteins, cytochromes, and the iron-sulfur protein, but greatly reduced for the polypeptides of molecular mass below 15 kDa. With Complex II depleted in the iron-sulfur protein the relative labeling of core protein I by exposure of the complex to (3H)succinic anhydride was significantly enhanced, whereas labeling of the polypeptides represented by SDS-PAGE bands 7 and 8 was significantly inhibited. Dual labeling of the subunits of Complex III by 14C- and 3H-labeled succinic anhydride before and after dissociation of the complex by sodium dodecyl sulfate, respectively, was measured with the complex in its oxidized, reduced, and antimycin-inhibited states. Subunits observed to be most accessible or reactive to succinic anhydride were core protein II, the iron-sulfur protein, and polypeptides of SDS-PAGE bands 7,8, and 9. Two additional polypeptides of molecular masses 23 and 12kDa, not normally resolved by gel-electrophoresis, were detected. Reduction of the complex resulted in a significant change of 14C/3H labeling ratio of core protein only, whereas treatment of the complex with antimycin resulted in decreases in 14C/3H labeling ratios of core proteins I and II, cytochrome c1, and a polypeptide of molecular mass 13kDa identified as an antimycin-binding protein.

  8. 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

  9. 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).

  10. 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). PMID:26971832

  11. Separation of NADH-fumarate reductase and succinate dehydrogenase activities in Trypanosoma cruzi.

    PubMed

    Christmas, P B; Turrens, J F

    2000-02-15

    A recent review suggested that the activity of NADH-fumarate reductase from trypanosomatids could be catalyzed by succinate dehydrogenase working in reverse (Tielens and van Hellemond, Parasitol. Today 14, 265-271, 1999). The results reported in this study demonstrate that the two activities can easily be separated without any loss in either activity, suggesting that fumarate reductase and succinate dehydrogenase are separate enzymes.

  12. 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.

  13. 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.

  14. [Succinic acid production from sucrose and sugarcane molasses by metabolically engineered Escherichia coli].

    PubMed

    Li, Feng; Ma, Jiangfeng; Wu, Mingke; Ji, Yaliang; Chen, Wufang; Ren, Xinyi; Jiang, Min

    2015-04-01

    Sugarcane molasses containing large amounts of sucrose is an economical substrate for succinic acid production. However, Escherichia coli AFP111 cannot metabolize sucrose although it is a promising candidate for succinic acid production. To achieve sucrose utilizing ability, we cloned and expressed cscBKA genes encoding sucrose permease, fructokinase and invertase of non-PTS sucrose-utilization system from E. coli W in E. coli AFP111 to generate a recombinant strain AFP111/pMD19T-cscBKA. After 72 h of anaerobic fermentation of the recombinant in serum bottles, 20 g/L sucrose was consumed and 12 g/L succinic acid was produced. During dual-phase fermentation comprised of initial aerobic growth phase followed by anaerobic fermentation phase, the concentration of succinic acid from sucrose and sugarcane molasses was 34 g/L and 30 g/L, respectively, at 30 h of anaerobic phase in a 3 L fermentor. The results show that the introduction of non-PTS sucrose-utilization system has sucrose-metabolizing capability for cell growth and succinic acid production, and can use cheap sugarcane molasses to produce succinic acid.

  15. Metabolic evolution and (13) C flux analysis of a succinate dehydrogenase deficient strain of Yarrowia lipolytica.

    PubMed

    Yuzbashev, Tigran V; Bondarenko, Pavel Yu; Sobolevskaya, Tatiana I; Yuzbasheva, Evgeniya Yu; Laptev, Ivan A; Kachala, Vadim V; Fedorov, Alexander S; Vybornaya, Tatiana V; Larina, Anna S; Sineoky, Sergey P

    2016-11-01

    Bio-based succinic acid production can redirect industrial chemistry processes from using limited hydrocarbons to renewable carbohydrates. A fermentation process that does not require pH-titrating agents will be advantageous to the industry. Previously, a Yarrowia lipolytica strain that was defective for succinate dehydrogenase was constructed and was found to accumulate up to 17.5 g L(-1) of succinic acid when grown on glycerol without buffering. Here, a derivative mutant was isolated that produced 40.5 g L(-1) of succinic acid in 36 h with a yield of 0.32 g g(-1) glycerol. A combination approach of induced mutagenesis and metabolic evolution allowed isolation of another derivative that could utilize glucose efficiently and accumulated 50.2 g L(-1) succinic acid in 54 h with a yield of 0.43 g g(-1) . The parent strain of these isolated mutants was used for [1,6-(13) C2 ]glucose assimilation analysis. At least 35% glucose was estimated to be utilized through the pentose phosphate pathway, while ≥84% succinic acid was formed through the oxidative branch of the tricarboxylic acid cycle. Biotechnol. Bioeng. 2016;113: 2425-2432. © 2016 Wiley Periodicals, Inc. PMID:27182846

  16. 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.

  17. 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. PMID:20801644

  18. 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. PMID:27394995

  19. Succinic acid in aqueous solution: connecting microscopic surface composition and macroscopic surface tension.

    PubMed

    Werner, Josephina; Julin, Jan; Dalirian, Maryam; Prisle, Nønne L; Öhrwall, Gunnar; Persson, Ingmar; Björneholm, Olle; Riipinen, Ilona

    2014-10-21

    The water-vapor interface of aqueous solutions of succinic acid, where pH values and bulk concentrations were varied, has been studied using surface sensitive X-ray photoelectron spectroscopy (XPS) and molecular dynamics (MD) simulations. It was found that succinic acid has a considerably higher propensity to reside in the aqueous surface region than its deprotonated form, which is effectively depleted from the surface due to the two strongly hydrated carboxylate groups. From both XPS experiments and MD simulations a strongly increased concentration of the acid form in the surface region compared to the bulk concentration was found and quantified. Detailed analysis of the surface of succinic acid solutions at different bulk concentrations led to the conclusion that succinic acid saturates the aqueous surface at high bulk concentrations. With the aid of MD simulations the thickness of the surface layer could be estimated, which enabled the quantification of surface concentration of succinic acid as a multiple of the known bulk concentration. The obtained enrichment factors were successfully used to model the surface tension of these binary aqueous solutions using two different models that account for the surface enrichment. This underlines the close correlation of increased concentration at the surface relative to the bulk and reduced surface tension of aqueous solutions of succinic acid. The results of this study shed light on the microscopic origin of surface tension, a macroscopic property. Furthermore, the impact of the results from this study on atmospheric modeling is discussed.

  20. Is it possible to produce succinic acid at a low pH?

    PubMed

    Yuzbashev, Tigran V; Yuzbasheva, Evgeniya Y; Laptev, Ivan A; Sobolevskaya, Tatiana I; Vybornaya, Tatiana V; Larina, Anna S; Gvilava, Ilia T; Antonova, Svetlana V; Sineoky, Sergey P

    2011-01-01

    Bio-based succinate is still a matter of special emphasis in biotechnology and adjacent research areas. The vast majority of natural and engineered producers are bacterial strains that accumulate succinate under anaerobic conditions. Recently, we succeeded in obtaining an aerobic yeast strain capable of producing succinic acid at low pH. Herein, we discuss some difficulties and advantages of microbial pathways producing "succinic acid" rather than "succinate." It was concluded that the peculiar properties of the constructed yeast strain could be clarified in view of a distorted energy balance. There is evidence that in an acidic environment, the majority of the cellular energy available as ATP will be spent for proton and anion efflux. The decreased ATP:ADP ratio could essentially reduce the growth rate or even completely inhibit growth. In the same way, the preference of this elaborated strain for certain carbon sources could be explained in terms of energy balance. Nevertheless, the opportunity to exclude alkali and mineral acid waste from microbial succinate production seems environmentally friendly and cost-effective.

  1. Succinic acid production from corn cob hydrolysates by genetically engineered Corynebacterium glutamicum.

    PubMed

    Wang, Chen; Zhang, Hengli; Cai, Heng; Zhou, Zhihui; Chen, Yilu; Chen, Yali; Ouyang, Pingkai

    2014-01-01

    Corynebacterium glutamicum wild type lacks the ability to utilize the xylose fractions of lignocellulosic hydrolysates. In the present work, we constructed a xylose metabolic pathway in C. glutamicum by heterologous expression of the xylA and xylB genes coming from Escherichia coli. Dilute-acid hydrolysates of corn cobs containing xylose and glucose were used as a substrate for succinic acid production by recombinant C. glutamicum NC-2. The results indicated that the available activated charcoal pretreatment in dilute-acid hydrolysates of corn cobs could be able to overcome the inhibitory effect in succinic acid production. Succinic acid was shown to be efficiently produced from corn cob hydrolysates (55 g l(-1) xylose and 4 g l(-1) glucose) under oxygen deprivation with addition of sodium carbonate. Succinic acid concentration reached 40.8 g l(-1) with a yield of 0.69 g g(-1) total sugars within 48 h. It was the first report of succinic acid production from corn cob hydrolysates by metabolically engineered C. glutamicum. This study suggested that dilute-acid hydrolysates of corn cobs may be an alternative substrate for the efficient production of succinic acid by C. glutamicum. PMID:24078255

  2. 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.

  3. 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.

  4. Effect of macrolide usage on emergence of erythromycin-resistant Campylobacter isolates in chickens.

    PubMed

    Lin, Jun; Yan, Meiguan; Sahin, Orhan; Pereira, Sonia; Chang, Yun-Juan; Zhang, Qijing

    2007-05-01

    In this work we conducted both in vitro and in vivo experiments to examine the development and mechanisms of erythromycin (Ery) resistance in Campylobacter jejuni and Campylobacter coli. In vitro plating revealed that both Campylobacter species had similar but low spontaneous mutation frequencies (3 x 10(-9) to <5.41 x 10(-10)) for Ery resistance. Chickens infected with C. jejuni or C. coli were subjected to single or multiple treatments with medicated water containing tylosin (0.53 g/liter), which transiently reduced the level of Campylobacter colonization but did not select for Ery-resistant (Ery(r)) mutants in the treated birds. However, when tylosin was given to the chickens in feed at a growth-promoting dose (0.05 g/kg feed), Ery(r) mutants emerged in the birds after prolonged exposure to the antibiotic. The vast majority of the in vitro- and in vivo-selected Campylobacter mutants with Ery MICs of 8 to 256 microg/ml lacked the known resistance-associated mutations in the 23S rRNA gene, while the highly resistant mutants (Ery MIC > 512 microg/ml) had the A2074G mutation in the 23S rRNA gene. Inactivation of CmeABC, a multidrug efflux pump, dramatically reduced the Ery MIC in all of the examined mutants regardless of the presence of the A2074G mutation. Together, these results reveal distinct features associated with Ery resistance development in Campylobacter, demonstrate the significant role of CmeABC in Ery resistance, and suggest that long-term use of a macrolide as a growth promoter selects for the emergence of Ery(r) Campylobacter in animal reservoirs. PMID:17353243

  5. Computer assisted modeling of ethyl sulfate pharmacokinetics.

    PubMed

    Schmitt, Georg; Halter, Claudia C; Aderjan, Rolf; Auwaerter, Volker; Weinmann, Wolfgang

    2010-01-30

    For 12 volunteers of a drinking experiment the concentration-time-courses of ethyl sulfate (EtS) and ethanol were simulated and fitted to the experimental data. The concentration-time-courses were described with the same mathematical model as previously used for ethyl glucuronide (EtG). The kinetic model based on the following assumptions and simplifications: a velocity constant k(form) for the first order formation of ethyl sulfate from ethanol and an exponential elimination constant k(el). The mean values (and standard deviations) obtained for k(form) and k(el) were 0.00052 h(-1) (0.00014) and 0.561 h(-1) (0.131), respectively. Using the ranges of these parameters it is possible to calculate minimum and maximum serum concentrations of EtS based on stated ethanol doses and drinking times. The comparison of calculated and measured concentrations can prove the plausibility of alleged ethanol consumption and add evidence to the retrospective calculation of ethanol concentrations based on EtG concentrations. PMID:19913378

  6. 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.

  7. 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.

  8. Biological denitrification using poly(butanediol succinate) as electron donor.

    PubMed

    Shen, Zhiqiang; Yin, Yanan; Wang, Jianlong

    2016-07-01

    Poly(butanediol succinate) (PBS), a biodegradable polymer, was used as both solid carbon source and biofilm carrier for biological nitrate removal process, in which PBS was filled in a packed-bed bioreactor. The denitrification performance and the microbial diversity of biofilm attached on the surface of PBS were investigated. The experimental results showed that the volumetric denitrification rate was 0.60 kg m(-3) day(-1) when NO3-N loading rate was 0.63 kg m(-3) day(-1), and the average NO2-N concentration was below 0.20 mg L(-1). The effluent pH value decreased slightly from a range of 6.98-7.87 to 6.46-7.18. The analysis of microbial community structure of biofilm by pyrosequencing method showed that Proteobacteria was the most abundant phylum (89.87 %), and β-Proteobacteria represented the most abundant class. Among the 76 identified genera, Dechloromonas (10.26 %), Alicycliphilus (9.15 %), Azospira (8.92 %), and Sinobacteraceae-uncultured (8.75 %) were the abundant genera. PBS, as a promising alternative carbon source, is a suitable solid carbon source and biofilm carrier for nitrate removal. PMID:26960320

  9. [Succinate dehydrogenase (SDH)-deficient renal cell carcinoma].

    PubMed

    Agaimy, A

    2016-03-01

    Succinate dehydrogenase (SDH) represents a type II mitochondrial complex related to the respiratory chain and Krebs cycle. The complex is composed of four major subunits, SDHA, SDHB, SDHC and SDHD. The oncogenic role of this enzyme complex has only recently been recognized and the complex is currently considered an important oncogenic signaling pathway with tumor suppressor properties. In addition to the familial paraganglioma syndromes (types 1-5) as prototypical SDH-related diseases, many other tumors have been defined as SDH-deficient, in particular a subset of gastrointestinal stromal tumors (GIST), rare hypophyseal adenomas, a subset of pancreatic neuroendocrine neoplasms (recently added) and a variety of other tumor entities, the latter mainly described as rare case reports. As a central core subunit responsible for the integrity of the SDH complex, the expression of SDHB is lost in all SDH-deficient neoplasms irrespective of the specific SDH subunit affected by a genetic mutation in addition to concurrent loss of the subunit specifically affected by genetic alteration. Accordingly, all SDH-deficient neoplasms are by definition SDHB-deficient. The SDH-deficient renal cell carcinoma (RCC) has only recently been well-characterized and it is included as a specific subtype of RCC in the new World Health Organization (WHO) classification published in 2016. In this review, the major clinicopathological, immunohistochemical and genetic features of this rare disease entity are presented and discussed in the context of the broad differential diagnosis. PMID:26979428

  10. 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.

  11. 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. PMID:23969233

  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. 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.

  14. Theoretical study of the decomposition of ethyl and ethyl 3-phenyl glycidate.

    PubMed

    Josa, Daniela; Peña-Gallego, Angeles; Rodríguez-Otero, Jesús; Cabaleiro-Lago, Enrique M

    2013-01-01

    The mechanism of the decomposition of ethyl and ethyl 3-phenyl glycidate in gas phase was studied by density functional theory (DFT) and MP2 methods. A proposed mechanism for the reaction indicates that the ethyl side of the ester is eliminated as ethylene through a concerted six-membered cyclic transition state, and the unstable intermediate glycidic acid decarboxylates rapidly to give the corresponding aldehyde. Two possible pathways for glycidic acid decarboxylation were studied: one via a five-membered cyclic transition state, and the other via a four-membered cyclic transition state. The results of the calculations indicate that the decarboxylation reaction occurs via a mechanism with five-membered cyclic transition state.

  15. Comparison of erythromycin versus metoclopramide for gastric feeding intolerance in patients with traumatic brain injury: A randomized double-blind study

    PubMed Central

    Makkar, Jeetinder Kaur; Gauli, Basanta; Jain, Kajal; Jain, Divya; Batra, Yatinder Kumar

    2016-01-01

    Background: No randomized controlled trial demonstrates the efficacy of erythromycin or metoclopramide in patients with traumatic brain injury (TBI). This study was conducted to determine the efficacy of metoclopramide and erythromycin for improving gastric aspirate volume (GAV) in patients with TBI. Materials and Methods: Patients with Glasgow coma score more than 5 admitted to trauma Intensive Care Unit within 72 h of head injury were assessed for eligibility. 115 patients were prospectively randomized to receive metoclopramide, erythromycin, or placebo eighth hourly. Gastric feeding intolerance was defined as GAV more than 150 ml with abdominal symptoms. Two consecutive high GAV was defined as feeding failure. Feeding failure was treated by increasing the frequency of dose to 6 hourly in metoclopramide and erythromycin group. Combination therapy with both drugs was given as rescue in the placebo group. Results: Incidence of high GAV was as high as 60.5% in placebo group. Use of erythromycin was associated with a decrease in the incidence of feeding intolerance to 28.9% (P = 0.006). Although feed intolerance decreased to 43.6% in metoclopramide group, values did not reach statistical significance. The proportion of patients not having high GAV at different days were significantly higher in erythromycin group (P = 0.027, log-rank test). There was no difference in the proportion of patients not having feeding failure in three groups with increasing number of days. Conclusion: There was a significant decrease in the incidence of high GAV with the use of erythromycin when compared to metoclopramide and placebo. PMID:27375386

  16. 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. PMID:25958619

  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. Pulse radiolysis of aqueous solutions of ethyl acrylate and hydroxy ethyl acrylate

    NASA Astrophysics Data System (ADS)

    Safrany, A.; Biro, A.; Wojnarovits, L.

    1993-10-01

    Ethyl- and hydroxy ethyl acrylate show high reactivities with hydrated electron and hydroxyl radical intermediates of water radiolysis. The electron adduct reversibly protonate with pK values of 5.7 and 7.3. The adducts may take part in irreversible protonation at the β carbon atom forming α-carboxyl alkyl radicals. Same type of radical forms in reaction of acrylates with OH: at low concentration the adduct mainly disappear in self termination reactions. Above 5 mmol dm -1 the signals showed the startup of oligomerization.

  19. Killing of Streptococcus pneumoniae by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin using drug minimum inhibitory concentrations and mutant prevention concentrations.

    PubMed

    Blondeau, J M; Shebelski, S D; Hesje, C K

    2015-06-01

    Streptococcus pneumoniae continues to be a significant respiratory pathogen, and increasing antimicrobial resistance compromises the use of β-lactam and macrolide antibiotics. Bacterial eradication impacts clinical outcome, and bacterial loads at the site of infection may fluctuate. Killing of two macrolide- and quinolone-susceptible clinical S. pneumoniae isolates by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin against varying bacterial densities was determined using the measured minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). For kill experiments, 10(6)-10(9) CFU/mL were exposed to the drug and were sampled at 0, 0.5, 1, 2, 3, 4, 6, 12 and 24 h following drug exposure. The log(10) reduction and percent reduction (kill) of viable cells was recorded. MICs and MPCs (mg/L) for azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin were 0.063-0.125/0.5-1, 0.031-0.063/0.25-0.5, 0.063/0.25-0.5, 0.008/0.016 and 0.031/0.25, respectively. Killing 10(6)-10(9) CFU/mL of bacteria by the drug MIC yielded incomplete killing, however log10 reductions occurred by 12 h and 24 h for all drugs. Exposure of 10(6)-10(9) CFU/mL to MPC drug concentrations resulted in the following log(10) reduction by 6h of drug exposure: azithromycin, 1.3-3.9; clarithromycin, 1.9-5.8; erythromycin, 0.8-4.7; telithromycin, 0.3-1.7; and gemifloxacin, 1.8-4.2. Bacterial loads at the site of infection may range from 10(6) to 10(9), and kill experiments utilising a higher bacterial inoculum provided a more accurate measure of antibiotic performance in high biomass situations. Killing was slower with telithromycin. Kill was greater and fastest with MPC versus MIC drug concentrations.

  20. Structural and functional consequences of succinate dehydrogenase subunit B mutations.

    PubMed

    Kim, E; Rath, E M; Tsang, V H M; Duff, A P; Robinson, B G; Church, W B; Benn, D E; Dwight, T; Clifton-Bligh, R J

    2015-06-01

    Mitochondrial dysfunction, due to mutations of the gene encoding succinate dehydrogenase (SDH), has been implicated in the development of adrenal phaeochromocytomas, sympathetic and parasympathetic paragangliomas, renal cell carcinomas, gastrointestinal stromal tumours and more recently pituitary tumours. Underlying mechanisms behind germline SDH subunit B (SDHB) mutations and their associated risk of disease are not clear. To investigate genotype-phenotype correlation of SDH subunit B (SDHB) variants, a homology model for human SDH was developed from a crystallographic structure. SDHB mutations were mapped, and biochemical effects of these mutations were predicted in silico. Results of structural modelling indicated that many mutations within SDHB are predicted to cause either failure of functional SDHB expression (p.Arg27*, p.Arg90*, c.88delC and c.311delAinsGG), or disruption of the electron path (p.Cys101Tyr, p.Pro197Arg and p.Arg242His). GFP-tagged WT SDHB and mutant SDHB constructs were transfected (HEK293) to determine biological outcomes of these mutants in vitro. According to in silico predictions, specific SDHB mutations resulted in impaired mitochondrial localisation and/or SDH enzymatic activity. These results indicated strong genotype-functional correlation for SDHB variants. This study reveals new insights into the effects of SDHB mutations and the power of structural modelling in predicting biological consequences. We predict that our functional assessment of SDHB mutations will serve to better define specific consequences for SDH activity as well as to provide a much needed assay to distinguish pathogenic mutations from benign variants. PMID:25972245

  1. MAPPING OF SUCCINATE DEHYDROGENASE LOSSES IN 2258 EPITHELIAL NEOPLASMS

    PubMed Central

    Miettinen, Markku; Sarlomo-Rikala, Maarit; Cue, Peter Mc.; Czapiewski, Piotr; Langfor, Renata; Waloszczyk, Piotr; Wazny, Krzysztof; Biernat, Wojciech; Lasota, Jerzy; Wang, Zengfeng

    2013-01-01

    Losses in the succinate dehydrogenase (SDH) complex characterize 20–30% of extra-adrenal paragangliomas and 7–8% of gastric GISTs, and rare renal cell carcinomas. This loss is reflected as lack of the normally ubiquitous immunohistochemical expression of the SDH subunit B (SDHB). In paragangliomas, SDHB loss correlates with homozygous loss of any of the SDH subunits, typically by loss-of-function mutations. The occurrence of SDHB losses in other epithelial malignancies is unknown. In this study, we immunohistochemically examined 2258 epithelial, mostly malignant neoplasms including common carcinomas of all sites. Among renal cell carcinomas, SDHB loss was observed in 4 of 711 cases (0.6%) including a patient with an SDHB-deficient GIST. Histologically the SDHB-negative renal carcinomas varied. There was one clear cell carcinoma with a high nuclear grade, one papillary carcinoma type 2, one unclassified carcinoma with a glandular pattern, and one oncocytoid low-grade carcinoma as previously described for SDHB-negative renal carcinoma. None of these patients was known to have paragangliomas or had loss of SDHA expression in the tumor. Three of these patients had metastases at presentation (2 in the adrenal, one in the retroperitoneal lymph nodes). There were no cases with SDHB-loss among 64 renal oncocytomas. SDHB-losses were not seen in other carcinomas, except in one prostatic adenocarcinoma (1/57), one lymphoepithelial carcinoma of the stomach, and one (1/40) seminoma. Based on this study, SDHB-losses occur in 0.6% of renal cell carcinomas and extremely rarely in other carcinomas. Some of these renal carcinomas may be clinically aggressive. The clinical significance and molecular genetics of these SDHB-negative tumors requires further study. PMID:23531856

  2. ICESp1116, the genetic element responsible for erm(B)-mediated, inducible resistance to erythromycin in Streptococcus pyogenes.

    PubMed

    Brenciani, Andrea; Tiberi, Erika; Morici, Eleonora; Oryasin, Erman; Giovanetti, Eleonora; Varaldo, Pietro E

    2012-12-01

    ICESp1116, responsible for erm(B)-mediated, inducible erythromycin resistance in Streptococcus pyogenes, was comprehensively characterized, and its chromosomal integration site was determined. It displayed a unique mosaic organization consisting of a scaffold, related to TnGallo1 from Streptococcus gallolyticus, with two inserted fragments separated by IS1216. One fragment, containing erm(B), displayed high-level identity to a portion of the S. pyogenes plasmid pSM19035; the other, containing a truncated tet(M) gene, displayed high-level identity to the right-hand portion of Clostridium difficile Tn5397.

  3. FDA Approved Registration of Erythromycin for Treatment of Bacterial Kidney Disease (BKD) in Juvenile and Adult Chinook Salmon : Annual Report, Reporting Period March 10, 1989 to March 9, 1990.

    SciTech Connect

    Moffitt, Christine A.

    1991-04-01

    Erythromycin is a therapeutic substance useful against bacterial kidney disease in salmon. In 1989 we began a multi year project to learn more about erythromycin applied to juvenile and adult salmon, with the goal of achieving registration of erythromycin with the US Food and Drug Administration. To begin the study, we studied the pharmacokinetics of erythromycin administered to both adult and juvenile chinook salmon. We monitored blood plasmas time curves from individual adult fish injected with two forms of injectable erythromycin using one of three routes of administration. In addition, we began experiments to evaluate hatchery applications of erythromycin to individually marked adult salmon, and we recovered blood tissues from these fish at the time of spawning. To determine how to use erythromycin in juvenile salmon, we evaluated the adsorption and elimination of erythromycin applied arterially and orally to individual juvenile fish. In feeding trials we determined the palatability to juvenile chinook salmon of feed made with one of two different carriers for erythromycin thiocyanate. 35 refs., 4 figs. , 3 tabs.

  4. Effects of methylmalonyl-CoA mutase gene knockouts on erythromycin production in carbohydrate-based and oil-based fermentations of Saccharopolyspora erythraea.

    PubMed

    Reeves, Andrew R; Brikun, Igor A; Cernota, William H; Leach, Benjamin I; Gonzalez, Melissa C; Weber, J Mark

    2006-07-01

    In carbohydrate-based fermentations of Saccharopolyspora erythraea, a polar knockout of the methylmalonyl-CoA mutase (MCM) gene, mutB, improved erythromycin production an average of 126% (within the range of 102-153% for a 0.95 confidence interval). In oil-based fermentations, where erythromycin production by the wild-type strain averages 184% higher (141-236%, 0.95 CI) than in carbohydrate-based fermentations, the same polar knockout in mutB surprisingly reduced erythromycin production by 66% (53-76%, 0.95 CI). A metabolic model is proposed where in carbohydrate-based fermentations MCM acts as a drain on the methylmalonyl-CoA metabolite pool, and in oil-based fermentations, MCM acts in the reverse direction to fill the methylmalonyl-CoA pool. Therefore, the model explains, in part, how the well-known oil-based process improvement for erythromycin production operates at the biochemical level; furthermore, it illustrates how the mutB erythromycin strain improvement mutation operates at the genetic level in carbohydrate-based fermentations.

  5. Significance of CO2 donor on the production of succinic acid by Actinobacillus succinogenes ATCC 55618

    PubMed Central

    2011-01-01

    Background Succinic acid is a building-block chemical which could be used as the precursor of many industrial products. The dissolved CO2 concentration in the fermentation broth could strongly regulate the metabolic flux of carbon and the activity of phosphoenolpyruvate (PEP) carboxykinase, which are the important committed steps for the biosynthesis of succinic acid by Actinobacillus succinogenes. Previous reports showed that succinic acid production could be promoted by regulating the supply of CO2 donor in the fermentation broth. Therefore, the effects of dissolved CO2 concentration and MgCO3 on the fermentation process should be investigated. In this article, we studied the impacts of gaseous CO2 partial pressure, dissolved CO2 concentration, and the addition amount of MgCO3 on succinic acid production by Actinobacillus succinogenes ATCC 55618. We also demonstrated that gaseous CO2 could be removed when MgCO3 was fully supplied. Results An effective CO2 quantitative mathematical model was developed to calculate the dissolved CO2 concentration in the fermentation broth. The highest succinic acid production of 61.92 g/L was obtained at 159.22 mM dissolved CO2 concentration, which was supplied by 40 g/L MgCO3 at the CO2 partial pressure of 101.33 kPa. When MgCO3 was used as the only CO2 donor, a maximal succinic acid production of 56.1 g/L was obtained, which was just decreased by 7.03% compared with that obtained under the supply of gaseous CO2 and MgCO3. Conclusions Besides the high dissolved CO2 concentration, the excessive addition of MgCO3 was beneficial to promote the succinic acid synthesis. This was the first report investigating the replaceable of gaseous CO2 in the fermentation of succinic acid. The results obtained in this study may be useful for reducing the cost of succinic acid fermentation process. PMID:22040346

  6. Optimization of ethyl ester production assisted by ultrasonic irradiation.

    PubMed

    Noipin, K; Kumar, S

    2015-01-01

    This study presents the optimization of the continuous flow potassium hydroxide-catalyzed synthesis of ethyl ester from palm oil with ultrasonic assistance. The process was optimized by application of factorial design and response surface methodology. The independent variables considered were ethanol to oil molar ratio, catalyst concentration, reaction temperature and ultrasonic amplitude; and the response was ethyl ester yield. The results show that ethanol to oil molar ratio, catalyst concentration, and ultrasonic amplitude have positive effect on ethyl ester yield, whereas reaction temperature has negative influence on ethyl ester yield. Second-order models were developed to predict the responses analyzed as a function of these three variables, and the developed models predicts the results in the experimental ranges studied adequately. This study shows that ultrasonic irradiation improved the ethyl ester production process to achieve ethyl ester yields above 92%. PMID:25116594

  7. The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy

    PubMed Central

    Hu, Liang; Feng, Yu; Wang, Song; Zhang, Wei-yan; Yin, Ning; Mo, Xu-Ming

    2016-01-01

    Background Pulmonary arterial hypertension is characterized by increased pressure overload that leads to right ventricular hypertrophy (RVH). GPR91 is a formerly orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate; however, its role in RVH remains unknown. Methods and Results We investigated the role of succinate-GPR91 signaling in a pulmonary arterial banding (PAB) model of RVH induced by pressure overload in SD rats. GPR91 was shown to be located in cardiomyocytes. In the sham and PAB rats, succinate treatment further aggravated RVH, up-regulated RVH-associated genes and increased p-Akt/t-Akt levels in vivo. In vitro, succinate treatment up-regulated the levels of the hypertrophic gene marker anp and p-Akt/t-Akt in cardiomyocytes. All these effects were inhibited by the PI3K antagonist wortmannin both in vivo and in vitro. Finally, we noted that the GPR91-PI3K/Akt axis was also up-regulated compared to that in human RVH. Conclusions Our findings indicate that succinate-GPR91 signaling may be involved in RVH via PI3K/Akt signaling in vivo and in vitro. Therefore, GPR91 may be a novel therapeutic target for treating pressure overload-induced RVH. PMID:26824665

  8. Succinate-dependent energy generation and pyruvate dehydrogenase complex activity in isolated Ascaris suum mitochondria

    SciTech Connect

    Campbell, T.A.

    1988-01-01

    Body wall muscle from the parasitic nematode, Ascaris suum, contain unique anaerobic mitochondria that preferentially utilize fumarate and branched-chain enoyl CoA's as terminal electron acceptors instead of oxygen. While electron transport in these organelles is well characterized, the role of oxygen in succinate-dependent phosphorylation is still not clearly defined. Therefore, the present study was designed to more fully characterize succinate metabolism in these organelles as well as the in vitro regulation of a key mitochondrial enzyme, the pyruvate dehydrogenase complex (PDC). In the absence of added adenine nucleotides, incubations in succinate resulted in substantial elevations in intramitochrondrial ATP levels, but ATP/ADP ratios were considerably higher in incubations with malate. The stimulation of phosphorylation in aerobic incubations with succinate was rotenone sensitive and appears to be Site I dependent. Increase substrate level phosphorylation, coupled to propionate formation, or additional sites of electron-transport associated ATP synthesis were not significant. Under aerobic conditions, {sup 14}CO{sub 2} evolution from 1,4-({sup 14}C)succinate was stimulated and NADH/NAD{sup +} ratios were elevated, but the formation of {sup 14}C propionate was unchanged.

  9. Doxofylline and methylprednisolone sodium succinate are stable and compatible under normal injection conditions.

    PubMed

    Xu, Fan; Feng, Enfu; Su, Li; Xu, Guili

    2013-03-01

    To assess the physical compatibility and chemical stability of doxofylline with methylprednisolone sodium succinate in 0.9% sodium chloride or 5% dextrose injection for intravenous infusion. Twenty mL doxofylline solution (0.74 mg/mL) and 1 mL methylprednisolone sodium succinate solution (0.15 mg/mL) were added into 250 mL polyolefin bags containing 5% dextrose injection or 0.9% sodium chloride injection, and stored for 24 h at 20-25(°)C. Chemical compatibility was measured with high-performance liquid chromatography (HPLC), and physical compatibility was determined visually. The results showed that samples were clear and colorless when viewed in normal fluorescent room light. The pH value exhibited little change. The particulate content of > 25 μm was low and within the specification limit. The particulate content of > 10 μm decreased over time and was similar to the control solution. Analysis of chemical stability revealed that doxofylline is stable with methylprednisolone sodium succinate for up to 24 h, and the degradation of methylprednisolone sodium succinate is unrelated to doxofylline, but is closely related to the pH value of the solution. Doxofylline and methylprednisolone sodium succinate did not affect the stability of each other. PMID:23455194

  10. A novel process for recovery of fermentation-derived succinic acid: process design and economic analysis.

    PubMed

    Orjuela, Alvaro; Orjuela, Andrea; Lira, Carl T; Miller, Dennis J

    2013-07-01

    Recovery and purification of organic acids produced in fermentation constitutes a significant fraction of total production cost. In this paper, the design and economic analysis of a process to recover succinic acid (SA) via dissolution and acidification of succinate salts in ethanol, followed by reactive distillation to form succinate esters, is presented. Process simulation was performed for a range of plant capacities (13-55 million kg/yr SA) and SA fermentation titers (50-100 kg/m(3)). Economics were evaluated for a recovery system installed within an existing fermentation facility producing succinate salts at a cost of $0.66/kg SA. For a SA processing capacity of 54.9 million kg/yr and a titer of 100 kg/m(3) SA, the model predicts a capital investment of $75 million and a net processing cost of $1.85 per kg SA. Required selling price of diethyl succinate for a 30% annual return on investment is $1.57 per kg.

  11. Triggering the succinate receptor GPR91 enhances pressure overload-induced right ventricular hypertrophy

    PubMed Central

    Yang, Lei; Yu, Di; Fan, Huan-Huan; Feng, Yu; Hu, Liang; Zhang, Wei-Yan; Zhou, Kai; Mo, Xu-Ming

    2014-01-01

    Background: Pulmonary arterial hypertension (PAH) leads to pressure overload in the right ventricle (RV) and induces right ventricular hypertrophy (RVH). GPR91 is an orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate, which increases in RVH; however, its role remains unknown. Methods and results: We studied succinate-GPR91 signaling in a pulmonary arterial banding (PAB) model of RVH in the SD rats due to pressure overload. We report that GPR91 was located in cardiomyocytes. We found that the expressions of GPR91 and p-Akt in the RV significantly increased in the PAB model compared with the sham. In the PAB rats, the treatment of succinate further increased the p-Akt levels and aggravated RVH in vivo. In in vitro studies, succinate stimulated the up-regulation of the hypertrophic gene marker anp. All these effects were inhibited by the antagonist of PI3K, wortmannin, both in vivo and in vitro. Finally, we found that the GPR91-PI3K/Akt axis was also up-regulated compared with the sham in human RVH. Conclusions: Our results suggest that succinate-GPR91 is involved in RVH via PI3K/Akt signaling in vivo and in vitro. GPR91 may be a novel therapeutic target for RVH induced by pressure overload. PMID:25337184

  12. Synthesis and Monolayer Behaviors of Succinic Acid-Type Gemini Surfactants Containing Semifluoroalkyl Groups.

    PubMed

    Kawase, Tokuzo; Nagase, Youhei; Oida, Tatsuo

    2016-01-01

    In this work, novel succinic acid-type gemini surfactants containing semifluoroalkyl groups, dl- and meso-2,3-bis[Rf-(CH2)n]-succinic acids (Rf = C4F9, C6F13, C8F17; n = 2, 9), were successfully synthesized, and the effects of Rf, methylene chain length (n), and stereochemistry on their monolayer behaviors were studied. Critical micelle concentrations (CMC) of dl- and meso-2,3-bis[C4F9(CH2)9]-succinic acids were one order of magnitude smaller than that of the corresponding 1+1 type surfactant, C4F9(CH2)9COOH. From surface pressure-area (π-A) measurements, the lift-off areas of the geminis were found to decrease in the order C4F9 ≥ C6F13 > C8F17, regardless of methylene chain length and stereochemistry. The zero-pressure molecular areas of the geminis were twice those of the corresponding 1+1 type surfactants. Based on Gibbs compression modulus analysis, it was clarified that 2,3-bis[C8F17(CH2)n]-succinic gemini with short methylene chains (n = 2) would form more rigid monolayers than those having long methylene chains (n = 9). Unlike for 2,3-bis(alkyl)-succinic acids, the effects of stereochemistry on the monolayer behavior of semifluoroalkylated geminis were small.

  13. Pretreatment of spent sulphite liquor via ultrafiltration and nanofiltration for bio-based succinic acid production.

    PubMed

    Pateraki, Chrysanthi; Ladakis, Dimitrios; Stragier, Lutgart; Verstraete, Willy; Kookos, Ioannis; Papanikolaou, Seraphim; Koutinas, Apostolis

    2016-09-10

    Ultrafiltration and nanofiltration of spent sulphite liquor (SSL) has been employed to evaluate the simultaneous production of lignosulphonates and bio-based succinic acid using the bacterial strains Actinobacillus succinogenes and Basfia succiniciproducens. Ultrafiltration with membranes of 10, 5 and 3kDa molecular weight cut-off results in significant losses of lignosulphonates (26-50%) in the permeate stream, while nanofiltration using membrane with 500Da molecular weight cut-off results in high retention yields of lignosulphonates (95.6%) in the retentate stream. Fed-batch bioreactor cultures using permeates from ultrafiltrated SSL resulted in similar succinic acid concentration (27.5g/L) and productivity (0.4g/L/h) by both strains. When permeates from nanofiltrated SSL were used, the strain B. succiniciproducens showed the highest succinic acid concentration (33.8g/L), yield (0.58g per g of consumed sugars) and productivity (0.48g/L/h). The nanofiltration of 1t of thick spent sulphite liquor could lead to the production of 306.3kg of lignosulphonates and 52.7kg of succinic acid, whereas the ultrafiltration of 1t of thick spent sulphite liquor using a 3kDa membrane could result in the production of 237kg of lignosulphonates and 71.8kg of succinic acid when B. succiniproducens is used in both cases. PMID:27374402

  14. Synthesis and Monolayer Behaviors of Succinic Acid-Type Gemini Surfactants Containing Semifluoroalkyl Groups.

    PubMed

    Kawase, Tokuzo; Nagase, Youhei; Oida, Tatsuo

    2016-01-01

    In this work, novel succinic acid-type gemini surfactants containing semifluoroalkyl groups, dl- and meso-2,3-bis[Rf-(CH2)n]-succinic acids (Rf = C4F9, C6F13, C8F17; n = 2, 9), were successfully synthesized, and the effects of Rf, methylene chain length (n), and stereochemistry on their monolayer behaviors were studied. Critical micelle concentrations (CMC) of dl- and meso-2,3-bis[C4F9(CH2)9]-succinic acids were one order of magnitude smaller than that of the corresponding 1+1 type surfactant, C4F9(CH2)9COOH. From surface pressure-area (π-A) measurements, the lift-off areas of the geminis were found to decrease in the order C4F9 ≥ C6F13 > C8F17, regardless of methylene chain length and stereochemistry. The zero-pressure molecular areas of the geminis were twice those of the corresponding 1+1 type surfactants. Based on Gibbs compression modulus analysis, it was clarified that 2,3-bis[C8F17(CH2)n]-succinic gemini with short methylene chains (n = 2) would form more rigid monolayers than those having long methylene chains (n = 9). Unlike for 2,3-bis(alkyl)-succinic acids, the effects of stereochemistry on the monolayer behavior of semifluoroalkylated geminis were small. PMID:26743669

  15. Ionic liquid pretreatment to increase succinic acid production from lignocellulosic biomass.

    PubMed

    Wang, Caixia; Yan, Daojiang; Li, Qiang; Sun, Wei; Xing, Jianmin

    2014-11-01

    In this study, pinewood and corn stover pretreated with the ionic liquid (IL) 1-allyl-3-methylimidazolium chloride (AmimCl) were used as a feedstock for succinic acid production. Results reveal that 5% (v/v) AmimCl inhibited bacterial growth, whereas 0.01% (v/v) AmimCl inhibited succinic acid production. AmimCl was effective in extracting cellulose from pinewood and in degrading pinewood into a uniform pulp, as revealed by scanning electron microscopy (SEM). The rate of enzymatic hydrolysis of pinewood extract reached 72.16%. The combinations of AmimCl pretreatment with steam explosion or with hot compressed water were effective in treating corn stover, whereas AmimCl treatment alone did not result in a significant improvement. Pinewood extract produced 20.7g/L succinic acid with an average yield of 0.37g per gram of biomass. Workflow calculations indicated pine wood pretreated with IL has a theoretical yield of succinic acid of 57.1%. IL pretreatment led to increase in succinic acid yields.

  16. 21 CFR 172.872 - Methyl ethyl cellulose.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Methyl ethyl cellulose. 172.872 Section 172.872... CONSUMPTION Multipurpose Additives § 172.872 Methyl ethyl cellulose. The food additive methyl ethyl cellulose... a cellulose ether having the general formula [C6H(10 -x-y)O5(CH3)x(C2H5)y]n, where x is the...

  17. 21 CFR 172.872 - Methyl ethyl cellulose.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Methyl ethyl cellulose. 172.872 Section 172.872... CONSUMPTION Multipurpose Additives § 172.872 Methyl ethyl cellulose. The food additive methyl ethyl cellulose... a cellulose ether having the general formula [C6H(10 -x-y)O5(CH3)x(C2H5)y]n, where x is the...

  18. 21 CFR 172.872 - Methyl ethyl cellulose.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Methyl ethyl cellulose. 172.872 Section 172.872... CONSUMPTION Multipurpose Additives § 172.872 Methyl ethyl cellulose. The food additive methyl ethyl cellulose... a cellulose ether having the general formula [C6H(10 -x-y)O5(CH3)x(C2H5)y]n, where x is the...

  19. Ethyl Lithiodiazoacetate: Extremely Unstable Intermediate Handled Efficiently in Flow.

    PubMed

    Müller, Simon T R; Hokamp, Tobias; Ehrmann, Svenja; Hellier, Paul; Wirth, Thomas

    2016-08-16

    Ethyl diazoacetate (EDA) is one of the most prominent diazo reagents. It is frequently used in metal-carbene-type reactions. However, EDA can also be used as a nucleophile under base catalysis. Whilst the addition of EDA to aldehydes can be performed using organic bases, the addition of EDA to other carbonyl electrophiles requires the use of organometallics such as lithium diisopropylamide (LDA). The generated ethyl lithiodiazoacetate is highly reactive and decomposes rapidly, even at low temperatures. Herein, we report a continuous flow protocol that overcomes the problems associated with the instantaneous decomposition of ethyl lithiodiazoacetate. The addition of ethyl lithiodiazoacetate to ketones provides direct access to tertiary diazoalcohols in good yields.

  20. Testing for ethanol markers in hair: discrepancies after simultaneous quantification of ethyl glucuronide and fatty acid ethyl esters.

    PubMed

    Kintz, P; Nicholson, D

    2014-10-01

    The hair of 97 cases were analysed for ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE, including ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate) according to the Society of Hair Testing guidelines to examine the role of both tests in documenting chronic excessive alcohol drinking, particularly when the results are in contradiction. 27 (27.8%) results were EtG negative and FAEE positive, when applying the SoHT cut-offs, probably due to the use of alcohol-containing hair products. Four cases (4.1%) were EtG positive and FAEE negative that were attributed to the use of herbal lotions containing EtG. PMID:24794020

  1. Performance of anaerobic sequencing batch reactor in the treatment of pharmaceutical wastewater containing erythromycin and sulfamethoxazole mixture.

    PubMed

    Aydin, S; Ince, B; Cetecioglu, Z; Ozbayram, E G; Shahi, A; Okay, O; Arikan, O; Ince, O

    2014-01-01

    This study evaluates the joint effects of erythromycin-sulfamethoxazole (ES) combinations on anaerobic treatment efficiency and the potential for antibiotic degradation during anaerobic sequencing batch reactor operation. The experiments involved two identical anaerobic sequencing batch reactors. One reactor, as control unit, was fed with synthetic wastewater while the other reactor (ES) was fed with a synthetic substrate mixture including ES antibiotic combinations. The influence of ES antibiotic mixtures on chemical oxygen demand (COD) removal, volatile fatty acid production, antibiotic degradation, biogas production, and composition were investigated. The influent antibiotic concentration was gradually increased over 10 stages, until the metabolic collapse of the reactors, which occurred at 360 days for the ES reactor. The results suggest that substrate/COD utilization and biogas/methane generation affect performance of the anaerobic reactors at higher concentration. In addition, an average of 40% erythromycin and 37% sulfamethoxazole reduction was achieved in the ES reactor. These results indicated that these antibiotics were partly biodegradable in the anaerobic reactor system.

  2. Risk assessment of chlortetracycline, oxytetracycline, sulfamethazine, sulfathiazole, and erythromycin in aquatic environment: are the current environmental concentrations safe?

    PubMed

    Ji, Kyunghee; Kim, Sunmi; Han, Sunyoung; Seo, Jihyun; Lee, Sangwoo; Park, Yoonsuk; Choi, Kyunghee; Kho, Young-Lim; Kim, Pan-Gyi; Park, Jeongim; Choi, Kyungho

    2012-10-01

    To understand potential risks of major pharmaceutical residues in waters, we evaluated ecotoxicities of five major veterinary pharmaceuticals, i.e., chlortetracycline, oxytetracycline, sulfamethazine, sulfathiazole, and erythromycin, which have been frequently detected in freshwater environment worldwide. We conducted acute and chronic toxicity tests using two freshwater invertebrates (Daphnia magna and Moina macrocopa) and a fish (Oryzias latipes). In general, D. magna exhibited greater sensitivity than M. macrocopa, and chronic reproduction was the most sensitive endpoints for both organisms. The population growth rate was adversely influenced by exposure to chlortetracycline, sulfamethazine, or sulfathiazole in water fleas, but reduction in population size was not expected. In O. latipes, the tested pharmaceuticals affected several reproduction related endpoints including time to hatch and growth. Based on the toxicity values from the present study and literature, algae appeared to be the most sensitive organism, followed by Daphnia and fish. Hazard quotients derived from measured environmental concentrations (MECs) and predicted no effect concentrations (PNECs) for erythromycin and oxytetracycline exceeded unity, suggesting that potential ecological effects at highly contaminated sites cannot be ruled out. Long-term consequences of veterinary pharmaceutical contamination in the environment deserve further investigation. PMID:22711548

  3. Risk assessment of chlortetracycline, oxytetracycline, sulfamethazine, sulfathiazole, and erythromycin in aquatic environment: are the current environmental concentrations safe?

    PubMed

    Ji, Kyunghee; Kim, Sunmi; Han, Sunyoung; Seo, Jihyun; Lee, Sangwoo; Park, Yoonsuk; Choi, Kyunghee; Kho, Young-Lim; Kim, Pan-Gyi; Park, Jeongim; Choi, Kyungho

    2012-10-01

    To understand potential risks of major pharmaceutical residues in waters, we evaluated ecotoxicities of five major veterinary pharmaceuticals, i.e., chlortetracycline, oxytetracycline, sulfamethazine, sulfathiazole, and erythromycin, which have been frequently detected in freshwater environment worldwide. We conducted acute and chronic toxicity tests using two freshwater invertebrates (Daphnia magna and Moina macrocopa) and a fish (Oryzias latipes). In general, D. magna exhibited greater sensitivity than M. macrocopa, and chronic reproduction was the most sensitive endpoints for both organisms. The population growth rate was adversely influenced by exposure to chlortetracycline, sulfamethazine, or sulfathiazole in water fleas, but reduction in population size was not expected. In O. latipes, the tested pharmaceuticals affected several reproduction related endpoints including time to hatch and growth. Based on the toxicity values from the present study and literature, algae appeared to be the most sensitive organism, followed by Daphnia and fish. Hazard quotients derived from measured environmental concentrations (MECs) and predicted no effect concentrations (PNECs) for erythromycin and oxytetracycline exceeded unity, suggesting that potential ecological effects at highly contaminated sites cannot be ruled out. Long-term consequences of veterinary pharmaceutical contamination in the environment deserve further investigation.

  4. Real-time fluid dynamics investigation and physiological response for erythromycin fermentation scale-up from 50 L to 132 m3 fermenter.

    PubMed

    Zou, Xiang; Xia, Jian-ye; Chu, Ju; Zhuang, Ying-ping; Zhang, Si-liang

    2012-06-01

    The physiological response of erythromycin fermentation scale-up from 50 L to 132 m(3) scale was investigated. A relatively high oxygen uptake rate (OUR) in early phase of fermentation was beneficial for erythromycin biosynthesis. Correspondingly, the maximal consistency coefficient (K) reflecting non-Newtonian fluid characteristics in 50 L and 132 m(3) fermenter also appeared in same phase. Fluid dynamics in different scale bioreactor was further investigated by real-time computational fluid dynamics modeling. The results of simulation showed that the impeller combination in 50 L fermenter could provide more modest flow field environment compared with that in 132 m(3) fermenter. The decrease of oxygen transfer rate (OTR) in 132 m(3) fermenter was the main cause for impairing cell physiological metabolism and erythromycin biosynthesis. These results were helpful for understanding the relationship between hydrodynamic environment and physiological response of cells in bioreactor during the scale-up of fermentation process. PMID:22139481

  5. Solid/liquid phase diagram of the ammonium sulfate/succinic acid/water system.

    PubMed

    Pearson, Christian S; Beyer, Keith D

    2015-05-14

    We have studied the low-temperature phase diagram and water activities of the ammonium sulfate/succinic acid/water system using differential scanning calorimetry and infrared spectroscopy of thin films. Using the results from our experiments, we have mapped the solid/liquid ternary phase diagram, determined the water activities based on the freezing point depression, and determined the ice/succinic acid phase boundary as well as the ternary eutectic composition and temperature. We also compared our results to the predictions of the extended AIM aerosol thermodynamics model (E-AIM) and found good agreement for the ice melting points in the ice primary phase field of this system; however, differences were found with respect to succinic acid solubility temperatures. We also compared the results of this study with those of previous studies that we have published on ammonium sulfate/dicarboxylic acid/water systems. PMID:25431860

  6. α-Tocopheryl Succinate Affects Malignant Cell Viability, Proliferation, and Differentiation.

    PubMed

    Savitskaya, M A; Onischenko, G E

    2016-08-01

    The widespread occurrence of malignant tumors motivates great attention to finding and investigating effective new antitumor preparations. Such preparations include compounds of the vitamin E family. Among them, α-tocopheryl succinate (vitamin E succinate (VES)) has the most pronounced antitumor properties. In this review, various targets and mechanisms of the antitumor effect of vitamin E succinate are characterized. It has been shown that VES has multiple intracellular targets and effects, and as a result VES is able to induce apoptosis in tumor cells, inhibit their proliferation, induce differentiation, prevent metastasizing, and inhibit angiogenesis. However, VES has minimal effects on normal cells and tissues. Due to the variety of targets and selectivity of action, VES is a promising agent against malignant neoplasms. More detailed studies in this area can contribute to development of effective and safe chemotherapeutic preparations.

  7. α-Tocopheryl Succinate Affects Malignant Cell Viability, Proliferation, and Differentiation.

    PubMed

    Savitskaya, M A; Onischenko, G E

    2016-08-01

    The widespread occurrence of malignant tumors motivates great attention to finding and investigating effective new antitumor preparations. Such preparations include compounds of the vitamin E family. Among them, α-tocopheryl succinate (vitamin E succinate (VES)) has the most pronounced antitumor properties. In this review, various targets and mechanisms of the antitumor effect of vitamin E succinate are characterized. It has been shown that VES has multiple intracellular targets and effects, and as a result VES is able to induce apoptosis in tumor cells, inhibit their proliferation, induce differentiation, prevent metastasizing, and inhibit angiogenesis. However, VES has minimal effects on normal cells and tissues. Due to the variety of targets and selectivity of action, VES is a promising agent against malignant neoplasms. More detailed studies in this area can contribute to development of effective and safe chemotherapeutic preparations. PMID:27677550

  8. dl-. cap alpha. -tocopheryl succinate enhances the effect of. gamma. -irradiation on neuroblastoma cells in culture

    SciTech Connect

    Sarri, A.; Prasad, K.N.

    1984-01-01

    The effect of dl-..cap alpha..-tocopheryl (vitamin E) succinate in modifying the radiation response of mouse neuroblastoma (NBP/sub 2/) and mouse fibroblast (L-cells) cells in culture was studied on the criterion of growth inhibition (due to cell death and inhibition of cell division). Results show that vitamin E succinate markedly enhanced the effect of /sub 60/CO-..gamma..-irradiation on NB cells, but it did not significantly modify the effect of irradiation on mouse fibroblasts. Sodium succinate plus ethanol (0.25% final concentration) did not modify the radiation response of NB cells or fibroblasts. Butylated hydroxyanisole, a lipid soluble antioxidant, also enhanced the effect of irradiation on NB cells, indicating that the effect of vitamin E in modifying the radiation response may be mediated, in part, by antioxidation mechanisms.

  9. Crystallization and immersion freezing ability of oxalic and succinic acid in multicomponent aqueous organic aerosol particles

    NASA Astrophysics Data System (ADS)

    Wagner, Robert; Höhler, Kristina; Möhler, Ottmar; Saathoff, Harald; Schnaiter, Martin

    2015-04-01

    This study reports on heterogeneous ice nucleation efficiency of immersed oxalic and succinic acid crystals in the temperature range from 245 to 215 K, as investigated with expansion cooling experiments using suspended particles. In contrast to previous laboratory work with emulsified solution droplets where the precipitation of solid inclusions required a preceding freezing/evaporation cycle, we show that immersed solids readily form by homogeneous crystallization within aqueous solution droplets of multicomponent organic mixtures, which have noneutonic compositions with an excess of oxalic or succinic acid. Whereas succinic acid crystals did not act as heterogeneous ice nuclei, immersion freezing by oxalic acid dihydrate crystals led to a reduction of the ice saturation ratio at freezing onset by 0.066-0.072 compared to homogeneous freezing, which is by a factor of 2 higher than previously reported laboratory data. These observations emphasize the importance of oxalic acid in heterogeneous ice nucleation.

  10. Profile of microflora of the posterior intestine of Chinook salmon before, during, and after administration of rations with and without erythromycin

    USGS Publications Warehouse

    Moffitt, C.M.; Mobin, S.M.A.

    2006-01-01

    We describe the resident heterotrophic aerobic microflora of the salmonid posterior intestine before, during, and after the administration of rations with erythromycin in a hatchery raceway environment. We compare the profiles of medicated Chinook salmon Oncorhynchus tshawytscha with those of control fish that were not fed erythromycin. The combined counts of bacteria and yeasts per gram of fish intestine originating from four upstream raceways ranged from 3.0 ?? 102 to 9.6 ?? 105 colony-forming units (CFU) over the study period. Yeasts were commonly identified in the gut, and abundances ranged from 0% to more than 80% of the CFU. Erythromycin therapy decreased the total microbial population and altered the bacterial diversity in the gut during treatment. The intestinal microbial populations in fish medicated with erythromycin increased rapidly after treatment ceased, and by 25 d after treatment the CFU were similar in samples from both medicated and control fish populations. Of 325 isolates from fish selected for biochemical profiles, we identified a total of eight gram-positive and eight gram-negative genera. Bacillus spp. were common throughout sampling and were identified in samples of fish feed. Erythromycin-resistant, gram-positive bacteria were observed throughout the sampling in medicated and control fish. We identified seven gram-positive and two gram-negative genera in 74 selected isolates from control and erythromycin feeds. Our studies suggest that the aerobic microflora of the posterior intestine varies over time, and it is likely that few resistant genera of concern to human health are present.

  11. Acetate:succinate CoA-transferase in the hydrogenosomes of Trichomonas vaginalis: identification and characterization.

    PubMed

    van Grinsven, Koen W A; Rosnowsky, Silke; van Weelden, Susanne W H; Pütz, Simone; van der Giezen, Mark; Martin, William; van Hellemond, Jaap J; Tielens, Aloysius G M; Henze, Katrin

    2008-01-18

    Acetate:succinate CoA-transferases (ASCT) are acetate-producing enzymes in hydrogenosomes, anaerobically functioning mitochondria and in the aerobically functioning mitochondria of trypanosomatids. Although acetate is produced in the hydrogenosomes of a number of anaerobic microbial eukaryotes such as Trichomonas vaginalis, no acetate producing enzyme has ever been identified in these organelles. Acetate production is the last unidentified enzymatic reaction of hydrogenosomal carbohydrate metabolism. We identified a gene encoding an enzyme for acetate production in the genome of the hydrogenosome-containing protozoan parasite T. vaginalis. This gene shows high similarity to Saccharomyces cerevisiae acetyl-CoA hydrolase and Clostridium kluyveri succinyl-CoA:CoA-transferase. Here we demonstrate that this protein is expressed and is present in the hydrogenosomes where it functions as the T. vaginalis acetate:succinate CoA-transferase (TvASCT). Heterologous expression of TvASCT in CHO cells resulted in the expression of an active ASCT. Furthermore, homologous overexpression of the TvASCT gene in T. vaginalis resulted in an equivalent increase in ASCT activity. It was shown that the CoA transferase activity is succinate-dependent. These results demonstrate that this acetyl-CoA hydrolase/transferase homolog functions as the hydrogenosomal ASCT of T. vaginalis. This is the first hydrogenosomal acetate-producing enzyme to be identified. Interestingly, TvASCT does not share any similarity with the mitochondrial ASCT from Trypanosoma brucei, the only other eukaryotic succinate-dependent acetyl-CoA-transferase identified so far. The trichomonad enzyme clearly belongs to a distinct class of acetate:succinate CoA-transferases. Apparently, two completely different enzymes for succinate-dependent acetate production have evolved independently in ATP-generating organelles. PMID:18024431

  12. A lipid membrane intercalating conjugated oligoelectrolyte enables electrode driven succinate production in Shewanella

    SciTech Connect

    Thomas, AW; Garner, LE; Nevin, KP; Woodard, TL; Franks, AE; Lovley, DR; Sumner, JJ; Sund, CJ; Bazan, GC

    2013-06-01

    An amphiphilic conjugated oligoelectrolyte (COE) that spontaneously intercalates into lipid membranes enables Shewanella oneidensis to use a graphite electrode as the sole electron donor for succinate production. Current consumed in a poised electrochemical system by Shewanella with micromolar concentrations of COE correlates well with the succinate produced via fumarate reduction as determined by HPLC analysis. Confocal microscopy confirms incorporation of the COE into the microbes on the electrode surface. This work presents a unique strategy to induce favorable bio-electronic interactions for the production of reduced microbial metabolites.

  13. Indications for /sup 99m/technetium dimercapto-succinic acid scan in children

    SciTech Connect

    Gordon, I.

    1987-03-01

    The /sup 99m/technetium dimercapto-succinic acid scan provides an image of functional renal parenchyma. This static scan has specific indications and cannot be used simply in place of a /sup 99m/technetium diethylenetriaminepentaacetic acid scan. The major clinical indications for this investigation are the detection and/or evaluation of a renal scar, the small or absent kidney, an occult duplex system, certain renal masses, systemic hypertension or suspected vasculitis. The physiology of the /sup 99m/technetium dimercapto-succinic acid scan is reviewed briefly.

  14. Poly(butylene succinate) and its copolymers: research, development and industrialization.

    PubMed

    Xu, Jun; Guo, Bao-Hua

    2010-11-01

    Poly(butylene succinate) (PBS) and its copolymers are a family of biodegradable polymers with excellent biodegradability, thermoplastic processability and balanced mechanical properties. In this article, production of the monomers succinic acid and butanediol, synthesis, processing and properties of PBS and its copolymers are reviewed. The physical properties and biodegradation rate of PBS materials can be varied in a wide range through copolymerization with different types and various contents of monomers. PBS has a wide temperature window for thermoplastic processing, which makes the resin suitable for extrusion, injection molding, thermoforming and film blowing. Finally, we summarized industrialization and applications of PBS.

  15. The possible role of hydrothermal vents in chemical evolution: Succinic acid radiolysis and thermolysis

    NASA Astrophysics Data System (ADS)

    Cruz-Castañeda, J.; Colín-García, M.; Negrón-Mendoza, A.

    2014-07-01

    In this research, the behavior under a high radiation field or high temperature of succinic acid, a dicarboxylic acid clue in metabolic routes, is studied. For this purpose, the molecule was irradiated with gamma rays in oxygen-free aqueous solutions, and the thermal decomposition was studied in a static system at temperatures up to 90 °C, simulating a white hydrothermal vent. Our results indicate that a succinic acid is a relatively stable compound under irradiation. The gamma radiolysis yields carbon dioxide and di- and tricarboxylic acids such as malonic, carboxysuccinic, and citric acids. The main products obtained by the thermal treatment were CO2 and propionic acid.

  16. Metabolic evolution of two reducing equivalent-conserving pathways for high-yield succinate production in Escherichia coli.

    PubMed

    Zhu, Xinna; Tan, Zaigao; Xu, Hongtao; Chen, Jing; Tang, Jinlei; Zhang, Xueli

    2014-07-01

    Reducing equivalents are an important cofactor for efficient synthesis of target products. During metabolic evolution to improve succinate production in Escherichia coli strains, two reducing equivalent-conserving pathways were activated to increase succinate yield. The sensitivity of pyruvate dehydrogenase to NADH inhibition was eliminated by three nucleotide mutations in the lpdA gene. Pyruvate dehydrogenase activity increased under anaerobic conditions, which provided additional NADH. The pentose phosphate pathway and transhydrogenase were activated by increased activities of transketolase and soluble transhydrogenase SthA. These data suggest that more carbon flux went through the pentose phosphate pathway, thus leading to production of more reducing equivalent in the form of NADPH, which was then converted to NADH through soluble transhydrogenase for succinate production. Reverse metabolic engineering was further performed in a parent strain, which was not metabolically evolved, to verify the effects of activating these two reducing equivalent-conserving pathways for improving succinate yield. Activating pyruvate dehydrogenase increased succinate yield from 1.12 to 1.31mol/mol, whereas activating the pentose phosphate pathway and transhydrogenase increased succinate yield from 1.12 to 1.33mol/mol. Activating these two pathways in combination led to a succinate yield of 1.5mol/mol (88% of theoretical maximum), suggesting that they exhibited a synergistic effect for improving succinate yield.

  17. Cognitive effects of creatine ethyl ester supplementation.

    PubMed

    Ling, Jonathan; Kritikos, Minos; Tiplady, Brian

    2009-12-01

    Supplementation with creatine-based substances as a means of enhancing athletic performance has become widespread. Until recently, however, the effects of creatine supplementation on cognitive performance has been given little attention. This study used a new form of creatine--creatine ethyl ester--to investigate whether supplementation would improve performance in five cognitive tasks, using a double-blind, placebo-controlled study. Creatine dosing led to an improvement over the placebo condition on several measures. Although creatine seems to facilitate cognition on some tasks, these results require replication using objective measures of compliance. The improvement is discussed in the context of research examining the influence of brain energy capacity on cognitive performance. PMID:19773644

  18. 21 CFR 172.872 - Methyl ethyl cellulose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.872 Methyl ethyl cellulose. The food additive methyl ethyl cellulose may be safely used in food in accordance with the following prescribed conditions. (a) The additive...

  19. IRIS TOXICOLOGICAL REVIEW OF METHYL ETHYL KETONE (2003 Final)

    EPA Science Inventory

    EPA is announcing the release of the final report, "Toxicological Review of Methyl Ethyl Ketone: in support of the Integrated Risk Information System (IRIS)". The updated Summary for Methyl Ethyl Ketone and accompanying Quickview have also been added to the IRIS Database.

  20. Electronic structure and normal vibrations of the 1-ethyl-3-methylimidazolium ethyl sulfate ion pair.

    PubMed

    Dhumal, Nilesh R; Kim, Hyung J; Kiefer, Johannes

    2011-04-21

    Electronic and structural properties of the ion pair 1-ethyl-3-methylimidazolium ethyl sulfate are studied using density functional methods. Three locally stable conformers of the ion pair complex are considered to analyze molecular interactions between its cation and anion. Manifestations of these interactions in the vibrational spectra are discussed and compared with experimental IR and Raman spectroscopy data. NBO analysis and difference electron density coupled with molecular electron density topography are used to interpret the frequency shifts of the normal vibrations of the ion pair, compared to the free anion and cation. Excitation energies of low-lying singlet excited states of the conformers are also studied. The density functional theory results are found to be in a reasonable agreement with experimental UV/vis absorption spectra.

  1. 40 CFR 180.483 - O-[2-(1,1-Dimethylethyl)-5-pyrimidinyl] O-ethyl-O-(1-methyl-ethyl) phosphorothioate; tolerances...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false O- O-ethyl-O-(1-methyl-ethyl... FOOD Specific Tolerances § 180.483 O- O-ethyl-O-(1-methyl-ethyl) phosphorothioate; tolerances for residues. Time-limited tolerances are established for residues of the insecticide O-...

  2. Spectroscopy reveals that ethyl esters interact with proteins in wine.

    PubMed

    Di Gaspero, Mattia; Ruzza, Paolo; Hussain, Rohanah; Vincenzi, Simone; Biondi, Barbara; Gazzola, Diana; Siligardi, Giuliano; Curioni, Andrea

    2017-02-15

    Impairment of wine aroma after vinification is frequently associated to bentonite treatments and this can be the result of protein removal, as recently demonstrated for ethyl esters. To evaluate the existence of an interaction between wine proteins and ethyl esters, the effects induced by these fermentative aroma compounds on the secondary structure and stability of VVTL1, a Thaumatin-like protein purified from wine, was analyzed by Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy. The secondary structure of wine VVTL1 was not strongly affected by the presence of selected ethyl esters. In contrast, VVTL1 stability was slightly increased by the addition of ethyl-octanoate, -decanoate and -dodecanoate, but decreased by ethyl-hexanoate. This indicates the existence of an interaction between VVTL1 and at least some aroma compounds produced during fermentation. The data suggest that proteins removal from wine by bentonite can result in indirect removal of at least some aroma compounds associated with them. PMID:27664648

  3. Antimicrobial and Anti-Virulence Activity of Capsaicin Against Erythromycin-Resistant, Cell-Invasive Group A Streptococci.

    PubMed

    Marini, Emanuela; Magi, Gloria; Mingoia, Marina; Pugnaloni, Armanda; Facinelli, Bruna

    2015-01-01

    Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of Capsicum plants (chili peppers), which are grown as food and for medicinal purposes since ancient times, and is responsible for the pungency of their fruit. Besides its multiple pharmacological and physiological properties (pain relief, cancer prevention, and beneficial cardiovascular, and gastrointestinal effects) capsaicin has recently attracted considerable attention because of its antimicrobial and anti-virulence activity. This is the first study of its in vitro antibacterial and anti-virulence activity against Streptococcus pyogenes (Group A streptococci, GAS), a major human pathogen. The test strains were previously characterized, erythromycin-susceptible (n = 5) and erythromycin-resistant (n = 27), cell-invasive pharyngeal isolates. The MICs of capsaicin were 64-128 μg/mL (the most common MIC was 128 μg/mL). The action of capsaicin was bactericidal, as suggested by MBC values that were equal or close to the MICs, and by early detection of dead cells in the live/dead assay. No capsaicin-resistant mutants were obtained in single-step resistance selection studies. Interestingly, growth in presence of sublethal capsaicin concentrations induced an increase in biofilm production (p ≤ 0.05) and in the number of bacteria adhering to A549 monolayers, and a reduction in cell-invasiveness and haemolytic activity (both p ≤ 0.05). Cell invasiveness fell so dramatically that a highly invasive strain became non-invasive. The dose-response relationship, characterized by opposite effects of low and high capsaicin doses, suggests a hormetic response. The present study documents that capsaicin has promising bactericidal activity against erythromycin-resistant, cell-invasive pharyngeal GAS isolates. The fact that sublethal concentrations inhibited cell invasion and reduced haemolytic activity, two important virulence traits of GAS, is also interesting, considering that cell

  4. Antimicrobial and Anti-Virulence Activity of Capsaicin Against Erythromycin-Resistant, Cell-Invasive Group A Streptococci

    PubMed Central

    Marini, Emanuela; Magi, Gloria; Mingoia, Marina; Pugnaloni, Armanda; Facinelli, Bruna

    2015-01-01

    Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of Capsicum plants (chili peppers), which are grown as food and for medicinal purposes since ancient times, and is responsible for the pungency of their fruit. Besides its multiple pharmacological and physiological properties (pain relief, cancer prevention, and beneficial cardiovascular, and gastrointestinal effects) capsaicin has recently attracted considerable attention because of its antimicrobial and anti-virulence activity. This is the first study of its in vitro antibacterial and anti-virulence activity against Streptococcus pyogenes (Group A streptococci, GAS), a major human pathogen. The test strains were previously characterized, erythromycin-susceptible (n = 5) and erythromycin-resistant (n = 27), cell-invasive pharyngeal isolates. The MICs of capsaicin were 64–128 μg/mL (the most common MIC was 128 μg/mL). The action of capsaicin was bactericidal, as suggested by MBC values that were equal or close to the MICs, and by early detection of dead cells in the live/dead assay. No capsaicin-resistant mutants were obtained in single-step resistance selection studies. Interestingly, growth in presence of sublethal capsaicin concentrations induced an increase in biofilm production (p ≤ 0.05) and in the number of bacteria adhering to A549 monolayers, and a reduction in cell-invasiveness and haemolytic activity (both p ≤ 0.05). Cell invasiveness fell so dramatically that a highly invasive strain became non-invasive. The dose-response relationship, characterized by opposite effects of low and high capsaicin doses, suggests a hormetic response. The present study documents that capsaicin has promising bactericidal activity against erythromycin-resistant, cell-invasive pharyngeal GAS isolates. The fact that sublethal concentrations inhibited cell invasion and reduced haemolytic activity, two important virulence traits of GAS, is also interesting, considering that cell

  5. Antimicrobial and Anti-Virulence Activity of Capsaicin Against Erythromycin-Resistant, Cell-Invasive Group A Streptococci.

    PubMed

    Marini, Emanuela; Magi, Gloria; Mingoia, Marina; Pugnaloni, Armanda; Facinelli, Bruna

    2015-01-01

    Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of Capsicum plants (chili peppers), which are grown as food and for medicinal purposes since ancient times, and is responsible for the pungency of their fruit. Besides its multiple pharmacological and physiological properties (pain relief, cancer prevention, and beneficial cardiovascular, and gastrointestinal effects) capsaicin has recently attracted considerable attention because of its antimicrobial and anti-virulence activity. This is the first study of its in vitro antibacterial and anti-virulence activity against Streptococcus pyogenes (Group A streptococci, GAS), a major human pathogen. The test strains were previously characterized, erythromycin-susceptible (n = 5) and erythromycin-resistant (n = 27), cell-invasive pharyngeal isolates. The MICs of capsaicin were 64-128 μg/mL (the most common MIC was 128 μg/mL). The action of capsaicin was bactericidal, as suggested by MBC values that were equal or close to the MICs, and by early detection of dead cells in the live/dead assay. No capsaicin-resistant mutants were obtained in single-step resistance selection studies. Interestingly, growth in presence of sublethal capsaicin concentrations induced an increase in biofilm production (p ≤ 0.05) and in the number of bacteria adhering to A549 monolayers, and a reduction in cell-invasiveness and haemolytic activity (both p ≤ 0.05). Cell invasiveness fell so dramatically that a highly invasive strain became non-invasive. The dose-response relationship, characterized by opposite effects of low and high capsaicin doses, suggests a hormetic response. The present study documents that capsaicin has promising bactericidal activity against erythromycin-resistant, cell-invasive pharyngeal GAS isolates. The fact that sublethal concentrations inhibited cell invasion and reduced haemolytic activity, two important virulence traits of GAS, is also interesting, considering that cell

  6. Mechanistic insight into alkylation of the ethyl acetoacetate anion with different ethyl halides

    NASA Astrophysics Data System (ADS)

    Marković, S.; Đurđević, J.; Vukosavljević, M.; Petrović, Z.

    2013-12-01

    The alkylation reactions of the ambident ethyl acetoacetate anion with C2H5X (X = F, Cl, Br, and I) in the O2, C3, and O4 positions of the anion were investigated at the B3LYP/6-311+G( d,p) level of theory. It was found that the ethylation reaction does not occur in the position O4, as well as with ethyl fluoride in any position of the anion, due to very high activation energies and thermodynamic instability of the hypothetic products. The activation energies for the reactions in the position O2 are lower in comparison to the position C3, but the products of the reactions in the C3 position are more stable than those in the position O4, implying that the C/O products ratio is controlled by both thermodynamic and kinetic factors, leading to the O2-product with the chloride, and C3-product with the iodide as leaving group.

  7. Parameters Affecting Ethyl Ester Production by Saccharomyces cerevisiae during Fermentation▿

    PubMed Central

    Saerens, S. M. G.; Delvaux, F.; Verstrepen, K. J.; Van Dijck, P.; Thevelein, J. M.; Delvaux, F. R.

    2008-01-01

    Volatile esters are responsible for the fruity character of fermented beverages and thus constitute a vital group of aromatic compounds in beer and wine. Many fermentation parameters are known to affect volatile ester production. In order to obtain insight into the production of ethyl esters during fermentation, we investigated the influence of several fermentation variables. A higher level of unsaturated fatty acids in the fermentation medium resulted in a general decrease in ethyl ester production. On the other hand, a higher fermentation temperature resulted in greater ethyl octanoate and decanoate production, while a higher carbon or nitrogen content of the fermentation medium resulted in only moderate changes in ethyl ester production. Analysis of the expression of the ethyl ester biosynthesis genes EEB1 and EHT1 after addition of medium-chain fatty acid precursors suggested that the expression level is not the limiting factor for ethyl ester production, as opposed to acetate ester production. Together with the previous demonstration that provision of medium-chain fatty acids, which are the substrates for ethyl ester formation, to the fermentation medium causes a strong increase in the formation of the corresponding ethyl esters, this result further supports the hypothesis that precursor availability has an important role in ethyl ester production. We concluded that, at least in our fermentation conditions and with our yeast strain, the fatty acid precursor level rather than the activity of the biosynthetic enzymes is the major limiting factor for ethyl ester production. The expression level and activity of the fatty acid biosynthetic enzymes therefore appear to be prime targets for flavor modification by alteration of process parameters or through strain selection. PMID:17993562

  8. [Determination of succinic acid in desvenlafaxine succinate by high performance ion-exclusion chromatography and high performance ion-exchange chromatography].

    PubMed

    Zong, Yanping; Li, Jinghua; Sun, Wei; Liu, Guixia; Lu, Jinghua; Shan, Guangzhi

    2016-02-01

    New methods were developed for the determination of succinic acid in desvenlafaxine succinate (DVS) by high performance ion-exclusion chromatography (HPIEC) and high performance ion-exchange chromatography (HPIC). HPIEC and HPIC methods were used separately to determinate the succinic acid in DVS. With HPIEC, the sample was diluted with 2. 50 x 10(-3) mol/L sulfuric acid solution and filtrated by 0. 22 µm polyether sulfone filter membrane, and then analyzed by HPIEC directly without any further pretreatment. The analytical column was Phenomenex Rezex ROA-organic Acid H+(8%) (300 mmx7. 8 mm). The mobile phase was 2. 50x10(-3) mol/L sulfuric acid solution at the flow rate of 0. 5 mL/min. The column temperature was set at 40 °C, and the detection wavelength was 210 nm. The injection volume was 10 KL. The assay was quantified by external standard method. With HPIC, the sample was diluted with ultrapure water and filtrated by 0. 22 µm polyether sulfone filter membrane, and then analyzed by HPIC directly without any further pretreatment. The analytical column was Dionex IonPac AS11-HC (250 mm x 4 mm) with a guard column IonPacAG11-HC (50 mm x 4 mm). Isocratic KOH elute generator was used at the flow rate of 1. 0 mL/min. The detection was performed by a Dionex suppressed (DIONEX AERS 500 4-mm) conductivity detector. The injection volume was 10 µL. The content computation was performed with peak area external reference method. The results of HPIEC method for succinic acid were 28. 8%, 28. 9% and 28. 9%, while the results of HPIEC method were 28. 2%, 28. 6% and 28. 6%. The results of HPIEC and HPIC methods were not significantly different. The two methods can both be used to determine the contents of succinic acid in DVS. The surveillance analytical method should be chosen according to the situation. PMID:27382725

  9. [Determination of succinic acid in desvenlafaxine succinate by high performance ion-exclusion chromatography and high performance ion-exchange chromatography].

    PubMed

    Zong, Yanping; Li, Jinghua; Sun, Wei; Liu, Guixia; Lu, Jinghua; Shan, Guangzhi

    2016-02-01

    New methods were developed for the determination of succinic acid in desvenlafaxine succinate (DVS) by high performance ion-exclusion chromatography (HPIEC) and high performance ion-exchange chromatography (HPIC). HPIEC and HPIC methods were used separately to determinate the succinic acid in DVS. With HPIEC, the sample was diluted with 2. 50 x 10(-3) mol/L sulfuric acid solution and filtrated by 0. 22 µm polyether sulfone filter membrane, and then analyzed by HPIEC directly without any further pretreatment. The analytical column was Phenomenex Rezex ROA-organic Acid H+(8%) (300 mmx7. 8 mm). The mobile phase was 2. 50x10(-3) mol/L sulfuric acid solution at the flow rate of 0. 5 mL/min. The column temperature was set at 40 °C, and the detection wavelength was 210 nm. The injection volume was 10 KL. The assay was quantified by external standard method. With HPIC, the sample was diluted with ultrapure water and filtrated by 0. 22 µm polyether sulfone filter membrane, and then analyzed by HPIC directly without any further pretreatment. The analytical column was Dionex IonPac AS11-HC (250 mm x 4 mm) with a guard column IonPacAG11-HC (50 mm x 4 mm). Isocratic KOH elute generator was used at the flow rate of 1. 0 mL/min. The detection was performed by a Dionex suppressed (DIONEX AERS 500 4-mm) conductivity detector. The injection volume was 10 µL. The content computation was performed with peak area external reference method. The results of HPIEC method for succinic acid were 28. 8%, 28. 9% and 28. 9%, while the results of HPIEC method were 28. 2%, 28. 6% and 28. 6%. The results of HPIEC and HPIC methods were not significantly different. The two methods can both be used to determine the contents of succinic acid in DVS. The surveillance analytical method should be chosen according to the situation.

  10. Succinic Acid as a Byproduct in a Corn-based Ethanol Biorefinery

    SciTech Connect

    MBI International

    2007-12-31

    MBI endeavored to develop a process for succinic acid production suitable for integration into a corn-based ethanol biorefinery. The project investigated the fermentative production of succinic acid using byproducts of corn mill operations. The fermentation process was attuned to include raw starch, endosperm, as the sugar source. A clean-not-sterile process was established to treat the endosperm and release the monomeric sugars. We developed the fermentation process to utilize a byproduct of corn ethanol fermentations, thin stillage, as the source of complex nitrogen and vitamin components needed to support succinic acid production in A. succinogenes. Further supplementations were eliminated without lowering titers and yields and a productivity above 0.6 g l-1 hr-1was achieved. Strain development was accomplished through generation of a recombinant strain that increased yields of succinic acid production. Isolation of additional strains with improved features was also pursued and frozen stocks were prepared from enriched, characterized cultures. Two recovery processes were evaluated at pilot scale and data obtained was incorporated into our economic analyses.

  11. Nano-encapsulation of coenzyme Q10 using octenyl succinic anhydride modified starch

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Octenyl succinic anhydride modified starch (OSA-ST) was used to encapsulate Coenzyme Q10 (CoQ10). CoQ10 was dissolved in rice bran oil (RBO), and incorporated into an aqueous OSA-ST solution. High pressure homogenization (HPH) of the mixture was conducted at 170 MPa for 5-6 cycles. The resulting ...

  12. Formation and stability of Vitamin E enriched nanoemulsions stabilized by Octenyl Succinic Anhydride modified starch

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin E (VE) is highly susceptible to autoxidation; therefore, it requires systems to encapsulate and protect it from autoxidation.In this study,we developed VE delivery systems, which were stabilized by Capsul® (MS), a starch modified with octenyl succinic anhydride. Influences of interfacial ten...

  13. Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance.

    PubMed

    Ferreyra, Jessica A; Wu, Katherine J; Hryckowian, Andrew J; Bouley, Donna M; Weimer, Bart C; Sonnenburg, Justin L

    2014-12-10

    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 present 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.

  14. Integration of Succinic Acid Production in a Dry Mill Ethanol Facility

    SciTech Connect

    2006-08-01

    This project seeks to address both issues for a dry mill ethanol biorefinery by lowering the cost of sugars with the development of an advanced pretreatment process, improving the economics of succinic acid (SA), and developing a model of an ethanol dry mill to evaluate the impact of adding different products and processes to a dry mill.

  15. Trypanosomatidae produce acetate via a mitochondrial acetate:succinate CoA transferase.

    PubMed

    Van Hellemond, J J; Opperdoes, F R; Tielens, A G

    1998-03-17

    Hydrogenosome-containing anaerobic protists, such as the trichomonads, produce large amounts of acetate by an acetate:succinate CoA transferase (ASCT)/succinyl CoA synthetase cycle. The notion that mitochondria and hydrogenosomes may have originated from the same alpha-proteobacterial endosymbiont has led us to look for the presence of a similar metabolic pathway in trypanosomatids because these are the earliest-branching mitochondriate eukaryotes and because they also are known to produce acetate. The mechanism of acetate production in these organisms, however, has remained unknown. Four different members of the trypanosomatid family: promastigotes of Leishmania mexicana mexicana, L. infantum and Phytomonas sp., and procyclics of Trypanosoma brucei were analyzed as well as the parasitic helminth Fasciola hepatica. They all use a mitochondrial ASCT for the production of acetate from acetyl CoA. The succinyl CoA that is produced during acetate formation by ASCT is recycled presumably to succinate by a mitochondrial succinyl CoA synthetase, concomitantly producing ATP from ADP. The ASCT of L. mexicana mexicana promastigotes was further characterized after partial purification of the enzyme. It has a high affinity for acetyl CoA (Km 0.26 mM) and a low affinity for succinate (Km 6.9 mM), which shows that significant acetate production can occur only when high mitochondrial succinate concentrations prevail. This study identifies a metabolic pathway common to mitochondria and hydrogenosomes, which strongly supports a common origin for these two organelles.

  16. Efficient production of succinic acid from Palmaria palmata hydrolysate by metabolically engineered Escherichia coli.

    PubMed

    Olajuyin, Ayobami Matthew; Yang, Maohua; Liu, Yilan; Mu, Tingzhen; Tian, Jiangnan; Adaramoye, Oluwatosin Adekunle; Xing, Jianmin

    2016-08-01

    Succinic acid, a C4 dicarboxylic acid is used in many fields such as food, agriculture, pharmaceutical and polymer industries. In this study, microbial production of succinic acid from Palmaria palmata was investigated for the first time. In engineered Escherichia coli KLPPP, lactate dehydrogenase, pyruvate formate lyase, phosphotransacetylase-acetate kinase and pyruvate oxidase genes were deleted while phosphoenolpyruvate carboxykinase was overexpressed. The recombinant exhibited higher molar yield of succinic acid on galactose (1.20±0.02mol/mol) than glucose (0.48±0.03mol/mol). The concentration and molar yield of succinic acid were 22.40±0.12g/L and 1.13±0.02mol/mol total sugar respectively after 72h dual phase fermentation from P. palmata hydrolysate which composed of glucose (12.57±0.17g/L) and galactose (18.03±0.10g/L). The results demonstrate that P. palmata red macroalgae biomass represents a novel and an economically alternative feedstock for biochemicals production. PMID:27203224

  17. Ultrasonic pretreatment and acid hydrolysis of sugarcane bagasse for succinic acid production using Actinobacillus succinogenes.

    PubMed

    Xi, Yong-lan; Dai, Wen-yu; Xu, Rong; Zhang, Jiu-hua; Chen, Ke-quan; Jiang, Min; Wei, Ping; Ouyang, Ping-kai

    2013-11-01

    Immense interest has been devoted to the production of bulk chemicals from lignocellulose biomass. Diluted sulfuric acid treatment is currently one of the main pretreatment methods. However, the low total sugar concentration obtained via such pretreatment limits industrial fermentation systems that use lignocellulosic hydrolysate. Sugarcane bagasse hemicellulose hydrolysate is used as the carbon and nitrogen sources to achieve a green and economical production of succinic acid in this study. Sugarcane bagasse was ultrasonically pretreated for 40 min, with 43.9 g/L total sugar obtained after dilute acid hydrolysis. The total sugar concentration increased by 29.5 %. In a 3-L fermentor, using 30 g/L non-detoxified total sugar as the carbon source, succinic acid production increased to 23.7 g/L with a succinic acid yield of 79.0 % and a productivity of 0.99 g/L/h, and 60 % yeast extract in the medium could be reduced. Compared with the detoxified sugar preparation method, succinic acid production and yield were improved by 20.9 and 20.2 %, respectively. PMID:23649828

  18. Nucleation kinetics of urea succinic acid –ferroelectric single crystal

    SciTech Connect

    Dhivya, R.; Vizhi, R. Ezhil E-mail: revizhi@gmail.com; Babu, D. Rajan

    2015-06-24

    Single crystals of Urea Succinic Acid (USA) were grown by slow cooling technique. The crystalline system was confirmed by powder X-ray diffraction. The metastable zonewidth were carried out for various temperatures i.e., 35°, 40°, 45° and 50°C. The induction period is experimentally determined and various nucleation parameters have been estimated.

  19. Metabolic evolution of energy-conserving pathways for succinate production in Escherichia coli

    PubMed Central

    Zhang, Xueli; Jantama, Kaemwich; Moore, Jonathan C.; Jarboe, Laura R.; Shanmugam, Keelnatham T.; Ingram, Lonnie O.

    2009-01-01

    During metabolic evolution to improve succinate production in Escherichia coli strains, significant changes in cellular metabolism were acquired that increased energy efficiency in two respects. The energy-conserving phosphoenolpyruvate (PEP) carboxykinase (pck), which normally functions in the reverse direction (gluconeogenesis; glucose repressed) during the oxidative metabolism of organic acids, evolved to become the major carboxylation pathway for succinate production. Both PCK enzyme activity and gene expression levels increased significantly in two stages because of several mutations during the metabolic evolution process. High-level expression of this enzyme-dominated CO2 fixation and increased ATP yield (1 ATP per oxaloacetate). In addition, the native PEP-dependent phosphotransferase system for glucose uptake was inactivated by a mutation in ptsI. This glucose transport function was replaced by increased expression of the GalP permease (galP) and glucokinase (glk). Results of deleting individual transport genes confirmed that GalP served as the dominant glucose transporter in evolved strains. Using this alternative transport system would increase the pool of PEP available for redox balance. This change would also increase energy efficiency by eliminating the need to produce additional PEP from pyruvate, a reaction that requires two ATP equivalents. Together, these changes converted the wild-type E. coli fermentation pathway for succinate into a functional equivalent of the native pathway that nature evolved in succinate-producing rumen bacteria. PMID:19918073

  20. Efficient production of succinic acid from macroalgae hydrolysate by metabolically engineered Escherichia coli.

    PubMed

    Bai, Bing; Zhou, Jie-min; Yang, Mao-hua; Liu, Yi-lan; Xu, Xiao-hui; Xing, Jian-min

    2015-06-01

    In this study, microbial production of succinic acid from macroalgae (i.e., Laminaria japonica) was investigated for the first time. The engineered Escherichia coli BS002 exhibited higher molar yield of succinic acid on mannitol (1.39±0.01mol/mol) than glucose (1.01±0.05mol/mol). After pretreatment and enzymatic hydrolysis, L. japonica hydrolysate was mainly glucose (10.31±0.32g/L) and mannitol (10.12±0.17g/L), which was used as the substrate for succinic acid fermentation with the recombinant BS002. A final 17.44±0.54g/L succinic acid was obtained from the hydrolysate after 72h dual-phase fermentation. The yield was as high as 1.24±0.08mol/mol total sugar, which reached 73% of the maximum theoretical yield. The results demonstrate that macroalgae biomass represents a novelty and economical alternative feedstock for biochemicals production.

  1. 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, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Ethanaminium, N-ethyl-2-hydroxy-N,N... 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...

  2. 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, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Ethanaminium, N-ethyl-2-hydroxy-N,N... 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...

  3. Purification and characterization of macrolide 2'-phosphotransferase from a strain of Escherichia coli that is highly resistant to erythromycin.

    PubMed

    O'Hara, K; Kanda, T; Ohmiya, K; Ebisu, T; Kono, M

    1989-08-01

    Macrolide 2'-phosphotransferase [MPH(2')] was purified 90-fold from an erythromycin-resistant strain of Escherichia coli, and its enzymatic properties were investigated. MPH(2') is an inducible intracellular enzyme which showed high levels of activity with 14-member-ring macrolides and extremely low levels with 16-member-ring macrolides. The optimum pH for inactivation of oleandomycin was 8.2, and the optimum temperature of the reaction was 40 degrees C. Enzyme activity was lost by heat treatment at 50 degrees C for 1 min. The isoelectric point and molecular weight of the enzyme were 5.3 and 34,000, respectively. Purine nucleotides, such as GTP, ITP, and ATP, were effective as cofactors in the inactivation of macrolides. Iodine, EDTA, or divalent cations inhibited MPH(2') activity.

  4. Chronic toxicity of erythromycin thiocyanate to Daphnia magna in a flow-through, continuous exposure test system

    USGS Publications Warehouse

    Meinertz, J.R.; Schreier, T.M.; Bernardy, J.A.

    2011-01-01

    Approval of a new animal drug application for AQUAMYCIN 100?? (erythromycin thiocyanate; ET) to treat freshwater salmonid species with bacterial kidney disease is being pursued in the US. As part of the approval process, ETs impact on an aquatic environment had to be described in an environmental assessment. The environmental assessment was lacking data to characterize the effect ET would have on a chronically exposed aquatic invertebrate organism. A major step to fulfilling the environmental assessment was completed after conducting a comprehensive study continuously exposing Daphnia magna to ET for 21 days. Results indicated that the no observable effect concentration for ET was 179 ??g/L. ?? 2011 Springer Science+Business Media, LLC (outside the USA).

  5. Chronic toxicity of diphenhydramine hydrochloride and erythromycin thiocyanate to Daphnia, Daphnia magna, in a continuous exposure test system

    USGS Publications Warehouse

    Meinertz, J.R.; Schreier, T.M.; Bernardy, J.A.; Franz, J.L.

    2010-01-01

    Diphenhydramine hydrochloride (DH; Benadryl TM, an over-the-counter antihistamine) and erythromycin thiocyanate (ET; a commonly used macrolide antibiotic) are pharmaceutical compounds whose chronic toxicity to Daphnia magna had not been characterized. Continuous exposure to DH concentrations about 5 times greater than the maximum reported environmental concentration of 0.023 lg/L for 21 days or to ET concentrations about 40 times the maximum reported environmental concentration of 6 (mu or u)g/L for 21 days did not significantly impact D. magna survival and production. In this study the no observable effect concentration for DH was 0.12 (mu or u)g/L and for ET was 248 (mu or u)g/L.

  6. Long-Lasting Outbreak of Erythromycin- and Ciprofloxacin-Resistant Campylobacter jejuni Subspecies jejuni From 2003 to 2013 in Men Who Have Sex With Men, Quebec, Canada.

    PubMed

    Gaudreau, Christiane; Rodrigues-Coutlée, Sophie; Pilon, Pierre A; Coutlée, François; Bekal, Sadjia

    2015-11-15

    From January 2003 to December 2013, sexual transmission of 2 clades of Campylobacter jejuni subspecies jejuni isolates resulted in a prolonged outbreak among men who have sex with men living in Quebec, Canada. The outbreak isolates were acquired locally and were resistant to erythromycin and ciprofloxacin.

  7. Effects of chlorophyll-derived efflux pump inhibitor pheophorbide a and pyropheophorbide a on erythromycin resistance of Staphylococcus aureus, Enterococcus faecalis, Salmonella Typhimurium and Escherichia coli

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to validate the hypothesis that pheophorbide a and pyropheophorbide a reduce erythromycin resistance of reference strains of facultative anaerobic bacteria with multidrug or macrolide efflux pumps, as indicative of their effect on bacteria indigenous to anaerobic swine ...

  8. Draft Genome Sequence of Erythromycin-Resistant Streptococcus gallolyticus subsp. gallolyticus NTS 31106099 Isolated from a Patient with Infective Endocarditis and Colorectal Cancer.

    PubMed

    Kambarev, Stanimir; Caté, Clément; Corvec, Stéphane; Pecorari, Frédéric

    2015-04-23

    Streptococcus gallolyticus subsp. gallolyticus is known for its close association with infective endocarditis and colorectal cancer in humans. Here, we report the draft genome sequence of highly erythromycin-resistant strain NTS 31106099 isolated from a patient with infective endocarditis and colorectal cancer.

  9. Reduced persistence of the macrolide antibiotics erythromycin, clarithromycin and azithromycin in agricultural soil following several years of exposure in the field.

    PubMed

    Topp, Edward; Renaud, Justin; Sumarah, Mark; Sabourin, Lyne

    2016-08-15

    The macrolide antibiotics erythromycin, clarithromycin and azithromycin are very important in human and animal medicine, and can be entrained onto agricultural ground through application of sewage sludge or manures. In the present study, a series of replicated field plots were left untreated or received up to five annual spring applications of a mixture of three drugs to achieve a nominal concentration for each of 10 or 0.1mgkg(-1) soil; the latter an environmentally relevant concentration. Soil samples were incubated in the laboratory, and supplemented with antibiotics to establish the dissipation kinetics of erythromycin and clarithromycin using radioisotope methods, and azithromycin using HPLC-MS/MS. All three drugs were dissipated significantly more rapidly in soils with a history of field exposure to 10mgkg(-1) macrolides, and erythromycin and clarithromycin were also degraded more rapidly in field soil exposed to 0.1mgkg(-1) macrolides. Rapid mineralization of (14)C-labelled erythromycin and clarithromycin are consistent with biodegradation. Analysis of field soils revealed no carryover of parent compound from year to year. Azithromycin transformation products were detected consistent with removal of the desosamine and cladinose moieties. Overall, these results have revealed that following several years of exposure to macrolide antibiotics these are amenable to accelerated degradation. The potential accelerated degradation of these drugs in soils amended with manure and sewage sludge should be investigated as this phenomenon would attenuate environmental exposure and selection pressure for clinically relevant resistance. PMID:27096634

  10. Enhancement of the antibiotic activity of erythromycin by volatile compounds of Lippia alba (Mill.) N.E. Brown against Staphylococcus aureus

    PubMed Central

    Veras, Helenicy N. H.; Campos, Adriana R.; Rodrigues, Fabíola F. G.; Botelho, Marco A.; Coutinho, Henrique D. M.; Menezes, Irwin R. A.; da Costa, José Galberto M.

    2011-01-01

    Background: Lippia alba (Mill.) N.E. Brown, popularly known as “erva-cidreira,” is commonly found in northeastern Brazil. The leaves tea is used to treat digestive disturbances, nausea, cough, and bronchitis. Objective: This work reports the chemical composition and erythromycin-modifying activity by gaseous contact against Staphylococcus aureus. Materials and Methods: The leaves of L. alba were subjected to hydrodistillation, and the essential oil extracted was examined with respect to the chemical composition, by gas chromatography-mass spectrometry (GC-MS), and the essential oil extracted was evaluated for antibacterial and antibiotic-modifying activity by gaseous contact. Results: The overall yield of essential oil obtained by hydrodistillation was 0.52%. The GC-MS analysis has led to the identification of the main components: geranial (31.4%) and neral (29.5%). It was verified that the essential oil interfered with erythromycin antibiotic activity against S. aureus ATCC 25923 was enhanced (221.4%) in the presence of 12% essential oil. The 3% essential oil increased the effect against S. aureus ATCC 25923 (41.6%) and S. aureus ATCC 6538 (58.3%). Conclusion: The essential oil of L. alba influences the activity of erythromycin and may be used as an adjuvant in antibiotic therapy against respiratory tract bacterial pathogens. Conclusion: The essential oil of L. alba influences the activity of erythromycin and may be used as an adjuvant in antibiotic therapy against respiratory tract bacterial pathogens. PMID:22262937

  11. Biodegradation of pyrazosulfuron-ethyl by Acinetobacter sp. CW17.

    PubMed

    Wang, Yanhui; Du, Liangwei; Chen, Yingxi; Liu, Xiaoliang; Zhou, Xiaomao; Tan, Huihua; Bai, Lianyang; Zeng, Dongqiang

    2012-03-01

    The pyrazosulfuron-ethyl-degrading bacterium, designated as CW17, was isolated from contaminated soil near the warehouse of the factory producing pyrazosulfuron-ethyl in Changsha city, China. The strain CW17 was identified as Acinetobacter sp. based on analyses of 94 carbon source utilization or chemical sensitivity in Biolog microplates, conventional phenotypic characteristics, and 16S rRNA gene sequencing. When pyrazosulfuron-ethyl was provided as the sole carbon source, the effects of pyrazosulfuron-ethyl concentration, pH, and temperature on biodegradation were examined. The degradation rates of pyrazosulfuron-ethyl at initial concentrations of 5.0, 20.0, and 50.0 mg/L were 48.0%, 77.0%, and 32.6%, respectively, after inoculation for 7 days. The growth of the strain was inhibited at low pH buffers. The chemical degradation occurs much faster at low pH than at neutral and basic pH conditions. The degradation rate of pyrazosulfuron-ethyl at 30°C was faster than those at 20 and 37°C by CW17 strains. Two metabolites of degradation were analyzed by liquid chromatography-mass spectroscopy (LC/MS). Based on the identified products, strain CW17 seemed to be able to degrade pyrazosulfuron-ethyl by cleavage of the sulfonylurea bridge. PMID:22388979

  12. Comparing pyridoxine and doxylamine succinate-pyridoxine HCl for nausea and vomiting of pregnancy: A matched, controlled cohort study.

    PubMed

    Pope, Eliza; Maltepe, Caroline; Koren, Gideon

    2015-07-01

    Nausea and vomiting of pregnancy (NVP) is a common gestational condition. This is the first study to compare the use of vitamin B6 (pyridoxine) versus Diclectin (doxylamine succinate-pyridoxine HCl) for NVP symptoms. Participants were pregnant women with NVP who used either pyridoxine or doxylamine succinate-pyridoxine HCl for ≥4 days prior to calling the Motherisk NVP Helpline. Women receiving pyridoxine only (n = 80) were matched to a woman taking doxylamine succinate-pyridoxine HCl only (n = 80), accounting for potential confounders and baseline level of NVP, measured by the Pregnancy Unique Quantification of Emesis (PUQE) score. Change in NVP severity after a week of therapy with either pyridoxine or doxylamine succinate-pyridoxine HCl was quantified using the PUQE-24 scale, which describes NVP symptoms 24 hours prior to their call. Doxylamine succinate-pyridoxine HCl use found a significant reduction in PUQE score, compared with pyridoxine (+0.5 versus -0.2, P < .05; negative denotes worsening). This association was especially prominent in women with more severe symptoms, where doxylamine succinate-pyridoxine HCl use saw a mean improvement of 2.6 versus 0.4 with pyridoxine (P < .05). As well, doxylamine succinate-pyridoxine HCl use was associated with fewer women experiencing moderate to severe scores after a week of treatment, compared with the pyridoxine group (7 versus 17, P < .05), despite similar baseline PUQE scores.

  13. Effects of eliminating pyruvate node pathways and of coexpression of heterogeneous carboxylation enzymes on succinate production by Enterobacter aerogenes.

    PubMed

    Tajima, Yoshinori; Yamamoto, Yoko; Fukui, Keita; Nishio, Yousuke; Hashiguchi, Kenichi; Usuda, Yoshihiro; Sode, Koji

    2015-02-01

    Lowering the pH in bacterium-based succinate fermentation is considered a feasible approach to reduce total production costs. Newly isolated Enterobacter aerogenes strain AJ110637, a rapid carbon source assimilator under weakly acidic (pH 5.0) conditions, was selected as a platform for succinate production. Our previous work showed that the ΔadhE/PCK strain, developed from AJ110637 with inactivated ethanol dehydrogenase and introduced Actinobacillus succinogenes phosphoenolpyruvate carboxykinase (PCK), generated succinate as a major product of anaerobic mixed-acid fermentation from glucose under weakly acidic conditions (pH <6.2). To further improve the production of succinate by the ΔadhE/PCK strain, metabolically engineered strains were designed based on the elimination of pathways that produced undesirable products and the introduction of two carboxylation pathways from phosphoenolpyruvate and pyruvate to oxaloacetate. The highest production of succinate was observed with strain ES04/PCK+PYC, which had inactivated ethanol, lactate, acetate, and 2,3-butanediol pathways and coexpressed PCK and Corynebacterium glutamicum pyruvate carboxylase (PYC). This strain produced succinate from glucose with over 70% yield (gram per gram) without any measurable formation of ethanol, lactate, or 2,3-butanediol under weakly acidic conditions. The impact of lowering the pH from 7.0 to 5.5 on succinate production in this strain was evaluated under pH-controlled batch culture conditions and showed that the lower pH decreased the succinate titer but increased its yield. These findings can be applied to identify additional engineering targets to increase succinate production. PMID:25416770

  14. Effects of eliminating pyruvate node pathways and of coexpression of heterogeneous carboxylation enzymes on succinate production by Enterobacter aerogenes.

    PubMed

    Tajima, Yoshinori; Yamamoto, Yoko; Fukui, Keita; Nishio, Yousuke; Hashiguchi, Kenichi; Usuda, Yoshihiro; Sode, Koji

    2015-02-01

    Lowering the pH in bacterium-based succinate fermentation is considered a feasible approach to reduce total production costs. Newly isolated Enterobacter aerogenes strain AJ110637, a rapid carbon source assimilator under weakly acidic (pH 5.0) conditions, was selected as a platform for succinate production. Our previous work showed that the ΔadhE/PCK strain, developed from AJ110637 with inactivated ethanol dehydrogenase and introduced Actinobacillus succinogenes phosphoenolpyruvate carboxykinase (PCK), generated succinate as a major product of anaerobic mixed-acid fermentation from glucose under weakly acidic conditions (pH <6.2). To further improve the production of succinate by the ΔadhE/PCK strain, metabolically engineered strains were designed based on the elimination of pathways that produced undesirable products and the introduction of two carboxylation pathways from phosphoenolpyruvate and pyruvate to oxaloacetate. The highest production of succinate was observed with strain ES04/PCK+PYC, which had inactivated ethanol, lactate, acetate, and 2,3-butanediol pathways and coexpressed PCK and Corynebacterium glutamicum pyruvate carboxylase (PYC). This strain produced succinate from glucose with over 70% yield (gram per gram) without any measurable formation of ethanol, lactate, or 2,3-butanediol under weakly acidic conditions. The impact of lowering the pH from 7.0 to 5.5 on succinate production in this strain was evaluated under pH-controlled batch culture conditions and showed that the lower pH decreased the succinate titer but increased its yield. These findings can be applied to identify additional engineering targets to increase succinate production.

  15. Effects of Eliminating Pyruvate Node Pathways and of Coexpression of Heterogeneous Carboxylation Enzymes on Succinate Production by Enterobacter aerogenes

    PubMed Central

    Yamamoto, Yoko; Fukui, Keita; Nishio, Yousuke; Hashiguchi, Kenichi; Usuda, Yoshihiro; Sode, Koji

    2014-01-01

    Lowering the pH in bacterium-based succinate fermentation is considered a feasible approach to reduce total production costs. Newly isolated Enterobacter aerogenes strain AJ110637, a rapid carbon source assimilator under weakly acidic (pH 5.0) conditions, was selected as a platform for succinate production. Our previous work showed that the ΔadhE/PCK strain, developed from AJ110637 with inactivated ethanol dehydrogenase and introduced Actinobacillus succinogenes phosphoenolpyruvate carboxykinase (PCK), generated succinate as a major product of anaerobic mixed-acid fermentation from glucose under weakly acidic conditions (pH <6.2). To further improve the production of succinate by the ΔadhE/PCK strain, metabolically engineered strains were designed based on the elimination of pathways that produced undesirable products and the introduction of two carboxylation pathways from phosphoenolpyruvate and pyruvate to oxaloacetate. The highest production of succinate was observed with strain ES04/PCK+PYC, which had inactivated ethanol, lactate, acetate, and 2,3-butanediol pathways and coexpressed PCK and Corynebacterium glutamicum pyruvate carboxylase (PYC). This strain produced succinate from glucose with over 70% yield (gram per gram) without any measurable formation of ethanol, lactate, or 2,3-butanediol under weakly acidic conditions. The impact of lowering the pH from 7.0 to 5.5 on succinate production in this strain was evaluated under pH-controlled batch culture conditions and showed that the lower pH decreased the succinate titer but increased its yield. These findings can be applied to identify additional engineering targets to increase succinate production. PMID:25416770

  16. Ethyl Esterification for MALDI-MS Analysis of Protein Glycosylation.

    PubMed

    Reiding, Karli R; Lonardi, Emanuela; Hipgrave Ederveen, Agnes L; Wuhrer, Manfred

    2016-01-01

    Ethyl esterification is a technique for the chemical modification of sialylated glycans, leading to enhanced stability when performing matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS), as well as allowing the efficient detection of both sialylated and non-sialylated glycans in positive ion mode. In addition, the method shows specific reaction products for α2,3- and α2,6-linked sialic acids, leading to an MS distinguishable mass difference. Here, we describe the ethyl esterification protocol for 96 glycan samples, including enzymatic N-glycan release, the aforementioned ethyl esterification, glycan enrichment, MALDI target preparation, and the MS(/MS) measurement. PMID:26700047

  17. On the cause of low thermal stability of ethyl halodiazoacetates

    PubMed Central

    Mortén, Magnus; Hennum, Martin

    2016-01-01

    Summary Rates for the thermal decomposition of ethyl halodiazoacetates (halo = Cl, Br, I) have been obtained, and reported herein are their half-lives. The experimental results are supported by DFT calculations, and we provide a possible explanation for the reduced thermal stability of ethyl halodiazoacetates compared to ethyl diazoacetate and for the relative decomposition rates between the chloro, bromo and iodo analogs. We have also briefly studied the thermal, non-catalytic cyclopropanation of styrenes and compared the results to the analogous Rh(II)-catalyzed reactions. PMID:27559411

  18. Preconditioning with ethyl 3,4-dihydroxybenzoate augments aerobic respiration in rat skeletal muscle

    PubMed Central

    Nimker, Charu; Singh, Deependra Pratap; Saraswat, Deepika; Bansal, Anju

    2016-01-01

    Muscle respiratory capacity decides the amount of exertion one’s skeletal muscle can undergo, and endurance exercise is believed to increase it. There are also certain preconditioning methods by which muscle respiratory and exercise performance can be enhanced. In this study, preconditioning with ethyl 3,4-dihydroxybenzoate (EDHB), a prolyl hydroxylase domain enzyme inhibitor, has been investigated to determine its effect on aerobic metabolism and bioenergetics in skeletal muscle, thus facilitating boost in physical performance in a rat model. We observed that EDHB supplementation increases aerobic metabolism via upregulation of HIF-mediated GLUT1 and GLUT4, thus enhancing glucose uptake in muscles. There was also a twofold rise in the activity of enzymes of tricarboxylic acid (TCA) cycle and glycolysis, ie, hexokinase and phosphofructokinase. There was an increase in citrate synthase and succinate dehydrogenase activity, resulting in the rise in the levels of ATP due to enhanced Krebs cycle activity as substantiated by enhanced acetyl-CoA levels in EDHB-treated rats as compared to control group. Increased lactate dehydrogenase activity, reduced expression of monocarboxylate transporter 1, and increase in monocarboxylate transporter 4 suggest transport of lactate from muscle to blood. There was a concomitant decrease in plasma lactate, which might be due to enhanced transport of lactate from blood to the liver. This was further supported by the rise in liver pyruvate levels and liver glycogen levels in EDHB-supplemented rats as compared to control rats. These results suggest that EDHB supplementation leads to improved physical performance due to the escalation of aerobic respiration quotient, ie, enhanced muscle respiratory capacity. PMID:27800513

  19. 46 CFR 151.50-42 - Ethyl ether.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... shall be designed and tested to meet the rules of the American Bureau of Shipping for a head of water at... liquid. (g) Precautions shall be taken to prevent the contamination of ethyl ether by strong...

  20. Multidimensional chromatographic approach applied to the identification of novel aroma compounds in wine. Identification of ethyl cyclohexanoate, ethyl 2-hydroxy-3-methylbutyrate and ethyl 2-hydroxy-4-methylpentanoate.

    PubMed

    Campo, E; Cacho, J; Ferreira, V

    2006-12-29

    A multidimensional chromatographic strategy has been developed and optimized with the purpose of identifying different odorants potentially relevant to the aroma and flavor of aged wines from Madeira or Sherry. Different techniques of extraction and fractionation were studied in order to get clear olfactometric and spectrometric signals from the target odorants. The best results were obtained with a dynamic headspace extraction followed by a fractionation on a normal phase medium pressure liquid chromatography on a silicagel column. Large volumes (50 microl) of the concentrated fractions were further analyzed in a dual gas chromatography-mass spectrometric system (GC-MS) equipped with two olfactometric ports. The strategy made it possible to identify in wine by first time the presence of the powerful strawberry-smelling compound, ethyl cyclohexanoate, and of two other novel fruity esters, ethyl 2-hydroxy-3-methylbutyrate and ethyl 2-hydroxy-4-methylpentanoate. Some other unidentified odorants could be isolated and their mass spectra are given. PMID:17069823

  1. Residual behavior of quizalofop ethyl on onion (Allium cepa L.).

    PubMed

    Sahoo, S K; Mandal, Kousik; Singh, Gurmail; Kumar, Rajinder; Chahil, G S; Battu, R S; Singh, Balwinder

    2013-02-01

    Quizalofop ethyl, a phenoxy propionate herbicide, is used for postemergence control of annual and perennial grass weeds in broad-leaved crops in India. The experiments were designed to study the dissipation kinetics of quizalofop ethyl on onion for two seasons. A simple, rapid, and sensitive method for estimation of quizalofop ethyl residues in onion and soil was developed and validated. The recoveries of quizalofop ethyl residues from onion and soil at different spiking level range from 84.81 to 92.68 %. The limit of quantification of this method was found to be 0.01 μg g(-1). The risk assessment through consumption of the onion in comparison to its acceptable daily intake which is an important parameter for the safety of the consumer was also evaluated. Standardized methodology supported by recovery studies was adopted to estimate residues of quizalofop ethyl on onion and soil. The average initial deposits of quizalofop ethyl on onion were observed to be 0.25 and 0.33 mg kg(-1), following single application of the herbicide at 50 g active ingredient (a.i.) ha(-1) during 2009 and 2010, respectively. The half-life values (T (1/2)) of quizalofop ethyl on onion crop were worked out to be 0.85 and 0.79 days, respectively, during 2009 and 2010. At harvest time, the residues of quizalofop ethyl on onion and soil were found to be below the determination limit of 0.01 mg kg(-1) following single application of the herbicide at 50 and 100 g a.i. ha(-1) for both the periods.

  2. Atmospheric Oxidation Mechanisms for Diethyl Ether and its Oxidation Products, Ethyl Formate and Ethyl Acetate.

    NASA Astrophysics Data System (ADS)

    Orlando, J. J.; Tyndall, G. S.

    2006-12-01

    Carbon-containing compounds are present in the earth's atmosphere as the result of emissions from natural and anthropogenic sources. Their oxidation in the atmosphere, initiated by such oxidants as OH, ozone, and nitrate radicals, leads to potentially harmful secondary pollutants such as ozone, carbonyl species, organic acids and aerosols. Ethers and esters are two classes of compounds that contribute to the complex array of organic compounds found in anthropogenically-influenced air. Additional ester is present as a result of the oxidation of the ethers. In this paper, the oxidation of diethyl ether and its two main oxidation products, ethyl formate and ethyl acetate, are studied over ranges of temperature, oxygen partial pressure, and NOx concentration, using an environmental chamber / FTIR absorption technique. Major end-products (the esters from diethyl ether; organic acids and anhydrides from the esters) are quantified, and these data are interpreted in terms of the chemistry of the various alkoxy and peroxy radicals generated. Emphasis is placed on the effects of chemical activation on the behavior of the alkoxy radicals, as well as on a novel peroxy radical rearrangement that may contribute to the observed products of ether oxidation under some conditions. Finally, the data are used, in conjunction with data on similar species, to provide a general representation of ether and ester oxidation in the atmosphere.

  3. Icosapent ethyl: a review of its use in severe hypertriglyceridemia.

    PubMed

    Kim, Esther S; McCormack, Paul L

    2014-12-01

    Icosapent ethyl (Vascepa®) is a high-purity ethyl ester of eicosapentaenoic acid (EPA) that is de-esterified to EPA following oral administration. Both EPA and docosahexaenoic acid (DHA) are long-chain omega-3 fatty acids that have been associated with triglyceride (TG)-lowering. However, DHA has been associated with increased low-density lipoprotein cholesterol (LDL-C) levels. Icosapent ethyl contains ≥96 % of the EPA ethyl ester, does not contain DHA, and is approved in the USA for use as an adjunct to diet to lower TG levels in adult patients with severe (≥500 mg/dL [≥5.65 mmol/L]) hypertriglyceridemia. In a pivotal phase III trial, oral icosapent ethyl 4 g/day significantly decreased the placebo-corrected median TG levels by 33.1 %. It did not increase LDL-C, had favorable effects on other lipid parameters, and had a tolerability profile similar to that of placebo. Therefore, icosapent ethyl is an effective and well-tolerated agent for the treatment of severe hypertriglyceridemia in adults. PMID:25428605

  4. Role of interleukin-8 (IL-8) and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases.

    PubMed Central

    Oishi, K; Sonoda, F; Kobayashi, S; Iwagaki, A; Nagatake, T; Matsushima, K; Matsumoto, K

    1994-01-01

    To evaluate of the role of interleukin-8 (IL-8), a chemotactic cytokine, in the continuous neutrophil accumulation in the airways of patients with chronic airway disease (CAD) and persistent Pseudomonas aeruginosa infection, we investigated the cell population, IL-8 levels, IL-1 beta levels, tumor necrosis factor (TNF) activities, and neutrophil elastase (NE) activities of bronchoalveolar lavage (BAL) fluids in 17 CAD patients (with P. aeruginosa infections [CAD+PA], n = 9; without any bacterial infections [CAD-PA], n = 8) and 8 normal volunteers. We found significant elevations of neutrophil numbers, IL-8/albumin ratios, and NE/albumin ratios in BAL fluids from CAD patients, in the following rank order: CAD+PA > CAD-PA > normal volunteers. IL-1 beta/albumin ratios were elevated only in CAD+PA, while no TNF bioactivity was detected in BAL fluids. The neutrophil numbers correlated significantly with the IL-8/albumin ratios and NE/albumin ratios in the BAL fluids of CAD patients. When anti-human IL-8 immunoglobulin G was used for neutralizing neutrophil chemotactic factor (NCF) activities in BAL fluids, the mean reduction rate of NCF activities in CAD+PA patients was significantly higher than that in CAD-PA patients. We also evaluated the effects of low-dose, long-term erythromycin therapy in BAL fluids from three CAD+PA and two CAD-PA patients. Treatment with erythromycin caused significant reductions of neutrophil numbers, IL-8/albumin ratios, and NE/albumin ratios in BAL fluids from these patients. To elucidate the mechanism of erythromycin therapy, we also examined whether erythromycin suppressed IL-8 production by human alveolar macrophages and neutrophils in vitro. We demonstrated a moderate inhibitory effect of erythromycin on IL-8 production in Pseudomonas-stimulated neutrophils but not in alveolar macrophages. Our data support the view that persistent P. aeruginosa infection enhances IL-8 production and IL-8-derived NCF activity, causing neutrophil

  5. [Effects of Light Near-Infrared Radiation on Rats Assessed by Succinate Dehydrogenase Activity in Lymphocytes on Blood Smears].

    PubMed

    Khunderyakova, N V; Zakharchenko, A V; Zakharchenko, M V; Muller, H; Fedotcheva, I; Kondrashova, M N

    2015-01-01

    Biological effects of light near infrared radiation (850 nm), with modulation acoustic frequency of 101 Hz, was studied. The study was conducted on rats, the effect was recorded by succinate dehydrogenase activity in lymphocytes on the blood smear after administration of the activating dose of adrenaline, which simulates the state of the organism in the early stages of the pathogenic effects (stress). A pronounced regulating effect of infrared radiation on the activity of succinate dehydrogenase in animals activated by adrenaline was shown. Infrared radiation has a normalizing effect reducing the degree of inhibition or activation of the enzyme induced by adrenaline and had no effect on the control animals. Thus, by modulating the activity of succinate dehydrogenase infrared radiation regulates energy production in the mitochondria supported by the most powerful oxidation substrate--succinic acid, which is especially pronounced under stress. PMID:26841503

  6. [Effects of Light Near-Infrared Radiation on Rats Assessed by Succinate Dehydrogenase Activity in Lymphocytes on Blood Smears].

    PubMed

    Khunderyakova, N V; Zakharchenko, A V; Zakharchenko, M V; Muller, H; Fedotcheva, I; Kondrashova, M N

    2015-01-01

    Biological effects of light near infrared radiation (850 nm), with modulation acoustic frequency of 101 Hz, was studied. The study was conducted on rats, the effect was recorded by succinate dehydrogenase activity in lymphocytes on the blood smear after administration of the activating dose of adrenaline, which simulates the state of the organism in the early stages of the pathogenic effects (stress). A pronounced regulating effect of infrared radiation on the activity of succinate dehydrogenase in animals activated by adrenaline was shown. Infrared radiation has a normalizing effect reducing the degree of inhibition or activation of the enzyme induced by adrenaline and had no effect on the control animals. Thus, by modulating the activity of succinate dehydrogenase infrared radiation regulates energy production in the mitochondria supported by the most powerful oxidation substrate--succinic acid, which is especially pronounced under stress.

  7. Comments on recently published "L-threonine phthalate" and pure and doped "L-lysinium succinate" crystals

    NASA Astrophysics Data System (ADS)

    Petrosyan, A. M.

    2016-04-01

    It is shown that the recently published papers on "L-threonine phthalate" (Theras et al. (2015) [2]) and pure and doped "L-lysinium succinate" (Kalaivani et al. (2015) [11,16]) misidentified the targeted compounds.

  8. 40 CFR 180.595 - Flufenpyr-ethyl; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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], and its metabolite, S-3153 acid-4-OH; -phenoxy]-acetic acid, free and conjugated, in or on...

  9. Comparative analysis of the anxiolytic effects of 3-hydroxypyridine and succinic acid derivatives.

    PubMed

    Volchegorskii, I A; Miroshnichenko, I Yu; Rassokhina, L M; Faizullin, R M; Malkin, M P; Pryakhina, K E; Kalugina, A V

    2015-04-01

    Threefold administration of 3-hydroxypyridine derivatives emoxipine and mexidol in optimal doses corresponding to the therapeutic dose range for humans produced an anxiolytic effect and stimulated risk behavior in the elevated plus maze test in rats. These effects were most pronounced after injection of 3-hydroxypyridine derivative emoxipine. Combination of 3-hydroxypyridine cation and succinate anion in the mexidol structure led to attenuation of the anxiolytic effect and less pronounced stimulation of the risk behavior. By the anxiolytic effect and induction of risk behavior, emoxipine and mexidol were close to the reference substance amitriptyline. Reamberin, a succinic acid derivative, had no pronounced tranquilizing properties, but risk behavior induction was similar to that produced by mexidol. In contrast to other test agents, the reference substance α-lipoic acid produced anxiogenic effects and suppressed risk behavior. The obtained results suggest that Russian-made 3-hydroxypyridine derivatives emoxipine and mexidol are promising preparations for the treatment of anxiety disorders. PMID:25894772

  10. Effect of diphenylhydantoin on gamma aminobutyric acid (GABA) and succinate activity in rat Purkinje cells.

    PubMed Central

    Hitchcock, E; Gabra-Sanders, T

    1977-01-01

    A study has been made of the effect of diphenylhydantoin (DPH) upon the levels of gamma aminobutyric acid (GABA) and succinic dehydrogenase in rat Purkinje cells. DPH was administered over 26 days in chronic experiments using controls receiving the same injection vehicle without DPH. Animals in this group received daily 1.25 mg/kg body weight, 12.5 mg/kg body weight, and 50 mg/kg body weight DPH. Acute experiments were carried out over the course of not more than four days, three groups of animals receiving 75 mg/kg body weight, 87.5 mg/kg body weight, and 100 mg/kg body weight DPH. No effect upon succinic dehydrogenase could be demonstrated at any dose level. There was a significant progressive loss of GABA with increasing dosage of DPH. Images PMID:903771

  11. Ferulenol specifically inhibits succinate ubiquinone reductase at the level of the ubiquinone cycle

    SciTech Connect

    Lahouel, Mesbah; Zini, Roland; Zellagui, Ammar; Rhouati, Salah; Carrupt, Pierre-Alain; Morin, Didier; E-mail: didier.morin@creteil.inserm.fr

    2007-03-30

    The natural compound ferulenol, a sesquiterpene prenylated coumarin derivative, was purified from Ferula vesceritensis and its mitochondrial effects were studied. Ferulenol caused inhibition of oxidative phoshorylation. At low concentrations, ferulenol inhibited ATP synthesis by inhibition of the adenine nucleotide translocase without limitation of mitochondrial respiration. At higher concentrations, ferulenol inhibited oxygen consumption. Ferulenol caused specific inhibition of succinate ubiquinone reductase without altering succinate dehydrogenase activity of the complex II. This inhibition results from a limitation of electron transfers initiated by the reduction of ubiquinone to ubiquinol in the ubiquinone cycle. This original mechanism of action makes ferulenol a useful tool to study the physiological role and the mechanism of electron transfer in the complex II. In addition, these data provide an additional mechanism by which ferulenol may alter cell function and demonstrate that mitochondrial dysfunction is an important determinant in Ferula plant toxicity.

  12. Development and evaluation of occlusive systems employing polyvinyl alcohol for transdermal delivery of sumatriptan succinate.

    PubMed

    Balaguer-Fernández, C; Padula, C; Femenía-Font, A; Merino, V; Santi, P; López-Castellano, A

    2010-02-01

    The aim of the present study was to develop a sumatriptan succinate transdermal system for applying migraine treatments efficiently and easily. For this system polyvinyl alcohol was employed as a matrix and Azone((R)) was added as a permeability enhancer. The physical characteristics, mechanical properties, and in vivo bioadhesion of the systems were evaluated, as was in vitro permeation across porcine skin. A uniform distribution of the drug in the matrix was observed, and moisture uptake values were constant. With regard to mechanical parameters, occlusive layer inclusion made the system more resistant, and no significant differences were detected with respect to other systems. Although Azone((R)) reduced the bioadhesivity of the systems, adherence to skin was maintained 24 h after application. Permeation studies showed that the systems formulated with Azone((R)) provided the highest permeability profiles for sumatriptan succinate.

  13. Toxicity of citric and succinic acids for the pycnidiospores ofBotryodiplodia theobromae.

    PubMed

    Aderiye, B I; Laleye, S A; Ojo, B

    1998-01-01

    The toxic effect of citric and succinic acids on the germination of the pycnidiospores ofBotryodiplodia theobromae, mycelial growth and the killing rate of theB. theobromae spores was investigated. The percentage inhibition of germination of viable fungal spores by 0.01% succinic or citric acid ranged between 51.6 and 58.1%, respectively.B. theobromae was found to grow in 2% malt extract broth at 28 degrees C at the rate of 0.13 CFU/h. Citric acid exhibited a higher killing rate of 0.26 CFU/h and was more effective against the germination of the fungal spores. At concentrations of 0.3% and above, citric acid could be used as pre- and post-infectional fungicide.

  14. Structure-barrier property relationship of biodegradable poly(butylene succinate) and poly[(butylene succinate)-co-(butylene adipate)] nanocomposites: influence of the rigid amorphous fraction.

    PubMed

    Charlon, S; Marais, S; Dargent, E; Soulestin, J; Sclavons, M; Follain, N

    2015-11-28

    Composites composed of polyesters, poly(butylene succinate) (PBS) or poly[(butylene succinate)-co-(butylene adipate)] (PBSA), and 5 wt% of montmorillonite (CNa) or organo-modified montmorillonite (C30B) were melt-processed and transformed into films by either compression-molding or extrusion-calendering. XRD, rheological measurements and TEM images clearly indicated that films containing CNa are microcomposites, while nanocomposites were observed for those containing C30B. Using Flash DSC, it was possible, for the first time, not only to measure the heat capacity step at the glass transition of these two materials in their amorphous state, but also to investigate whether the preparation technique influenced the Rigid Amorphous Fraction (RAF) in our PBS- and PBSA-based nanocomposites. In this work, we have successfully shown the correlation between the microstructure of the films and their barrier properties, and especially the role played by the RAF. Indeed, the lowest permeabilities to gases and to water were determined in the films containing the highest RAF in both PBS- and PBSA-based materials. PMID:26489904

  15. Structure-barrier property relationship of biodegradable poly(butylene succinate) and poly[(butylene succinate)-co-(butylene adipate)] nanocomposites: influence of the rigid amorphous fraction.

    PubMed

    Charlon, S; Marais, S; Dargent, E; Soulestin, J; Sclavons, M; Follain, N

    2015-11-28

    Composites composed of polyesters, poly(butylene succinate) (PBS) or poly[(butylene succinate)-co-(butylene adipate)] (PBSA), and 5 wt% of montmorillonite (CNa) or organo-modified montmorillonite (C30B) were melt-processed and transformed into films by either compression-molding or extrusion-calendering. XRD, rheological measurements and TEM images clearly indicated that films containing CNa are microcomposites, while nanocomposites were observed for those containing C30B. Using Flash DSC, it was possible, for the first time, not only to measure the heat capacity step at the glass transition of these two materials in their amorphous state, but also to investigate whether the preparation technique influenced the Rigid Amorphous Fraction (RAF) in our PBS- and PBSA-based nanocomposites. In this work, we have successfully shown the correlation between the microstructure of the films and their barrier properties, and especially the role played by the RAF. Indeed, the lowest permeabilities to gases and to water were determined in the films containing the highest RAF in both PBS- and PBSA-based materials.

  16. Investigation of griseofulvin and hydroxypropylmethyl cellulose acetate succinate miscibility in ball milled solid dispersions.

    PubMed

    Al-Obaidi, Hisham; Lawrence, M Jayne; Al-Saden, Noor; Ke, Peng

    2013-02-25

    Solid dispersions of varying weight ratios compositions of the nonionic drug, griseofulvin and the hydrophilic, anionic polymer, hydroxylpropylmethyl cellulose acetate succinate, have been prepared by ball milling and the resulting samples characterized using a combination of Fourier transform infra-red spectroscopy, X-ray powder diffraction and differential scanning calorimetry. The results suggest that griseofulvin forms hydrogen bonds with the hydroxylpropylmethyl cellulose acetate succinate polymer when prepared in the form of a solid dispersion but not when prepared in a physical mixture of the same composition. As anticipated, the actual measured glass transition temperature of the solid dispersions displayed a linear relationship between that predicted using the Gordon-Taylor and Fox equations assuming ideal mixing, but interestingly only at griseofulvin contents less than 50 wt%. At griseofulvin concentrations greater than this, the measured glass transition temperature of the solid dispersions was almost constant. Furthermore, the crystalline content of the solid dispersions, as determined by differential scanning calorimetry and X-ray powder diffraction followed a similar trend in that the crystalline content significantly decreased at ratios less than 50 wt% of griseofulvin. When the physical mixtures of griseofulvin and the hydroxylpropylmethyl cellulose acetate succinate polymer were analyzed using the Flory-Huggins model, a negative free energy of mixing with an interaction parameter of -0.23 were obtained. Taken together these results suggest that anionic hydrophilic hydroxylpropylmethyl cellulose acetate succinate polymer is a good solvent for crystalline nonionic griseofulvin with the solubility of griseofulvin in the solid dispersion being was estimated to be within the range 40-50 wt%. Below this solubility limit, the amorphous drug exists as amorphous glassy solution while above these values the system is supersaturated and glassy suspension and

  17. A succinate-based composition reverses menopausal symptoms without sex hormone replacement therapy.

    PubMed

    Maevsky, E I; Peskov, A B; Uchitel, M L; Pogorelov, A G; Saharova, N Yu; Vihlyantseva, E F; Bogdanova, L A; Kondrashova, M N

    2008-01-01

    Menopausal transition is often accompanied by a variety of adverse pathological symptoms, currently treated with hormone replacement therapy, which is associated with a number of health risks. This report investigated the role of a food supplement--a composition of energy-exchange metabolites, with succinate as the main component--for treating menopausal syndrome. We studied the impact of a 4-week succinate-based food composition (SBC) treatment on the estral cycle, and bone mass and calcium content of aging mice. The impact of SBC on hormone levels and on the progression of several neurovegetative and psycho-emotional symptoms was further investigated in a randomized, double-blind, placebo-controlled clinical study of early menopausal women. Data were collected from questionnaires, Kupperman index scores, Spielberger-Hanin tests, and blood analysis of hormone levels taken at baseline and throughout the 5-week study. A "rejuvenating" effect of SBC on menopausal animals was observed, expressed as restoration of the estral cycle and an increase in the weight and calcium content of bone tissue. Furthermore, in the randomized, placebo-controlled clinical study in menopausal women, SBC-based monotherapy significantly lowered most subjectively evaluated characteristics of menopausal syndrome and increased blood serum levels of estradiol fourfold. This monotherapy also alleviated symptoms of some neurovegetative and psycho-emotional disorders, such as hot flushes, headache, and anxiety. Succinate-based therapy alleviated many biochemical symptoms of menopause in aging mice and early menopausal women, as well as neurovegetative and psycho-emotional disorders in women. Succinate-based therapy appeared to be free of adverse side effects.

  18. Conversion of levulinate into succinate through catalytic oxidative carbon-carbon bond cleavage with dioxygen.

    PubMed

    Liu, Junxia; Du, Zhongtian; Lu, Tianliang; Xu, Jie

    2013-12-01

    Grand Cleft Oxo: Levulinate, available from biomass, is oxidized into succinate through manganese(III)-catalyzed selective cleavage of CC bonds with molecular oxygen. In addition to levulinate, a wide range of aliphatic methyl ketones also undergo oxidative CC bond cleavage at the carbonyl group. This procedure offers a route to valuable dicarboxylic acids from biomass resources by nonfermentive approaches. PMID:23922234

  19. Volatility of NH3 from internally mixed sodium succinate-NH4SO4 particles

    NASA Astrophysics Data System (ADS)

    Wang, Na; Zhang, Yunhong

    2016-04-01

    Contributing the complicacy of atmospheric constituents, aerosol particles may undergo complicated heterogeneous reactions that have profound consequences on their hygroscopic properties and volatility. Ammonia (NH3) is a ubiquitous trace atmospheric gas in the troposphere and has negative effects on human health and climate forcing of ambient aerosols. In addition, atmospheric cycle of NH3 is complex in atmosphere, therefore it necessary to get insights to the complexity of gas-to-aerosol NH3 partitioning, which results in large uncertainties in the sources and distributions of NH3. By using in-situ Fourier transform infrared spectroscopy and attenuated total reflection (FTIR-ATR), we report here the volatility of NH3 from the laboratory generated sodium succinate with ammonium sulfate ((NH4)2SO4) at a 1:1 molar ratio as well as its effect on the hygroscopicity of the mixtures. The loss of the NH4+ peak at 1451cm-1 and the formation of peaks at 1718 and 1134 cm-1 due to C = O stretching asymmetric vibration of -COOH and ν3 (SO42-) stretching of sodium sulfate indicate that sodium succinate reacts with (NH4)2SO4, releasing NH3 and forming succinic acid and sodium sulfate on dehydration process. The formation of less hygroscopic succinic acid and volatility of NH3 in mixtures leads to a significant decrease in the total water content. To the best of our knowledge, this is the first report of the reaction between (NH4)2SO4 and dicarboxylate salts, which may represent an important particle-gas partitioning for ammonia and thus elucidate another underlying ammonia cycle in atmosphere. These results could be helpful to understand the mutual transformation process of dicarboxylic acids and dicarboxylate salts.

  20. Marked and variable inhibition by chemical fixation of cytochrome oxidase and succinate dehydrogenase in single motoneurons

    NASA Technical Reports Server (NTRS)

    Chalmers, G. R.; Edgerton, V. R.

    1989-01-01

    The effect of tissue fixation on succinate dehydrogenase and cytochrome oxidase activity in single motoneurons of the rat was demonstrated using a computer image processing system. Inhibition of enzyme activity by chemical fixation was variable, with some motoneurons being affected more than others. It was concluded that quantification of enzymatic activity in chemically fixed tissue provides an imprecise estimate of enzyme activities found in fresh-frozen tissues.

  1. Effect of vitamin E succinate on inflammatory cytokines induced by high-intensity interval training

    PubMed Central

    Sarir, Hadi; Emdadifard, Ghodsieh; Farhangfar, Homayoun; TaheriChadorneshin, Hossein

    2015-01-01

    Aim and Scope: The anti-inflammatory effect of vitamin E under moderate exercises has been evaluated. However, the effect of vitamin E succinate, which has more potent anti-inflammatory effect than other isomers of vitamin E has not been evaluated. Therefore, the aim of the present study was to evaluate the effects of vitamin E succinate on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) production induced by high-intensity interval training (HIIT). Materials and Methods: In the present study, 24 rats were randomly divided into control (C), supplementation (S), HIIT, and HIIT + supplementation (HIIT+S) groups. HIIT training protocol on a treadmill (at a speed of 40–54 m/min) and vitamin E succinate supplementation (60 mg/kg/day) was conducted for 6 weeks. Results: Serum IL-6 in the HIIT group significantly increased compared with the C group (350.42 ± 123.31 pg/mL vs 158.60 ± 41.96 pg/mL; P = 0.002). Also, serum TNF-α concentrations significantly enhanced (718.15 ± 133.42 pg/mL vs 350.87 ± 64.93 pg/mL; P = 0.001) in the HIIT group compared with the C group. Treatment of the training group with vitamin E numerically reduced IL-6 and TNF-α when compared with the HIIT group (217.31 ± 29.21 and 510.23 ± 217.88, respectively, P > 0.05). However, no significant changes were observed in serum TNF-α (P = 0.31) and IL-6 (P = 0.52) concentrations in the HIIT + S group compared with the C group. Conclusion: HIIT-induced IL-6 and TNF-α decreased by administration of Vitamin E succinate. PMID:26958053

  2. Fumarate and Succinate Regulate Expression of Hypoxia-inducible Genes via TET Enzymes.

    PubMed

    Laukka, Tuomas; Mariani, Christopher J; Ihantola, Tuukka; Cao, John Z; Hokkanen, Juho; Kaelin, William G; Godley, Lucy A; Koivunen, Peppi

    2016-02-19

    The TET enzymes are members of the 2-oxoglutarate-dependent dioxygenase family and comprise three isoenzymes in humans: TETs 1-3. These TETs convert 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) in DNA, and high 5-hmC levels are associated with active transcription. The importance of the balance in these modified cytosines is emphasized by the fact that TET2 is mutated in several human cancers, including myeloid malignancies such as acute myeloid leukemia (AML). We characterize here the kinetic and inhibitory properties of Tets and show that the Km value of Tets 1 and 2 for O2 is 30 μm, indicating that they retain high activity even under hypoxic conditions. The AML-associated mutations in the Fe(2+) and 2-oxoglutarate-binding residues increased the Km values for these factors 30-80-fold and reduced the Vmax values. Fumarate and succinate, which can accumulate to millimolar levels in succinate dehydrogenase and fumarate hydratase-mutant tumors, were identified as potent Tet inhibitors in vitro, with IC50 values ∼400-500 μm. Fumarate and succinate also down-regulated global 5-hmC levels in neuroblastoma cells and the expression levels of some hypoxia-inducible factor (HIF) target genes via TET inhibition, despite simultaneous HIFα stabilization. The combination of fumarate or succinate treatment with TET1 or TET3 silencing caused differential effects on the expression of specific HIF target genes. Altogether these data show that hypoxia-inducible genes are regulated in a multilayered manner that includes epigenetic regulation via TETs and 5-hmC levels in addition to HIF stabilization. PMID:26703470

  3. Succinate dehydrogenase activity and soma size of motoneurons innervating different portions of the rat tibialis anterior

    NASA Technical Reports Server (NTRS)

    Ishihara, A.; Roy, R. R.; Edgerton, V. R.

    1995-01-01

    The spatial distribution, soma size and oxidative enzyme activity of gamma and alpha motoneurons innervating muscle fibres in the deep (away from the surface of the muscle) and superficial (close to the surface of the muscle) portions of the tibialis anterior in normal rats were determined. The deep portion had a higher percentage of high oxidative fibres than the superficial portion of the muscle. Motoneurons were labelled by retrograde neuronal transport of fluorescent tracers: Fast Blue and Nuclear Yellow were injected into the deep portion and Nuclear Yellow into the superficial portion of the muscle. Therefore, motoneurons innervating the deep portion were identified by both a blue fluorescent cytoplasm and a golden-yellow fluorescent nucleus, while motoneurons innervating the superficial portion were identified by only a golden-yellow fluorescent nucleus. After staining for succinate dehydrogenase activity on the same section used for the identification of the motoneurons, soma size and succinate dehydrogenase activity of the motoneurons were measured. The gamma and alpha motoneurons innervating both the deep and superficial portions were located primarily at L4 and were intermingled within the same region of the dorsolateral portion of the ventral horn in the spinal cord. Mean soma size was similar for either gamma or alpha motoneurons in the two portions of the muscle. The alpha motoneurons innervating the superficial portion had a lower mean succinate dehydrogenase activity than those innervating the deep portion of the muscle. An inverse relationship between soma size and succinate dehydrogenase activity of alpha, but not gamma, motoneurons innervating both the deep and superficial portions was observed. Based on three-dimensional reconstructions within the spinal cord, there were no apparent differences in the spatial distribution of the motoneurons, either gamma or alpha, associated with the deep and superficial compartments of the muscle. The data

  4. Volatility of NH3 from internally mixed sodium succinate-NH4SO4 particles

    NASA Astrophysics Data System (ADS)

    Wang, Na; Zhang, Yunhong

    2016-04-01

    Contributing the complicacy of atmospheric constituents, aerosol particles may undergo complicated heterogeneous reactions that have profound consequences on their hygroscopic properties and volatility. Ammonia (NH3) is a ubiquitous trace atmospheric gas in the troposphere and has negative effects on human health and climate forcing of ambient aerosols. In addition, atmospheric cycle of NH3 is complex in atmosphere, therefore it necessary to get insights to the complexity of gas-to-aerosol NH3 partitioning, which results in large uncertainties in the sources and distributions of NH3. By using in-situ Fourier transform infrared spectroscopy and attenuated total reflection (FTIR-ATR), we report here the volatility of NH3 from the laboratory generated sodium succinate with ammonium sulfate ((NH4)2SO4) at a 1:1 molar ratio as well as its effect on the hygroscopicity of the mixtures. The loss of the NH4+ peak at 1451cm‑1 and the formation of peaks at 1718 and 1134 cm‑1 due to C = O stretching asymmetric vibration of -COOH and ν3 (SO42‑) stretching of sodium sulfate indicate that sodium succinate reacts with (NH4)2SO4, releasing NH3 and forming succinic acid and sodium sulfate on dehydration process. The formation of less hygroscopic succinic acid and volatility of NH3 in mixtures leads to a significant decrease in the total water content. To the best of our knowledge, this is the first report of the reaction between (NH4)2SO4 and dicarboxylate salts, which may represent an important particle-gas partitioning for ammonia and thus elucidate another underlying ammonia cycle in atmosphere. These results could be helpful to understand the mutual transformation process of dicarboxylic acids and dicarboxylate salts.

  5. Model-guided metabolic gene knockout of gnd for enhanced succinate production in Escherichia coli from glucose and glycerol substrates.

    PubMed

    Mienda, Bashir Sajo; Shamsir, Mohd Shahir; Illias, Rosli Md

    2016-04-01

    The metabolic role of 6-phosphogluconate dehydrogenase (gnd) under anaerobic conditions with respect to succinate production in Escherichia coli remained largely unspecified. Herein we report what are to our knowledge the first metabolic gene knockout of gnd to have increased succinic acid production using both glucose and glycerol substrates in E. coli. Guided by a genome scale metabolic model, we engineered the E. coli host metabolism to enhance anaerobic production of succinic acid by deleting the gnd gene, considering its location in the boundary of oxidative and non-oxidative pentose phosphate pathway. This strategy induced either the activation of malic enzyme, causing up-regulation of phosphoenolpyruvate carboxylase (ppc) and down regulation of phosphoenolpyruvate carboxykinase (ppck) and/or prevents the decarboxylation of 6 phosphogluconate to increase the pool of glyceraldehyde-3-phosphate (GAP) that is required for the formation of phosphoenolpyruvate (PEP). This approach produced a mutant strain BMS2 with succinic acid production titers of 0.35 g l(-1) and 1.40 g l(-1) from glucose and glycerol substrates respectively. This work further clearly elucidates and informs other studies that the gnd gene, is a novel deletion target for increasing succinate production in E. coli under anaerobic condition using glucose and glycerol carbon sources. The knowledge gained in this study would help in E. coli and other microbial strains development for increasing succinate production and/or other industrial chemicals.

  6. Actinobacillus succinogenes ATCC 55618 Fermentation Medium Optimization for the Production of Succinic Acid by Response Surface Methodology

    PubMed Central

    Zhu, Li-Wen; Wang, Cheng-Cheng; Liu, Rui-Sang; Li, Hong-Mei; Wan, Duan-Ji; Tang, Ya-Jie

    2012-01-01

    As a potential intermediary feedstock, succinic acid takes an important place in bulk chemical productions. For the first time, a method combining Plackett-Burman design (PBD), steepest ascent method (SA), and Box-Behnken design (BBD) was developed to optimize Actinobacillus succinogenes ATCC 55618 fermentation medium. First, glucose, yeast extract, and MgCO3 were identified to be key medium components by PBD. Second, preliminary optimization was run by SA method to access the optimal region of the key medium components. Finally, the responses, that is, the production of succinic acid, were optimized simultaneously by using BBD, and the optimal concentration was located to be 84.6 g L−1 of glucose, 14.5 g L−1 of yeast extract, and 64.7 g L−1 of MgCO3. Verification experiment indicated that the maximal succinic acid production of 52.7 ± 0.8 g L−1 was obtained under the identified optimal conditions. The result agreed with the predicted value well. Compared with that of the basic medium, the production of succinic acid and yield of succinic acid against glucose were enhanced by 67.3% and 111.1%, respectively. The results obtained in this study may be useful for the industrial commercial production of succinic acid. PMID:23093852

  7. Model-guided metabolic gene knockout of gnd for enhanced succinate production in Escherichia coli from glucose and glycerol substrates.

    PubMed

    Mienda, Bashir Sajo; Shamsir, Mohd Shahir; Illias, Rosli Md

    2016-04-01

    The metabolic role of 6-phosphogluconate dehydrogenase (gnd) under anaerobic conditions with respect to succinate production in Escherichia coli remained largely unspecified. Herein we report what are to our knowledge the first metabolic gene knockout of gnd to have increased succinic acid production using both glucose and glycerol substrates in E. coli. Guided by a genome scale metabolic model, we engineered the E. coli host metabolism to enhance anaerobic production of succinic acid by deleting the gnd gene, considering its location in the boundary of oxidative and non-oxidative pentose phosphate pathway. This strategy induced either the activation of malic enzyme, causing up-regulation of phosphoenolpyruvate carboxylase (ppc) and down regulation of phosphoenolpyruvate carboxykinase (ppck) and/or prevents the decarboxylation of 6 phosphogluconate to increase the pool of glyceraldehyde-3-phosphate (GAP) that is required for the formation of phosphoenolpyruvate (PEP). This approach produced a mutant strain BMS2 with succinic acid production titers of 0.35 g l(-1) and 1.40 g l(-1) from glucose and glycerol substrates respectively. This work further clearly elucidates and informs other studies that the gnd gene, is a novel deletion target for increasing succinate production in E. coli under anaerobic condition using glucose and glycerol carbon sources. The knowledge gained in this study would help in E. coli and other microbial strains development for increasing succinate production and/or other industrial chemicals. PMID:26878126

  8. Regulation of succinate-fuelled mitochondrial respiration in liver and skeletal muscle of hibernating thirteen-lined ground squirrels.

    PubMed

    Brown, Jason C L; Chung, Dillon J; Cooper, Alex N; Staples, James F

    2013-05-01

    Hibernating ground squirrels (Ictidomys tridecemlineatus) alternate between two distinct metabolic states throughout winter: torpor, during which metabolic rate (MR) and body temperature (Tb) are considerably suppressed, and interbout euthermia (IBE), during which MR and Tb briefly return to euthermic levels. Previous studies showed suppression of succinate-fuelled respiration during torpor in liver and skeletal muscle mitochondria; however, these studies used only a single, saturating succinate concentration. Therefore, they could not address whether mitochondrial metabolic suppression occurs under physiological substrate concentrations or whether differences in the kinetics of mitochondrial responses to changing substrate concentration might also contribute to mitochondrial metabolic regulation during torpor. The present study confirmed that succinate oxidation is reduced during torpor in liver and skeletal muscle at 37 and 10°C over a 100-fold range of succinate concentrations. At 37°C, this suppression resulted from inhibition of succinate dehydrogenase (SDH), which had a greater affinity for oxaloacetate (an SDH inhibitor) during torpor. At 10°C, SDH was not inhibited, suggesting that SDH inhibition initiates but does not maintain mitochondrial suppression during torpor. Moreover, in both liver and skeletal muscle, mitochondria from torpid animals maintained relatively higher respiration rates at low succinate concentrations, which reduces the extent of energy savings that can be achieved during torpor, but may also maintain mitochondrial oxidative capacity above some lower critical threshold, thereby preventing cellular and/or mitochondrial injury during torpor and facilitating rapid recruitment of oxidative capacity during arousal.

  9. Examination of sex differences in fatty acid ethyl ester and ethyl glucuronide hair analysis.

    PubMed

    Gareri, Joey; Rao, Chitra; Koren, Gideon

    2014-06-01

    Clinical studies examining performance of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in identifying excessive alcohol consumption have been primarily conducted in male populations. An impact of hair cosmetics in producing both false-negative EtG results and false-positive FAEE results has been demonstrated, suggesting a possible bias in female populations. This study evaluates FAEE-positive hair samples (>0.50 ng/mg) from n = 199 female and n = 73 male subjects for EtG. Higher FAEE/EtG concordance was observed amongst male over female subjects. Performance of multiple proposed EtG cut-off levels were assessed; amongst female samples, FAEE/EtG concordance was 36.2% (30 pg/mg), 36.7% (27 pg/mg), and 43.7% (20 pg/mg). Non-coloured hair demonstrated a two-fold increase in concordance (41.8 v. 20.8%) over coloured hair in the female cohort. FAEE levels did not differ between male and female subjects; however they were lower in coloured samples (p = 0.046). EtG was lower in female subjects (p = 0.019) and coloured samples (p = 0.026). A total of n = 111 female samples were discordant. Amongst discordant samples (EtG-negative), 26% had evidence of recent alcohol use including consultation histories (n = 20) and detectable cocaethylene (n = 9); 29% of discordant samples were coloured. False-negative risk with ethyl glucuronide analysis in females was mediated by cosmetic colouring. These findings suggest that combined analysis of FAEE and EtG is optimal when assessing a female population and an EtG cut-off of 20 pg/mg is warranted when using combined analysis. While concordant FAEE/EtG-positive findings constitute clear evidence, discordant FAEE/EtG findings should still be considered suggestive evidence of chronic excessive alcohol consumption. PMID:24817046

  10. Yttrium-succinates coordination polymers: Hydrothermal synthesis, crystal structure and thermal decomposition

    SciTech Connect

    Amghouz, Zakariae; Roces, Laura; Garcia-Granda, Santiago; Garcia, Jose R.; Souhail, Badredine; Mafra, Luis; Shi, Fa-nian; Rocha, Joao

    2009-12-15

    New polymeric yttrium-succinates, Y{sub 2}(C{sub 4}H{sub 4}O{sub 4}){sub 3}(H{sub 2}O){sub 4}.6H{sub 2}O and Y{sub 2}(C{sub 4}H{sub 4}O{sub 4}){sub 3}(H{sub 2}O){sub 2}, have been synthesized, and their structures (solved by single crystal XRD) are compared with that of Y{sub 2}(C{sub 4}H{sub 4}O{sub 4}){sub 3}(H{sub 2}O){sub 2}.H{sub 2}O. Three compounds were obtained as single phases, and their thermal behaviour is described. - Graphical abstract: In the field of coordination polymers or MOF's, few studies report on the polymorphs of Ln(III)-succinic acid. Here, we describe the hydrothermal synthesis and structural characterization of two novel yttrium-succinates coordination polymers, respectively 2D and 3D, Y{sub 2}(C{sub 4}H{sub 4}O{sub 4}){sub 3}(H{sub 2}O){sub 4}.6H{sub 2}O and Y{sub 2}(C{sub 4}H{sub 4}O{sub 4}){sub 3}(H{sub 2}O){sub 2}.

  11. Succinate dehydrogenase mutant of Listonella anguillarum protects rainbow trout against vibriosis.

    PubMed

    Altinok, Ilhan; Capkin, Erol; Karsi, Attila

    2015-10-13

    Listonella anguillarum is a Gram-negative facultative anaerobic rod causing hemorrhagic septicemia in marine and rarely in freshwater fish. Succinate dehydrogenase (SDH) plays an important role in the tricarboxylic acid (TCA) cycle by oxidizing succinate to fumarate while reducing ubiquinone to ubiquinol. Recent studies indicate that central metabolic pathways, including the TCA cycle, contribute to bacterial virulence. However, the role of SDH in L. anguillarum virulence has not been studied. Here, we report in-frame deletion of the succinate dehydrogenase iron-sulfur protein (SDHB) and its role in L. anguillarum virulence in rainbow trout. To accomplish this goal, upstream and downstream regions of the L. anguillarum sdhB gene were amplified in-frame and cloned into a suicide plasmid. The chromosomal sdhB gene of L. anguillarum was deleted by homologous recombination. Virulence and immunogenicity of the L. anguillarum ΔsdhB mutant (LaΔsdhB) were determined in rainbow trout. Results show that LaΔsdhB was highly attenuated in rainbow trout, and fish immunized with LaΔsdhB displayed high relative survival rate after exposure to wild type L. anguillarum. These findings indicate SDH is important in L. anguillarum virulence in rainbow trout, and LaΔsdhB could be used as an immersion, oral, or injection vaccine to protect rainbow trout against vibriosis.

  12. Crystallization and preliminary X-ray crystallographic studies of succinic semialdehyde dehydrogenase from Streptococcus pyogenes

    PubMed Central

    Jang, Eun Hyuk; Lim, Jong Eun; Chi, Young Min; Lee, Ki Seog

    2012-01-01

    Succinic semialdehyde dehydrogenase (SSADH) plays a critical role in the metabolism of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and catalyzes the NAD(P)+-coupled oxidation of succinic semialdehyde (SSA) to succinic acid (SA). SSADH from Streptococcus pyogenes has been purified and crystallized as the apoenzyme and in a complex with NAD+. The crystals of native and NAD+-complexed SSADH diffracted to resolutions of 1.6 and 1.7 Å, respectively, using a synchrotron-radiation source. Both crystals belonged to the orthorhombic space group P21212­1, with unit-cell parameters a = 93.3, b = 100.3, c = 105.1 Å for the native crystal and a = 93.3, b = 100.3, c = 105.0 Å for the complex crystal. Preliminary molecular replacement confirmed the presence of one dimer in both crystals, corresponding to a Matthews coefficient (V M) of 2.37 Å3 Da−1 and a solvent content of 48.0%. PMID:22442224

  13. Microbial production of Propionic and Succinic acid from Sorbitol using Propionibacterium acidipropionici.

    PubMed

    Duarte, Juliana C; Valença, Gustavo P; Moran, Paulo J S; Rodrigues, J Augusto R

    2015-01-01

    Three sequential fermentative batches were carried out with cell recycle in four simultaneously operating bioreactors maintained at pH 6.5, 30°C, and 100 rpm. P. acidipropionici ATCC 4875 was able to produce propionic and succinic acid from sorbitol. The concentration of propionic acid decreased slightly from 39.5 ± 5.2 g L(-1) to 34.4 ± 1.9 g L(-1), and that of succinic acid increased significantly from 6.1 ± 2.1 g L(-1) to 14.8 ± 0.9 g L(-1) through the sequential batches. In addition, a small amount of acetic acid was produced that decreased from 3.3 ± 0.4 g L(-1) to 2.0 ± 0.3 g L(-1) through the batches. The major yield for propionic acid was 0.613 g g(-1) in the first batch and succinic acid it was 0.212 g g(-1) in the third batch. The minor yield of acetic acid was 0.029 g g(-1), in the second and third batches.

  14. Novel FT-IR Microspectroscopic Census of Simple Starch Granules for Octenyl Succinate Ester Modification

    SciTech Connect

    Bai, Y.; Shi, Y; Wetzel, D

    2009-01-01

    Fourier transform infrared (FT-IR) microspectroscopy was used to investigate reaction homogeneity of octenyl succinic anhydride modification on waxy maize starch and detect uniformity of blends of modified and native starches. For the first time, the level and uniformity of chemical substitution on individual starch granules were analyzed by FT-IR microspectroscopy. More than 100 starch granules of each sample were analyzed one by one by FT-IR microspectroscopy. In comparison to the native starch, modified starch had two additional bands at 1723 and 1563 cm{sup -1}, indicative of ester formation in the modified starch. For the 3% modification level, the degree of substitution (DS) was low (0.019) and the distribution of the ester group was not uniform among starch granules. For the modified starch with DS of 0.073, 99% of individual starch granules had a large carbonyl band area, indicating that most granules were modified to a sufficient extent that the presence of their carbonyl ester classified them individually as being modified. However, the octenyl succinate concentration varied between granules, suggesting that the reaction was not uniform. When modified starch (DS = 0.073) was blended with native starch (3:7, w/w) to achieve a mixture with an average DS of 0.019, FT-IR microspectroscopy was able to detect heterogeneity of octenyl succinate in the blend and determine the ratio of the modified starch to the native starch granules.

  15. Engineering of Corynebacterium glutamicum for growth and succinate production from levoglucosan, a pyrolytic sugar substrate.

    PubMed

    Kim, Eun-Mi; Um, Youngsoon; Bott, Michael; Woo, Han Min

    2015-10-01

    Thermochemical processing provides continuous production of bio-oils from lignocellulosic biomass. Levoglucosan, a pyrolytic sugar substrate C6H10O5 in a bio-oil, has been used for ethanol production using engineered Escherichia coli. Here we provide the first example for succinate production from levoglucosan with Corynebacterium glutamicum, a well-known industrial amino acid producer. Heterologous expression of a gene encoding a sugar kinase from Lipomyces starkeyi, Gibberella zeae or Pseudomonas aeruginosa was employed for levoglucosan conversion in C. glutamicum because the wild type was unable to utilize levoglucosan as sole carbon source. As result, expression of a levoglucosan kinase (LGK) of L. starkeyi only enabled growth with levoglucosan as sole carbon source in CgXII minimal medium by catalyzing conversion of levoglucosan to glucose-6-phosphate. Subsequently, the lgk gene was expressed in an aerobic succinate producer of C. glutamicum, strain BL-1. The recombinant strain showed a higher succinate yield (0.25 g g(-1)) from 2% (w/v) levoglucosan than the reference strain BL-1 from 2% (w/v) glucose (0.19 g g(-1)), confirming that levoglucosan is an attractive carbon substrate for C. glutamicum producer strains. In summary, we demonstrated that a pyrolytic sugar could be a potential carbon source for microbial cell factories. PMID:26363018

  16. Advantage of Upregulation of Succinate Dehydrogenase in Staphylococcus aureus Biofilms ▿

    PubMed Central

    Gaupp, Rosmarie; Schlag, Steffen; Liebeke, Manuel; Lalk, Michael; Götz, Friedrich

    2010-01-01

    Previous studies have demonstrated that various tricarboxylic acid (TCA) cycle genes, particularly the succinate dehydrogenase genes (sdhCAB), are upregulated in Staphylococcus aureus biofilms. To better study the role of this enzyme complex, an sdhCAB deletion mutant (Δsdh) was constructed. Compared to the wild type (wt) the mutant was impaired in planktonic growth under aerobic conditions, excreted acetic acid could not be reused and accumulated continuously, succinate was excreted and found in the culture supernatant, and metabolome analysis with cells grown in chemically defined medium revealed reduced uptake/metabolism of some amino acids from the growth medium. Moreover, the mutant was able to counteract the steadily decreasing extracellular pH by increased urease activity. The addition of fumarate to the growth medium restored the wt phenotype. The mutant showed a small-colony variant (SCV)-like phenotype, a slight increase in resistance to various aminoglycoside antibiotics, and decreased pigmentation. The decreased growth under aerobic conditions is due to the interruption of the TCA cycle (indicated by the accumulation of succinate and acetic acid) with the consequence that many fewer reduction equivalents (NADH and FADH2) can fuel the respiratory chain. The results indicate that the TCA cycle is required for acetate and amino acid catabolism; its upregulation under biofilm conditions is advantageous under such nutrient- and oxygen-limited conditions. PMID:20207757

  17. Integrated production of cellulosic bioethanol and succinic acid from industrial hemp in a biorefinery concept.

    PubMed

    Kuglarz, Mariusz; Alvarado-Morales, Merlin; Karakashev, Dimitar; Angelidaki, Irini

    2016-01-01

    The aim of this study was to develop integrated biofuel (cellulosic bioethanol) and biochemical (succinic acid) production from industrial hemp (Cannabis sativa L.) in a biorefinery concept. Two types of pretreatments were studied (dilute-acid and alkaline oxidative method). High cellulose recovery (>95%) as well as significant hemicelluloses solubilization (49-59%) after acid-based method and lignin solubilization (35-41%) after alkaline H2O2 method were registered. Alkaline pretreatment showed to be superior over the acid-based method with respect to the rate of enzymatic hydrolysis and ethanol productivity. With respect to succinic acid production, the highest productivity was obtained after liquid fraction fermentation originated from steam treatment with 1.5% of acid. The mass balance calculations clearly showed that 149kg of EtOH and 115kg of succinic acid can be obtained per 1ton of dry hemp. Results obtained in this study clearly document the potential of industrial hemp for a biorefinery. PMID:26551652

  18. [Absorption of Uranium with Tea Oil Tree Sawdust Modified by Succinic Acid].

    PubMed

    Zhang, Xiao-feng; Chen, Di-yun; Peng, Yan; Liu, Yong-sheng; Xiong, Xue-ying

    2015-05-01

    In order to explore how the modification of succinic acid improves the adsorption of tea oil tree sawdust for uranium, the tea oil tree sawdust was modified by succinic acid, after the pretreatments of crushing, screening, alkalization and acidification. Infrared analysis indicated carboxylic acid groups and ester groups were added to the sawdust after modification, and scanning electron microscope demonstrated after modification the appearance of tea oil tree sawdust was transferred from the structure like compact and straight stripped into the structure like loose and wrinkled leaves, which meant modification increased its inner pores. By the static experiments, effects of reaction time between adsorbent and solvent, dosage of adsorbent, temperature, pH value and initial concentration of uranium were investigated. The results showed that after the modification by succinic acid, the absorption rate of tea oil tree sawdust for uranium increased significantly by about 20% in 12.5 mg · L(-1) initial concentration uranium solution. Adsorption equilibrium was achieved within 180 min, and the kinetic data can be well described by the pseudo-second-order kinetic model. The experimental adsorption isotherm followed the Langmuir and Freundlich models. In addition, the maximum adsorption amounts of tea oil tree sawdust after modification calculated from Langmuir equation raised from 21.413 3 to 31.545 7 mg · g(-1) at 35°C and pH 4.0. PMID:26314117

  19. Aqueous Phase Photo-Oxidation of Succinic Acid: Changes in Hygroscopic Properties and Reaction Products

    NASA Astrophysics Data System (ADS)

    Hudson, P. K.; Ninokawa, A.; Hofstra, J.; de Lijser, P.

    2013-12-01

    Atmospheric aerosol particles have been identified as important factors in understanding climate change. The extent to which aerosols affect climate is determined, in part, by hygroscopic properties which can change as a result of atmospheric processing. Dicarboxylic acids, components of atmospheric aerosol, have a wide range of hygroscopic properties and can undergo oxidation and photolysis reactions in the atmosphere. In this study, the hygroscopic properties of succinic acid aerosol, a non-hygroscopic four carbon dicarboxylic acid, were measured with a humidified tandem differential mobility analyzer (HTDMA) and compared to reaction products resulting from the aqueous phase photo-oxidation reaction of hydrogen peroxide and succinic acid. Reaction products were determined and quantified using gas chromatography-flame ionization detection (GC-FID) and GC-mass spectrometry (GC-MS) as a function of hydrogen peroxide:succinic acid concentration ratio and photolysis time. Although reaction products include larger non-hygroscopic dicarboxylic acids (e.g. adipic acid) and smaller hygroscopic dicarboxylic acids (e.g. malonic and oxalic acids), comparison of hygroscopic growth curves to Zdanovskii-Stokes-Robinson (ZSR) predictions suggests that the hygroscopic properties of many of the product mixtures are largely independent of the hygroscopicity of the individual components. This study provides a framework for future investigations to fully understand and predict the role of chemical reactions in altering atmospheric conditions that affect climate.

  20. Enhanced succinic acid productivity by expression of mgtCB gene in Escherichia coli mutant.

    PubMed

    Wang, Jing; Yang, Le; Wang, Dan; Dong, Lichun; Chen, Rachel

    2016-04-01

    In this study, a novel engineering Escherichia coli strain (CBMG111) with the expression of mgtCB gene was constructed for the enhanced fermentative production of succinic acid by utilizing the synergetic effect of mgtC gene to improve the growth of strains at the environment of low Mg(2+) concentration and mgtB to enhance the transport of Mg(2+) into cells. After the effect of the expression of the individual genes (mgtA, mgtB, mgtC) on the growth of E. coli was clarified, the fermentative production of succinic acid by CBMG111 was studied with the low-price mixture of Mg(OH)2 and NH3·H2O as the alkaline neutralizer and the biomass hydrolysates as the carbon sources, which demonstrated that the expression of mgtCB gene can significantly increase the productivity of succinic acid (2.97 g L(-1) h(-1)) compared with that by using the engineering strain with the overexpression of mgtA gene. PMID:26711444

  1. Efficient and repeated production of succinic acid by turning sugarcane bagasse into sugar and support.

    PubMed

    Chen, Pengcheng; Tao, Shengtao; Zheng, Pu

    2016-07-01

    Here we reported an endeavor in making full use of sugarcane bagasse for biological production of succinic acid. Through NaOH pre-treatment and multi-enzyme hydrolysis, a reducing sugar solution mainly composed of glucose and xylose was obtained from the sugarcane bagasse. By optimizing portions of cellulase, xylanase, β-glucanase and pectinase in the multi-enzyme "cocktail", the hydrolysis percentage of the total cellulose in pre-treated sugarcane bagasse can be as high as 88.5%. A. succinogenes CCTCC M2012036 was used for converting reducing sugars into succinic acid in a 3-L bioreactor with a sugar-fed strategy to prevent cell growth limitation. Importantly, cells were found to be adaptive on the sugarcane bagasse residue, offering possibilities of repeated batch fermentation and replacement for MgCO3 with soluble NaHCO3 in pH modulation. Three cycles of fermentation without activity loss were realized with the average succinic acid yield and productivity to be 80.5% and 1.65g·L(-1)·h(-1). PMID:27035471

  2. Study on oil absorbency of succinic anhydride modified banana cellulose in ionic liquid.

    PubMed

    Shang, Wenting; Sheng, Zhanwu; Shen, Yixiao; Ai, Binling; Zheng, Lili; Yang, Jingsong; Xu, Zhimin

    2016-05-01

    Banana cellulose contained number of hydrophilic hydroxyl groups which were succinylated to be hydrophobic groups with high oil affinity. Succinic anhydride was used to modify banana cellulose in 1-allyl-3-methylimidazolium chloride ionic liquid in this study. The modified banana cellulose had a high oil absorption capacity. The effects of reaction time, temperature, and molar ratio of succinic anhydride to anhydroglucose on the degree of substitution of modified banana cellulose were evaluated. The optimal reaction condition was at a ratio of succinic anhydride and anhydroglucose 6:1 (m:m), reaction time 60min and temperature 90°C. The maximum degree of acylation reaction reached to 0.37. The characterization analysis of the modified banana cellulose was performed using X-ray diffractometer, Fourier transform infrared spectrometer, scanning electron microscopy and thermogravimetry. The oil absorption capacity and kinetics of the modified banana cellulose were evaluated at the modified cellulose dose (0.025-0.3g), initial oil amount (5-30g), and temperature (15-35°C) conditions. The maximum oil absorption capacity was 32.12g/g at the condition of the cellulose dose (0.05g), initial oil amount (25g) and temperature (15°C). The kinetics of oil absorption of the cellulose followed a pseudo-second-order model. The results of this study demonstrated that the modified banana cellulose could be used as an efficient bio-sorbent for oil adsorption. PMID:26877005

  3. Redox stress is not essential for the pseudo-hypoxic phenotype of succinate dehydrogenase deficient cells.

    PubMed

    Selak, Mary A; Durán, Raul V; Gottlieb, Eyal

    2006-01-01

    HIFalpha prolyl hydroxylases (PHDs) are a family of enzymes that regulate protein levels of the alpha subunit of the hypoxia inducible transcription factor (HIF) under different oxygen levels. PHDs catalyse the conversion of a prolyl residue, molecular oxygen and alpha-ketoglutarate to hydroxy-prolyl, carbon dioxide and succinate in a reaction dependent on ferrous iron and ascorbate as cofactors. Recently it was shown that pseudo-hypoxia, HIF induction under normoxic conditions, is an important feature of tumours generated as a consequence of inactivation of the mitochondrial tumour suppressor 'succinate dehydrogenase' (SDH). Two models have been proposed to describe the link between SDH inhibition and HIF activation. Both models suggest that a mitochondrial-generated signal leads to the inhibition of PHDs in the cytosol, however, the models differ in the nature of the proposed messenger. The first model postulates that mitochondrial-generated hydrogen peroxide mediates signal transduction while the second model implicates succinate as the molecular messenger which leaves the mitochondrion and inhibits PHDs in the cytosol. Here we show that pseudo-hypoxia can be observed in SDH-suppressed cells in the absence of oxidative stress and in the presence of effective antioxidant treatment.

  4. Nano-encapsulation of coenzyme Q10 using octenyl succinic anhydride modified starch.

    PubMed

    Cheuk, Sherwin Y; Shih, Frederick F; Champagne, Elaine T; Daigle, Kim W; Patindol, James A; Mattison, Christopher P; Boue, Stephen M

    2015-05-01

    Octenyl succinic anhydride modified starch (OSA-ST) was used to encapsulate coenzyme Q10 (CoQ10). CoQ10 was dissolved in rice bran oil and incorporated into an aqueous OSA-ST solution. High pressure homogenisation of the mixture was conducted at 170 MPa for 56 cycles. The resulting emulsion had a particle size range of 200-300 nm and the absolute zeta potential varied between 8.4 and 10.6 mV. CoQ10 retention of the emulsion and freeze dried products, determined by a hexane rinse, was 98.2%. Reconstitution of the freeze dried product in Mcllvaine citrate-phosphate buffers with pH values of 3-5 and temperatures at 4 and 25 °C had very little effect on the range and distribution of the nanoparticles' size. The inflection point of the zeta potential and pH plot occurred at the first pKa of succinic acid (pH 4.2), indicating succinate as the main influence over zeta potential.

  5. Integrated production of cellulosic bioethanol and succinic acid from industrial hemp in a biorefinery concept.

    PubMed

    Kuglarz, Mariusz; Alvarado-Morales, Merlin; Karakashev, Dimitar; Angelidaki, Irini

    2016-01-01

    The aim of this study was to develop integrated biofuel (cellulosic bioethanol) and biochemical (succinic acid) production from industrial hemp (Cannabis sativa L.) in a biorefinery concept. Two types of pretreatments were studied (dilute-acid and alkaline oxidative method). High cellulose recovery (>95%) as well as significant hemicelluloses solubilization (49-59%) after acid-based method and lignin solubilization (35-41%) after alkaline H2O2 method were registered. Alkaline pretreatment showed to be superior over the acid-based method with respect to the rate of enzymatic hydrolysis and ethanol productivity. With respect to succinic acid production, the highest productivity was obtained after liquid fraction fermentation originated from steam treatment with 1.5% of acid. The mass balance calculations clearly showed that 149kg of EtOH and 115kg of succinic acid can be obtained per 1ton of dry hemp. Results obtained in this study clearly document the potential of industrial hemp for a biorefinery.

  6. Water uptake properties of internally mixed sodium halide and succinic acid particles

    NASA Astrophysics Data System (ADS)

    Miñambres, Lorena; Méndez, Estíbaliz; Sánchez, María N.; Castaño, Fernando; Basterretxea, Francisco J.

    2011-10-01

    Sea salt aerosols include appreciable fractions of organic material, that can affect properties such as hygroscopicity, phase transition or chemical reactivity. Although sodium chloride is the major component of marine salt, bromide and iodide ions tend to accumulate onto particle surfaces and influence their behaviour. The hygroscopic properties of internally mixed submicrometric particles composed of succinic acid (SA) and NaX (where X = F, Cl, Br or I) have been studied by infrared absorption spectroscopy in an aerosol flow cell at ambient temperature for different relative succinic acid/NaX compositions. The results show that deliquescence relative humidities of SA/NaF and SA/NaCl are equal to those of the pure sodium halides. SA/NaBr particles, on the other hand, deliquesce at lower relative humidities than pure NaBr particles, the effect being more marked as the SA/NaBr mass ratio approaches unity. The SA/NaI system behaves as a non-deliquescent system, absorbing liquid water at all relative humidities, as in pure NaI. Succinic acid phase in the particles has been spectroscopically monitored at given values of both RH and SA/NaX solute mass ratio. The different hygroscopic properties as the halogen ion is changed can be rationalized in terms of simple thermodynamic arguments and can be attributed to the relative contributions of ion-molecule interactions in the solid particles. The observed behaviour is of interest for tropospheric sea salt aerosols mixed with organic acids.

  7. Differential fate of erythromycin and beta-lactam resistance genes from swine lagoon waste under different aquatic conditions.

    PubMed

    Knapp, Charles W; Zhang, Wen; Sturm, Belinda S M; Graham, David W

    2010-05-01

    The attenuation and fate of erythromycin-resistance-methylase (erm) and extended-spectrum beta-lactamse (bla) genes were quantified over time in aquatic systems by adding 20-L swine waste to 11,300-L outdoor mesocosms that simulated receiving water conditions below intensive agricultural operations. The units were prepared with two different light-exposure scenarios and included artificial substrates to assess gene movement into biofilms. Of eleven genes tested, only erm(B), erm(F), bla(SHV) and bla(TEM) were found in sufficient quantity for monitoring. The genes disappeared rapidly from the water column and first-order water-column disappearance coefficients were calculated. However, detected gene levels became elevated in the biofilms within 2 days, but then disappeared over time. Differences were observed between sunlight and dark treatments and among individual genes, suggesting that ecological and gene-specific factors play roles in the fate of these genes after release into the environment. Ultimately, this information will aid in generating better predictive models for gene fate. PMID:20053492

  8. Postantibiotic effects and postantibiotic sub-MIC effects of erythromycin, roxithromycin, tilmicosin, and tylosin on Pasteurella multocida.

    PubMed

    Lim, J; Yun, H

    2001-06-01

    When intermittent dosing is used during treatment, the concentrations of antibiotics fluctuate and subinhibitory concentrations may occur between doses. Postantibiotic effects (PAEs) and postantibiotic subinhibitory effects (PA SMEs) on bacteria may provide additional, valuable information for the rational use of a drug in clinical practice. In this study tilmicosin was the most active antibiotic tested against P. multocida type D with MICs ranging from 4-16 mg/l. Roxithromycin and tilmicosin induced a statistically significantly longer PAE than did tylosin against P. multocida types A and D (P < 0.05). The duration of PAEs and PA SMEs were proportional to the concentrations of drugs used for exposure. The PA SMEs were substantially longer than PAEs on P. multocida. Tilmicosin had a longer PA SME compared with erythromycin, roxithromycin and tylosin for P. multocida. The computerized incubator used in the present study provided an efficient and convenient determination of PAE and PA SME, allowing frequent measurements of the bacterial growth. PMID:11397617

  9. Erythromycin and 5S rRNA binding properties of the spinach chloroplast ribosomal protein CL22.

    PubMed Central

    Carol, P; Rozier, C; Lazaro, E; Ballesta, J P; Mache, R

    1993-01-01

    The spinach chloroplast ribosomal protein (r-protein) CL22 contains a central region homologous to the Escherichia coli r-protein L22 plus long N- and C-terminal extensions. We show in this study that the CL22 combines two properties which in E. coli ribosome are split between two separate proteins. The CL22 which binds to the 5S rRNA can also be linked to an erythromycin derivative added to the 50S ribosomal subunit. This latter property is similar to that of the E. coli L22 and suggests a similar localization in the 50S subunit. We have overproduced the r-protein CL22 and deleted forms of this protein in E. coli. We show that the overproduced CL22 binds to the chloroplast 5S rRNA and that the deleted protein containing the N- and C-terminal extensions only has lost the 5S rRNA binding property. We suggest that the central homologous regions of the CL22 contains the RNA binding domain. Images PMID:8441674

  10. Synthesis, characterization and in vitro evaluation of amphiphilic ion pairs of erythromycin and kanamycin antibiotics with liposaccharides.

    PubMed

    Pignatello, Rosario; Simerska, Pavla; Leonardi, Antonio; Abdelrahim, Adel S; Petronio, Giulio Petronio; Fuochi, Virginia; Furneri, Pio Maria; Ruozi, Barbara; Toth, Istvan

    2016-09-14

    The hydrophilic ion paring strategy (HIP) is a method explored to improve the cell/tissue uptake of poorly adsorbed drugs and to optimize their physico-chemical characteristics. In this context, we here describe the synthesis of some ion pairs of two model cationic antibiotics, erythromycin (ERY) and kanamycin A (KAN), with liposaccharides having different levels of lipophilicity and charge. The formation of drug-liposaccharide complexes was confirmed by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) analysis. The effect of the amphiphilic liposaccharide moieties on the antimicrobial activity of ERY and KAN was assessed by measuring the minimal inhibitory concentration (MIC) of the compounds against a panel of bacterial strains that were susceptible or resistant to the parent antibiotics. The ion pairing did not depress the in vitro antibiotic activity, although no lowering of MIC values was registered. The experimental findings would motivate the future investigation of this ion pairing strategy in drug design, for instance allowing improvement of the encapsulation efficiency of hydrophilic antibiotics in lipid-based nanocarriers, or changing their in vivo biodistribution and pharmacokinetic profile. PMID:27236014

  11. A histomorphometric study of the effect of doxycycline and erythromycin on bone formation in dental alveolar socket of rat

    PubMed Central

    Shahabooei, Mohammad; Razavi, Sayed Mohammad; Minaiyan, Mohsen; Birang, Reza; Behfarnia, Parichehr; Yaghini, Jaber; Naghsh, Narges; Ghalayani, Parichehr; Hajisadeghi, Samira

    2015-01-01

    Background: The aim of the present study was to evaluate whether subantimicrobial doses of doxycycline (DOX) and erythromycin (EM) used for the treatment of peri-implant osteolysis due to their anti-osteoclastogenesis can interfere with the osseous wound healing process in rat alveolar socket. Materials and Methods: Forty-five male Wistar rats had their first maxillary right molar extracted and were divided into three groups. DOX and EM at the doses of 5 mg/kg/day orally (p.o.) and 2 mg/kg/day intraperitoneally (i.p.) were administered respectively to two separate groups for 7 days after operation. In the control group the animals received normal saline (5 ml/kg). Five rats were sacrificed at 7, 14 and 21 days post-extraction in each study group. A histomorphometric analysis was used to evaluate new bone formation inside the alveolar socket. Significant level was set at 0.05. Results: The findings showed that the percentage of new bone formation (NBF) enhanced significantly on days 7 and 14. There was no significant difference in the NBF between DOX and EM groups. Conclusion: Short-term treatment with both DOX and EM enhanced new bone formation without any advances in favor of each drug. PMID:25878996

  12. Erythromycin- and copper-resistant Enterococcus hirae from marine sediment and co-transfer of erm(B) and tcrB to human Enterococcus faecalis.

    PubMed

    Pasquaroli, Sonia; Di Cesare, Andrea; Vignaroli, Carla; Conti, Giulia; Citterio, Barbara; Biavasco, Francesca

    2014-09-01

    An erythromycin-, copper- and cadmium-resistant isolate of Enterococcus hirae from marine sediment was shown to harbor the plasmid pRE25 and to co-transfer erm(B) and tcrB to Enterococcus faecalis JH2-2. These data highlight the scope for antibiotic resistance selection by the marine environment through heavy metals and its possible involvement in antibiotic-resistant enterococcal infections.

  13. Comparison of minimum inhibitory concentration by broth microdilution testing versus standard disc diffusion testing in the detection of penicillin, erythromycin and ciprofloxacin resistance in viridans group streptococci.

    PubMed

    Maeda, Yasunori; Goldsmith, Colin E; Coulter, Wilson A; Mason, Charlene; Dooley, James S G; Lowery, Colm J; Millar, B Cherie; Moore, John E

    2011-12-01

    The aim of this study was to investigate the reliability of disc diffusion testing with penicillin, erythromycin and ciprofloxacin within the viridans group streptococci (VGS). In total, the antibiotic susceptibilities of 167 VGS isolates were compared by standard disc diffusion and broth microdilution methods, and these phenotypic data were compared to the carriage of the respective gene resistance determinants [ermB and mefA/E (macrolides); QRDR, gyrA, gyrB, parC and parE (quinolones)]. Overall, there were 35 discrepancies [resistant by MIC and susceptible by zone diameter (21.0%)] between MIC and disc diameter when penicillin susceptibility was interpreted by Clinical and Laboratory Standards Institute criteria. Scattergrams showed a bimodal distribution between non-susceptible and susceptible strains when erythromycin susceptibility was tested by both methods. Thirty-four (20.4%) isolates were categorized as resistant by MIC breakpoints, while disc diameter defined these as having intermediate resistance. With ciprofloxacin, three isolates (1.8%) showed minor discrepancies between MIC breakpoints and disc diameter. Isolates non-susceptible to all three antimicrobial agents tested were reliably distinguished from susceptible isolates by disc diffusion testing, except for the detection of low-level resistance to penicillin, where broth microdilution or an alternative quantitative MIC method should be used. Otherwise, we conclude that disc diffusion testing is a reliable method to detect strains of VGS non-susceptible to penicillin, erythromycin and ciprofloxacin, as demonstrated with their concordance to their gene resistance characteristics.

  14. Effects of Low-Dose and Long-Term Treatment with Erythromycin on Interleukin-17 and Interleukin-23 in Peripheral Blood and Induced Sputum in Patients with Stable Chronic Obstructive Pulmonary Disease

    PubMed Central

    Tan, Caimei; Huang, Huijuan; Zhang, Jianquan; He, Zhiyi; Zhong, Xiaoning; Bai, Jing

    2016-01-01

    Objective. To study the effects of low-dose and long-term treatment with erythromycin on IL-17 and IL-23, in peripheral blood and induced sputum, in patients with stable chronic obstructive pulmonary disease (COPD). Methods. Patients were randomly divided into placebo-treated group, group A (12 months of additive treatment with erythromycin, N = 18), and group B (6 months of additive treatment with erythromycin followed by 6 months of follow-up, N = 18). Inflammatory cells in induced sputum, pulmonary function, and the 6-minute walk distance (6MWD) were analyzed. Concentrations of IL-17 and IL-23 in peripheral blood and sputum were measured using enzyme-linked immunosorbent assays. Results. After treatment, sputum and peripheral blood concentrations of IL-17 and IL-23 significantly decreased in groups A and B compared with placebo-treated group. There were no significant differences after erythromycin withdrawal at months 9 and 12 in group B compared with placebo-treated group. An increase in 6MWD was observed after treatment. Conclusions. Erythromycin was beneficial and reduced airway inflammation in COPD patients. Underlying mechanisms may involve inhibition of IL-17 and IL-23 mediated airway inflammation. COPD patients treated with erythromycin for 6 months experienced improved exercise capacity. Finally, treatment for 12 months may be more effective than treatment for 6 months. PMID:27127346

  15. Toward homosuccinate fermentation: metabolic engineering of Corynebacterium glutamicum for anaerobic production of succinate from glucose and formate.

    PubMed

    Litsanov, Boris; Brocker, Melanie; Bott, Michael

    2012-05-01

    Previous studies have demonstrated the capability of Corynebacterium glutamicum for anaerobic succinate production from glucose under nongrowing conditions. In this work, we have addressed two shortfalls of this process, the formation of significant amounts of by-products and the limitation of the yield by the redox balance. To eliminate acetate formation, a derivative of the type strain ATCC 13032 (strain BOL-1), which lacked all known pathways for acetate and lactate synthesis (Δcat Δpqo Δpta-ackA ΔldhA), was constructed. Chromosomal integration of the pyruvate carboxylase gene pyc(P458S) into BOL-1 resulted in strain BOL-2, which catalyzed fast succinate production from glucose with a yield of 1 mol/mol and showed only little acetate formation. In order to provide additional reducing equivalents derived from the cosubstrate formate, the fdh gene from Mycobacterium vaccae, coding for an NAD(+)-coupled formate dehydrogenase (FDH), was chromosomally integrated into BOL-2, leading to strain BOL-3. In an anaerobic batch process with strain BOL-3, a 20% higher succinate yield from glucose was obtained in the presence of formate. A temporary metabolic blockage of strain BOL-3 was prevented by plasmid-borne overexpression of the glyceraldehyde 3-phosphate dehydrogenase gene gapA. In an anaerobic fed-batch process with glucose and formate, strain BOL-3/pAN6-gap accumulated 1,134 mM succinate in 53 h with an average succinate production rate of 1.59 mmol per g cells (dry weight) (cdw) per h. The succinate yield of 1.67 mol/mol glucose is one of the highest currently described for anaerobic succinate producers and was accompanied by a very low level of by-products (0.10 mol/mol glucose).

  16. Fragrance material review on ethyl phenyl carbinyl acetate.

    PubMed

    McGinty, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of ethyl phenyl carbinyl acetate when used as a fragrance ingredient is presented. Ethyl phenyl carbinyl acetate is a member of the fragrance structural group Aryl Alkyl Alcohol Simple Acid Esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for ethyl phenyl carbinyl acetate were evaluated, then summarized, and includes: physical properties; acute toxicity; skin irritation; and skin sensitization data. A safety assessment of the entire AAASAE will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances.

  17. Fragrance material review on 2-(p-tolyloxy)ethyl acetate.

    PubMed

    McGinty, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of 2-(p-tolyloxy)ethyl acetate when used as a fragrance ingredient is presented. 2-(p-tolyloxy)ethyl acetate is a member of the fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 2-(p-tolyloxy)ethyl acetate were evaluated, then summarized, and includes physical properties data. A safety assessment of the entire AAASAE will be published simultaneously with this document. Please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances.

  18. Fragrance material review on 2-(p-tolyloxy)ethyl acetate.

    PubMed

    McGinty, D; Letizia, C S; Api, A M

    2012-09-01

    A toxicologic and dermatologic review of 2-(p-tolyloxy)ethyl acetate when used as a fragrance ingredient is presented. 2-(p-tolyloxy)ethyl acetate is a member of the fragrance structural group aryl alkyl alcohol simple acid esters (AAASAE). The AAASAE fragrance ingredients are prepared by reacting an aryl alkyl alcohol with a simple carboxylic acid (a chain of 1-4 carbons) to generate formate, acetate, propionate, butyrate, isobutyrate and carbonate esters. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 2-(p-tolyloxy)ethyl acetate were evaluated, then summarized, and includes physical properties data. A safety assessment of the entire AAASAE will be published simultaneously with this document. Please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all AAASAE in fragrances. PMID:22414652

  19. NEW GROUND-STATE MEASUREMENTS OF ETHYL CYANIDE

    SciTech Connect

    Brauer, Carolyn S.; Pearson, John C.; Drouin, Brian J.; Yu, Shanshan

    2009-09-01

    The spectrum of ethyl cyanide, or propionitrile (CH{sub 3}CH{sub 2}CN), has been repeatedly observed in the interstellar medium with large column densities and surprisingly high temperatures in hot core sources. The construction of new, more sensitive, observatories accessing higher frequencies such as Herschel, ALMA, and SOFIA have made it important to extend the laboratory data for ethyl cyanide to coincide with the capabilities of the new instruments. We report extensions of the laboratory measurements of the rotational spectrum of ethyl cyanide in its ground vibrational state to 1.6 THz. A global analysis of the ground state, which includes all of the previous data and 3356 newly assigned transitions, has been fitted to within experimental error to J = 132, K = 36, using both Watson A-reduced and Watson S-reduced Hamiltonians.

  20. Performance of biodegradable microcapsules of poly(butylene succinate), poly(butylene succinate-co-adipate) and poly(butylene terephthalate-co-adipate) as drug encapsulation systems.

    PubMed

    Brunner, Cornelia Theresa; Baran, Erkan Türker; Pinho, Elisabete Duarte; Reis, Rui Luís; Neves, Nuno Meleiro

    2011-06-01

    Poly(butylene succinate) (PBSu), poly(butylene succinate-co-adipate) (PBSA) and poly(butylene terephthalate-co-adipate) (PBTA) microcapsules were prepared by the double emulsion/solvent evaporation method. The effect of polymer and poly(vinyl alcohol) (PVA) concentration on the microcapsule morphologies, drug encapsulation efficiency (EE) and drug loading (DL) of bovine serum albumin (BSA) and all-trans retinoic acid (atRA) were all investigated. As a result, the sizes of PBSu, PBSA and PBTA microcapsules were increased significantly by varying polymer concentrations from 6 to 9%. atRA was encapsulated into the microcapsules with an high level of approximately 95% EE. The highest EE and DL of BSA were observed at 1% polymer concentration in values of 60 and 37%, respectively. 4% PVA was found as the optimum concentration and resulted in 75% EE and 14% DL of BSA. The BSA release from the capsules of PBSA was the longest, with 10% release in the first day and a steady release of 17% until the end of day 28. The release of atRA from PBSu microcapsules showed a zero-order profile for 2 weeks, keeping a steady release rate during 4 weeks with a 9% cumulative release. Similarly, the PBSA microcapsules showed a prolonged and a steady release of atRA during 6 weeks with 12% release. In the case of PBTA microcapsules, after a burst release of 10% in the first day, showed a parabolic release profile of atRA during 42 days, releasing 36% of atRA.

  1. Nitrosamine-induced carcinogenesis. The alkylation of N-7 of guanine of nucleic acids of the rat by diethylnitrosamine, N-ethyl-N-nitrosourea and ethyl methanesulphonate

    PubMed Central

    Swann, P. F.; Magee, P. N.

    1971-01-01

    1. The extent of ethylation of N-7 of guanine in the nucleic acids of rat tissue in vivo by diethylnitrosamine, N-ethyl-N-nitrosourea and ethyl methanesulphonate was measured. 2. All compounds produced measurable amounts of 7-ethyl-guanine. 3. A single dose of diethylnitrosamine or N-ethyl-N-nitrosourea produced tumours of the kidney in the rat. Three doses of ethyl methanesulphonate produced kidney tumours, but a single dose did not. 4. A single dose of diethylnitrosamine produced twice as much ethylation of N-7 of guanine in DNA of kidney as did N-ethyl-N-nitrosourea. A single dose of both compounds induced kidney tumours, although of a different histological type. 5. A single dose of ethyl methanesulphonate produced ten times as much ethylation of N-7 of guanine in kidney DNA as did N-ethyl-N-nitrosourea without producing tumours. 6. The relevance of these findings to the hypothesis that alkylation of a cellular component is the mechanism of induction of tumours by nitroso compounds is discussed. PMID:5145908

  2. Assistance of ethyl glucuronide and ethyl sulfate in the interpretation of postmortem ethanol findings.

    PubMed

    Krabseth, Hege; Mørland, Jørg; Høiseth, Gudrun

    2014-09-01

    Postmortem ethanol formation is a well-known problem in forensic toxicology. The aim of this study was to interpret findings of ethanol in blood, in a large collection of forensic autopsy cases, by use of the nonoxidative ethanol metabolites, ethyl glucuronide (EtG), and ethyl sulfate (EtS). In this study, according to previously published literature, antemortem ethanol ingestion was excluded in EtS-negative cases. Among 493 ethanol-positive forensic autopsy cases, collected during the study period, EtS was not detected in 60 (12 %) of the cases. Among cases with a blood alcohol concentration (BAC) of ≤ 0.54 g/kg, antemortem ethanol ingestion was excluded in 38 % of the cases, while among cases with a BAC of ≥ 0.55 g/kg, antemortem ethanol ingestion was excluded in 2.2 % of the cases. For all cases where ethanol was measured at a concentration >1.0 g/kg, EtS was detected. The highest blood ethanol concentration in which EtS was not detected was 1.0 g/kg. The median concentrations of EtG and EtS in blood were 9.5 μmol/L (range: not detected (n.d.) 618.1) and 9.2 μmol/L (range: n.d. 182.5), respectively. There was a statistically significant positive correlation between concentration levels of ethanol and of EtG (Spearman's rho=0.671, p<0.001) and EtS (Spearman's rho=0.670, p<0.001), respectively. In conclusion, this study showed that in a large number of ethanol-positive forensic autopsy cases, ethanol was not ingested before the time of death, particularly among cases where ethanol was present in lower blood concentrations. Routine measurement of EtG and EtS should therefore be recommended, especially in cases with BAC below 1 g/kg. PMID:24935750

  3. Blood kinetics of ethyl glucuronide and ethyl sulphate in heavy drinkers during alcohol detoxification.

    PubMed

    Høiseth, Gudrun; Morini, Luca; Polettini, Aldo; Christophersen, Asbjørg; Mørland, Jørg

    2009-07-01

    Studies of ethyl glucuronide (EtG) blood kinetics have so far been performed on healthy volunteers with ingestion of low to moderate doses of ethanol. These data are not necessarily transferable to heavy drinkers where the consumed doses of ethanol are much higher. The aim of this study was to investigate the pharmacokinetics of EtG and ethyl sulphate (EtS) in blood in heavy drinkers after termination of alcohol ingestion. Sixteen patients from an alcohol withdrawal clinic were included directly after admission. Time of end of drinking, estimated daily intake of ethanol (EDI) and medical history were recorded. Three to five blood samples over 20-43 h were collected from each patient subsequent to admission. The median EDI was 172 g (range 60-564). The first sample was collected median 2.5 h after end of drinking (range 0.5-23.5). Two patients had levels of EtG and EtS below LOQ in all samples, the first collected 19.25 and 23.5 h after cessation of drinking, respectively. Of the remaining 14 patients, one subject, suffering from both renal and hepatic disease, showed concentrations of EtG and EtS substantially higher than the rest of the material. This patient's initial value of EtG was 17.9 mg/L and of EtS 5.9 mg/L, with terminal elimination half lives of 11.9 h for EtG and 12.5 h for EtS. Among the remaining 13 patients, the initial median values were 0.7 g/L (range 0-3.7) for ethanol, 1.7 mg/L (range 0.1-5.9) for EtG and 0.9 mg/L (range 0.1-1.9) for EtS. Elimination occurred with a median half-life of 3.3 h for EtG (range 2.6-4.3) and 3.6 h for EtS (range 2.7-5.4). In conclusion, elimination of EtG in heavy drinkers did not significantly differ from healthy volunteers, and EtS appeared to have similar elimination rate. In the present work, there was one exception to this, and we propose that this could be explained by the patient's renal disease, which would delay excretion of these conjugated metabolites. PMID:19395207

  4. Assessing the concentrations and risks of toxicity from the antibiotics ciprofloxacin, sulfamethoxazole, trimethoprim and erythromycin in European rivers.

    PubMed

    Johnson, Andrew C; Keller, Virginie; Dumont, Egon; Sumpter, John P

    2015-04-01

    This study evaluated the potential concentrations of four antibiotics: ciprofloxacin (CIP), sulfamethoxazole (SUF), trimethoprim (TRI) and erythromycin (ERY) throughout the rivers of Europe. This involved reviewing national consumption rates together with assessing excretion and sewage treatment removal rates. From this information, it was possible to construct best, expected and worst case scenarios for the discharge of these antibiotics into rivers. Consumption data showed surprising variations, up to 200-fold in the popularity of different antibiotics across different European nations. Using the water resources model GWAVA which has a spatial resolution of approximately 6×9 km, river water concentrations throughout Europe were predicted based on 31-year climate data. The modelled antibiotic concentrations were within the range of measurements reported previously in European effluents and rivers. With the expected scenario, the predicted annual-average antibiotic concentrations ranged between 0 and 10 ng/L for 90% by length of surface waters. In the worst case scenario concentrations could reach between 0.1 and 1 μg/L at the most exposed locations. As both predicted and observed sewage effluent concentrations were below reported effect levels for the most sensitive aquatic wildlife, no direct toxicity in rivers is expected. Predicted river concentrations for CIP and ERY were closest to effect levels in wildlife, followed by SUF which was 2-3 orders of magnitude lower. TRI appeared to be of the least concern with around 6 orders of magnitude difference between predicted and effect levels. However, mixture toxicity may elevate this risk and antibiotic levels of 0.1-1 μg/L in hotspots may contribute to local environmental antibiotic resistance in microorganisms.

  5. Impacts of coexisting antibiotics, antibacterial residues, and heavy metals on the occurrence of erythromycin resistance genes in urban wastewater.

    PubMed

    Gao, Pin; He, Shi; Huang, Shenglin; Li, Kanzhu; Liu, Zhenhong; Xue, Gang; Sun, Weimin

    2015-05-01

    Antibiotic resistance is a global challenge and represents a growing threat on human health worldwide. Wastewater treatment plants (WWTPs) are generally considered as hotspots for control and/or dissemination of antibiotic resistance. The role of antibiotics, antibacterial residues, and heavy metals played on the evolution and spread of antibiotic resistance is still not well understood. Here, the occurrence of antibiotics (i.e., macrolides, tetracyclines, sulfonamides, and quinolones), antibacterial residues (i.e., triclosan), as well as heavy metals (i.e., cadmium, chromium, copper, zinc, lead, and nickel) in urban wastewater was investigated. Also, the abundances of erythromycin resistance genes (ERY-ARGs) including ere(A), ere(B), mef(A)/mef(E), erm(A), erm(B), erm(C), and msr(A)/msr(B) genes were screened. A relationship between certain antibiotics, antibacterial residues, and heavy metals and ERY-ARGs was demonstrated. ERY presented significant correlations (0.883 < r < 0.929, P < 0.05) with ere(A), ere(B), and mef(A)/mef(E) genes, while tetracycline exhibited a significant correlation (r = 0.829, P < 0.05) with erm(B) genes. It is noteworthy that triclosan correlated significantly (0.859 < r < 0.956, P < 0.05) with ere(A), ere(B), mef(A)/mef(E), and erm(B) genes. In addition, significantly positive correlations (0.823 < r < 0.871, P < 0.05) were observed between zinc and lead and certain ERY-ARGs (i.e., ere(B), mef(A)/mef(E), erm(B), etc.). Further investigations should be involved to elucidate the co-selection and/or cross-selection mechanisms due to co-existence of these selective factors in urban wastewater.

  6. Selection of suitable reference genes for gene expression studies in Staphylococcus capitis during growth under erythromycin stress.

    PubMed

    Cui, Bintao; Smooker, Peter M; Rouch, Duncan A; Deighton, Margaret A

    2016-08-01

    Accurate and reproducible measurement of gene transcription requires appropriate reference genes, which are stably expressed under different experimental conditions to provide normalization. Staphylococcus capitis is a human pathogen that produces biofilm under stress, such as imposed by antimicrobial agents. In this study, a set of five commonly used staphylococcal reference genes (gyrB, sodA, recA, tuf and rpoB) were systematically evaluated in two clinical isolates of Staphylococcus capitis (S. capitis subspecies urealyticus and capitis, respectively) under erythromycin stress in mid-log and stationary phases. Two public software programs (geNorm and NormFinder) and two manual calculation methods, reference residue normalization (RRN) and relative quantitative (RQ), were applied. The potential reference genes selected by the four algorithms were further validated by comparing the expression of a well-studied biofilm gene (icaA) with phenotypic biofilm formation in S. capitis under four different experimental conditions. The four methods differed considerably in their ability to predict the most suitable reference gene or gene combination for comparing icaA expression under different conditions. Under the conditions used here, the RQ method provided better selection of reference genes than the other three algorithms; however, this finding needs to be confirmed with a larger number of isolates. This study reinforces the need to assess the stability of reference genes for analysis of target gene expression under different conditions and the use of more than one algorithm in such studies. Although this work was conducted using a specific human pathogen, it emphasizes the importance of selecting suitable reference genes for accurate normalization of gene expression more generally.

  7. Ethyl glucuronide and ethyl sulfate in meconium and hair-potential biomarkers of intrauterine exposure to ethanol.

    PubMed

    Morini, L; Marchei, E; Vagnarelli, F; Garcia Algar, O; Groppi, A; Mastrobattista, L; Pichini, S

    2010-03-20

    This study investigated ethyl glucuronide (EtG) and ethyl sulfate (EtS) concentration in meconium and in maternal and neonatal hair (HEtG and HFAEEs, respectively) as potential markers of intrauterine exposure to ethanol together with meconium fatty acid ethyl esters (FAEEs) in a cohort of 99 mother-infant dyads, 49 coming from the Arcispedale of Reggio Emilia (Italy) and 50 from the Hospital del Mar of Barcelona (Spain). FAEEs, EtG and EtS were measured in meconium samples using liquid chromatography-tandem mass spectrometry. A head space-solid phase microextraction-gas chromatography-mass spectrometry was used to test HEtG and HFAEEs in hair samples from mothers and their newborns. Eighty-two meconium samples (82.8%) tested positive for EtG, 19 (19.2%) for EtS while 22 (22.2%) showed FAEEs levels higher than 2 nmol/g, the cut-off used to differentiate daily maternal ethanol consumption during pregnancy from occasional or no use. Although EtG and EtS in meconium did not correlate with total FAEEs concentration, a good correlation between EtG, EtS and ethyl stearate was observed. Moreover, EtG correlated well with ethyl palmitoleate, while EtS with ethyl laurate, myristate and linolenate. Neither maternal nor neonatal hair appears as good predictors of gestational ethanol consumption and subsequent fetal exposure in these mother-infant dyads. In conclusion, these data show that meconium is so far the best matrix in evaluating intrauterine exposure to ethanol, with EtG and EtS being potentially good alternative biomarkers to FAEEs. PMID:20060246

  8. Simultaneous saccharification and fermentation of acid-pretreated rapeseed meal for succinic acid production using Actinobacillus succinogenes.

    PubMed

    Chen, Kequan; Zhang, Han; Miao, Yelian; Wei, Ping; Chen, Jieyu

    2011-04-01

    Rapeseed meal was evaluated for succinic acid production by simultaneous saccharification and fermentation using Actinobacillus succinogenes ATCC 55618. Diluted sulfuric acid pretreatment and subsequent hydrolysis with pectinase was used to release sugars from rapeseed meal. The effects of culture pH, pectinase loading and yeast extract concentration on succinic acid production were investigated. When simultaneous saccharification and fermentation of diluted acid pretreated rapeseed meal with a dry matter content of 12.5% (w/v) was performed at pH 6.4 and a pectinase loading of 2% (w/w, on dry matter) without supplementation of yeast extract, a succinic acid concentration of 15.5 g/L was obtained at a yield of 12.4 g/100g dry matter. Fed-batch simultaneous saccharification and fermentation was carried out with supplementation of concentrated pretreated rapeseed meal and pectinase at 18 and 28 h to yield a final dry matter content of 20.5% and pectinase loading of 2%, with the succinic acid concentration enhanced to 23.4 g/L at a yield of 11.5 g/100g dry matter and a productivity of 0.33 g/(Lh). This study suggests that rapeseed meal may be an alternative substrate for the efficient production of succinic acid by A. succinogenes without requiring nitrogen source supplementation.

  9. Evidence for chloroplastic succinate dehydrogenase participating in the chloroplastic respiratory and photosynthetic electron transport chains of Chlamydomonas reinhardtii

    SciTech Connect

    Willeford, K.O.; Gombos, Z.; Gibbs, M. )

    1989-07-01

    A method for isolating intact chloroplasts from Chlamydomonas reinhardtii F-60 was developed from the Klein, Chen, Gibbs, Platt-Aloia procedure. Protoplasts, generated by treatment with autolysine, were lysed with a solution of digitonin and fractionated on Percoll step gradients. The chloroplasts were assessed to be 90% intact (ferricyanide assay) and free from cytoplasmic contamination (NADP isocitrate dehydrogenase activity) and to range from 2 to 5% in mitochondrial contamination (cytochrome c oxidase activity). About 25% of the cellular succinate dehydrogenase activity (21.6 micromoles per milligram chlorophyll per hour, as determined enzymically) was placed within the chloroplast. Chloroplastic succinate dehydrogenase had a K{sub m} for succinate of 0.55 millimolar and was associated with the thylakoidal material derived from the intact chloroplasts. This same thylakoidal material, with an enzymic assay of 21.6 micromoles per milligram chlorophyll per hour was able to initiate a light-dependent uptake of oxygen at a rate of 16.4 micromoles per milligram chlorophyll per hour when supplied with succinate and methyl viologen. Malonate was an apparent competitive inhibitor of this reaction. The succinate dehydrogenase activity present in the chloroplast was sufficient to account for the photoanaerobic rate of acetate dissimilation in H{sub 2} adapted Chlamydomonas.

  10. Decreased succinate dehydrogenase activity of gamma and alpha motoneurons in mouse spinal cords following 13 weeks of exposure to microgravity.

    PubMed

    Ishihara, Akihiko; Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Ohira, Yoshinobu

    2013-10-01

    Cell body size and succinate dehydrogenase activity of motoneurons in the dorsolateral region of the ventral horn in the lumbar and cervical segments of the mouse spinal cord were assessed after long-term exposure to microgravity and compared with those of ground-based controls. Mice were housed in a mouse drawer system on the International Space Station for 13 weeks. The mice were transported to the International Space Station by the Space Shuttle Discovery and returned to Earth by the Space Shuttle Atlantis. No changes in the cell body size of motoneurons were observed in either segment after exposure to microgravity, but succinate dehydrogenase activity of small-sized (<300 μm(2)) gamma and medium-sized (300-700 μm(2)) alpha motoneurons, which have higher succinate dehydrogenase activity than large-sized (>700 μm(2)) alpha motoneurons, in both segments was lower than that of ground-based controls. We concluded that exposure to microgravity for longer than 3 months induced decreased succinate dehydrogenase activity of both gamma and slow-type alpha motoneurons. In particular, the decreased succinate dehydrogenase activity of gamma motoneurons was observed only after long-term exposure to microgravity. PMID:23943522

  11. Modulation of drug release rate of diltiazem-HCl from hydrogel matrices of succinic acid-treated ispaghula husk.

    PubMed

    Gohel, M C; Amin, A F; Chhabaria, M T; Panchal, M K; Lalwani, A N

    2000-01-01

    The feasibility of using succinic acid-treated ispaghula husk in matrix-based tablets of diltiazem-HCl was investigated. The sample prepared using 4:1 weight ratio of ispaghula husk to succinic acid showed improved swelling and gelling. A 3(2) factorial design was employed to investigate the effect of amount of succinic acid-treated ispaghula husk and dicalcium phosphate (DCP) on the percentage of the drug dissolved in 60, 300, and 480 min from the compressed tablets. The results of multiple linear regression analysis revealed that the significance of the amount of succinic acid-treated ispaghula husk was greater in magnitude than that of the amount of DCP in controlling the drug release. Acceptable batches were identified from a contour plot with constraints on the percentage drug released at the three sampling times. A mathematical model was also evolved to describe the entire dissolution profile. The results of F-test revealed that the Higuchi model fits well to the in vitro dissolution data. The tablets showed considerable radial and axial swelling in distilled water. Succinic acid-treated ispaghula husk can be used as an economical hydrophilic matrixing agent.

  12. Succinate Accumulation and Ischemia-Reperfusion Injury: Of Mice but Not Men, a Study in Renal Ischemia-Reperfusion.

    PubMed

    Wijermars, L G M; Schaapherder, A F; Kostidis, S; Wüst, R C I; Lindeman, J H

    2016-09-01

    A recent seminal paper implicated ischemia-related succinate accumulation followed by succinate-driven reactive oxygen species formation as a key driver of ischemia-reperfusion injury. Although the data show that the mechanism is universal for all organs tested (kidney, liver, heart, and brain), a remaining question is to what extent these observations in mice translate to humans. We showed in this study that succinate accumulation is not a universal event during ischemia and does not occur during renal graft procurement; in fact, tissue succinate content progressively decreased with increasing graft ischemia time (p < 0.007). Contrasting responses were also found with respect to mitochondrial susceptibility toward ischemia and reperfusion, with rodent mitochondria robustly resistant toward warm ischemia but human and pig mitochondria highly susceptible to warm ischemia (p < 0.05). These observations suggest that succinate-driven reactive oxygen formation does not occur in the context of kidney transplantation. Moreover, absent allantoin release from the reperfused grafts suggests minimal oxidative stress during clinical reperfusion. PMID:26999803

  13. Redox State of Flavin Adenine Dinucleotide Drives Substrate Binding and Product Release in Escherichia coli Succinate Dehydrogenase

    PubMed Central

    Cheng, Victor W.T.; Piragasam, Ramanaguru Siva; Rothery, Richard A.; Maklashina, Elena; Cecchini, Gary; Weiner, Joel H.

    2016-01-01

    The Complex II family of enzymes, comprising the respiratory succinate dehydrogenases and fumarate reductases, catalyze reversible interconversion of succinate and fumarate. In contrast to the covalent flavin adenine dinucleotide (FAD) cofactor assembled in these enzymes, the soluble fumarate reductases (e.g. that from Shewanella frigidimarina) that assemble a noncovalent FAD cannot catalyze succinate oxidation but retain the ability to reduce fumarate. In this study, an SdhA-H45A variant that eliminates the site of the 8α-N3-histidyl covalent linkage between the protein and the FAD was examined. The variants SdhA-R286A/K/Y and -H242A/Y, that target residues thought to be important for substrate binding and catalysis were also studied. The variants SdhA-H45A and -R286A/K/Y resulted in assembly of a noncovalent FAD cofactor, which led to a significant decrease (−87 mV or more) in its reduction potential. The variant enzymes were studied by electron paramagnetic resonance spectroscopy following stand-alone reduction and potentiometric titrations. The “free” and “occupied” states of the active site were linked to the reduced and oxidized states of the FAD, respectively. Our data allows for a proposed model of succinate oxidation that is consistent with tunnel diode effects observed in the succinate dehydrogenase enzyme and a preference for fumarate reduction catalysis in fumarate reductase homologues that assemble a noncovalent FAD. PMID:25569225

  14. Cytoplasm-to-myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers

    NASA Technical Reports Server (NTRS)

    Tseng, B. S.; Kasper, C. E.; Edgerton, V. R.

    1994-01-01

    The relationship between myonuclear number, cellular size, succinate dehydrogenase activity, and myosin type was examined in single fiber segments (n = 54; 9 +/- 3 mm long) mechanically dissected from soleus and plantaris muscles of adult rats. One end of each fiber segment was stained for DNA before quantitative photometric analysis of succinate dehydrogenase activity; the other end was double immunolabeled with fast and slow myosin heavy chain monoclonal antibodies. Mean +/- S.D. cytoplasmic volume/myonucleus ratio was higher in fast and slow plantaris fibers (112 +/- 69 vs. 34 +/- 21 x 10(3) microns3) than fast and slow soleus fibers (40 +/- 20 vs. 30 +/- 14 x 10(3) microns3), respectively. Slow fibers always had small volumes/myonucleus, regardless of fiber diameter, succinate dehydrogenase activity, or muscle of origin. In contrast, smaller diameter (< 70 microns) fast soleus and plantaris fibers with high succinate dehydrogenase activity appeared to have low volumes/myonucleus while larger diameter (> 70 microns) fast fibers with low succinate dehydrogenase activity always had large volume/myonucleus. Slow soleus fibers had significantly greater numbers of myonuclei/mm than did either fast soleus or fast plantaris fibers (116 +/- 51 vs. 55 +/- 22 and 44 +/- 23), respectively. These data suggest that the myonuclear domain is more limited in slow than fast fibers and in the fibers with a high, compared to a low, oxidative metabolic capability.

  15. Decreased succinate dehydrogenase activity of gamma and alpha motoneurons in mouse spinal cords following 13 weeks of exposure to microgravity.

    PubMed

    Ishihara, Akihiko; Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Ohira, Yoshinobu

    2013-10-01

    Cell body size and succinate dehydrogenase activity of motoneurons in the dorsolateral region of the ventral horn in the lumbar and cervical segments of the mouse spinal cord were assessed after long-term exposure to microgravity and compared with those of ground-based controls. Mice were housed in a mouse drawer system on the International Space Station for 13 weeks. The mice were transported to the International Space Station by the Space Shuttle Discovery and returned to Earth by the Space Shuttle Atlantis. No changes in the cell body size of motoneurons were observed in either segment after exposure to microgravity, but succinate dehydrogenase activity of small-sized (<300 μm(2)) gamma and medium-sized (300-700 μm(2)) alpha motoneurons, which have higher succinate dehydrogenase activity than large-sized (>700 μm(2)) alpha motoneurons, in both segments was lower than that of ground-based controls. We concluded that exposure to microgravity for longer than 3 months induced decreased succinate dehydrogenase activity of both gamma and slow-type alpha motoneurons. In particular, the decreased succinate dehydrogenase activity of gamma motoneurons was observed only after long-term exposure to microgravity.

  16. A New Specific Succinate-Glutamate Metabolomic Hallmark in Sdhx-Related Paragangliomas

    PubMed Central

    Imperiale, Alessio; Moussallieh, François-Marie; Sebag, Frédéric; Brunaud, Laurent; Barlier, Anne; Elbayed, Karim; Bachellier, Philippe; Goichot, Bernard; Pacak, Karel; Namer, Izzie-Jacques; Taïeb, David

    2013-01-01

    Paragangliomas (PGLs) are frequently associated with germline mutations in genes involved in energy metabolism. The purpose of the present study was to assess whether the tumor metabolomic profile of patients with hereditary and apparently sporadic PGLs enables the distinction of different subtypes of tumors. Twenty-eight unrelated patients with a histological diagnosis of PGLs were included in the present study. Twelve had germline mutations in SDHx genes (5 SDHB, 7 SDHD), 6 VHL, and 10 were apparently sporadic. Intact tumor samples from these patients (one per patient) were evaluated with 1H high-resolution magic angle spinning (HRMAS) NMR spectroscopy. SDHx-related tumors were characterized by an increase in succinate levels in comparison to other tumor subtypes (p = 0.0001 vs VHL and p = 0.000003 vs apparently sporadic). Furthermore, we found significantly lower values of glutamate in SDHx-related tumors compared to other subtypes (p = 0.0007 vs VHL and p = 0.003 vs apparently sporadic). Moreover, SDHx-tumors also exhibited lower values of ATP/ADP/AMP (p = 0.01) compared to VHL. VHL tumors were found to have the highest values of glutathione (GSH) compared to other tumors. Based on 4 metabolites (succinate, glutamate, GSH, and ATP/ADP/AMP), tumors were accurately distinguished from the other ones on both 3- and 2-class PLS-DA models. The present study shows that HRMAS NMR spectroscopy is a very promising method for investigating the metabolomic profile of various PGLs. The present data suggest the existence of a specific succinate-glutamate hallmark of SDHx PGLs. The relevance of such a metabolomic hallmark is expected to be very useful in designing novel treatment options as well as improving the diagnosis and follow-up of these tumors, including metastatic ones. PMID:24312232

  17. Enhanced succinic acid production in Aspergillus saccharolyticus by heterologous expression of fumarate reductase from Trypanosoma brucei.

    PubMed

    Yang, Lei; Lübeck, Mette; Ahring, Birgitte K; Lübeck, Peter S

    2016-02-01

    Aspergillus saccharolyticus exhibits great potential as a cell factory for industrial production of dicarboxylic acids. In the analysis of the organic acid profile, A. saccharolyticus was cultivated in an acid production medium using two different pH conditions. The specific activities of the enzymes, pyruvate carboxylase (PYC), malate dehydrogenase (MDH), and fumarase (FUM), involved in the reductive tricarboxylic acid (rTCA) branch, were examined and compared in cells harvested from the acid production medium and a complete medium. The results showed that ambient pH had a significant impact on the pattern and the amount of organic acids produced by A. saccharolyticus. The wild-type strain produced higher amount of malic acid and succinic acid in the pH buffered condition (pH 6.5) compared with the pH non-buffered condition. The enzyme assays showed that the rTCA branch was active in the acid production medium as well as the complete medium, but the measured enzyme activities were different depending on the media. Furthermore, a soluble NADH-dependent fumarate reductase gene (frd) from Trypanosoma brucei was inserted and expressed in A. saccharolyticus. The expression of the frd gene led to an enhanced production of succinic acid in frd transformants compared with the wild-type in both pH buffered and pH non-buffered conditions with highest amount produced in the pH buffered condition (16.2 ± 0.5 g/L). This study demonstrates the feasibility of increasing succinic acid production through the cytosolic reductive pathway by genetic engineering in A. saccharolyticus.

  18. Stability-indicating micellar electrokinetic chromatography method for the analysis of sumatriptan succinate in pharmaceutical formulations.

    PubMed

    Al Azzam, Khaldun M; Saad, Bahruddin; Tat, Chai Yuan; Mat, Ishak; Aboul-Enein, Hassan Y

    2011-12-15

    A micellar electrokinetic chromatography method for the determination of sumatriptan succinate in pharmaceutical formulations was developed. The effects of several factors such as pH, surfactant and buffer concentration, applied voltage, capillary temperature, and injection time were investigated. Separation took about 5 min using phenobarbital as internal standard. The separation was carried out in reversed polarity mode at 20 °C, 26 kV and using hydrodynamic injection for 10s. Separation was achieved using a bare fused-silica capillary 50 μm×40 cm and background electrolyte of 25 mM sodium dihydrogen phosphate-adjusted with concentrated phosphoric acid to pH 2.2, containing 125 mM sodium dodecyl sulfate and detection was at 226 nm. The method was validated with respect to linearity, limits of detection and quantification, accuracy, precision and selectivity. The calibration curve was linear over the range of 100-2000 μg mL(-1). The relative standard deviations of intra-day and inter-day precision for migration time, peak area, corrected peak area, ratio of corrected peak area and ratio of peak area were less than 0.68, 3.48, 3.28, 2.97 and 2.83% and 2.01, 5.50, 4.46, 4.92 and 4.07%, respectively. The proposed method was successfully applied to the determinations of the analyte in tablet. Forced degradation studies were conducted by introducing a sample of sumatriptan succinate standard solution to different forced degradation conditions using neutral (water), basic (0.1 M NaOH), acidic (0.1 M HCl), oxidative (10% H(2)O(2)) and photolytic (exposure to UV light at 254 nm for 2 h). It is concluded that the stability-indicating method for sumatriptan succinate can be used for the analysis of the drug in various samples.

  19. Structural properties of aqueous metoprolol succinate solutions. Density, viscosity, and refractive index at 311 K

    NASA Astrophysics Data System (ADS)

    Deosarkar, S. D.; Kalyankar, T. M.

    2013-06-01

    Density, viscosity and refractive index of aqueous solutions of metoprolol succinate of different concentrations (0.005-0.05 mol dm-3) were measured at 38°C. Apparent molar volume of resultant solutions were calculated and fitted to the Masson's equation and apparent molar volume at infinite dilution was determined graphically. Viscosity data of solutions has been fitted to the Jone-Dole equation and viscosity A- and B-coefficients were determined graphically. Physicochemical data obtained were discussed in terms of molecular interactions.

  20. Multifunctional Nanobiocomposite of Poly[(butylene succinate)-co-adipate] and Clay.

    PubMed

    Al-Thabaiti, Shaeel A; Ray, Suprakas Sinha; Basahel, Sulaiman Nassir; Mokhtar, Mohamed

    2015-03-01

    The processing and characterization of multifunctional nanobiocomposite of biodegradable poly[(butylene succinate)-co-adipate] (PBSA) and organically modified synthetic fluorine mica (OSFM) are reported. The nanobiocomposite of PBSA with OSFM was prepared using melt- blending, and the structure and morphology of the nanocomposite were characterized using X-ray diffraction and transmission electron microscopy. The mechanical and material properties measurements showed the concurrent improvement in temperature dependence storage modulus, tensile properties, gas barrier, and thermal stability of neat PBSA after nanocomposite formation. Such improved inherent properties along with the environmentally-friendly feature are expected to widen the use of PBSA for short-term food-packaging applications. PMID:26413685