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Sample records for acid lowering agent

  1. Lipid-lowering agents.

    PubMed

    Ewang-Emukowhate, Mfon; Wierzbicki, Anthony S

    2013-09-01

    The role of lipid lowering in reducing the risk of mortality and morbidity from cardiovascular disease (CVD) is well established. Treatment particularly aimed at decreasing low-density lipoprotein cholesterol (LDL-C) is effective in reducing the risk of death from coronary heart disease and stroke. Statins form the cornerstone of treatment. However, in some individuals with a high risk of CVD who are unable to achieve their target LDL-C due to either intolerance or lack of efficacy, there is the need for alternative therapies. This review provides an overview of the different classes of currently available lipid-lowering medications including statins, fibrates, bile acid sequestrants (resins), and omega-3 fatty acids. Data are presented on their indications, pharmacology, and the relevant end point clinical trial data with these drugs. It also discusses the human trial data on some novel therapeutic agents that are being developed including those for homozygous familial hypercholesterolemia--the antisense oligonucleotide mipomersen and the microsomal transfer protein inhibitor lomitapide. Data are presented on phase II and III trials on agents with potentially wider applications, cholesterol ester transfer protein inhibitors and proprotein convertase subtilisin kexin 9 inhibitors. The data on a licensed gene therapy for lipoprotein lipase deficiency are also presented. PMID:23811423

  2. Lipid-lowering agents.

    PubMed

    Ewang-Emukowhate, Mfon; Wierzbicki, Anthony S

    2013-09-01

    The role of lipid lowering in reducing the risk of mortality and morbidity from cardiovascular disease (CVD) is well established. Treatment particularly aimed at decreasing low-density lipoprotein cholesterol (LDL-C) is effective in reducing the risk of death from coronary heart disease and stroke. Statins form the cornerstone of treatment. However, in some individuals with a high risk of CVD who are unable to achieve their target LDL-C due to either intolerance or lack of efficacy, there is the need for alternative therapies. This review provides an overview of the different classes of currently available lipid-lowering medications including statins, fibrates, bile acid sequestrants (resins), and omega-3 fatty acids. Data are presented on their indications, pharmacology, and the relevant end point clinical trial data with these drugs. It also discusses the human trial data on some novel therapeutic agents that are being developed including those for homozygous familial hypercholesterolemia--the antisense oligonucleotide mipomersen and the microsomal transfer protein inhibitor lomitapide. Data are presented on phase II and III trials on agents with potentially wider applications, cholesterol ester transfer protein inhibitors and proprotein convertase subtilisin kexin 9 inhibitors. The data on a licensed gene therapy for lipoprotein lipase deficiency are also presented.

  3. In vitro Xanthine Oxidase Inhibitory Studies of Lippia nodiflora and Isolated Flavonoids and Phenylethanoid Glycosides as Potential Uric Acid-lowering Agents.

    PubMed

    Cheng, Lee-Chuen; Murugaiyah, Vikneswaran; Chan, Kit-Lam

    2015-06-01

    Lippia nodiflora has been traditionally used for treatment of knee joint pain. Hitherto, no studies have been reported on the effective use of L. nodiflora against hyperuricemia, gout or other metabolic disorders. In this present study, L. nodiflora was examined for its ability to lower uric acid levels using an in vitro xanthine oxidase inhibitory assay. The whole plant methanolic extract was subjected to bioactivity-guided fractionation to yield 4 fractions (F1-F4). F3 displayed the highest potency and was further purified by column chromatography to afford two phenylethanoid glycosides, arenarioside (1) and verbascoside (2), and three flavonoids, 6-hydroxyluteolin (3), 6-hydroxyluteolin-7-O-glycoside (4), and nodifloretin (5). These compounds inhibited xanthine oxidase activity, with IC50 values between 7.52 ± 0.01 and 130.00 ± 2.25 μM, of which 3 was the most potent. In contrast, allopurinol, serving as a positive control, was 0.22 ± 0.00 μM. Thus, L. nodiflora, and its chemical constituents are worthy of further studies as potential anti-hyperuricemic agents.

  4. Aluminum bioavailability from the approved food additive leavening agent acidic sodium aluminum phosphate, incorporated into a baked good, is lower than from water.

    PubMed

    Yokel, Robert A; Florence, Rebecca L

    2006-10-01

    There are estimates of oral aluminum (Al) bioavailability from drinking water, but little information on Al bioavailability from foods. Foods contribute approximately 95% and drinking water 1-2% of the typical human's daily Al intake. The objectives were to estimate oral Al bioavailability from a representative food containing the food additive acidic sodium aluminum phosphate (acidic SALP), a leavening agent in baked goods. Rats were acclimated to a special diet that resulted in no stomach contents 14 h after its withdrawal. They were trained to rapidly consume a biscuit containing 1.5% acidic SALP. Oral Al bioavailability was then determined from a biscuit containing 1% or 2% acidic SALP, synthesized to contain (26)Al. The rats received concurrent (27)Al infusion. Blood was repeatedly withdrawn and serum analyzed for (26)Al by accelerator mass spectrometry. Total Al was determined by atomic absorption spectrometry. Oral (26)Al bioavailability was determined from the area under the (26)Al, compared to (27)Al, serum concentrationxtime curves. Oral Al bioavailability (F) from biscuit containing 1% or 2% acidic (26)Al-SALP averaged approximately 0.11% and 0.13%; significantly less than from water, which was previously shown to be approximately 0.3%. The time to maximum serum (26)Al concentration was 4.2 and 6h after consumption of biscuit containing 1% or 2% (26)Al-acidic SALP, respectively, compared to 1-2h following (26)Al in water. These results of oral Al bioavailability from acidic (26)Al-SALP in a biscuit (F approximately 0.1%) and results from (26)Al in water (F approximately 0.3%) x the contributions of food and drinking water to the typical human's daily Al intake ( approximately 5-10mg from food and 0.1mg from water, respectively) suggest food provides approximately 25-fold more Al to systemic circulation, and potential Al body burden, than does drinking water.

  5. Eicosapentaenoic Acid Inhibits Oxidation of ApoB-containing Lipoprotein Particles of Different Size In Vitro When Administered Alone or in Combination With Atorvastatin Active Metabolite Compared With Other Triglyceride-lowering Agents.

    PubMed

    Mason, R Preston; Sherratt, Samuel C R; Jacob, Robert F

    2016-07-01

    Eicosapentaenoic acid (EPA) is a triglyceride-lowering agent that reduces circulating levels of the apolipoprotein B (apoB)-containing lipoprotein particles small dense low-density lipoprotein (sdLDL), very-low-density lipoprotein (VLDL), and oxidized low-density lipoprotein (LDL). These benefits may result from the direct antioxidant effects of EPA. To investigate this potential mechanism, these particles were isolated from human plasma, preincubated with EPA in the absence or presence of atorvastatin (active) metabolite, and subjected to copper-initiated oxidation. Lipid oxidation was measured as a function of thiobarbituric acid reactive substances formation. EPA inhibited sdLDL (IC50 ∼2.0 μM) and LDL oxidation (IC50 ∼2.5 μM) in a dose-dependent manner. Greater antioxidant potency was observed for EPA in VLDL. EPA inhibition was enhanced when combined with atorvastatin metabolite at low equimolar concentrations. Other triglyceride-lowering agents (fenofibrate, niacin, and gemfibrozil) and vitamin E did not significantly affect sdLDL, LDL, or VLDL oxidation compared with vehicle-treated controls. Docosahexaenoic acid was also found to inhibit oxidation in these particles but over a shorter time period than EPA. These data support recent clinical findings and suggest that EPA has direct antioxidant benefits in various apoB-containing subfractions that are more pronounced than those of other triglyceride-lowering agents and docosahexaenoic acid. PMID:26945158

  6. Glutamic acid as anticancer agent: An overview.

    PubMed

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  7. Anticancer agents derived from natural cinnamic acids.

    PubMed

    Su, Ping; Shi, Yaling; Wang, Jinfeng; Shen, Xiuxiu; Zhang, Jie

    2015-01-01

    Cancer is the most dangerous disease that causes deaths all over the world. Natural products have afforded a rich source of drugs in a number of therapeutic fields including anticancer agents. Many significant drugs have been derived from natural sources by structural optimization of natural products. Cinnamic acid has gained great interest due to its antiproliferative, antioxidant, antiangiogenic and antitumorigenic potency. Currently it has been observed that cinnamic acid and its analogs such as caffeic acid, sinapic acid, ferulic acid, and isoferulic acid display various pharmacological activities, such as immunomodulation, anti-inflammation, anticancer and antioxidant. They have served to be the major sources of potential leading anticancer compounds. In this review, we focus on the anticancer potency of cinnamic acid derivatives and novel strategies to design these derivatives. We hope this review will be useful for researchers who are interested in developing anticancer agents.

  8. Folic acid supplementation lowers blood arsenic2

    PubMed Central

    Gamble, Mary V; Liu, Xinhua; Slavkovich, Vesna; Pilsner, J Richard; Ilievski, Vesna; Factor-Litvak, Pam; Levy, Diane; Alam, Shafiul; Islam, Mominul; Parvez, Faruque; Ahsan, Habibul; Graziano, Joseph H

    2007-01-01

    Background Chronic arsenic exposure currently affects >100 million persons worldwide. Methylation of ingested inorganic arsenic (InAs) to monomethylarsonic (MMAs) and dimethylarsinic (DMAs) acids relies on folate-dependent one-carbon metabolism and facilitates urinary arsenic elimination. Objective We hypothesized that folic acid supplementation to arsenic-exposed Bangladeshi adults would increase arsenic methylation and thereby lower total blood arsenic. Design In this randomized, double-blind, placebo-controlled trial, we evaluated blood concentrations of total arsenic, InAs, MMAs, and DMAs in 130 participants with low plasma folate (<9 nmol/L) before and after 12 wk of supplementation with folic acid (400 μg/d) or placebo. Results MMAs in blood was reduced by a mean ± SE of 22.24 ± 2.86% in the folic acid supplementation group and by 1.24 ± 3.59% in the placebe group (P < 0.0001). There was no change in DMAs in blood; DMAs is rapidly excreted in urine as evidenced by an increase in urinary DMAs (P = 0.0099). Total blood arsenic was reduced by 13.62% in the folic acid supplementation group and by 2.49% in the placebo group (P = 0.0199). Conclusions Folic acid supplementation to participants with low plasma concentrations of folate lowered blood arsenic concentrations, primarily by decreasing blood MMAs and increasing urinary DMAs. Therapeutic strategies to facilitate arsenic methylation, particularly in populations with folate deficiency or hyperhomocysteinemia or both, may lower blood arsenic concentrations and thereby contribute to the prevention of arsenic-induced illnesses. PMID:17921403

  9. Novel cajaninstilbene acid derivatives as antibacterial agents.

    PubMed

    Geng, Zhi-Zhong; Zhang, Jian-Jun; Lin, Jing; Huang, Mei-Yan; An, Lin-Kun; Zhang, Hong-Bin; Sun, Ping-Hua; Ye, Wen-Cai; Chen, Wei-Min

    2015-07-15

    Discovery of novel antibacterial agents with new structural scaffolds that combat drug-resistant pathogens is an urgent task. Cajaninstilbene acid, which is isolated from pigeonpea leaves, has shown antibacterial activity. In this study, a series of cajaninstilbene acid derivatives were designed and synthesized. The antibacterial activities of these compounds against gram-negative and gram-positive bacteria, as well as nine strains of methicillin-resistant staphylococcus aureus (MRSA) bacteria are evaluated,and the related structure-activity relationships are discussed. Assays suggest that some of the synthetic cajaninstilbene acid derivatives exhibit potent antibacterial activity against gram-positive bacterial strains and MRSA. Among these compounds, 5b, 5c, 5j and 5k show better antibacterial activity than the positive control compounds. The results of MTT assays illustrate the low cytotoxicity of the active compounds.

  10. Formulation and Evaluation of Nanocrystals of a Lipid Lowering Agent

    PubMed Central

    Louis, Dina

    2016-01-01

    Atorvastatin calcium, the lipid lowering agent, is taken as a model drug characterized by poor water solubility and bioavailability. In this study an attempt was made for preparation of nanocrystals using high pressure homogenization. A number of stabilizers were included as well as polymers at different concentrations, and the formulations were homogenized for ten cycles at a pressure of 1000 bars. The obtained nano crystals were evaluated by determining their size, zeta potential, saturated solubility and dissolution rate. Results revealed that Formulation 3, containing (10: 1) drug to sodium lauryl sulphate ratio, possessed the highest saturated solubility and dissolution rate, and hence was analyzed by X-ray diffraction analysis, differential scanning calorimetry, Fourrier transform infrared spectroscopy and scanning electron microscopy. An in-vivo study was carried out on the successful formulation in comparison to drug powder using rats as experimental animals. A significant increase in the area under the concentration-time curve Cpmax and MRT for nanocrystals was observed in comparison to the untreated atorvastatin calcium. PMID:27610148

  11. Formulation and Evaluation of Nanocrystals of a Lipid Lowering Agent.

    PubMed

    Louis, Dina

    2016-01-01

    Atorvastatin calcium, the lipid lowering agent, is taken as a model drug characterized by poor water solubility and bioavailability. In this study an attempt was made for preparation of nanocrystals using high pressure homogenization. A number of stabilizers were included as well as polymers at different concentrations, and the formulations were homogenized for ten cycles at a pressure of 1000 bars. The obtained nano crystals were evaluated by determining their size, zeta potential, saturated solubility and dissolution rate. Results revealed that Formulation 3, containing (10: 1) drug to sodium lauryl sulphate ratio, possessed the highest saturated solubility and dissolution rate, and hence was analyzed by X-ray diffraction analysis, differential scanning calorimetry, Fourrier transform infrared spectroscopy and scanning electron microscopy. An in-vivo study was carried out on the successful formulation in comparison to drug powder using rats as experimental animals. A significant increase in the area under the concentration-time curve Cpmax and MRT for nanocrystals was observed in comparison to the untreated atorvastatin calcium.

  12. Formulation and Evaluation of Nanocrystals of a Lipid Lowering Agent.

    PubMed

    Louis, Dina

    2016-01-01

    Atorvastatin calcium, the lipid lowering agent, is taken as a model drug characterized by poor water solubility and bioavailability. In this study an attempt was made for preparation of nanocrystals using high pressure homogenization. A number of stabilizers were included as well as polymers at different concentrations, and the formulations were homogenized for ten cycles at a pressure of 1000 bars. The obtained nano crystals were evaluated by determining their size, zeta potential, saturated solubility and dissolution rate. Results revealed that Formulation 3, containing (10: 1) drug to sodium lauryl sulphate ratio, possessed the highest saturated solubility and dissolution rate, and hence was analyzed by X-ray diffraction analysis, differential scanning calorimetry, Fourrier transform infrared spectroscopy and scanning electron microscopy. An in-vivo study was carried out on the successful formulation in comparison to drug powder using rats as experimental animals. A significant increase in the area under the concentration-time curve Cpmax and MRT for nanocrystals was observed in comparison to the untreated atorvastatin calcium. PMID:27610148

  13. Formulation and Evaluation of Nanocrystals of a Lipid Lowering Agent

    PubMed Central

    Louis, Dina

    2016-01-01

    Atorvastatin calcium, the lipid lowering agent, is taken as a model drug characterized by poor water solubility and bioavailability. In this study an attempt was made for preparation of nanocrystals using high pressure homogenization. A number of stabilizers were included as well as polymers at different concentrations, and the formulations were homogenized for ten cycles at a pressure of 1000 bars. The obtained nano crystals were evaluated by determining their size, zeta potential, saturated solubility and dissolution rate. Results revealed that Formulation 3, containing (10: 1) drug to sodium lauryl sulphate ratio, possessed the highest saturated solubility and dissolution rate, and hence was analyzed by X-ray diffraction analysis, differential scanning calorimetry, Fourrier transform infrared spectroscopy and scanning electron microscopy. An in-vivo study was carried out on the successful formulation in comparison to drug powder using rats as experimental animals. A significant increase in the area under the concentration-time curve Cpmax and MRT for nanocrystals was observed in comparison to the untreated atorvastatin calcium.

  14. Enhancement of Commercial Antifungal Agents by Kojic Acid

    PubMed Central

    Kim, Jong H.; Chang, Perng-Kuang; Chan, Kathleen L.; Faria, Natália C. G.; Mahoney, Noreen; Kim, Young K.; Martins, Maria de L.; Campbell, Bruce C.

    2012-01-01

    Natural compounds that pose no significant medical or environmental side effects are potential sources of antifungal agents, either in their nascent form or as structural backbones for more effective derivatives. Kojic acid (KA) is one such compound. It is a natural by-product of fungal fermentation commonly employed by food and cosmetic industries. We show that KA greatly lowers minimum inhibitory (MIC) or fungicidal (MFC) concentrations of commercial medicinal and agricultural antifungal agents, amphotericin B (AMB) and strobilurin, respectively, against pathogenic yeasts and filamentous fungi. Assays using two mitogen-activated protein kinase (MAPK) mutants, i.e., sakAΔ, mpkCΔ, of Aspergillus fumigatus, an agent for human invasive aspergillosis, with hydrogen peroxide (H2O2) or AMB indicate such chemosensitizing activity of KA is most conceivably through disruption of fungal antioxidation systems. KA could be developed as a chemosensitizer to enhance efficacy of certain conventional antifungal drugs or fungicides. PMID:23203038

  15. Acetal phosphatidic acids: novel platelet aggregating agents.

    PubMed

    Brammer, J P; Maguire, M H; Walaszek, E J; Wiley, R A

    1983-05-01

    1 Palmitaldehyde, olealdehyde and linolealdehyde acetal phosphatidic acids induced rapid shape change and dose-dependent biphasic aggregation of human platelets in platelet-rich plasma; aggregation was reversible at low doses and irreversible at high doses of the acetal phosphatidic acids. The palmitaldehyde congener elicited monophasic dose-dependent aggregation of sheep platelets in platelet-rich plasma.2 The threshold concentration for palmitaldehyde acetal phosphatidic acid (PGAP)-induced platelet aggregation was 2.5-5 muM for human platelets and 0.25-0.5 muM for sheep platelets. PGAP was 4-5 times as potent versus human platelets as the olealdehyde and linolealdehyde acetal phosphatidic acids, which were equipotent.3 PGAP-induced irreversible aggregation of [(14)C]-5-hydroxytryptamine ([(14)C]-5-HT)-labelled human platelets in platelet-rich plasma was accompanied by release of 44.0+/-2.4% (s.e.) of the platelet [(14)C]-5-HT; reversible aggregation was not associated with release. In contrast, PGAP-induced release of [(14)C]-5-HT-labelled sheep platelets was dose-dependent.4 The adenosine diphosphate (ADP) antagonist, 2-methylthio-AMP, and the cyclo-oxygenase inhibitor, aspirin, abolished PGAP-induced second phase aggregation and release in human platelets but did not affect the first, reversible, phase of aggregation. Both the first and second phases of PGAP-induced aggregation were abolished by chlorpromazine, by the phospholipase A(2) inhibitor, mepacrine, and by nmolar concentrations of prostaglandin E(1) (PGE(1)); these agents abolished the second, but not the first phase of ADP-induced aggregation.5 The related phospholipids, lecithin, lysolecithin and phosphatidic acid, at <100 muM, neither induced aggregation of human platelets in platelet-rich plasma, nor modified PGAP-induced aggregation; 1-palmityl lysophosphatidic acid elicited aggregation of human platelets at a threshold concentration of 100 muM.6 It is concluded that the acetal phosphatidic acids

  16. Effects of lipid-lowering agents on inflammation, haemostasis and blood pressure.

    PubMed

    Tziomalos, Konstantinos; Karagiannis, Asterios; Athyros, Vasilios G

    2014-01-01

    In addition to the modification of the lipid profile, most lipid-lowering agents appear to modulate other atherogenic pathways. We summarize the effects of lipid-lowering agents on inflammation, hemostasis and blood pressure. We also discuss the potential contribution of these actions on cardiovascular disease prevention. Most lipid-lowering agents appear to exert anti-inflammatory, antithrombotic and antihypertensive effects. These pleiotropic actions appear to contribute to the reduction in cardiovascular events and deep venous thrombosis during statin treatment. Regarding other lipid-lowering agents, it is unclear whether their effects on inflammation, thrombosis or blood pressure play a role in their antiatherogenic potential.

  17. Method of encapsulating polyaminopolycarboxylic acid chelating agents in liposomes

    DOEpatents

    Rahman, Yueh Erh

    1977-11-10

    A method is provided for transferring a polyaminopolycarboxylic acid chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes, which liposomes will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. The chelating agent is encapsulated within liposomes by drying a lipid mixture to form a thin film and wetting the lipid film with a solution containing the chelating agent. Mixing then results in the formation of a suspension of liposomes encapsulating the chelating agent, which liposomes can then be separated.

  18. Salicylic acid as a peeling agent: a comprehensive review

    PubMed Central

    Arif, Tasleem

    2015-01-01

    Salicylic acid has been used to treat various skin disorders for more than 2,000 years. The ability of salicylic acid to exfoliate the stratum corneum makes it a good agent for peeling. In particular, the comedolytic property of salicylic acid makes it a useful peeling agent for patients with acne. Once considered as a keratolytic agent, the role of salicylic acid as a desmolytic agent, because of its ability to disrupt cellular junctions rather than breaking or lysing intercellular keratin filaments, is now recognized and is discussed here. Salicylic acid as a peeling agent has a number of indications, including acne vulgaris, melasma, photodamage, freckles, and lentigines. The efficacy and safety of salicylic acid peeling in Fitzpatrick skin types I–III as well as in skin types V and VI have been well documented in the literature. This paper reviews the available data and literature on salicylic acid as a peeling agent and its possible indications. Its properties, efficacy and safety, the peeling procedure, and possible side effects are discussed in detail. An account of salicylism is also included. PMID:26347269

  19. Salicylic acid as a peeling agent: a comprehensive review.

    PubMed

    Arif, Tasleem

    2015-01-01

    Salicylic acid has been used to treat various skin disorders for more than 2,000 years. The ability of salicylic acid to exfoliate the stratum corneum makes it a good agent for peeling. In particular, the comedolytic property of salicylic acid makes it a useful peeling agent for patients with acne. Once considered as a keratolytic agent, the role of salicylic acid as a desmolytic agent, because of its ability to disrupt cellular junctions rather than breaking or lysing intercellular keratin filaments, is now recognized and is discussed here. Salicylic acid as a peeling agent has a number of indications, including acne vulgaris, melasma, photodamage, freckles, and lentigines. The efficacy and safety of salicylic acid peeling in Fitzpatrick skin types I-III as well as in skin types V and VI have been well documented in the literature. This paper reviews the available data and literature on salicylic acid as a peeling agent and its possible indications. Its properties, efficacy and safety, the peeling procedure, and possible side effects are discussed in detail. An account of salicylism is also included.

  20. Lower uric Acid linked with cognitive dysfunction in the elderly.

    PubMed

    Méndez-Hernández, Edna; Salas-Pacheco, José; Ruano-Calderón, Luis; Téllez-Valencia, Alfredo; Cisneros-Martínez, Jorge; Barraza-Salas, Marcelo; Arias-Carrión, Oscar

    2015-01-01

    Uric acid has been associated as a risk factor for cardiovascular disease. Recently, however, there is growing evidence that uric acid plays a role as antioxidant in the brain. In cognitive dysfunction, vascular and oxidative stress mechanisms play a role, but the link remains unknown. Therefore, we investigated the link between serum uric acid-levels and cognitive function in 62 elderly subjects. The statistical analysis was adjusted to age, sex and cardiovascular risk factors. Here, we found that lower serum uric acid levels are linked to cognitive dysfunction. In a Mexican population, higher levels of uric acid are associated with a decreased risk of dementia. PMID:25925000

  1. Effect of Acidic Agents on Surface Roughness of Dental Ceramics

    PubMed Central

    Kukiattrakoon, Boonlert; Hengtrakool, Chanothai; Kedjarune-Leggat, Ureporn

    2011-01-01

    Background: An increase in surface roughness of ceramics may decrease strength and affect the clinical success of ceramic restorations. However, little is known about the effect of acidic agents on ceramic restorations. The aim of this study was to evaluate the surface roughness of dental ceramics after being immersed in acidic agents. Methods: Eighty-three ceramic disk specimens (12.0 mm in diameter and 2.0 mm in thickness) were made from four types of ceramics (VMK 95, Vitadur Alpha, IPS Empress Esthetic, and IPS e.max Ceram). Baseline data of surface roughness were recorded by profilometer. The specimens were then immersed in acidic agents (citrate buffer solution, pineapple juice and green mango juice) and deionized water (control) at 37°C for 168 hours. One group was immersed in 4% acetic acid at 80°C for 168 hours. After immersion, surface roughness was evaluated by a profilometer at intervals of 24, 96, and 168 hours. Surface characteristics of specimens were studied using scanning electron microscopy (SEM). Data were analyzed using two-way repeated ANOVA and Tukey's multiple comparisons (α = 0.05). Results: For all studied ceramics, all surface roughness parameters were significantly increased after 168 hours immersion in all acidic agents (P < 0.05). After 168 hours in 4% acetic acid, there were significant differences for all roughness parameters from other acidic agents of all evaluated ceramics. Among all studied ceramics, Vitadur Alpha showed significantly the greatest values of all surface roughness parameters after immersion in 4% acetic acid (P < 0.001). SEM photomicrographs also presented surface destruction of ceramics in varying degrees. Conclusion: Acidic agents used in this study negatively affected the surface of ceramic materials. This should be considered when restoring the eroded tooth with ceramic restorations in patients who have a high risk of erosive conditions. PMID:22132009

  2. Electrical Properties of Poly-Lactic Acid with Nucleating Agent Added

    NASA Astrophysics Data System (ADS)

    Shinyama, Katsuyoshi; Oi, Toru; Fujita, Shigetaka

    We examined electrical properties of polylactic acid (PLA) with nucleating agent added. At that time, nucleating agent was added to PLA was then heat-treated at 100°C for 30 seconds. The crystallinity of the nucleating agent was added to PLA increased to more than 40%, and its crystallization speed also increased significantly. The temperature dependence of the conductivity (σ) was investigated, the σ of PLA to which nucleating agent had been added showed the tendency to become lower than the σ of PLA to which nucleating agent had not been added in σ at temperatures higher than 60°C. Furthermore, the temperature dependence of the dielectric breakdown strength (EB) was investigated, EB of nucleating agent was added to PLA was around 5.0 MV/cm at a temperature of 25°C. Of particular note was the fact that EB of nucleating agent was added to PLA measured at 100°C was around 4.7 MV/cm, around 3 times greater than the EB value for PLA to which nucleating agent had not been added. The temperature dependence of the relative dielectric constant (εr‧) and the relative dielectric loss factor (εr″) was investigated, the peak dielectric absorption value of εr″ for the PLA to which nucleating agent had been added showed a tendency that lower than that of the PLA to which nucleating agent had not been added.

  3. Cinnamic acid derivatives as anticancer agents-a review.

    PubMed

    De, P; Baltas, M; Bedos-Belval, F

    2011-01-01

    Cinnamic acid and its phenolic analogues are natural substances. Chemically, in cinnamic acids the 3-phenyl acrylic acid functionality offers three main reactive sites; substitution at the phenyl ring, addition at the α,β- unsaturation and the reactions of the carboxylic acid functionality. Owing to these chemical aspects cinnamic acid derivatives received much attention in medicinal research as traditional as well as recent synthetic antitumor agents. We observed that in spite of their rich medicinal tradition, cinnamic acid derivatives and their anticancer potentials remained underutilized for several decades since the first published clinical use in 1905. In last two decades, there has been huge attention towards various cinnamoyl derivatives and their antitumor efficacy. This review provides a comprehensive and unprecedented literature compilation concerning the synthesis and biological evaluation of various cinnamoyl acids, esters, amides, hydrazides and related derivatives in anticancer research. We envisage that our effort in this review contributes a much needed and timely addition to the literature of medicinal research.

  4. Lipid-lowering agents in the management of nonalcoholic fatty liver disease

    PubMed Central

    Tziomalos, Konstantinos

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also with higher cardiovascular morbidity. Accordingly, lipid-lowering agents are frequently considered in these patients to reduce cardiovascular risk. However, there have been concerns regarding the safety of these agents in patients with chronic liver diseases. In the present review, we discuss the safety of lipid-lowering agents in patients with NAFLD as well as their effects on both cardiovascular and liver disease in this population. Accumulating data suggest that statins are safe in patients with NAFLD and that they reduce the increased cardiovascular morbidity of this population. However, it is still unclear whether statins are also useful as a treatment for NAFLD per se, since there are very limited and conflicting data on their effects on liver histology. There is also very scarce evidence regarding the safety and efficacy of other lipid-lowering agents in patients with NAFLD. Randomized controlled studies are needed to evaluate the role of lipid-lowering agents and particularly statins for the prevention of both cardiovascular and liver disease-related complications in this high-risk population. PMID:25349644

  5. Nucleic acid in-situ hybridization detection of infectious agents

    NASA Astrophysics Data System (ADS)

    Thompson, Curtis T.

    2000-04-01

    Limitations of traditional culture methods and newer polymerase chain reaction (PCR)-based methods for detection and speciation of infectious agents demonstrate the need for more rapid and better diagnostics. Nucleic acid hybridization is a detection technology that has gained wide acceptance in cancer and prenatal cytogenetics. Using a modification of the nucleic acid hybridization technique known as fluorescence in-situ hybridization, infectious agents can be detected in a variety of specimens with high sensitivity and specificity. The specimens derive from all types of human and animal sources including body fluids, tissue aspirates and biopsy material. Nucleic acid hybridization can be performed in less than one hour. The result can be interpreted either using traditional fluorescence microscopy or automated platforms such as micro arrays. This paper demonstrates proof of concept for nucleic acid hybridization detection of different infectious agents. Interpretation within a cytologic and histologic context is possible with fluorescence microscopic analysis, thereby providing confirmatory evidence of hybridization. With careful probe selection, nucleic acid hybridization promises to be a highly sensitive and specific practical diagnostic alternative to culture, traditional staining methods, immunohistochemistry and complicated nucleic acid amplification tests.

  6. Biosynthesis of polyunsaturated fatty acids in lower eukaryotes.

    PubMed

    Uttaro, Antonio D

    2006-10-01

    Polyunsaturated fatty acids have important structural roles in cell membranes. They are also intermediates in the synthesis of biologically active molecules such as eicosanoids, which mediate fever, inflammation, blood pressure and neurotransmission. Arachidonic and docosahexaenoic acids are essential components of brain tissues and, through their involvement in the development of neural and retinal functions, important dietary nutrients for neonatal babies. Lower eukaryotes are particularly rich in C20-22 polyunsaturated fatty acids. Fungi and marine microalgae are currently used to produce nutraceutic oils. Other protists and algae are being studied because of the variability in their enzymes involved in polyunsaturated fatty acid biosynthesis. Such enzymes could be used as source for the production of transgenic organisms able to synthesize designed oils for human diet or, in the case of parasitic protozoa, they might be identified as putative chemotherapeutic targets. Polyunsaturated fatty acids can be synthesized by two different pathways: an anaerobic one, by using polyketide synthase related enzymes, and an aerobic one, which involves the action of elongases and oxygen dependent desaturases. Desaturases can be classified into three main types, depending on which of the consecutive steps of polyunsaturated fatty acid synthesis they are involved with. The enzymes may be specialized to act on: saturated substrates (type I); mono- and di-unsaturated fatty acids by introducing additional double bonds at the methyl-end site of the existing double bonds (type II); or the carboxy half ('front-end') of polyunsaturated ones (type III). Type III desaturases require the alternating action of elongases. A description of the enzymes that have been isolated and functionally characterized is provided, in order to highlight the different pathways found in lower eukaryotes.

  7. Degradability of fluorapatite-leucite ceramics in naturally acidic agents.

    PubMed

    Kukiattrakoon, Boonlert; Hengtrakool, Chanothai; Kedjarune-Leggat, Ureporn

    2010-10-01

    This study was conducted to evaluate the titratable acidity and effect of naturally acidic agents on the surface microhardness, elemental composition, and surface morphology of fluorapatite-leucite ceramics. One hundred and ten ceramic disks (IPS d.SIGN), 12.0 mm in diameter and 2.0 mm in thickness, were fabricated. Before immersion, the baseline data of Vickers microhardness and elemental composition were recorded. Four groups were immersed in acidic agents (citrate buffer solution, green mango juice, and pineapple juice) and deionized water (control) at 37ºC for 168 hours, whereas one group was immersed in 4% acetic acid at 80ºC for 168 hours. After immersion, specimens were evaluated and data were analyzed using one-way repeated ANOVA and Tukey's test (α=0.05). Microhardness values significantly decreased after immersion (p<0.05). In terms of elemental composition, the weight percentages of silicon, potassium, aluminum, and sodium also decreased after immersion (p<0.05). Results of this study showed that fluorapatite-leucite ceramics were affected by long-term immersion in acidic agents.

  8. Guanidinoacetic acid as a performance-enhancing agent.

    PubMed

    Ostojic, Sergej M

    2016-08-01

    Guanidinoacetic acid (GAA; also known as glycocyamine or guanidinoacetate) is the natural precursor of creatine, and under investigation as a novel dietary agent. It was first identified as a natural compound in humans ~80 years ago. In the 1950s, GAA's use as a therapeutic agent was explored, showing that supplemental GAA improved patient-reported outcomes and work capacity in clinical populations. Recently, a few studies have examined the safety and efficacy of GAA and suggest potential ergogenic benefits for physically active men and women. The purpose of this review is to examine possible applications of GAA supplementation for exercise performance enhancement, safety, and legislation issues. PMID:26445773

  9. Lewis acid-assisted detection of nerve agents in water.

    PubMed

    Butala, Rahul R; Creasy, William R; Fry, Roderick A; McKee, Michael L; Atwood, David A

    2015-06-01

    The five-coordinate compound, Salen((t)Bu)Al(Ac), prepared in situ from Salen((t)Bu)AlBr and NH4Ac, forms Lewis acid-base adducts in aqueous solution with the G-type nerve agents, Sarin and Soman, and the VX hydrolysis product, ethylmethylphosphonate (EMPA). The resulting compounds, [Salen((t)Bu)Al(NA)](+)[Ac] (-) (with NA = Sarin, Soman, and EMPA) are sufficiently stable to be identified by ESI-MS. Molecular ion peaks were detected for every compound with little or no fragmentation. The distinctive MS signatures for the [Salen((t)Bu)Al(NA)](+) compounds provide a new technique for identifying nerve agents from aqueous solution. The energetics of the displacement of Ac(-) by the nerve agents to form [Salen((t)Bu)Al(NA)](+)[Ac](-) were determined computationally.

  10. Synthesis of Silicon and Germanium Containing Heteroaromatic Sulfides as Cholesterol Level Lowering and Vasodilating Agents

    PubMed Central

    Rubina, Kira; Abele, Edgars; Arsenyan, Pavel; Abele, Ramona; Veveris, Maris

    2001-01-01

    Silicon and germanium containing heteroaromatic sulfides have been prepared using phase transfer catalytic (PTC) system thiol / Si or Ge containing alkyl halide / solid KOH / 18- crown-6 / toluene. The target sulfides were isolated in yields up to 92 %. It has been found that 2-{[dimethyl (β-triethylgermylethyl)-silylmethyl]thio}-1-methylimidazole and 2-{[dimethyl(β-triphenylsilylethyl) silyl-methyl]thio}benzothiazole are the most active cholesterol level lowering and vasodilating agents. PMID:18475980

  11. Noninsulin glucose-lowering agents for the treatment of patients on dialysis.

    PubMed

    Flynn, Colleen; Bakris, George L

    2013-03-01

    Chronic kidney disease (CKD) is a common complication of diabetes mellitus and the most common cause of end-stage renal disease (ESRD). As the worldwide prevalence of diabetes continues to increase, the number of patients with CKD will also increase. Therefore, it is essential that physicians know how to safely and effectively manage diabetes in the setting of CKD. Adequate glycaemic control in patients with diabetes is important to prevent ESRD and other complications and to decrease mortality. However, many glucose-lowering agents need to be dose-adjusted or should not be used in the setting of stage 3 CKD or higher (defined as an estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m(2)), particularly in patients with stage 5 CKD (eGFR <15 ml/min/1.73 m(2)) and in those receiving dialysis. Insulin therapy is appropriate for patients undergoing dialysis; however, several orally administered glucose-lowering agents can also be used safely in these patients. In this Review, we provide an overview of the use of noninsulin glucose-lowering agents in the dialysis population. PMID:23358424

  12. [Fumaric acid as therapeutic agent for multiple sclerosis].

    PubMed

    Haghikia, A; Linker, R; Gold, R

    2014-06-01

    After the approval of fumaric acid in February 2014 another first line agent is now available for the treatment of multiple sclerosis (MS). Along with the various beta interferon preparations, glatiramer acetate, teriflunomide and fumaric acid add to the repertoire of oral therapeutics for the initial treatment of relapsing remitting MS in daily practice. In order to employ these drugs in an individualized and precise medical manner and considering their efficacy and side effects, it seems worthwhile to learn the so far known mode of action and background history. Fumaric acid, as one of the newest drugs approved for MS, reveals the longest history as it was in use for decades as a treatment in psoriasis patients. Furthermore, fumaric acid is a good example for so far not extensively exploited option of drug reposition in medicine in general. The current review summarizes the outcomes of the clinical approval studies of fumaric acid in MS and discusses the dual mode of action, the immunomodulatory and tissue protective effect, as well as the reported adverse events under fumaric acid treatment. This review aims to serve an aid in the daily decision-making practice when choosing the baseline therapy for MS patients. PMID:24668400

  13. The Effectiveness of Physical Agents for Lower-Limb Soft Tissue Injuries: A Systematic Review.

    PubMed

    Yu, Hainan; Randhawa, Kristi; Côté, Pierre; Optima Collaboration

    2016-07-01

    Study Design Systematic review. Background Soft tissue injuries to the lower limb bring a substantial health and economic burden to society. Physical agents are commonly used to treat these injuries. However, the effectiveness of many such physical agents is not clearly established in the literature. Objective To evaluate the effectiveness and safety of physical agents for soft tissue injuries of the lower limb. Methods We searched 5 databases from 1990 to 2015 for randomized controlled trials (RCTs), cohort studies, and case-control studies. Paired reviewers independently screened the retrieved literature and appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a high risk of bias were excluded. We synthesized low-risk-of-bias studies according to principles of best-evidence synthesis. Results We screened 10261 articles. Of 43 RCTs identified, 20 had a high risk of bias and were excluded from the analysis, and 23 RCTs had a low risk of bias and were included in the analysis. The available higher-quality evidence suggests that patients with persistent plantar fasciitis may benefit from ultrasound or foot orthoses, while those with persistent midportion Achilles tendinopathy may benefit from shockwave therapy. However, the current evidence does not support the use of shockwave therapy for recent plantar fasciitis, low-Dye taping for persistent plantar fasciitis, low-level laser therapy for recent ankle sprains, or splints for persistent midportion Achilles tendinopathy. Finally, evidence on the effectiveness of the following interventions is not established in the current literature: (1) shockwave therapy for persistent plantar fasciitis, (2) cryotherapy or assistive devices for recent ankle sprains, (3) braces for persistent midportion Achilles tendinopathy, and (4) taping or electric muscle stimulation for patellofemoral pain syndrome. Conclusion Almost half the identified RCTs that evaluated the effectiveness of

  14. The Effectiveness of Physical Agents for Lower-Limb Soft Tissue Injuries: A Systematic Review.

    PubMed

    Yu, Hainan; Randhawa, Kristi; Côté, Pierre; Optima Collaboration

    2016-07-01

    Study Design Systematic review. Background Soft tissue injuries to the lower limb bring a substantial health and economic burden to society. Physical agents are commonly used to treat these injuries. However, the effectiveness of many such physical agents is not clearly established in the literature. Objective To evaluate the effectiveness and safety of physical agents for soft tissue injuries of the lower limb. Methods We searched 5 databases from 1990 to 2015 for randomized controlled trials (RCTs), cohort studies, and case-control studies. Paired reviewers independently screened the retrieved literature and appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a high risk of bias were excluded. We synthesized low-risk-of-bias studies according to principles of best-evidence synthesis. Results We screened 10261 articles. Of 43 RCTs identified, 20 had a high risk of bias and were excluded from the analysis, and 23 RCTs had a low risk of bias and were included in the analysis. The available higher-quality evidence suggests that patients with persistent plantar fasciitis may benefit from ultrasound or foot orthoses, while those with persistent midportion Achilles tendinopathy may benefit from shockwave therapy. However, the current evidence does not support the use of shockwave therapy for recent plantar fasciitis, low-Dye taping for persistent plantar fasciitis, low-level laser therapy for recent ankle sprains, or splints for persistent midportion Achilles tendinopathy. Finally, evidence on the effectiveness of the following interventions is not established in the current literature: (1) shockwave therapy for persistent plantar fasciitis, (2) cryotherapy or assistive devices for recent ankle sprains, (3) braces for persistent midportion Achilles tendinopathy, and (4) taping or electric muscle stimulation for patellofemoral pain syndrome. Conclusion Almost half the identified RCTs that evaluated the effectiveness of

  15. Microbial transformations of the antimelanoma agent betulinic acid.

    PubMed

    Kouzi, S A; Chatterjee, P; Pezzuto, J M; Hamann, M T

    2000-12-01

    Microbial transformation studies of the antimelanoma agent betulinic acid (1) were conducted. Screening experiments showed a number of microorganisms capable of biotransforming 1. Three of these cultures, Bacillus megaterium ATCC 14581, Cunninghamella elegans ATCC 9244, and Mucor mucedo UI-4605, were selected for preparative scale transformation. Bioconversion of 1 with resting-cell suspensions of phenobarbital-induced B. megaterium ATCC 14581 resulted in the production of the known betulonic acid (2) and two new metabolites: 3beta,7beta-dihydroxy-lup-20(29)-en-28-oic acid (3) and 3beta,6alpha, 7beta-trihydroxy-lup-20(29)-en-28-oic acid (4). Biotransformation of 1 with growing cultures of C. elegans ATCC 9244 produced one new metabolite characterized as 1beta,3beta, 7beta-trihydroxy-lup-20(29)-en-28-oic acid (5). Incubation of 1 with growing cultures of M. mucedo UI-4605 afforded metabolite 3. Structure elucidation of all metabolites was based on NMR and HRMS analyses. In addition, the antimelanoma activity of metabolites 2-5 was evaluated against two human melanoma cell lines, Mel-1 (lymph node) and Mel-2 (pleural fluid).

  16. Microbial transformations of the antimelanoma agent betulinic acid.

    PubMed

    Kouzi, S A; Chatterjee, P; Pezzuto, J M; Hamann, M T

    2000-12-01

    Microbial transformation studies of the antimelanoma agent betulinic acid (1) were conducted. Screening experiments showed a number of microorganisms capable of biotransforming 1. Three of these cultures, Bacillus megaterium ATCC 14581, Cunninghamella elegans ATCC 9244, and Mucor mucedo UI-4605, were selected for preparative scale transformation. Bioconversion of 1 with resting-cell suspensions of phenobarbital-induced B. megaterium ATCC 14581 resulted in the production of the known betulonic acid (2) and two new metabolites: 3beta,7beta-dihydroxy-lup-20(29)-en-28-oic acid (3) and 3beta,6alpha, 7beta-trihydroxy-lup-20(29)-en-28-oic acid (4). Biotransformation of 1 with growing cultures of C. elegans ATCC 9244 produced one new metabolite characterized as 1beta,3beta, 7beta-trihydroxy-lup-20(29)-en-28-oic acid (5). Incubation of 1 with growing cultures of M. mucedo UI-4605 afforded metabolite 3. Structure elucidation of all metabolites was based on NMR and HRMS analyses. In addition, the antimelanoma activity of metabolites 2-5 was evaluated against two human melanoma cell lines, Mel-1 (lymph node) and Mel-2 (pleural fluid). PMID:11141108

  17. Gradual surface degradation of restorative materials by acidic agents.

    PubMed

    Hengtrakool, Chanothai; Kukiattrakoon, Boonlert; Kedjarune-Leggat, Ureporn

    2011-01-01

    The aim of this study was to investigate the effect of acidic agents on surface roughness and characteristics of four restorative materials. Fifty-two discs were created from each restorative material: metal-reinforced glass ionomer cement (Ketac-S), resin-modified glass ionomer cement (Fuji II LC), resin composite (Filtek Z250), and amalgam (Valiant-PhD); each disc was 12 mm in diameter and 2.5 mm thick. The specimens were divided into four subgroups (n=13) and immersed for 168 hours in four storage media: deionized water (control); citrate buffer solution; green mango juice; and pineapple juice. Surface roughness measurements were performed with a profilometer, both before and after storage media immersion. Surface characteristics were examined using scanning electron microscopy (SEM). Statistical significance among each group was analyzed using two-way repeated ANOVA and Tukey's tests. Ketac-S demonstrated the highest roughness changes after immersion in acidic agents (p<0.05), followed by Fuji II LC. Valiant-PhD and Filtek Z250 illustrated some minor changes over 168 hours. The mango juice produced the greatest degradation effect of all materials tested (p<0.05). SEM photographs demonstrated gradual surface changes of all materials tested after immersions. Of the materials evaluated, amalgam and resin composite may be the most suitable for restorations for patients with tooth surface loss.

  18. Gradual surface degradation of restorative materials by acidic agents.

    PubMed

    Hengtrakool, Chanothai; Kukiattrakoon, Boonlert; Kedjarune-Leggat, Ureporn

    2011-01-01

    The aim of this study was to investigate the effect of acidic agents on surface roughness and characteristics of four restorative materials. Fifty-two discs were created from each restorative material: metal-reinforced glass ionomer cement (Ketac-S), resin-modified glass ionomer cement (Fuji II LC), resin composite (Filtek Z250), and amalgam (Valiant-PhD); each disc was 12 mm in diameter and 2.5 mm thick. The specimens were divided into four subgroups (n=13) and immersed for 168 hours in four storage media: deionized water (control); citrate buffer solution; green mango juice; and pineapple juice. Surface roughness measurements were performed with a profilometer, both before and after storage media immersion. Surface characteristics were examined using scanning electron microscopy (SEM). Statistical significance among each group was analyzed using two-way repeated ANOVA and Tukey's tests. Ketac-S demonstrated the highest roughness changes after immersion in acidic agents (p<0.05), followed by Fuji II LC. Valiant-PhD and Filtek Z250 illustrated some minor changes over 168 hours. The mango juice produced the greatest degradation effect of all materials tested (p<0.05). SEM photographs demonstrated gradual surface changes of all materials tested after immersions. Of the materials evaluated, amalgam and resin composite may be the most suitable for restorations for patients with tooth surface loss. PMID:21903509

  19. Cerebrolysin lowers kynurenic acid formation--an in vitro study.

    PubMed

    Baran, Halina; Kepplinger, Berthold

    2009-03-01

    The therapeutic effect of Cerebrolysin in the treatment of dementia and brain injury has been proposed because of neurotrophic properties of this compound. Since an increased kynurenine metabolism has been documented in several brain pathologies including dementia the aim of the present study was to investigate the biochemical properties of Cerebrolysin with respect to kynurenic acid (KYNA) formation in an in vitro study. KYNA is an endogenous metabolite of the kynurenine pathway of tryptophan degradation and is an antagonist of the glutamate ionotropic excitatory amino acid and of the nicotine cholinergic receptors. The activities of the KYNA synthesizing enzymes kynurenine aminotransferases I, II and III (KAT I, KAT II and KAT III) in rat liver, and rat and human brain homogenates were analysed in the presence of Cerebrolysin. KAT I, II and III activities were measured using a radio-enzymatic method in the presence of 1 mM pyruvate and 100 microM [H(3)]L-kynurenine. Cerebrolysin, dose-dependently and significantly reduced KAT I, KAT II and KAT III activities of rat liver homogenate. Furthermore, Cerebrolysin exerted a dose-dependent inhibition of rat and human brain KAT I, KAT II and KAT III activities, too. The inhibitory effect of Cerebrolysin was more pronounced for KAT I than for KAT II and KAT III. The present study for the first time demonstrates the ability of Cerebrolysin to lower KYNA formation in rat liver as well as in rat and human brain homogenates. We propose Cerebrolysin as a compound susceptible of therapeutic exploitation in some disorders associated with elevated KYNA metabolism in the brain and/or other tissues. We suggest that the anti-dementia effect of Cerebrolysin observed in Alzheimer patients could be in part due to Cerebrolysin induced reduction of KYNA levels, thus modulating the cholinergic and glutamatergic neurotransmissions.

  20. Lower serum uric acid level predicts mortality in dialysis patients

    PubMed Central

    Bae, Eunjin; Cho, Hyun-Jeong; Shin, Nara; Kim, Sun Moon; Yang, Seung Hee; Kim, Dong Ki; Kim, Yong-Lim; Kang, Shin-Wook; Yang, Chul Woo; Kim, Nam Ho; Kim, Yon Su; Lee, Hajeong

    2016-01-01

    Abstract We evaluated the impact of serum uric acid (SUA) on mortality in patients with chronic dialysis. A total of 4132 adult patients on dialysis were enrolled prospectively between August 2008 and September 2014. Among them, we included 1738 patients who maintained dialysis for at least 3 months and had available SUA in the database. We categorized the time averaged-SUA (TA-SUA) into 5 groups: <5.5, 5.5–6.4, 6.5–7.4, 7.5–8.4, and ≥8.5 mg/dL. Cox regression analysis was used to calculate the hazard ratio (HR) of all-cause mortality according to SUA group. The mean TA-SUA level was slightly higher in men than in women. Patients with lower TA-SUA level tended to have lower body mass index (BMI), phosphorus, serum albumin level, higher proportion of diabetes mellitus (DM), and higher proportion of malnourishment on the subjective global assessment (SGA). During a median follow-up of 43.9 months, 206 patients died. Patients with the highest SUA had a similar risk to the middle 3 TA-SUA groups, but the lowest TA-SUA group had a significantly elevated HR for mortality. The lowest TA-SUA group was significantly associated with increased all-cause mortality (adjusted HR, 1.720; 95% confidence interval, 1.007–2.937; P = 0.047) even after adjusting for demographic, comorbid, nutritional covariables, and medication use that could affect SUA levels. This association was prominent in patients with well nourishment on the SGA, a preserved serum albumin level, a higher BMI, and concomitant DM although these parameters had no significant interaction in the TA-SUA-mortality relationship except DM. In conclusion, a lower TA-SUA level <5.5 mg/dL predicted all-cause mortality in patients with chronic dialysis. PMID:27310949

  1. Surface characteristic changes of dental ceramics after cyclic immersion in acidic agents and titratable acidity.

    PubMed

    Junpoom, Peerapong; Kukiattrakoon, Boonlert; Hengtrakool, Chanothai

    2010-12-01

    The potential erosive effect of acidic food, sour fruits and drinks on all-ceramic restorations used in dentistry has not been clearly documented. Surface characteristic changes have been evaluated and compared for disc-shaped specimens (diameter 12.0 mm and thickness 2.0 mm) of fluorapatite-leucite and fluorapatite ceramics using various storage agents (deionized water, citrate buffer solution, pineapple juice, green mango juice, cola soft drink and 4% acetic acid). Immersion in pineapple juice, green mango juice, cola soft drink and 4% acetic acid for 16 hours produce significant increases in surface roughness for both types of ceramics investigated.

  2. Theophylline-7-acetic acid derivatives with amino acids as anti-tuberculosis agents.

    PubMed

    Voynikov, Yulian; Valcheva, Violeta; Momekov, Georgi; Peikov, Plamen; Stavrakov, Georgi

    2014-07-15

    A series of amides were synthesized by condensation of theophylline-7-acetic acid and eight commercially available amino acid methyl ester hydrochlorides. Consecutive hydrolysis of six of the amido-esters resulted in the formation of corresponding amido-acids. The newly synthesized compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. The activity varied depending on the amino acid fragments and in seven cases exerted excellent values with MICs 0.46-0.26 μM. Assessment of the cytotoxicity revealed that the compounds were not cytotoxic against the human embryonal kidney cell line HEK-293T. The theophylline-7-acetamides containing amino acid moieties appear to be promising lead compounds for the development of antimycobacterial agents.

  3. Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several benzoic acid analogs showed antifungal activity against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis. Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids increased by addition of a methyl, methoxyl...

  4. STATINS MORE THAN CHOLESTEROL LOWERING AGENTS IN ALZHEIMER DISEASE: THEIR PLEIOTROPIC FUNCTIONS AS POTENTIAL THERAPEUTIC TARGETS

    PubMed Central

    Barone, Eugenio; Domenico, Fabio Di; Butterfield, D. Allan

    2013-01-01

    Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive impairment, inability to perform activities of daily living and mood changes. Statins, long known to be beneficial in conditions where dyslipidemia occurs by lowering serum cholesterol levels, also have been proposed for use in neurodegenerative conditions, including AD. However, it is not clear that the purported effectiveness of statins in neurodegenerative disorders is directly related to cholesterol-lowering effects of these agents; rather, the pleiotropic functions of statins likely play critical roles. The aim of this review is to provide an overview on the new discoveries about the effects of statin therapy on the oxidative ad nitrosative stress levels as well as on the modulation of the heme oxygenase/biliverdin reductase (HO/BVR) system in the brain. We propose a novel mechanism of action for atorvastatin which, through the activation of HO/BVR-A system, may contribute to the neuroprotective effects thus suggesting a potential therapeutic role in AD and potentially accounting for the observation of decreased AD incidence with persons on statin. PMID:24231510

  5. Hydrochloric Acid and the Chlorine Budget of the Lower Stratosphere

    NASA Technical Reports Server (NTRS)

    Webster, C.; May, R.; Jaegle, L.; Hu, H.; Sander, S.; Gunson, M.; Toon, G.; Russell, J., III; Stimpfle, R.; Koplow, J.; Salawitch, R.; Michelsen, H.

    1994-01-01

    Concentrations of hc1 measured in the lower stratosphere in 1993 by the ALIAS instrument on the ER-2 aircraft reveal that only 40% of inorganic chlorine (CL sub y, inferred from in situ measurements of organic chlorinated source gases) is present as HC1, significantly lower than model predictions.

  6. Overcoming platinum resistance through the use of a copper-lowering agent.

    PubMed

    Fu, Siqing; Naing, Aung; Fu, Caroline; Kuo, Macus Tien; Kurzrock, Razelle

    2012-06-01

    Low levels of human copper transporter 1 (hCtr1) mRNA are associated with a shorter progression-free survival after platinum-based therapy. Pretreatment with a copper-lowering agent such as trientine enhanced hCtr1-mediated platinum uptake. Therefore, we conducted a pilot study (NCT01178112) of carboplatin and trientine with the goal of resensitizing patients with advanced cancer to platinum chemotherapy. This case report reviews the outcomes of 5 patients with platinum-resistant high-grade epithelial ovarian cancer enrolled on the study to date. Overall, they tolerated treatment well. Severe adverse events that occurred in 2 patients were myelosuppression, notably anemia requiring transfusion. Dose-limiting toxicity was not observed within the first 28 days (cycle 1). After 2 cycles of therapy, partial remission was achieved in 1 patient (10+ months), stable disease in 3 patients (2, 3.5+, and 5 months, respectively), and 1 patient had progressive disease. These cases provide preliminary clinical evidence that the role of decreasing copper levels in reversing platinum resistance merits additional clinical investigation. Evaluation of this novel strategy is warranted in larger studies to assess the efficacy of this approach for treating platinum-resistant advanced epithelial ovarian cancer in patients with high copper levels.

  7. Insulin-lowering agents in the management of polycystic ovary syndrome.

    PubMed

    De Leo, Vincenzo; la Marca, Antonio; Petraglia, Felice

    2003-10-01

    Polycystic ovary syndrome (PCOS) is a medical condition that has brought multiple specialists together. Gynecologists, endocrinologists, cardiologists, pediatricians, and dermatologists are all concerned with PCOS patients and share research data and design clinical trials to learn more about the syndrome. Insulin resistance is a common feature of PCOS and is more marked in obese women, suggesting that PCOS and obesity have a synergistic effect on the magnitude of the insulin disorder. Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome, such as hyperandrogenism, reproductive disorders, acne, hirsutism, and metabolic disturbances. Women with PCOS should be evaluated for cardiovascular risk factors, such as lipid profile and blood pressure. Modification of diet and lifestyle should be suggested to those who are obese. Several insulin-lowering agents have been tested in the management of PCOS. In particular, metformin is the only drug currently in widespread clinical use for treatment of PCOS. In a high percentage of patients, treatment with metformin is followed by regularization of menstrual cycle, reduction in hyperandrogenism and in cardiovascular risk factors, and improvement in response to therapies for induction of ovulation.

  8. epsilon-Aminocaproic acid esters as transdermal penetration enhancing agents.

    PubMed

    Dolezal, P; Hrabálek, A; Semecký, V

    1993-07-01

    The synthesis of epsilon-aminocaproic acid esters is described. Two representative members from a group of five of the 1-alkyl homologues synthetized as flexible analogues of 1-alkylazacyclohepatanone derivatives were evaluated in vitro for their effectiveness on the transport of theophylline through the excised human cadaver skin in comparison with Azone. The 1-octyl- and 1-dodecyl-epsilon-aminocaproic acid esters (OCEAC and DDEAC) show excellent penetration enhancement. Donor samples contained 2.5% theophylline and 1% enhancers tested in three different vehicles. Fluxes of theophylline were increased with OCEAC about 19 times from olive oil, 45 times from water, and about 38 times from water-propylene glycol (3:2) vehicle toward controls (with DDEAC about 17, 39, and 35 times, respectively) and they were markedly higher than Azone under the given conditions. Acute LD50's (i.p. in mice) of OCEAC (DDEAC) were 245 mg/kg (352 mg/kg), with a slightly lower toxicity than Azone. OCEAC and DDEAC did not exhibit acute dermal irritation in vivo on rabbits at a 5% concentration in white petrolatum.

  9. [Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibacterial agents (2011)].

    PubMed

    Goto, Hajime; Iwasaki, Mitsuhiro

    2015-04-01

    From October 2011 to September 2012, we collected the specimen from 316 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. All of 357 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, were examined. The isolated bacteria were: Staphylococcus aureus 51, Streptococcus pneumoniae 73, Haemophilus influenzae 88, Pseudomonas aeruginosa (non-mucoid) 34, P. aeruginosa (mucoid) 9, Klebsiella pneumoniae 21, and Moraxella catarrhalis 33. Of 51 S. aureus strains, those with 2 μg/mL or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 μg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 31 (60.8%) and 20 (39.2%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 μg/mL or less. Against MRSA, vancomycin showed the potent activity and inhibited the growth of all the strains at 1 μg/mL. Linezolid also showed the great activity and inhibited the growth of all the strains at 2 μg/mL. Carbapenems and penems showed the most potent activities against S. pneumoniae and panipenem inhibited the growth of all the strains at 0.125 μg/mL. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.5 and 1 μg/mL, respectively. In contrast, there were high-resistant strains (MIC: > 128 μg/mL) for erythromycin (53.4%) and clindamycin (3 5.6%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 μg/mL or less. Ciprofloxacin showed the most potent activity against P. aeruginosa (mucoid) and inhibited the growth of all the strains at 2 μg/mL or less. Against the non-mucoid type of P. aeruginosa, tobramycin had the most potent activity and its MIC90 was 2

  10. [Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibacterial agents (2009)].

    PubMed

    Goto, Hajime; Kumagai, Shigeru

    2015-02-01

    From October 2009 to September 2010, we collected the specimen from 432 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. All of 479 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, were examined. The isolated bacteria were: Staphylococcus aureus 90, Streptococcus pneumoniae 74, Haemophilus influenzae 82, Pseudomonas aeruginosa (non-mucoid) 60, P. aeruginosa (mucoid) 31, Klebsiella pneumoniae 41, and Moraxella catarrhalis 34. Of 90 S. aureus strains, those with 2 μg/mL or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 μg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 43 (47.8%) and 47 (52.2%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 μg/mL or less. Against MRSA, vancomycin and arbekacin showed the potent activity and inhibited the growth of all the strains at 2 and 4 μg/mL, respectively. Linezolid also showed the great activity and inhibited the growth of all the strains at 2 μg/mL. Carbapenems and penems showed the most potent activities against S. pneumoniae and panipenem inhibited the growth of all the strains at 0.125 μg/mL. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.25 and 0.5 μg/mL, respectively. In contrast, there were high-resistant strains (MIC: > 128 μg/mL) for erythromycin (51.4%) and clindamycin (35.1%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 μg/mL or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 1 μg/mL. Against the non-mucoid type of P. aeruginosa, tobramycin had the most potent activity and its MIC90 was 2

  11. [Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibacterial agents (2010)].

    PubMed

    Goto, Hajime; Iwasaki, Mitsuhiro

    2015-04-01

    From October 2010 to September 2011, we collected the specimen from 361 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. All of 399 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, were examined. The isolated bacteria were: Staphylococcus aureus 70, Streptococcus pneumoniae 65, Haemophilus influenzae 72, Pseudomonas aeruginosa (non-mucoid) 47, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 30, and Moraxella catarrhalis 39. Of 70 S. aureus strains, those with 2 μg/mL or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 μg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 45 (64.3%) and 25 (35.7%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 μg/mL or less. Against MRSA, vancomycin and arbekacin showed the potent activity and inhibited the growth of all the strains at 2 μg/mL. Linezolid also showed the great activity and inhibited the growth of all the strains at 2 μg/mL. Carbapenems and penems showed the most potent activities against S. pneumoniae and panipenem inhibited the growth of all the strains at 0.125 μg/mL. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.5 and 1 μg/mL, respectively. In contrast, there were high-resistant strains (MIC: > 128 μg/mL) for erythromycin (44.6%) and clindamycin (24.6%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 μg/mL or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 0.5 μg/mL. Against the non-mucoid type of P. aeruginosa, tobramycin had the most potent activity and its MIC90 was 2 μg/mL. Against K

  12. [Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibacterial agents (2008)].

    PubMed

    Goto, Hajime; Iwasaki, Mitsuhiro

    2015-02-01

    From October 2008 to September 2009, we collected the specimen from 374 patients with lower respiratory tract infections in 15 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 423 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 421 strains were examined. The isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 78, Haemophilus influenzae 89, Pseudomonas aeruginosa (non-mucoid) 61, P. aeruginosa (mucoid) 19, Klebsiella pneumoniae 28, and Moraxella catarrhalis 32. Of 78 S. aureus strains, those with 2 μg/mL or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 μg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 34 (43.6%) and 44 (56.4%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 μg/mL or less. Against MRSA vancomycin and arbekacin showed the potent activity and inhibited the growth of all the strains at 1 and 2 μg/mL, respectively. Linezolid also showed the great activity and inhibited the growth of all the strains at 1 μg/mL. Carbapenems and penems showed the most potent activities against S. pneumoniae and panipenem inhibited the growth of all the strains at 0.125 μg/mL. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.25 and 1 μg/mL, respectively. In contrast, there were high-resistant strains (MIC: > 128 μg/mL) for erythromycin (43.6%) and clindamycin (19.2%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 μg/mL or less. Tobramycin showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 2 μg/mL. Against the non-mucoid type of P. aeruginosa, tobramycin and ciprofloxacin had the most potent activity

  13. Development of shelf-stable, ready-to-eat (RTE) shrimps ( Litopenaeus vannamei ) using water activity lowering agent by response surface methodology.

    PubMed

    Cui, Hongbo; Xue, Changhu; Xue, Yong; Su, Wei; Li, Zhaojie; Cong, Haihua

    2013-12-01

    Three water-activity-lowering agents (composite phosphate, sorbitol and glycerol) were used to develop a kind of shelf-stable, ready-to-eat (RTE) shrimp. Formula of water-activity- lowering agents was optimized by response surface methodology (RSM) using a central composite design. Model equation was proposed with regard to the contents of composite phosphate (X1), sorbitol (X 2) and glycerol (X3) : [Formula: see text]. The model with a very low probability value (P < 0.0003) was highly significant and the value of lack-of-fit was 0.4028, indicating that the model could predict water activity of shrimps using different agents. Composite phosphate of 0.22%, sorbitol of 3.12% and glycerol of 2.51% were found to be the optimal condition to obtain the lowest water activity of 0.884. Compared to the control shrimps, RTE shrimps treated with water-activity-lowering agents had a longer shelflife and higher sensorial acceptability. During storage at temperature of 35 °C, the quality of RTE shrimps in term of appearance, flavor and texture was found to be superior to the untreated ones. Texture profile, TBARS value, contents of astaxanthin and free amino acid of treated samples were found to be decreased slower from origin value compared to that of untreated samples. These RTE shrimps were biologically safe and sensorially acceptable after 30 days of storage at temperature of 35 °C. Briefly, the application of water-activity-lowering agents extent the shelflife of RTE shrimps obviously and would be beneficial for the exploitation of white shrimp. PMID:24426026

  14. Use of esters of sulfonic acids as anti-sludge agents during the acidizing of formations containing sludging crude oils

    SciTech Connect

    Looney, J.R.; McDougall, L.A.

    1984-04-10

    An anti-sludge agent useful for acid stimulated hydrocarbon containing formations is an ester of sulfonic acid, e.g. monoethoxylated dodecyl benzene sulfonic acid, preferably used in combination with from 0.1 to 2 parts by weight of a surfactant.

  15. Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids were increased against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis, by addition of a methyl, methoxyl or a chloro group at position 4 of the aromatic ri...

  16. [Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibacterial agents (2007)].

    PubMed

    Goto, Hajime; Iwasaki, Mitsuhiro

    2015-02-01

    From October 2007 to September 2008, we collected the specimen from 362 patients with lower respiratory tract infections in 14 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 413 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 412 strains were examined. The isolated bacteria were: Staphylococcus aureus 65, Streptococcus pneumoniae 90, Haemophilus influenzae 88, Pseudomonas aeruginosa (non-mucoid) 53, P. aeruginosa (mucoid) 13, Klebsiella pneumoniae 19, and Moraxella catarrhalis 41. Of 65 S. aureus strains, those with 2 μg/mL or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 μg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 38 (58.5%) and 27 (41.5%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 μg/mL or less. Against MRSA, vancomycin and arbekacin showed the most potent activity and inhibited the growth of all the strains at 2 μg/mL. Linezolid also showed the same activity as them. Carbapenems and penems showed the most potent activities against S. pneumoniae and in particular, panipenem inhibited the growth of all the strains at 0.063 μg/mL or less. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.25 and 1 μg/mL, respectively. In contrast, there were high-resistant strains (MIC: over 128 μg/mL) for erythromycin (38.2%) and clindamycin (18.0%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 μg/mL or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 0.5 μg/mL. Against P. aeruginosa (non-mucoid), tobramycin had the most potent activity and its MIC90 was 2 μg/mL. Against K. pneumoniae, cefozopran had

  17. Hydrochloric acid and the chlorine budget of the lower statosphere

    NASA Technical Reports Server (NTRS)

    Webster, C. R.; May, R. D.; Jaegle, L.; Hu, H.; Sander, S. P.; Gunson, M. R.; Toon, G. C.; Russell, J. M., III; Stimpfle, R. M.; Koplow, J. P.

    1994-01-01

    Concentrations of HCl measurements in the lower stratosphere in 1993 by the ALIAS instrument on the ER-2 aircraft reveal that only 40% of inorganic chlorine (Cl(y), inferred from in situ measurements of organic chlorinated sources gases) is present as HCl, significantly lower than model predictions. Although the sum of measured HCl, ClO and ClONO2, the latter inferred from measurements of ClO and NO2 equals Cl(y) to within the incertainty of measurement, it is systematically less than Cl(y) by 30-50%. This discrepancy suggests that concentrations of ClONO2 may exceed those of HC; near 20 km altitude, consistent with a slower photolysis rate for ClONO2 than calculated using recommended cross sections. Comparison of profiles of HCl measured during 1992 and 1193 at mid-latitudes by balloon (BLISS and MARKIV), space shuttle (ATMOS), and satellite (HALOE) instruments with the aircraft data reveal an apparent pressure dependence to the HCl to Cl(y) ratio, consistent with a factor of 3-10 reduction in the photolysis rate for ClONO2 at ER-2 altitudes. However, the diurnal variation of ClO is well-simulated by models using the recommended photolysis rate, and simulations measurements of ClONO2 and HCl at mid-latitudes by ATMOS and MARKIV report HCl (HCL+ ClONO2) ratios greater than or equal to 50%. Premliminary measurements by ALIAS in the southern hemisphere report HCl/Cl(y) values of about 75%.

  18. Determining Multiple Responses of Pseudomonas aeruginosa PAO1 to an Antimicrobial Agent, Free Nitrous Acid.

    PubMed

    Gao, Shu-Hong; Fan, Lu; Peng, Lai; Guo, Jianhua; Agulló-Barceló, Míriam; Yuan, Zhiguo; Bond, Philip L

    2016-05-17

    Free nitrous acid (FNA) has recently been demonstrated as an antimicrobial agent on a range of micro-organisms, especially in wastewater-treatment systems. However, the antimicrobial mechanism of FNA is largely unknown. Here, we report that the antimicrobial effects of FNA are multitargeted. The response of a model denitrifier, Pseudomnas aeruginosa PAO1 (PAO1), common in wastewater treatment, was investigated in the absence and presence of inhibitory level of FNA (0.1 mg N/L) under anaerobic denitrifying conditions. This was achieved through coupling gene expression analysis, by RNA sequencing, and with a suite of physiological analyses. Various transcripts exhibited significant changes in abundance in the presence of FNA. Respiration was likely inhibited because denitrification activity was severely depleted, and decreased transcript levels of most denitrification genes occurred. As a consequence, the tricarboxylic acid (TCA) cycle was inhibited due to the lowered cellular redox state in the FNA-exposed cultures. Meanwhile, during FNA exposure, PAO1 rerouted its carbon metabolic pathway from the TCA cycle to pyruvate fermentation with acetate as the end product as a possible survival mechanism. Additionally, protein synthesis was significantly decreased, and ribosome preservation was evident. These findings improve our understanding of PAO1 in response to FNA and contribute toward the potential application for use of FNA as an antimicrobial agent. PMID:27116299

  19. Measurements of acetone, acetic acid, and formic acid in the northern midlatitude upper troposphere and lower stratosphere

    NASA Astrophysics Data System (ADS)

    Reiner, Thomas; MöHler, Ottmar; Arnold, Frank

    1999-06-01

    We have measured acetone, acetic acid, and formic acid concentrations in the upper troposphere and lower stratosphere over Germany. The measurements were performed by ion molecule reaction mass spectrometry using new kinetic data on ion molecule reactions of formic and acetic acids with negative ions obtained at our laboratory. Mean volume mixing ratios between 384 and 832 parts per trillion (pptv) for acetone, 110 and 357 pptv for acetic acid, and 59 and 215 pptv for formic acid were obtained. The correlation between formic acid and acetic acid was very poor (r2 = 0.14). A better correlation could be observed for acetone and acetic acid, with a correlation coefficient r2 = 0.46 and a slope (acetic acid/acetone) of 0.31. For acetic acid a maximum around 9 km was observed. A significant fraction of the acetic acid observed in the lower stratosphere may be due to in situ photochemical production by reactions of HO2 and CH3O2 with peroxy acetyl radicals produced by the photolysis of acetone. In the upper troposphere, vertical transport is much more efficient, and significant acetic acid production is only possible if HOx concentrations are elevated, making the production of acetic acid fast enough to compete with vertical transport.

  20. Spherical Nucleic Acids as Intracellular Agents for Nucleic Acid Based Therapeutics

    NASA Astrophysics Data System (ADS)

    Hao, Liangliang

    Recent functional discoveries on the noncoding sequences of human genome and transcriptome could lead to revolutionary treatment modalities because the noncoding RNAs (ncRNAs) can be applied as therapeutic agents to manipulate disease-causing genes. To date few nucleic acid-based therapeutics have been translated into the clinic due to challenges in the delivery of the oligonucleotide agents in an effective, cell specific, and non-toxic fashion. Unmodified oligonucleotide agents are destroyed rapidly in biological fluids by enzymatic degradation and have difficulty crossing the plasma membrane without the aid of transfection reagents, which often cause inflammatory, cytotoxic, or immunogenic side effects. Spherical nucleic acids (SNAs), nanoparticles consisting of densely organized and highly oriented oligonucleotides, pose one possible solution to circumventing these problems in both the antisense and RNA interference (RNAi) pathways. The unique three dimensional architecture of SNAs protects the bioactive oligonucleotides from unspecific degradation during delivery and supports their targeting of class A scavenger receptors and endocytosis via a lipid-raft-dependent, caveolae-mediated pathway. Owing to their unique structure, SNAs are able to cross cell membranes and regulate target genes expression as a single entity, without triggering the cellular innate immune response. Herein, my thesis has focused on understanding the interactions between SNAs and cellular components and developing SNA-based nanostructures to improve therapeutic capabilities. Specifically, I developed a novel SNA-based, nanoscale agent for delivery of therapeutic oligonucleotides to manipulate microRNAs (miRNAs), the endogenous post-transcriptional gene regulators. I investigated the role of SNAs involving miRNAs in anti-cancer or anti-inflammation responses in cells and in in vivo murine disease models via systemic injection. Furthermore, I explored using different strategies to construct

  1. Pyrimidinyl-arylpropionic acid derivatives: viable resources in the development of new antineoplastic agents.

    PubMed

    Xiong, Xishan; Wang, Li; Ye, Yangliang; Fu, Lili; Chen, Minli; Wang, Qingyi; Liu, Moyan; Tang, Jing; Dai, Bing; Shen, Jianhua; Mei, Changlin

    2010-08-01

    Numerous studies have documented that various naturally derived ligands or synthetic non-thiazolidinediones (TZD) as peroxisome proliferator-activated receptor gamma (PPARgamma) agonists have shown moderate or potent antitumor activities, which is PPARgamma independent or partially dependent. However, the PPARgamma agonistic or glucose-lowering activity is ranked first more often than antitumor activity to determine promising novel PPARgamma agonists for potential clinical use. In this study, we hypothesized that there might exist some compounds with less PPARgamma agonistic activity but potent antitumor activity. Thereafter, we evaluated the PPARgamma agonistic and antitumor activity of a novel series of alpha-aryloxy-alpha-methylhydrocinnamic acid derivatives synthesized with the initial aim of developing novel PPARgamma agonists as hypoglycemic agents. MTT assay results revealed that several compounds were able to inhibit cell proliferation in a dose-dependent manner with IC(50) 12.7-29.7 microM, better than that of rosiglitazone (45.9-141 microM), although the PPARgamma agonistic activity of most compounds is much lower than rosiglitazone. Some compounds induced cell cycle arrest and apoptosis tested by Flow Cytometry. Oral administration of DH9 (100 mg/kg/d) for 21 days to BALB/c nude mice bearing xenografts including MGC-803, NCI-H460, HT-29 and OS-RC-2 cells significantly retarded tumor growth. DG8 and DJ5 showed benefits in some of the above four xenografts. Our findings demonstrate that these compounds have potent antitumor activity in vitro and in vivo and pyrimidinyl-arylpropionic acid derivatives might be viable resources in the development of new antineoplastic agents.

  2. Preparation of co-spray dried cushioning agent containing stearic acid for protecting pellet coatings when compressed.

    PubMed

    Li, Xiao; Xu, De Sheng; Li, Min; Liu, Li; Heng, Paul

    2016-01-01

    This study investigated the applicability of stearic acid as a co-adjuvant in cushioning agent formulated to prevent coat damage when compressing coated pellets. The co-processed and physical blended fillers were prepared by spray drying and physically blending, respectively, with filler ingredients consisting of stearic acid, microcrystalline cellulose, fully gelatinized starch, and corn starch. Pellets containing drug were produced by coating onto non-pariels a drug layer of metformin followed by a sustained-release layer. Drug release from tablets composed of co-processed or physical blended fillers (0, 1, 5, and 10% stearic acid levels) and coated drug containing pellets were analyzed using similarity factor F2. Under the same force and the stearic acid level, co-processed fillers produced pellet containing tablets which showed higher F2 or t50 values and tensile strengths as well as lower yield pressures as compared with tablets containing physical blended fillers. It was shown that the destructive degree of pellet coating was significantly reduced after being co-processed by homogenization and the incorporation of stearic acid in the cushioning agents, as shown by the improved F2 and t50 values. In addition, disintegrate times of tablets containing co-processed agents decreased despite the hydrophobic stearic acid. In conclusion, the inclusion of stearic acid in co-processed cushioning agents was effective at protecting compacted coated pellets from compression-induced damage without compromising disintegratability. The findings could serve as a step towards resolving the technical challenges of balancing the drug release profiles, tablet tensile strength, and disintegration time of compacting coated pellets into multi-particulate-sustained release tablets.

  3. Colesevelam hydrochloride: usefulness of a specifically engineered bile acid sequestrant for lowering LDL-cholesterol.

    PubMed

    Corsini, Alberto; Windler, Eberhard; Farnier, Michel

    2009-02-01

    Several recent meta-analyses of numerous lipid-lowering outcome trials confirm the direct relationship between low-density lipoprotein-cholesterol (LDL-C) lowering and cardiovascular risk reduction. As a consequence, LDL-C goals are continuously being set lower. To achieve lipid lowering, several efficient drugs are available, however, the current pharmacopoeia remains limited for some critical patient situations. Colesevelam hydrochloride is a specifically engineered bile acid sequestrant that features a more favourable tolerability and drug interaction profile than traditional bile acid sequestrants, because of a better affinity and binding capacity to bile acids. In addition, colesevelam retains the nonsystemic mode of action of bile acid sequestrants. Moreover, colesevelam lowers LDL-C by 15-19% and 10-16%, respectively, in monotherapy and in combination to various lipid-lowering drugs, such as statins, ezetimibe and fenofibrates. Along with an efficient and sustainable effect on lipid profiles, colesevelam - as other bile acid sequestrants - has been shown to lower the glycosylated haemoglobin HbA1c by 0.5% on average in patients with type 2 diabetes. Overall, colesevelam represents an interesting add-on treatment to be used in high-risk patients with hypercholesterolaemia for whom standard lipid-lowering therapies are not enough or not well tolerated.

  4. Inhibitors of amino acids biosynthesis as antifungal agents.

    PubMed

    Jastrzębowska, Kamila; Gabriel, Iwona

    2015-02-01

    Fungal microorganisms, including the human pathogenic yeast and filamentous fungi, are able to synthesize all proteinogenic amino acids, including nine that are essential for humans. A number of enzymes catalyzing particular steps of human-essential amino acid biosynthesis are fungi specific. Numerous studies have shown that auxotrophic mutants of human pathogenic fungi impaired in biosynthesis of particular amino acids exhibit growth defect or at least reduced virulence under in vivo conditions. Several chemical compounds inhibiting activity of one of these enzymes exhibit good antifungal in vitro activity in minimal growth media, which is not always confirmed under in vivo conditions. This article provides a comprehensive overview of the present knowledge on pathways of amino acids biosynthesis in fungi, with a special emphasis put on enzymes catalyzing particular steps of these pathways as potential targets for antifungal chemotherapy.

  5. Dehydroascorbic acid as an anti-cancer agent.

    PubMed

    Toohey, John I

    2008-05-18

    Three discoveries together point the way to a potential treatment for cancer. In 1982, Poydock and colleagues found that dehydroascorbic acid has the remarkable ability to eliminate the aggressive mouse tumours, L1210, P388, Krebs sarcoma, and Ehrlich carcinoma. In 1993, Jakubowski found that cancer cells (but not normal cells) contain measurable quantities of homocysteine thiolactone. Recently, the author found that dehydroascorbic acid reacts with homocysteine thiolactone converting it to the toxic compound, 3-mercaptopropionaldehyde. Taken together, these findings suggest that rapidly-dividing tumour cells make unusually large amounts of homocysteine thiolactone and that administered dehydroascorbic acid enters the cells and converts the thiolactone to mercaptopropionaldehyde which kills the cancer cells. The effectiveness of dehydroascorbic acid might be further increased by combining it with methionine and/or methotrexate to increase the homocysteine concentration in cancer cells.

  6. Foam injection molding of poly(lactic acid) with physical blowing agents

    NASA Astrophysics Data System (ADS)

    Pantani, R.; Sorrentino, A.; Volpe, V.; Titomanlio, G.

    2014-05-01

    Foam injection molding uses environmental friendly blowing agents under high pressure and temperature to produce parts having a cellular core and a compact solid skin (the so-called "structural foam"). The addition of a supercritical gas reduces the part weight and at the same time improves some physical properties of the material through the promotion of a faster crystallization; it also leads to the reduction of both the viscosity and the glass transition temperature of the polymer melt, which therefore can be injection molded adopting lower temperatures and pressures. These aspects are of extreme interest for biodegradable polymers, which often present a very narrow processing window, with the suitable processing temperatures close to the degradation conditions. In this work, foam injection molding was carried out by an instrumented molding machine, able to measure the pressure evolution in different positions along the flow-path. The material adopted was a biodegradable polymer, namely the Poly(lactic acid), PLA. The effect of a physical blowing agent (PBA) on the viscosity was measured. The density reduction and the morphology of parts obtained by different molding conditions was assessed.

  7. Mechanisms for lowering of interfacial tension in alkali/acidic oil systems; Effect of added surfactant

    SciTech Connect

    Rudin, J. Wasan, D.T. . Dept. of Chemical Engineering)

    1992-08-01

    This paper reports that experimental studies are conducted in order to determine the physicochemical mechanism responsible for lowering of interfacial tension in alkali, surfactant, and surfactant-enhanced alkali/acidic oil systems. A well-defined model oil is chosen to examine the influence of various surfactants and surfactant mixtures, such as oleic acid and its ionic counterpart, sodium dodecyl sulfate, petroleum sulfonate, and isobutanol, on equilibrium interfacial tension. With added surfactant alone, the interfacial tension goes through an ultralow minimum with increasing acid concentration. This proves for the first time that the un-ionized acid species plays a major role in affecting interfacial tension, and the ionized acid species.

  8. The effect of bulking agents on the chemical stability of acid-sensitive compounds in freeze-dried formulations: sucrose inversion study.

    PubMed

    Lu, Enxian; Ewing, Susan; Gatlin, Larry; Suryanarayanan, Raj; Shalaev, Evgenyi

    2009-09-01

    The goal of the study was to evaluate the impact of amorphous bulking agents on the chemical stability of freeze-dried materials. Polyvinylpyrrolidone and dextran of different molecular weights and lactose were used as bulking agents, and sucrose was used as an example of an acid-sensitive compound. Lyophiles containing bulking agent and sucrose at 10:1 (w/w) ratio, citrate buffer, and optionally bromophenol blue (pH indicator) were tested by X-ray powder diffractometry, differential scanning calorimetry, and Karl Fischer titrimetry. Diffuse reflectance UV-vis spectroscopy was used to obtain the concentration ratio of the deprotonated (In(2-)) to the protonated (HIn(-)) indicator species, from which the Hammett acidity function (H(2-)) was calculated. The extent of sucrose inversion in lyophiles stored at 60 degrees C was quantified by HPLC. The bulking agent had a major impact on both the apparent solid-state acidity (H(2-)) and the degradation rate, with the degradation rate constants value highest for dextran lyophiles (most "acidic", lower H(2-)) followed by lactose and polyvinylpyrrolidone lyophile (least "acidic", higher H(2-)). The Hammett acidity function can be used as an empirical solid-state acidity scale, to predict the rank-order stability of acid-sensitive compounds in lyophiles prepared with different bulking agents. PMID:19544366

  9. High-fat diet lowers the nutritional status indicators of pantothenic acid in weaning rats.

    PubMed

    Yoshida, Erina; Fukuwatari, Tsutomu; Ohtsubo, Masako; Shibata, Katsumi

    2010-01-01

    Weaning rats were fed a 5% or 30% fat diet containing limited calcium pantothenate for 28 d. The plasma, liver and adrenal pantothenic acid levels in the rats fed on the 30% fat diet were significantly lower than with the 5% fat diet. The results suggest that the high-fat diet affected pantothenic acid metabolism. PMID:20699566

  10. Monascus fermentation of dioscorea for increasing the production of cholesterol-lowering agent--monacolin K and antiinflammation agent--monascin.

    PubMed

    Lee, Chun-Lin; Wang, Jyh-Jye; Kuo, Shing-Lin; Pan, Tzu-Ming

    2006-10-01

    Monacolin K, an inhibitor for cholesterol synthesis, is the secondary metabolite of Monascus species. The formation of the secondary metabolites of the Monascus species is affected by cultivation environment and method. This research uses sweet potato (Ipomoea batatas), potato (Solanum tuberosum), casava (Manihot esculenta), and dioscorea (Dioscorea batatas) as the substrates and discusses the best substrate to produce monacolin K. The results show that Monascus purpureus NTU 301, with dioscorea as the substrate, can produce monacolin K at 2,584 mg kg(-1), which is 5.37 times to that resulted when rice is used as the substrate. In addition, more amount of yellow pigment can be found in Monascus-fermented dioscorea than in Monascus-fermented rice. The certain composition of yellow pigment is identified as monascin, which has been shown as an antiinflammation agent exhibiting potent inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice in previous studies. Therefore, dioscorea is concluded to be the best substrate for Monascus species to produce the cholesterol-lowering agent-monacolin K and antiinflammation agent-monascin.

  11. Oleic acid-embedded nanoliposome as a selective tumoricidal agent.

    PubMed

    Jung, Sujin; Lee, Sangah; Lee, Hyejin; Yoon, Jaejin; Lee, E K

    2016-10-01

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cell), a molecular complex of human α-lactalbumin and oleic acid, is known to have selective cytotoxic activity against certain types of tumors. This cytotoxicity is known to stem from water-insoluble oleic acid. In this study, we manufactured an alternative complex using liposome as an oleic acid delivery vesicle. We named this nanolipoplex LIMLET (LIposome Made LEthal to Tumor cell). The LIMLET vesicle contained approximately 90,200 oleic acid molecules inserted into its lipophilic phospholipid bilayer and had a nominal mean diameter of 127nm. Using a WST-1 assay, its cytotoxicity against two cancer cell lines, MDA-MB-231 (human breast cancer) and A549 (human lung cancer), were tested. The results were compared with that of a normal cell line, Vero (from monkey kidney). We found that (1) LIMLET showed distinctive cytotoxicity against A549 and MDA-MB-231 cells, whereas bare liposomes (containing no oleic acid) had no toxicity, even at high concentrations, and (2) LIMLET demonstrated selective, concentration-dependent toxicity against the cancer cells: the LD50 values of MDA-MB-231 and A549 cells were 1.3 and 2.2nM LIMLET, respectively, whereas the LD50 of Vero was 5.7nM. The strength of the tumoricidal effect appeared to stem from the number of oleic acid molecules present. Our result suggests that LIMLET, like HAMLET, is an interesting nanolipoplex that can potentially be developed into tumor treatments. PMID:27424089

  12. Oleic acid-embedded nanoliposome as a selective tumoricidal agent.

    PubMed

    Jung, Sujin; Lee, Sangah; Lee, Hyejin; Yoon, Jaejin; Lee, E K

    2016-10-01

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cell), a molecular complex of human α-lactalbumin and oleic acid, is known to have selective cytotoxic activity against certain types of tumors. This cytotoxicity is known to stem from water-insoluble oleic acid. In this study, we manufactured an alternative complex using liposome as an oleic acid delivery vesicle. We named this nanolipoplex LIMLET (LIposome Made LEthal to Tumor cell). The LIMLET vesicle contained approximately 90,200 oleic acid molecules inserted into its lipophilic phospholipid bilayer and had a nominal mean diameter of 127nm. Using a WST-1 assay, its cytotoxicity against two cancer cell lines, MDA-MB-231 (human breast cancer) and A549 (human lung cancer), were tested. The results were compared with that of a normal cell line, Vero (from monkey kidney). We found that (1) LIMLET showed distinctive cytotoxicity against A549 and MDA-MB-231 cells, whereas bare liposomes (containing no oleic acid) had no toxicity, even at high concentrations, and (2) LIMLET demonstrated selective, concentration-dependent toxicity against the cancer cells: the LD50 values of MDA-MB-231 and A549 cells were 1.3 and 2.2nM LIMLET, respectively, whereas the LD50 of Vero was 5.7nM. The strength of the tumoricidal effect appeared to stem from the number of oleic acid molecules present. Our result suggests that LIMLET, like HAMLET, is an interesting nanolipoplex that can potentially be developed into tumor treatments.

  13. Alkyl esters of gallic acid as anticancer agents: a review.

    PubMed

    Locatelli, Claudriana; Filippin-Monteiro, Fabíola Branco; Creczynski-Pasa, Tânia Beatriz

    2013-02-01

    The current review presents the antitumoral properties of gallic acid and its ester derivatives. Numerous studies have indicated that the alkyl esters are more effective against tumor cell lines than gallic acid, and that this activity is related to their hydrophobic moiety. All related studies have shown that the antitumor activity is interconnected to the induction of apoptosis by different mechanisms and it depends on the cell type. The results presented in this review may help to emphasize that these compounds could be promising as a new alternative for the treatment of cancer, either alone or in combination with other antitumor drugs to potentiate their effects.

  14. Acidic antiinflammatory agents--correlations of some physical, pharmacological and clinical data.

    PubMed

    Lombardino, J G; Otterness, I G; Wiseman, E H

    1975-10-01

    Fifteen acidic antiinflammatory agents, for which some clinical data have previously been published, have been examined for their potency in the carrageenan-induced rat foot edema test, and for their acidity (pKa) and partition coefficients. Published serum half-life data and daily clinical (anti-arthritic) dose have been tabulated for these drugs and correlations between these various parameters are discussed. The rat foot edema carrageenan test has proved to be a fairly reliable predictor of clinical dose for most acidic antiinflammatory agents of moderate serum half-life. PMID:1042

  15. Biarylalkyl Carboxylic Acid Derivatives as Novel Antischistosomal Agents.

    PubMed

    Mäder, Patrick; Blohm, Ariane S; Quack, Thomas; Lange-Grünweller, Kerstin; Grünweller, Arnold; Hartmann, Roland K; Grevelding, Christoph G; Schlitzer, Martin

    2016-07-01

    Parasitic platyhelminths are responsible for serious infectious diseases, such as schistosomiasis, which affect humans as well as animals across vast regions of the world. The drug arsenal available for the treatment of these diseases is limited; for example, praziquantel is the only drug currently used to treat ≥240 million people each year infected with Schistosoma spp., and there is justified concern about the emergence of drug resistance. In this study, we screened biarylalkyl carboxylic acid derivatives for their antischistosomal activity against S. mansoni. These compounds showed significant influence on egg production, pairing stability, and vitality. Tegumental lesions or gut dilatation was also observed. Substitution of the terminal phenyl residue in the biaryl scaffold with a 3-hydroxy moiety and derivatization of the terminal carboxylic acid scaffold with carboxamides yielded compounds that displayed significant antischistosomal activity at concentrations as low as 10 μm with satisfying cytotoxicity values. The present study provides detailed insight into the structure-activity relationships of biarylalkyl carboxylic acid derivatives and thereby paves the way for a new drug-hit moiety for fighting schistosomiasis. PMID:27159334

  16. Gallic acid-based indanone derivatives as anticancer agents.

    PubMed

    Saxena, Hari Om; Faridi, Uzma; Srivastava, Suchita; Kumar, J K; Darokar, M P; Luqman, Suaib; Chanotiya, C S; Krishna, Vinay; Negi, Arvind S; Khanuja, S P S

    2008-07-15

    Gallic acid-based indanone derivatives have been synthesised. Some of the indanones showed very good anticancer activity in MTT assay. Compounds 10, 11, 12 and 14 possessed potent anticancer activity against various human cancer cell lines. The most potent indanone (10, IC(50)=2.2 microM), against MCF-7, that is, hormone-dependent breast cancer cell line, showed no toxicity to human erythrocytes even at higher concentrations (100 microg/ml, 258 microM). While, indanones 11, 12 and 14 showed toxicities to erythrocytes at higher concentrations.

  17. 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.

  18. Microbial degradation of chelating agents used in detergents with special reference to nitrilotriacetic acid (NTA).

    PubMed

    Egli, T; Bally, M; Uetz, T

    1990-01-01

    The extensive use of phosphate-based detergents and agricultural fertilizers is one of the main causes of the world-wide eutrophication of rivers and lakes. To ameliorate such problems partial or total substitution of phosphates in laundry detergents by synthetic, non-phosphorus containing complexing agents is practiced in several countries. The physiological, biochemical and ecological aspects of the microbial degradation of the complexing agents most frequently used, such as polyphosphates, aminopolycarboxylates (especially of nitrilotriacetic acid), and phosphonates are reviewed.

  19. Pectin functionalized with natural fatty acids as antimicrobial agent.

    PubMed

    Calce, Enrica; Mignogna, Eleonora; Bugatti, Valeria; Galdiero, Massimiliano; Vittoria, Vittoria; De Luca, Stefania

    2014-07-01

    Several pectin derivatives were prepared by chemical modifications of the polysaccharide with natural fatty acids. The obtained biodegradable pectin-based materials, pectin-linoleate, pectin-oleate and pectin-palmitate, were investigated for their antimicrobial activity against several bacterial strains, Staphylococcus aureus and Escherichia coli. Good results were obtained for pectin-oleate and pectin-linoleate, which inhibit the growth of the selected microorganisms by 50-70%. They exert the better antimicrobial activity against S. aureus. Subsequently, the pectin-oleate and the pectin-linoleate samples were coated on polyethylene films and were assessed for their capacity to capture the oxygen molecules, reducing its penetration into the polymeric support. These results confirmed a possible application of the new materials in the field of active food packaging.

  20. Pharmacokinetics of chlorogenic acid and corydaline in DA-9701, a new botanical gastroprokinetic agent, in rats.

    PubMed

    Jung, Ji Won; Kim, Ju Myung; Jeong, Jin Seok; Son, Miwon; Lee, Hye Suk; Lee, Myung Gull; Kang, Hee Eun

    2014-07-01

    1.Few studies describing the pharmacokinetic properties of chlorogenic acid (CA) and corydaline (CRD) which are marker compounds of a new prokinetic botanical agent, DA-9701, have been reported. The aim of the present study is to evaluate the pharmacokinetic properties CA and CRD following intravenous and oral administration of pure CA (1-8 mg/kg) or CRD (1.1-4.5 mg/kg) and their equivalent dose of DA-9701 to rats. 2.  Dose-proportional AUC and dose-independent clearance (10.3-12.1 ml/min/kg) of CA were observed following its administration. Oral administration of CA as DA-9701 did not influence the oral pharmacokinetic parameters of CA. Incomplete absorption of CA, its decomposition in the gastrointestinal tract, and/or pre-systemic metabolism resulted in extremely low oral bioavailability (F) of CA (0.478-0.899%). 3.  CRD showed greater dose-normalized AUC in the higher dose group than that in lower dose group(s) after its administration due to saturation of its metabolism via decreased non-renal clearance (by 51.3%) and first-pass extraction. As a result, the F of CRD following 4.5 mg/kg oral CRD (21.1%) was considerably greater than those of the lower dose groups (9.10 and 13.8%). However, oral administration of CRD as DA-9701 showed linear pharmacokinetics as a result of increased AUC and F in lower-dose groups (by 182% and 78.5%, respectively) compared to those of pure CRD. The greater oral AUC of CRD for DA-9701 than for pure CRD could be due to decreased hepatic and/or GI first-pass extraction of CRD by other components in DA-9701.

  1. Biodegradation of novel amino acid derivatives suitable for complexing agents in pulp bleaching applications.

    PubMed

    Metsärinne, Sirpa; Ronkainen, Erja; Tuhkanen, Tuula; Aksela, Reijo; Sillanpää, Mika

    2007-05-01

    The biodegradability of four novel diethanolamine derivative complexing agents was examined by using two biodegradation tests standardised by OECD (301B and 301F). Ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were employed as reference substances. Biodegradation of the new complexing agents was studied both with unacclimated and acclimated inocula as well as by simulating wastewater treatment in sequencing batch reactors (SBRs). These new complexing agents were of technical grade, and therefore, the results are only indicative but these new compounds hold promise for use as complexing agents in the pulp and paper industry. The novel complexing agents were not readily biodegradable but they showed slight biodegradation. Around 10-30% degradation was found in the SBR where degradation was followed by measurement of concentration. Moreover the novel complexing agents did not have any negative impact on reactor performance as measured by chemical oxygen demand reduction. In the standardised biodegradation tests at best around 50% degradation was observed with the acclimated inoculum and in the prolonged test whereas EDTA and DTPA exhibited no biodegradation. The elevated degradation in acclimated sludge indicates that the water treatment plant microbes are capable of decomposing these molecules under favourable conditions. The total concentration of novel complexing agents decreased slightly during biodegradation tests, while the EDTA and DTPA concentrations remained stable. PMID:17346781

  2. Thermoresponsive Acidic Microgels as Functional Draw Agents for Forward Osmosis Desalination.

    PubMed

    Hartanto, Yusak; Zargar, Masoumeh; Wang, Haihui; Jin, Bo; Dai, Sheng

    2016-04-19

    Thermoresponsive microgels with carboxylic acid functionalization have been recently introduced as an attractive draw agent for forward osmosis (FO) desalination, where the microgels showed promising water flux and water recovery performance. In this study, various comonomers containing different carboxylic acid and sulfonic acid functional groups were copolymerized with N-isopropylacrylamide (NP) to yield a series of functionalized thermoresponsive microgels possessing different acidic groups and hydrophobicities. The purified microgels were examined as the draw agents for FO application, and the results show the response of water flux and water recovery was significantly affected by various acidic comonomers. The thermoresponsive microgel with itaconic acid shows the best overall performance with an initial water flux of 44.8 LMH, water recovery up to 47.2% and apparent water flux of 3.1 LMH. This study shows that the incorporation of hydrophilic dicarboxylic acid functional groups into the microgels leads to the enhancement on water adsorption and overall performance. Our work elucidates in detail on the structure-property relationship of thermoresponsive microgels in their applications as FO draw agents and would be beneficial for future design and development of high performance FO desalination.

  3. Effect of antibrowning agents on browning and intermediate formation in the glucose-glutamic acid model.

    PubMed

    Lim, Seong-Il; Kwak, Eun-Jung; Lee, Ok-Hwan; Lee, Boo-Yong

    2010-10-01

    In this study, the inhibitory effects of antibrowning agents on browning and the formation of intermediates such as 3-deoxyglucosone (3-DG) and hydroxymethylfurfural (HMF) were evaluated with a glucose-glutamic acid model for soybean paste. The initial antibrowning capacity was measured in the following order: pentasodium tripolyphosphate < citric acid and oxalic acid < cysteine and glutathione < sodium sulfite. Our data showed that antibrowning agents, such as pentasodium tripolyphosphate, citric acid, and oxalic acid, were maintained antibrowning capacities during storage at both 4 and 30 °C, respectively. However, both cysteine and glutathione was reduced with storage time, especially in the air. A marked effect of nitrogen treatment was noted for 3 of the antibrowning agents after storage in air at 30 °C in the following order: sodium sulfite < cysteine < glutathione. The formation ratio of 3-DG and HMF was higher after storage at 30 °C than at 4 °C. These compounds were produced most abundantly in the presence of sodium sulfite, and the yields were not related significantly to the degree of browning. Citric acid and oxalic acid were identified as the most effective in inhibitors of browning and intermediates, even during storage in air at 30 °C.

  4. Thermoresponsive Acidic Microgels as Functional Draw Agents for Forward Osmosis Desalination.

    PubMed

    Hartanto, Yusak; Zargar, Masoumeh; Wang, Haihui; Jin, Bo; Dai, Sheng

    2016-04-19

    Thermoresponsive microgels with carboxylic acid functionalization have been recently introduced as an attractive draw agent for forward osmosis (FO) desalination, where the microgels showed promising water flux and water recovery performance. In this study, various comonomers containing different carboxylic acid and sulfonic acid functional groups were copolymerized with N-isopropylacrylamide (NP) to yield a series of functionalized thermoresponsive microgels possessing different acidic groups and hydrophobicities. The purified microgels were examined as the draw agents for FO application, and the results show the response of water flux and water recovery was significantly affected by various acidic comonomers. The thermoresponsive microgel with itaconic acid shows the best overall performance with an initial water flux of 44.8 LMH, water recovery up to 47.2% and apparent water flux of 3.1 LMH. This study shows that the incorporation of hydrophilic dicarboxylic acid functional groups into the microgels leads to the enhancement on water adsorption and overall performance. Our work elucidates in detail on the structure-property relationship of thermoresponsive microgels in their applications as FO draw agents and would be beneficial for future design and development of high performance FO desalination. PMID:27055090

  5. Hypochlorous Acid as a Potential Wound Care Agent

    PubMed Central

    Wang, L; Bassiri, M; Najafi, R; Najafi, K; Yang, J; Khosrovi, B; Hwong, W; Barati, E; Belisle, B; Celeri, C; Robson, MC

    2007-01-01

    Objective: Hypochlorous acid (HOCl), a major inorganic bactericidal compound of innate immunity, is effective against a broad range of microorganisms. Owing to its chemical nature, HOCl has never been used as a pharmaceutical drug for treating infection. In this article, we describe the chemical production, stabilization, and biological activity of a pharmaceutically useful formulation of HOCl. Methods: Stabilized HOCl is in the form of a physiologically balanced solution in 0.9% saline at a pH range of 3.5 to 4.0. Chlorine species distribution in solution is a function of pH. In aqueous solution, HOCl is the predominant species at the pH range of 3 to 6. At pH values less than 3.5, the solution exists as a mixture of chlorine in aqueous phase, chlorine gas, trichloride (Cl3−), and HOCl. At pH greater than 5.5, sodium hypochlorite (NaOCl) starts to form and becomes the predominant species in the alkaline pH. To maintain HOCl solution in a stable form, maximize its antimicrobial activities, and minimize undesirable side products, the pH must be maintained at 3.5 to 5. Results: Using this stabilized form of HOCl, the potent antimicrobial activities of HOCl are demonstrated against a wide range of microorganisms. The in vitro cytotoxicity profile in L929 cells and the in vivo safety profile of HOCl in various animal models are described. Conclusion: On the basis of the antimicrobial activity and the lack of animal toxicity, it is predicted that stabilized HOCl has potential pharmaceutical applications in the control of soft tissue infection. PMID:17492050

  6. In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents.

    SciTech Connect

    Chen, Baowei; Shah, Saumil S.; Shin, Yongsoon; Lei, Chenghong; Liu, Jun

    2011-10-02

    We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterward can be instantly released when needed for acute responses, and the biomolecular drug molecules can also be gradually released from the nanoporous support over a long time for a complete recovery. Organophosphorus acid anhydrolase (OPAA) was spontaneously and largely entrapped in functionalized mesoporous silica (FMS) due to the dominant electrostatic interaction. The OPAA-FMS composite exhibited a burst release in a pH 9.0 NaHCO(3)-Na(2)CO(3) buffer system and a gradual release in pH 7.4 simulated body fluid. The binding of OPAA to NH(2)-FMS can result in less tyrosinyl and tryptophanyl exposure OPAA molecules to aqueous environment. The bound OPAA in FMS displayed lower activity than the free OPAA in solution prior to the enzyme entrapment. However, the released enzyme maintained the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. The in vitro results in the rabbit serum demonstrate that both OPAA-FMS and the released OPAA may be used as a medical countermeasure against the organophosphorus nerve agents.

  7. In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents.

    PubMed

    Chen, Baowei; Shah, Saumil S; Shin, Yongsoon; Lei, Chenghong; Liu, Jun

    2012-02-15

    We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterward can be instantly released when needed for acute responses, and the biomolecular drug molecules can also be gradually released from the nanoporous support over a long time for a complete recovery. Organophosphorus acid anhydrolase (OPAA) was spontaneously and largely entrapped in functionalized mesoporous silica (FMS) due to the dominant electrostatic interaction. The OPAA-FMS composite exhibited a burst release in a pH 9.0 NaHCO₃-Na₂CO₃ buffer system and a gradual release in pH 7.4 simulated body fluid. The binding of OPAA to NH₂-FMS can result in less tyrosinyl and tryptophanyl exposure OPAA molecules to aqueous environment. The bound OPAA in FMS displayed lower activity than the free OPAA in solution prior to the enzyme entrapment. However, the released enzyme maintained the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. The in vitro results in the rabbit serum demonstrate that both OPAA-FMS and the released OPAA may be used as a medical countermeasure against the organophosphorus nerve agents.

  8. Comparison of the tumor-seeking agent Tc-99m(V) dimercaptosuccinic acid and the renal imaging agent Tc-99m dimercaptosuccinic acid in humans

    SciTech Connect

    Ohta, H.; Ishii, M.; Yoshizumi, M.; Endo, K.; Sakahara, H.; Nakajima, T.; Yomoda, I.; Masuda, H.; Horiuchi, K.; Hata, N.

    1985-03-01

    Being aware of the ideal nuclear properties of Tc-99m, interest has been focused on the design of the (+5) oxidation state Tc-99m(V) dimercaptosuccinic acid (Tc(V)-DMSA) as a tumor-seeking agent. Tc-99m(V) DMSA holds a TcO4(3-) core and, like PO4(3-), has excellent characteristics for tumor uptake, but has a different distribution than the well-known renal scanning agent, Tc-99m DMSA. The differences in chemical behavior of Tc-99m(V) DMSA and Tc-99m DMSA are discussed. Three cases in which neoplasms were studied with Tc-99m(V) DMSA and Tc-99m DMSA are presented. Tc-99m DMSA and Tc-99m(V) DMSA, having a common ligand and tracer but, with the metal ion core in a different oxidation state, the uptake characteristics are altered markedly.

  9. Calculations of phase equilibria for mixtures of triglycerides, fatty acids, and their esters in lower alcohols

    NASA Astrophysics Data System (ADS)

    Stepanov, D. A.; Ermakova, A.; Anikeev, V. I.

    2011-01-01

    The objects of study were mixtures containing triglycerides and lower alcohols and also the products of the transesterification of triglycerides, glycerol and fatty acid esters. The Redlich-Kwong-Soave equation of state was used as a thermodynamic model for the phase state of the selected mixtures over wide temperature, pressure, and composition ranges. Group methods were applied to determine the critical parameters of pure substances and their acentric factors. The parameters obtained were used to calculate the phase diagrams and critical parameters of mixtures containing triglycerides and lower alcohols and the products of the transesterification of triglycerides, glycerol and fatty acid esters, at various alcohol/oil ratios. The conditions of triglyceride transesterification in various lower alcohols providing the supercritical state of reaction mixtures were selected.

  10. Salicylic acid and some of its derivatives as antibacterial agents for viscose fabric.

    PubMed

    Kantouch, A; El-Sayed, A Atef; Salama, M; El-Kheir, A Abou; Mowafi, S

    2013-11-01

    Salicylic acid and three of its derivatives were used to provide antibacterial properties to viscose fabrics. The four bactericides used were bonded to the viscose fabrics using epichlorohydrin or polymer binders. Optimization of the salicylic acid and its derivatives as well as the concentration of polymers was reported. The ability of the polymer binders to attract and bind the four bactericides was observed. The overall results show that the antibacterial reactivity of salicylic acid and its derivatives are in the following order 5-bromosalicylic acid>salicylic acid>5-chlorosalicylic acid>4-chlorosalicylic acid. Using epichlorohydrin as a binding agent, unfortunately, inhibits the bactericidal activity of the four bactericides. The FTIR study concludes that the reaction between salicylic acid as well as its derivatives with epichlorohydrin takes place through the phenolic group of the acids. The unexpected deterioration in the bactericidal properties of salicylic acid and its derivatives as a result of the treatment with epichlorohydrin could be due to the nature of interaction between the epichlorohydrin molecule and the acids molecules. PVP and PU show superior ability to sustain the four bactericides used even after 10 washing cycles.

  11. Salicylic acid and some of its derivatives as antibacterial agents for viscose fabric.

    PubMed

    Kantouch, A; El-Sayed, A Atef; Salama, M; El-Kheir, A Abou; Mowafi, S

    2013-11-01

    Salicylic acid and three of its derivatives were used to provide antibacterial properties to viscose fabrics. The four bactericides used were bonded to the viscose fabrics using epichlorohydrin or polymer binders. Optimization of the salicylic acid and its derivatives as well as the concentration of polymers was reported. The ability of the polymer binders to attract and bind the four bactericides was observed. The overall results show that the antibacterial reactivity of salicylic acid and its derivatives are in the following order 5-bromosalicylic acid>salicylic acid>5-chlorosalicylic acid>4-chlorosalicylic acid. Using epichlorohydrin as a binding agent, unfortunately, inhibits the bactericidal activity of the four bactericides. The FTIR study concludes that the reaction between salicylic acid as well as its derivatives with epichlorohydrin takes place through the phenolic group of the acids. The unexpected deterioration in the bactericidal properties of salicylic acid and its derivatives as a result of the treatment with epichlorohydrin could be due to the nature of interaction between the epichlorohydrin molecule and the acids molecules. PVP and PU show superior ability to sustain the four bactericides used even after 10 washing cycles. PMID:24076193

  12. Synthesis of peptide nucleic acids containing a crosslinking agent and evaluation of their reactivities.

    PubMed

    Akisawa, Takuya; Ishizawa, Yuki; Nagatsugi, Fumi

    2015-03-13

    Peptide nucleic acids (PNAs) are structural mimics of nucleic acids that form stable hybrids with DNA and RNA. In addition, PNAs can invade double-stranded DNA. Due to these characteristics, PNAs are widely used as biochemical tools, for example, in antisense/antigene therapy. Interstrand crosslink formation in nucleic acids is one of the strategies for preparing a stable duplex by covalent bond formation. In this study, we have synthesized PNAs incorporating 4-amino-6-oxo-2-vinylpyrimidine (AOVP) as a crosslinking agent and evaluated their reactivities for targeting DNA and RNA.

  13. Solid supported in situ derivatization extraction of acidic degradation products of nerve agents from aqueous samples.

    PubMed

    Chinthakindi, Sridhar; Purohit, Ajay; Singh, Varoon; Tak, Vijay; Dubey, D K; Pardasani, Deepak

    2014-09-12

    This study deals with the solid supported in situ derivatization extraction of acidic degradation products of nerve agents present in aqueous samples. Target analytes were alkyl alkylphosphonic acids and alkylphosphonic acids, which are important environmental signatures of nerve agents. The method involved tert-butyldimethylchlorosilane mediated in situ silylation of analytes on commercially available diatomaceous solid phase extraction cartridges. Various parameters such as derivatizing reagent, its concentration, reaction time, temperature and eluting solvent were optimized. Recoveries of the analytes were determined by GC-MS which ranged from 60% to 86%. The limits of detection (LOD) and limit of quantification (LOQ) with selected analytes were achieved down to 78 and 213ngmL(-1) respectively, in selected ion monitoring mode. The successful applicability of method was also demonstrated on samples of biological origin such as plasma and to the samples received in 34th official proficiency test conducted by the Organization for Prohibition the of Chemical Weapons. PMID:25103280

  14. Gluconic acid: an antifungal agent produced by Pseudomonas species in biological control of take-all.

    PubMed

    Kaur, Rajvinder; Macleod, John; Foley, William; Nayudu, Murali

    2006-03-01

    Pseudomonas strain AN5 (Ps. str. AN5), a non-fluorescent Australian bacterial isolate, is an effective biological control (biocontrol) agent of the take-all disease of wheat caused by the fungus Gaeumannomyces graminis var. tritici (Ggt). Ps. str. AN5 controls Ggt by producing an antifungal compound which was purified by thin layer and column chromatography, and identified by NMR and mass spectroscopic analysis to be d-gluconic acid. Commercially bought pure gluconic acid strongly inhibited Ggt. Two different transposon mutants of Ps. str. AN5 which had lost take-all biocontrol did not produce d-gluconic acid. Gluconic acid production was restored, along with take-all biocontrol, when one of these transposon mutants was complemented with the corresponding open reading frame from wild-type genomic DNA. Gluconic acid was detected in the rhizosphere of wheat roots treated with the wild-type Ps. str. AN5, but not in untreated wheat or wheat treated with a transposon mutant strain which had lost biocontrol. The antifungal compounds phenazine-1-carboxylic acid and 2,4-diacetylphloroglucinol, produced by other Pseudomonads and previously shown to be effective in suppressing the take-all disease, were not detected in Ps. str. AN5 extracts. These results suggest that d-gluconic acid is the most significant antifungal agent produced by Ps. str. AN5 in biocontrol of take-all on wheat roots.

  15. Biotransformation of the Antimelanoma Agent Betulinic Acid by Bacillus megaterium ATCC 13368

    PubMed Central

    Chatterjee, Parnali; Kouzi, Samir A.; Pezzuto, John M.; Hamann, Mark T.

    2000-01-01

    Microbial transformation of the antimelanoma agent betulinic acid was studied. The main objective of this study was to utilize microorganisms as in vitro models to predict and prepare potential mammalian metabolites of this compound. Preparative-scale biotransformation with resting-cell suspensions of Bacillus megaterium ATCC 13368 resulted in the production of four metabolites, which were identified as 3-oxo-lup-20(29)-en-28-oic acid, 3-oxo-11α-hydroxy-lup-20(29)-en-28-oic acid, 1β-hydroxy-3-oxo-lup-20(29)-en-28-oic acid, and 3β,7β,15α-trihydroxy-lup-20(29)-en-28-oic acid based on nuclear magnetic resonance and high-resolution mass spectral analyses. In addition, the antimelanoma activities of these metabolites were evaluated with two human melanoma cell lines, Mel-1 (lymph node) and Mel-2 (pleural fluid). PMID:10966400

  16. Acid-base properties of 2-phenethyldithiocarbamoylacetic acid, an antitumor agent

    NASA Astrophysics Data System (ADS)

    Novozhilova, N. E.; Kutina, N. N.; Petukhova, O. A.; Kharitonov, Yu. Ya.

    2013-07-01

    The acid-base properties of the 2-phenethyldithiocarbamoylacetic acid (PET) substance belonging to the class of isothiocyanates and capable of inhibiting the development of tumors on many experimental models were studied. The acidity and hydrolysis constants of the PET substance in ethanol, acetone, aqueous ethanol, and aqueous acetone solutions were determined from the data of potentiometric (pH-metric) titration of ethanol and acetone solutions of PET with aqueous solidum hydroxide at room temperature.

  17. SK&F 97426-A a more potent bile acid sequestrant and hypocholesterolaemic agent than cholestyramine in the hamster.

    PubMed

    Benson, G M; Alston, D R; Bond, B C; Gee, A N; Glen, A; Haynes, C; Hickey, D M; Iqbal, S; Jackson, B; Jaxa-Chamiec, A A

    1993-06-01

    SK&F 97426-A is a novel bile acid sequestrant which was selected for comparison with cholestyramine in vivo because of its superior in vitro bile acid binding properties. The effects of the two sequestrants on faecal bile acid excretion, plasma total cholesterol, VLDL + LDL and HDL cholesterol and triglyceride concentrations and on liver enzymes involved in the synthesis and metabolism of cholesterol were investigated in normocholesterolaemic hamsters. Four studies were conducted to determine the relative potencies of the two resins using a range of doses of the sequestrants over treatment periods of up to 2 weeks. Curves fitted to the resulting data allowed common maximum responses and separate ED50s to be calculated for each sequestrant. The maximum response of both sequestrants was to increase bile acid excretion by 352% and lower plasma total cholesterol by 37-58%. LDL + VLDL and HDL cholesterol were reduced by 56-75% and 25-41%, respectively. SK&F 97426-A was 3 times more potent than cholestyramine at increasing the excretion of bile acids in the faeces and 2.1-3.4-fold and 2.3-3.2-fold more potent at lowering total plasma cholesterol and LDL plus VLDL cholesterol, respectively. In some of the experiments SK&F 97426-A was also more potent than cholestyramine at lowering HDL cholesterol. Plasma triglycerides were also lowered by both sequestrants by up to 31% after 1 week but the relative potency could not be determined. These HDL cholesterol and total triglyceride lowering effects of bile acid sequestrants in the hamster are known not to occur in people treated with cholestyramine. There were minimal differences between hamsters treated for 1 or 2 weeks in the relative potencies or ED50s calculated for the total plasma cholesterol, LDL + VLDL and HDL cholesterol. Both sequestrants may have been slightly more efficacious on these parameters after 2 weeks of treatment. Liver weights were reduced by about 15% by both sequestrants at 2% (w/w) in the diet for 1

  18. CJD and Scrapie Require Agent-Associated Nucleic Acids for Infection.

    PubMed

    Botsios, Sotirios; Manuelidis, Laura

    2016-08-01

    Unlike Alzheimer's and most other neurodegenerative diseases, Transmissible Spongiform Encephalopathies (TSEs) are all caused by actively replicating infectious particles of viral size and density. Different strain-specific TSE agents cause CJD, kuru, scrapie and BSE, and all behave as latent viruses that evade adaptive immune responses and can persist for years in lymphoreticular tissues. A foreign viral structure with a nucleic acid genome best explains these TSE strains and their endemic and epidemic spread in susceptible species. Nevertheless, it is widely believed that host prion protein (PrP), without any genetic material, encodes all these strains. We developed rapid infectivity assays that allowed us to reproducibly isolate infectious particles where >85% of the starting titer separated from the majority of host components, including PrP. Remarkably, digestion of all forms of PrP did not reduce brain particle titers. To ask if TSE agents, as other viruses, require nucleic acids, we exposed high titer FU-CJD and 22L scrapie particles to potent nucleases. Both agent-strains were propagated in GT1 neuronal cells to avoid interference by complex degenerative brain changes that can impede nuclease digestions. After exposure to nucleases that are active in sarkosyl, infectivity of both agents was reproducibly reduced by ≥99%. No gold-stained host proteins or any form of PrP were visibly altered by these nucleases. In contrast, co-purifying protected mitochondrial DNA and circular SPHINX DNAs were destroyed. These findings demonstrate that TSE agents require protected genetic material to infect their hosts, and should reopen investigation of essential agent nucleic acids. J. Cell. Biochem. 117: 1947-1958, 2016. © 2016 Wiley Periodicals, Inc. PMID:26773845

  19. Effect of carboxylic acids as compatibilizer agent on mechanical properties of thermoplastic starch and polypropylene blends.

    PubMed

    Martins, Andréa Bercini; Santana, Ruth Marlene Campomanes

    2016-01-01

    In this work, polypropylene/thermoplastic starch (PP/TPS) blends were prepared as an alternative material to use in disposable packaging, reducing the negative polymeric environmental impact. Unfortunately, this material displays morphological characteristics typical of immiscible polymer blends and a compatibilizer agent is needed. Three different carboxyl acids: myristic (C14), palmitic (C16) and stearic acids (C18) were used as natural compatibilizer agent (NCA). The effects of NCA on the mechanical, physical, thermal and morphological properties of PP/TPS blends were investigated and compared against PP/TPS with and without PP-grafted maleic anhydride (PPgMA). When compared to PP/TPS, blends with C18, PPgMA and C14 presented an improvement of 25, 22 and 17% in tensile strength at break and of 180, 194 and 259% in elongation at break, respectively. The highest increase, 54%, in the impact strength was achieved with C14 incorporation. Improvements could be seen, through scanning electron microscopy (SEM) images, in the compatibility between the immiscible components by acids incorporation. These results showed that carboxylic acids, specifically C14, could be used as compatibilizer agent and could substitute PPgMA. PMID:26453854

  20. Effect of carboxylic acids as compatibilizer agent on mechanical properties of thermoplastic starch and polypropylene blends.

    PubMed

    Martins, Andréa Bercini; Santana, Ruth Marlene Campomanes

    2016-01-01

    In this work, polypropylene/thermoplastic starch (PP/TPS) blends were prepared as an alternative material to use in disposable packaging, reducing the negative polymeric environmental impact. Unfortunately, this material displays morphological characteristics typical of immiscible polymer blends and a compatibilizer agent is needed. Three different carboxyl acids: myristic (C14), palmitic (C16) and stearic acids (C18) were used as natural compatibilizer agent (NCA). The effects of NCA on the mechanical, physical, thermal and morphological properties of PP/TPS blends were investigated and compared against PP/TPS with and without PP-grafted maleic anhydride (PPgMA). When compared to PP/TPS, blends with C18, PPgMA and C14 presented an improvement of 25, 22 and 17% in tensile strength at break and of 180, 194 and 259% in elongation at break, respectively. The highest increase, 54%, in the impact strength was achieved with C14 incorporation. Improvements could be seen, through scanning electron microscopy (SEM) images, in the compatibility between the immiscible components by acids incorporation. These results showed that carboxylic acids, specifically C14, could be used as compatibilizer agent and could substitute PPgMA.

  1. Vapor pressures of substituted polycarboxylic acids are much lower than previously reported

    NASA Astrophysics Data System (ADS)

    Huisman, A. J.; Krieger, U. K.; Zuend, A.; Marcolli, C.; Peter, T.

    2013-07-01

    The partitioning of compounds between the aerosol and gas phase is a primary focus in the study of the formation and fate of secondary organic aerosol. We present measurements of the vapor pressure of 2-methylmalonic (isosuccinic) acid, 2-hydroxymalonic (tartronic) acid, 2-methylglutaric acid, 3-hydroxy-3-carboxy-glutaric (citric) acid and DL-2,3-dihydroxysuccinic (DL-tartaric) acid, which were obtained from the evaporation rate of supersaturated liquid particles levitated in an electrodynamic balance. Our measurements indicate that the pure component liquid vapor pressures at 298.15 K for tartronic, citric and tartaric acids are much lower than the same quantity that was derived from solid state measurements in the only other room temperature measurement of these materials (made by Booth et al., 2010). This strongly suggests that empirical correction terms in a recent vapor pressure estimation model to account for the inexplicably high vapor pressures of these and similar compounds should be revisited, and that due caution should be used when the estimated vapor pressures of these and similar compounds are used as inputs for other studies.

  2. Dissolved and Particulate Amino Acids in the Lower Mississippi and Pearl Rivers (USA)

    NASA Astrophysics Data System (ADS)

    Duan, S.; Bianchi, T. S.

    2006-12-01

    Seasonal changes (monthly samples) in abundance and composition of dissolved and particulate amino acids were observed at one station in the lower Mississippi and Pearl Rivers (MS, USA) from September 2001 to August 2003. Spatial variability was also observed during a 4 day transmit from river-mile 225 to river mouth (Head of Passes, LA) in the Mississippi River, and a two-day downstream sampling from Jackson (MS) to Stennis Space Center (MS). Temporal data in the lower Mississippi River showed significantly lower concentrations of dissolved combined amino acids (DCAA, 0.45-1.4 μ M) and dissolved amino acids in high molecular weight fraction (HMW DAA, 0.13-0.27 μ M) than in the Pearl River (DCAA, 0.91-2.8 μ M; HMW DAA, 0.25-0.95 μ M). DCAA and HMW DAA in both rivers were generally higher during high-flow periods. DFAA was significantly lower than DCAA in both rivers (0.05-0.08 μ M), and displayed minimal seasonal variability. Total particulate amino acids (PAA) in both rivers were in the same range (0.7-1.4 μ M). A C- normalized yield of PAA (PAA-C/POC) was negatively correlated with suspended particulate matter and positively with chl-a in both rivers. No significant difference in PAA composition was observed in the two rivers. However, PAA in both rivers was relatively enriched in arginine, alanine, methionine and leucine, and depleted in aspartic acid, serine, and non-protein amino acids, compared to DCAA. While DCAA spatial variability in the lower Mississippi River was minimal, decreases in PAA (from 1.06 to 0.43 μ M) were consistent with particulate organic carbon (POC) and particulate nitrogen (PN). Frequent variations in the PAA-C/POC ratio were inversely correlated with suspended particulate matter and PAA (R = -0.7, n = 48), suggesting short- scale sedimentation and resuspension events. A gradual increase in % non-protein AA along with a loss of phytoplankton biomass along the river, suggested was indicative of bacterial utilization of labile

  3. Biochemical rationale for the use of fatty acid analogs as agents for studying myocardial metabolism

    SciTech Connect

    Elmaleh D.R.; Livni E.; Brownell, G.L.; Strauss, H.W.

    1987-01-01

    Since fatty acids are the major energy source for myocardial contractile work, the rate of utilization of these substrates/unit work performed, should be an indicator of the health of the muscle. (1-C-11) palmitic acid has been shown to be useful as a myocardial imaging agent for positron tomography. The main limitations for the use of this substrate are the fast washout and translocation of the activity from the normal myocardium and the back diffusion in ischemia. Since alpha and omega oxidation are only present to a limited degree, branched chain fatty acids should have a prolonged residence time in the myocardium. The similarity in structure, chain length, solubility, and charge of the branched to the non-branched fatty acids should make these compounds behave in similar fashion in terms of their blood clearance and entry into tissues. 15 refs., 3 tabs.

  4. Effects of lactic acid bacteria isolated from fermented mustard on lowering cholesterol

    PubMed Central

    Wang, Shu Chen; Chang, Chen Kai; Chan, Shu Chang; Shieh, Jiunn Shiuh; Chiu, Chih Kwang; Duh, Pin-Der

    2014-01-01

    Objective To evaluate the ability of lactic acid bacteria (LAB) strains isolated from fermented mustard to lower the cholesterol in vitro. Methods The ability of 50 LAB strains isolated from fermented mustard on lowering cholesterol in vitro was determined by modified o-phtshalaldehyde method. The LAB isolates were analyzed for their resistance to acid and bile salt. Strains with lowering cholesterol activity, were determined adherence to Caco-2 cells. Results Strain B0007, B0006 and B0022 assimilated more cholesterol than BCRC10474 and BCRC 17010. The isolated strains showed tolerance to pH 3.0 for 3 h despite variations in the degree of viability and bile-tolerant strains, with more than 108 CFU/mL after incubation for 24 h at 1% oxigall in MRS. In addition, strain B0007 and B0022 identified as Lactobacillus plantarum with 16S rDNA sequences were able to adhere to the Caco-2 cell lines. Conclusions These strains B0007 and B0022 may be potential functional sources for cholesterol-lowering activities as well as adhering to Caco-2 cell lines. PMID:25183271

  5. Soil washing of chromium- and cadmium-contaminated sludge using acids and ethylenediaminetetra acetic acid chelating agent.

    PubMed

    Gitipour, Saeid; Ahmadi, Soheil; Madadian, Edris; Ardestani, Mojtaba

    2016-01-01

    In this research, the effect of soil washing in the removal of chromium- and cadmium-contaminated sludge samples collected from Pond 2 of the Tehran Oil Refinery was investigated. These metals are considered as hazardous substances for human health and the environment. The carcinogenicity of chromate dust has been established for a long time. Cadmium is also a potential environmental toxicant. This study was carried out by collecting sludge samples from different locations in Pond 2. Soil washing was conducted to treat the samples. Chemical agents, such as acetic acid, ethylenediaminetetra acetic acid (EDTA) and hydrochloric acid, were used as washing solutions to remove chromium and cadmium from sludge samples. The results of this study indicated that the highest removal efficiencies from the sludge samples were achieved using a 0.3 M HCl solution with 82.69% and 74.47% for chromium and cadmium, respectively. EDTA (0.1 M) in the best condition extracted 66.81% of cadmium and 72.52% of chromium from the sludges. The lowest efficiency values for the samples, however, were achieved using 3 M acetic acid with 41.7% and 46.96% removals for cadmium and chromium, respectively. The analysis of washed sludge indicated that the heavy metals removal decreased in the order of 3 M acetic acid < 0.1 M EDTA<0.3 M HCl, thus hydrochloric acid appears to offer a greater potential as a washing agent in remediating the sludge samples.

  6. Soil washing of chromium- and cadmium-contaminated sludge using acids and ethylenediaminetetra acetic acid chelating agent.

    PubMed

    Gitipour, Saeid; Ahmadi, Soheil; Madadian, Edris; Ardestani, Mojtaba

    2016-01-01

    In this research, the effect of soil washing in the removal of chromium- and cadmium-contaminated sludge samples collected from Pond 2 of the Tehran Oil Refinery was investigated. These metals are considered as hazardous substances for human health and the environment. The carcinogenicity of chromate dust has been established for a long time. Cadmium is also a potential environmental toxicant. This study was carried out by collecting sludge samples from different locations in Pond 2. Soil washing was conducted to treat the samples. Chemical agents, such as acetic acid, ethylenediaminetetra acetic acid (EDTA) and hydrochloric acid, were used as washing solutions to remove chromium and cadmium from sludge samples. The results of this study indicated that the highest removal efficiencies from the sludge samples were achieved using a 0.3 M HCl solution with 82.69% and 74.47% for chromium and cadmium, respectively. EDTA (0.1 M) in the best condition extracted 66.81% of cadmium and 72.52% of chromium from the sludges. The lowest efficiency values for the samples, however, were achieved using 3 M acetic acid with 41.7% and 46.96% removals for cadmium and chromium, respectively. The analysis of washed sludge indicated that the heavy metals removal decreased in the order of 3 M acetic acid < 0.1 M EDTA<0.3 M HCl, thus hydrochloric acid appears to offer a greater potential as a washing agent in remediating the sludge samples. PMID:26599728

  7. Plant-derived antifungal agent poacic acid targets β-1,3-glucan.

    PubMed

    Piotrowski, Jeff S; Okada, Hiroki; Lu, Fachuang; Li, Sheena C; Hinchman, Li; Ranjan, Ashish; Smith, Damon L; Higbee, Alan J; Ulbrich, Arne; Coon, Joshua J; Deshpande, Raamesh; Bukhman, Yury V; McIlwain, Sean; Ong, Irene M; Myers, Chad L; Boone, Charles; Landick, Robert; Ralph, John; Kabbage, Mehdi; Ohya, Yoshikazu

    2015-03-24

    A rise in resistance to current antifungals necessitates strategies to identify alternative sources of effective fungicides. We report the discovery of poacic acid, a potent antifungal compound found in lignocellulosic hydrolysates of grasses. Chemical genomics using Saccharomyces cerevisiae showed that loss of cell wall synthesis and maintenance genes conferred increased sensitivity to poacic acid. Morphological analysis revealed that cells treated with poacic acid behaved similarly to cells treated with other cell wall-targeting drugs and mutants with deletions in genes involved in processes related to cell wall biogenesis. Poacic acid causes rapid cell lysis and is synergistic with caspofungin and fluconazole. The cellular target was identified; poacic acid localized to the cell wall and inhibited β-1,3-glucan synthesis in vivo and in vitro, apparently by directly binding β-1,3-glucan. Through its activity on the glucan layer, poacic acid inhibits growth of the fungi Sclerotinia sclerotiorum and Alternaria solani as well as the oomycete Phytophthora sojae. A single application of poacic acid to leaves infected with the broad-range fungal pathogen S. sclerotiorum substantially reduced lesion development. The discovery of poacic acid as a natural antifungal agent targeting β-1,3-glucan highlights the potential side use of products generated in the processing of renewable biomass toward biofuels as a source of valuable bioactive compounds and further clarifies the nature and mechanism of fermentation inhibitors found in lignocellulosic hydrolysates. PMID:25775513

  8. Plant-derived antifungal agent poacic acid targets β-1,3-glucan

    PubMed Central

    Piotrowski, Jeff S.; Okada, Hiroki; Lu, Fachuang; Li, Sheena C.; Hinchman, Li; Ranjan, Ashish; Smith, Damon L.; Higbee, Alan J.; Ulbrich, Arne; Coon, Joshua J.; Deshpande, Raamesh; Bukhman, Yury V.; McIlwain, Sean; Ong, Irene M.; Myers, Chad L.; Boone, Charles; Landick, Robert; Ralph, John; Kabbage, Mehdi; Ohya, Yoshikazu

    2015-01-01

    A rise in resistance to current antifungals necessitates strategies to identify alternative sources of effective fungicides. We report the discovery of poacic acid, a potent antifungal compound found in lignocellulosic hydrolysates of grasses. Chemical genomics using Saccharomyces cerevisiae showed that loss of cell wall synthesis and maintenance genes conferred increased sensitivity to poacic acid. Morphological analysis revealed that cells treated with poacic acid behaved similarly to cells treated with other cell wall-targeting drugs and mutants with deletions in genes involved in processes related to cell wall biogenesis. Poacic acid causes rapid cell lysis and is synergistic with caspofungin and fluconazole. The cellular target was identified; poacic acid localized to the cell wall and inhibited β-1,3-glucan synthesis in vivo and in vitro, apparently by directly binding β-1,3-glucan. Through its activity on the glucan layer, poacic acid inhibits growth of the fungi Sclerotinia sclerotiorum and Alternaria solani as well as the oomycete Phytophthora sojae. A single application of poacic acid to leaves infected with the broad-range fungal pathogen S. sclerotiorum substantially reduced lesion development. The discovery of poacic acid as a natural antifungal agent targeting β-1,3-glucan highlights the potential side use of products generated in the processing of renewable biomass toward biofuels as a source of valuable bioactive compounds and further clarifies the nature and mechanism of fermentation inhibitors found in lignocellulosic hydrolysates. PMID:25775513

  9. Synergistic effects of nucleating agents and plasticizers on the crystallization behavior of poly(lactic acid).

    PubMed

    Shi, Xuetao; Zhang, Guangcheng; Phuong, Thanh Vu; Lazzeri, Andrea

    2015-01-01

    The synergistic effect of nucleating agents and plasticizers on the thermal and mechanical performance of PLA nanocomposites was investigated with the objective of increasing the crystallinity and balancing the stiffness and toughness of PLA mechanical properties. Calcium carbonate, halloysite nanotubes, talc and LAK (sulfates) were compared with each other as heterogeneous nucleating agents. Both the DSC isothermal and non-isothermal studies indicated that talc and LAK were the more effective nucleating agents among the selected fillers. Poly(D-lactic acid) (PDLA) acted also as a nucleating agent due to the formation of the PLA stereocomplex. The half crystallization time was reduced by the addition of talc to about 2 min from 37.5 min of pure PLA by the isothermal crystallization study. The dynamic mechanical thermal study (DMTA) indicated that nanofillers acted as both reinforcement fillers and nucleating agents in relation to the higher storage modulus. The plasticized PLA studied by DMTA indicated a decreasing glass transition temperature with the increasing of the PEG content. The addition of nanofiller increased the Young's modulus. PEG had the plasticization effect of increasing the break deformation, while sharply decreasing the stiffness and strength of PLA. The synergistic effect of nanofillers and plasticizer achieved the balance between stiffness and toughness with well-controlled crystallization. PMID:25608041

  10. Advanced glycation end products as biomarkers and gerontotoxins - A basis to explore methylglyoxal-lowering agents for Alzheimer's disease?

    PubMed

    Krautwald, Martina; Münch, Gerald

    2010-10-01

    Alzheimer's disease (AD) is the most common dementing disorder of late life. Although there might be various different triggering events in the early stages of the disease, they seem to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. In this review, we put forward the hypothesis that advanced glycation end products (AGEs) and their precursors, including methylglyoxal, are both biomarkers and causative agents ("gerontotoxins") characteristic for this disorder. Accumulation of AGEs is a normal feature of aging, but is accelerated in AD, where AGEs can be detected in amyloid plaques and neurofibrillary tangles. AGE modification may explain many of the neuropathological and biochemical features of AD such as extensive protein cross-linking, inflammation, oxidative stress and neuronal cell death. We suggest that methylglyoxal is one of the major carbonyl species responsible for the formation of AGEs. We propose that one promising pharmacological approach to prevent the formation of AGEs would be to lower the methylglyoxal concentration. This can be achieved, for example, by decreasing the concentration of methylglyoxal precursors such as d-glyceraldehyde-3-phosphate by allowing a higher flux through the pentose phosphate pathway or by increasing methylglyoxal detoxification through the glyoxalase system. Alternatively, methylglyoxal could be scavenged by various types of carbonyl scavengers. PMID:20211718

  11. Lower esophageal sphincter pressure, acid secretion, and blood gastrin after coffee consumption.

    PubMed

    Van Deventer, G; Kamemoto, E; Kuznicki, J T; Heckert, D C; Schulte, M C

    1992-04-01

    This study tested the hypothesis that differences in the processing of raw coffee beans can account for some of the variability in gastric effects of coffee drinking. Coffees were selected to represent several ways that green coffee beans are treated, ie, processing variables. These included instant and ground coffee processing, decaffeination method (ethyl acetate or methylene chloride extraction), instant coffee processing temperature (112 degrees F or 300 degrees F), and steam treatment. Lower esophageal sphincter pressure, acid secretion, and blood gastrin was measured in eight human subjects after they consumed each of the different coffees. Consumption of coffee was followed by a sustained decrease in lower esophageal sphincter pressure (P less than 0.05) except for three of the four coffees treated with ethyl acetate regardless of whether or not they contained caffeine. Caffeinated ground coffee stimulated more acid secretion that did decaf ground coffees (P less than 0.05), but not more than a steam-treated caffeinated coffee. Instant coffees did not differ in acid-stimulating ability. Ground caffeinated coffee resulted in higher blood gastrin levels than other ground coffees (P less than 0.05). Freeze-dried instant coffee also tended toward higher gastrin stimulation. It is concluded that some of the observed variability in gastric response to coffee consumption can be traced to differences in how green coffee beans are processed.

  12. Prevention of comorbidity and acute attack of gout by uric acid lowering therapy.

    PubMed

    Joo, Kowoon; Kwon, Seong-Ryul; Lim, Mie-Jin; Jung, Kyong-Hee; Joo, Hoyeon; Park, Won

    2014-05-01

    The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA)<6 mg/dL and 147 patients with mean sUA≥6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis.

  13. Lower esophageal sphincter pressure, acid secretion, and blood gastrin after coffee consumption.

    PubMed

    Van Deventer, G; Kamemoto, E; Kuznicki, J T; Heckert, D C; Schulte, M C

    1992-04-01

    This study tested the hypothesis that differences in the processing of raw coffee beans can account for some of the variability in gastric effects of coffee drinking. Coffees were selected to represent several ways that green coffee beans are treated, ie, processing variables. These included instant and ground coffee processing, decaffeination method (ethyl acetate or methylene chloride extraction), instant coffee processing temperature (112 degrees F or 300 degrees F), and steam treatment. Lower esophageal sphincter pressure, acid secretion, and blood gastrin was measured in eight human subjects after they consumed each of the different coffees. Consumption of coffee was followed by a sustained decrease in lower esophageal sphincter pressure (P less than 0.05) except for three of the four coffees treated with ethyl acetate regardless of whether or not they contained caffeine. Caffeinated ground coffee stimulated more acid secretion that did decaf ground coffees (P less than 0.05), but not more than a steam-treated caffeinated coffee. Instant coffees did not differ in acid-stimulating ability. Ground caffeinated coffee resulted in higher blood gastrin levels than other ground coffees (P less than 0.05). Freeze-dried instant coffee also tended toward higher gastrin stimulation. It is concluded that some of the observed variability in gastric response to coffee consumption can be traced to differences in how green coffee beans are processed. PMID:1551346

  14. Acid-mediated formation of trifluoromethyl sulfonates from sulfonic acids and a hypervalent iodine trifluoromethylating agent.

    PubMed

    Koller, Raffael; Huchet, Quentin; Battaglia, Philip; Welch, Jan M; Togni, Antonio

    2009-10-28

    A variety of sulfonic acids have been trifluoromethylated using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one under mild conditions in good to excellent yields. Initial mechanistic investigations of this reaction show a clean second-order kinetics and only very weak substrate electronic effects.

  15. Studies on chemical modification and biology of a natural product, gambogic acid (II): Synthesis and bioevaluation of gambogellic acid and its derivatives from gambogic acid as antitumor agents.

    PubMed

    Wang, Jinxin; Ma, Junhai; You, Qidong; Zhao, Li; Wang, Fan; Li, Chong; Guo, Qinglong

    2010-09-01

    Gambogic acid (GA) has been reported to be a potent apoptosis inducer. The fact that it is amenable to chemical modification makes GA an attractive molecule for the development of anticancer agents. We firstly reported the synthesis of gambogellic acid, which was generated under acid catalysis from readily available GA by a base-catalyzed diene intramolecular annelation. Sequentially, thirteen new compounds were synthesized and their inhibitory activity on HT-29, Bel-7402, BGC-823, and A549 cell lines were evaluated in vitro by MTT assay, and (38, 40)-epoxy-33-chlorogambogellic acid (4) was identified as a BGC-823 cell apoptosis inducer through MTT cell assay, observations of morphological changes, and Annexin-V/PI double-staining assay. Compound 4 showed significant effects in inducing apoptosis and might serve as a potential lead compound for discovery of new anticancer drugs. Further structure-activity relationships (SARs) of gambogic acid derivatives were discussed.

  16. Peptide-cleaving agents for human islet amyloid polypeptide containing substrate recognition site based on quinoxaline: cleavage efficiency enhanced by lowering substrate concentration.

    PubMed

    Chei, Woosuk; Ju, Heeyeon; Suh, Junghun

    2012-02-15

    Oligomers of human islet amyloid polypeptide (h-IAPP) are believed to be the pathogenic species for type 2 diabetes mellitus. Peptide-cleaving agents selective for oligomers of h-IAPP were synthesized by using quinoxaline derivatives as recognition sites attached to the Co(III) complex of cyclen in this study. When the initial concentration of h-IAPP was lowered from 4.0 to 0.20 μM, cleavage yield of the new agents was enhanced by 3 times reaching 16-22 mol%. This shows that the agents would have significant activities at subnano molar concentrations if the concentration of h-IAPP is lowered to the in vivo values. This further indicates that the peptide-cleaving agents prepared previously in this laboratory possess sufficiently high activity for application as a new therapeutic option for Alzheimer's disease, type 2 diabetes mellitus, and Parkinson's disease.

  17. Production of Epigastric Pain in Duodenal Ulcer by Lower Oesophageal Acid Perfusion

    PubMed Central

    Earlam, Richard J.

    1970-01-01

    Thirty-six patients with duodenal ulceration were divided into group 1 (30), who had epigastric pain, and group 2 (6), who had pain in the upper abdomen but not in the epigastrium, and were studied by perfusing the lower oesophagus with dilute acid in an attempt to reproduce epigastric pain. In group 1, 25 suffered epigastric pain, indistinguishable from that which they normally had, after perfusion of 30 ml. of 0·1N HC1 in under four minutes (mean values), but none of group 2 had pain. ImagesFig. 1 PMID:5491256

  18. Glucose-lowering effects of intestinal bile acid sequestration through enhancement of splanchnic glucose utilization.

    PubMed

    Prawitt, Janne; Caron, Sandrine; Staels, Bart

    2014-05-01

    Intestinal bile acid (BA) sequestration efficiently lowers plasma glucose concentrations in type 2 diabetes (T2D) patients. Because BAs act as signaling molecules via receptors, including the G protein-coupled receptor TGR5 and the nuclear receptor FXR (farnesoid X receptor), to regulate glucose homeostasis, BA sequestration, which interrupts the entero-hepatic circulation of BAs, constitutes a plausible action mechanism of BA sequestrants. An increase of intestinal L-cell glucagon-like peptide-1 (GLP-1) secretion upon TGR5 activation is the most commonly proposed mechanism, but recent studies also argue for a direct entero-hepatic action to enhance glucose utilization. We discuss here recent findings on the mechanisms of sequestrant-mediated glucose lowering via an increase of splanchnic glucose utilization through entero-hepatic FXR signaling.

  19. Synthesis and evaluation of new quinazolone derivatives of nalidixic acid as potential antibacterial and antifungal agents.

    PubMed

    Grover, Gaurav; Kini, Suvarna G

    2006-02-01

    In continuation of our work on synthesis of biheterocycles carrying the biodynamic heterocyclic systems at position 3, a series of new nalidixic acid derivatives having quinazolones moiety were synthesised to achieve enhanced biological activity and wide spectrum of activity. Nalidixic acid was first converted into its acid chloride using thionyl chloride as an acylating agent at laboratory temperature. Later it was converted to methyl ester. Nalidixoyl chloride formed vigorously reacts with methanol to give a methyl ester of nalidixic acid. The ester on addition of hydrazine hydrate furnished nalidixic acid hydrazide. Appropriate anthranilic acid was refluxed with acetic anhydride to form Benzoxazine/Acetanthranil. 5-iodo-derivative of anthranilic acid was prepared and also utilised to obtain 6-iodo-Benzoxazine/Acetanthranil. Also, 6-nitro-Benzoxazine/Acetanthranil was obtained by nitration of acetanthranil using conc. H(2)SO(4) and fuming HNO(3). Equimolar proportions of the appropriate synthesised acetanthranils and nalidixic acid hydrazide in the presence of ethanol were refluxed to synthesise quinazolones. Elemental analysis and IR spectra confirmed nalidixic acid hydrazide formation. The structures of the compounds obtained have been established on the basis of Spectral (IR, (1)H NMR and mass) data. The current study also involves in vitro antimicrobial screening (using Agar dilution and Punch well diffusion method) of synthesised quinazolone derivatives bearing nalidixic acid moiety on randomly collected microbial strains. The derivatives Ga (NAH), Gb (QN) and Gd (NiQNA) showed marked inhibitory activity against enteric pathogen like Aeromonas hydrophila, a causative agent of diarrhoea in both children as well as adults. Among the respiratory pathogens included in study, derivative Gd (NiQNA) was found to be active against Streptococcus pyogenes. No significant inhibitory activity was seen by any of synthesised derivatives against Coagulase negative

  20. Nucleic Acid Aptamers as Potential Therapeutic and Diagnostic Agents for Lymphoma

    PubMed Central

    Shum, Ka-To; Zhou, Jiehua; Rossi, John J.

    2014-01-01

    Lymphomas are cancers that arise from white blood cells and usually present as solid tumors. Treatment of lymphoma often involves chemotherapy, and can also include radiotherapy and/or bone marrow transplantation. There is an un-questioned need for more effective therapies and diagnostic tool for lymphoma. Aptamers are single stranded DNA or RNA oligonucleotides whose three-dimensional structures are dictated by their sequences. The immense diversity in function and structure of nucleic acids enable numerous aptamers to be generated through an iterative in vitro selection technique known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Aptamers have several biochemical properties that make them attractive tools for use as potential diagnostic and pharmacologic agents. Isolated aptamers may directly inhibit the function of target proteins, or they can also be formulated for use as delivery agents for other therapeutic or imaging cargoes. More complex aptamer identification methods, using whole cancer cells (Cell-SELEX), may identify novel targets and aptamers to affect them. This review focuses on recent advances in the use of nucleic acid aptamers as diagnostic and therapeutic agents and as targeted delivery carriers that are relevant to lymphoma. Some representative examples are also discussed. PMID:25057429

  1. The advanced glycation end product-lowering agent ALT-711 is a low-affinity inhibitor of thiamine diphosphokinase.

    PubMed

    Krautwald, Martina; Leech, Dale; Horne, Stacey; Steele, Megan L; Forbes, Josephine; Rahmadi, Anton; Griffith, Renate; Münch, Gerald

    2011-08-01

    Advanced glycation end products (AGEs) are involved in age-related diseases, including the complications of diabetes and chronic renal impairment with arterial stiffening. Alagebrium chloride (ALT-711) is an AGE-lowering agent with beneficial effects in renal structural and functional parameters in diabetes, decreased diabetes-accelerated atherosclerosis, and age-related myocardial stiffening. ALT-711 exhibits a structural homology to thiamine, and it was suggested to interfere with thiamine metabolism. Thiamine is converted to thiamine diphosphate (TDP) by thiamine diphosphokinase (TDPK). TDP is a cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and transketolase. A decreased activity of these enzymes due to TDP deficiency results in disorders such as beriberi and Wernicke-Korsakoff syndrome. Therefore, we investigated whether ALT-711 is an inhibitor of TDPK. Molecular modeling studies showed that ALT-711 fits into the thiamine-binding pocket of TDPK, and there are three interactions between the thiazolium ring and the enzyme, as well as parallel stacking between the phenyl ring and the indole ring of Trp222B. Enzyme kinetic experiments also showed that ALT-711 dose-dependently decreased TDPK activity with K(i)s, calculated by different experiments and fitting models ranging from 0.88 to 1.09 mM. Fitting of the kinetic data favored mixed-mode inhibition with a major role for competitive inhibition. In summary, our results suggest that ALT-711 is a low-affinity inhibitor of TDPK, but is unlikely to interfere with thiamine metabolism at therapeutic concentrations. However, when new AGE-crosslink breakers based on thiamine are designed, care should be taken that they do not act as more potent competitive inhibitors than ALT-711. PMID:21612515

  2. Discovery of wall teichoic acid inhibitors as potential anti-MRSA β-lactam combination agents.

    PubMed

    Wang, Hao; Gill, Charles J; Lee, Sang H; Mann, Paul; Zuck, Paul; Meredith, Timothy C; Murgolo, Nicholas; She, Xinwei; Kales, Susan; Liang, Lianzhu; Liu, Jenny; Wu, Jin; Santa Maria, John; Su, Jing; Pan, Jianping; Hailey, Judy; Mcguinness, Debra; Tan, Christopher M; Flattery, Amy; Walker, Suzanne; Black, Todd; Roemer, Terry

    2013-02-21

    Innovative strategies are needed to combat drug resistance associated with methicillin-resistant Staphylococcus aureus (MRSA). Here, we investigate the potential of wall teichoic acid (WTA) biosynthesis inhibitors as combination agents to restore β-lactam efficacy against MRSA. Performing a whole-cell pathway-based screen, we identified a series of WTA inhibitors (WTAIs) targeting the WTA transporter protein, TarG. Whole-genome sequencing of WTAI-resistant isolates across two methicillin-resistant Staphylococci spp. revealed TarG as their common target, as well as a broad assortment of drug-resistant bypass mutants mapping to earlier steps of WTA biosynthesis. Extensive in vitro microbiological analysis and animal infection studies provide strong genetic and pharmacological evidence of the potential effectiveness of WTAIs as anti-MRSA β-lactam combination agents. This work also highlights the emerging role of whole-genome sequencing in antibiotic mode-of-action and resistance studies.

  3. Evaluation of unnatural cyclic amino acids as boron delivery agents for treatment of melanomas and gliomas

    PubMed Central

    Barth, Rolf F.; Kabalka, George W.; Yang, Weilian; Huo, Tianyao; Nakkula, Robin J.; Shaikh, Aarif L.; Haider, Syed A.; Chandra, Subhash

    2014-01-01

    Unnatural cyclic amino acids (UNAA) are a new class of boron delivery agents that are in a pre-clinical stage of evaluation. In the present study, the biodistribution of racemic forms of the cis-and trans- isomers of the boronated UNAA 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC) and 1-amino-3-boronocycloheptanecarboxylic acid (ABCHC) was studied in B16 melanoma bearing mice and this was compared to L-p-boronophenylalanine (BPA). Boron concentrations were determined by inductively coupled plasma-optical emission spectroscopy (ICPOES) at 2.5 hrs following intraperitoneal (i.p.) injection of the test agents at a concentration equivalent to 24 mg B/kg. While all compounds attained comparable tumor boron concentrations, the tumor/blood (T/Bl) boron concentration ratios were far superior for both cis-ABCPC and cis-ABCHC compared to BPA (T/Bl = 16.4, and 15.1 vs. 5.4). Secondary ion mass spectrometry (SIMS) imaging revealed that the cis-ABCPC delivered boron to the nuclei, as well as the cytoplasm of B16 cells. Next, a biodistribution study of cis-ABCPC and BPA was carried out in F98 glioma bearing rats following i.p. administration. Both compounds attained comparable tumor boron concentrations but the tumor/brain (T/Br) boron ratio was superior for cis-ABCPC compared to BPA (6 vs. 3.3). Since UNAAs are water soluble and cannot be metabolized by tumor cells, they potentially could be more effective boron delivery agents than BPA. Our data suggest that further studies are warranted to evaluate these compounds prior to the initiation of clinical studies. PMID:24393770

  4. Synthesis and biological evaluation of pseudolaric acid B derivatives as potential immunosuppressive agents.

    PubMed

    Chen, Shou-Qiang; Wang, Jie; Zhao, Chuan; Sun, Qiang-Wen; Wang, Yi-Teng; Ai, Ting; Li, Tan; Gao, Ying; Wang, Huo; Chen, Hong

    2015-01-01

    Pseudolaric acid B (PB) derivatives with immunosuppressive activity were found by our group. In order to find potential immunosuppressive agents with high efficacy and low toxicity, a series of novel PB derivatives were synthesized and evaluated on their immunosuppressive activities. Most of the synthesized compounds were tested in vitro on murine T and B proliferation. In particular, compound 11 exhibited excellent inhibitory activity toward murine T cells (up to 19-fold enhancement compared to that of mycophenolatemofetil) and little cytotoxicity toward normal murine spleen cells. These experimental data demonstrated that some of these PB derivatives have great potential for future immunosuppressive studies.

  5. The therapeutic efficacy of oral cholecystographic agent (iopanoic acid) in the management of hyperthyroidism

    SciTech Connect

    Bal, C.; Nair, N. )

    1990-07-01

    Five randomly chosen patients with thyrotoxicosis were administered 1 gm of the oral cholecystographic agent iopanoic acid daily for 21 days. There was a marked fall in T3 levels by 75% of the pretherapy value by 96 hr; values remained normal over the 21-day period. T4 values fell significantly by seven days of therapy, and the decreased values were sustained. FT3 and FT4I also showed corresponding decreases in value. All subjects showed clinical improvement by both subjective and objective criteria. During therapy, escape from the effect of iopanoic acid was not encountered. However, after stopping the drug for 2-4 wk, the patients' iodine-131 uptake become as high as the pretherapy level, enabling them to undergo radioiodine treatment for thyrotoxicosis. The treatment strategy can be aimed at achieving quick euthyroidism and in planning radioiodine treatment as early as possible in high risk patients. This treatment may also be useful in preoperative control of thyrotoxicosis.

  6. Potential Use of Phenolic Acids as Anti-Candida Agents: A Review

    PubMed Central

    Teodoro, Guilherme R.; Ellepola, Kassapa; Seneviratne, Chaminda J.; Koga-Ito, Cristiane Y.

    2015-01-01

    There has been a sharp rise in the occurrence of Candida infections and associated mortality over the last few years, due to the growing body of immunocompromised population. Limited number of currently available antifungal agents, undesirable side effects and toxicity, as well as emergence of resistant strains pose a considerable clinical challenge for the treatment of candidiasis. Therefore, molecules that derived from natural sources exhibiting considerable antifungal properties are a promising source for the development of novel anti-candidal therapy. Phenolic compounds isolated from natural sources possess antifungal properties of interest. Particularly, phenolic acids have shown promising in vitro and in vivo activity against Candida species. However, studies on their mechanism of action alone or in synergism with known antifungals are still scarce. This review attempts to discuss the potential use, proposed mechanisms of action and limitations of the phenolic acids in anti-candidal therapy. PMID:26733965

  7. Lower Serum Bilirubin and Uric Acid Concentrations in Patients with Parkinson's Disease in China.

    PubMed

    Qin, Xiao-Ling; Zhang, Qing-Shan; Sun, Li; Hao, Meng-Wei; Hu, Zhao-Ting

    2015-05-01

    The objective of the study is to investigate the correlation between bilirubin and uric acid (UA) concentrations and symptoms of Parkinson's disease (PD) in Chinese population. A total of 425 PD patients and 460 controls were included in the current study. Patients were diagnosed by a neurologist and assessed using the Hoehn & Yahr (H&Y) scale. Venous blood samples were collected, and bilirubin and UA concentrations were analyzed. Compared to controls, indirect bilirubin (IBIL) and UA concentrations were lower in PD patients (P IBIL = 0.015, P UA = 0.000). Serum IBIL in different age subgroups and H&Y stage subgroups were also lower compared to the control group (P IBIL = 0.000, P UA = 0.000) but were not significantly different among these subgroups. Females in the control group had significantly lower serum IBIL and UA concentrations than males (P IBIL = 0.000, P UA = 0.000) and the PD group (P IBIL = 0.027, P UA = 0.000). In early PD (patients with <2-year medical history and no treatment), serum IBIL and UA concentrations were also lower than the controls (P IBIL = 0.013, P UA = 0.000). Although IBIL concentration was positively correlated with UA concentration in controls (R IBIL = 0.229, P IBIL = 0.004), this positive association was not observed in the PD group (R IBIL = -0.032, P IBIL = 0.724). Decreased levels of serum IBIL and UA were observed in PD patients. It is possible that individuals with decreased serum bilirubin and UA concentrations lack the endogenous defense system to prevent peroxynitrite and other free radicals from damaging and destroying dopaminergic cells in the substantia nigra. Our results provide a basis for further investigation into the role of bilirubin in PD.

  8. Gas chromatography-mass spectrometry of hexafluoroacetone derivatives: First time utilization of a gaseous phase derivatizing agent for analysis of extraterrestrial amino acids.

    PubMed

    Geffroy-Rodier, C; Buch, A; Sternberg, R; Papot, S

    2012-07-01

    Within the perspective of the current and next space missions to Mars (MSL 2011 and Exomars 2016-2018), the detection and enantioselective separation of building blocks such as the amino acids are important subjects which are becoming fundamental for the search for traces of life on the surface and subsurface of Mars. In this work, we have developed and optimized a method adapted to space experimentation to derivatize and analyze amino acids, using hexafluoroacetone as the derivatizing agent. The temperature, duration of the derivative transfer to the analyser, and chromatographic separation parameters have been optimized to meet the instrument design constraints imposed on devices for extraterrestrial experiments. The work presented in this rationale has established that hexafluoroacetone, in addition to its intrinsic qualities, such as the production of light-weight derivatives (no racemization) and great resistance to the drastic operating conditions, has indeed facilitated simple and fast derivatization that appears to be suitable for in situ analysis in space. By using hexafluoroacetone as the derivatizing agent, we successfully identified, 21 amino acids including 12 of the 20 proteinic amino acids without stirring or extraction steps. Ten of these derivatized amino acids were enantioselectively separated. The precision and accuracy measurements for the D/L ratio showed that the proposed method was also suitable for the determination of both enantioselective forms of most of the tested amino acids. The limits of detection obtained were lower than the ppb level of organic molecules detected in Martian meteorites.

  9. A Novel Function for Kojic Acid, a Secondary Metabolite from Aspergillus Fungi, as Antileishmanial Agent

    PubMed Central

    Rodrigues, Ana Paula D.; Farias, Luis Henrique S.; Carvalho, Antonio Sérgio C.; Santos, Alberdan S.; do Nascimento, José Luiz M.; Silva, Edilene O.

    2014-01-01

    Kojic acid (KA) is a fungal metabolite used as a topical treatment skin-whitening cosmetic agent for melasma in humans; however its potential as an anti-leishmanial agent is unknown. Chemotherapy is one of the most effective treatments for Leishmaniasis. However, the drugs available are expensive, invasive, require long-term treatment and have severe side effects. Thus, the development of new effective leishmanicidal agents is a necessity. In this study we investigated the anti-leishmanial effect of KA on L. amazonensis, following in vitro and in vivo infections. KA (50 μg/mL) was found to decrease the growth by 62% (IC50 34 μg/mL) and 79% (IC50 27.84 μg/mL) of promastigotes and amastigotes in vitro, respectively. Ultrastructural analysis of KA-treated amastigotes showed the presence of vesicles bodies into the flagellar pocket, and an intense intracellular vacuolization and swelling of the mitochondrion. During the in vitro interaction of parasites and the host cell, KA reverses the superoxide anions (O2-) inhibitory mechanism promoted by parasite. In addition, 4 weeks after KA-topical formulation treatment of infected animals, a healing process was observed with a high production of collagen fibers and a decrease in parasite burden. Thus, these results demonstrated the great potential of KA as an anti-leishmanial compound. PMID:24621481

  10. Salvianolic acid A as a multifunctional agent ameliorates doxorubicin-induced nephropathy in rats

    PubMed Central

    Fan, Hua-Ying; Yang, Ming-Yan; Qi, Dong; Zhang, Zuo-Kai; Zhu, Lin; Shang-Guan, Xiu-Xin; Liu, Ke; Xu, Hui; Che, Xin

    2015-01-01

    Nephrotic syndrome (NS) is still a therapeutic challenge. To date there is no ideal treatment. Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury. Salvianolic acid A (SAA) is the major active component of Salviae Miltiorrhizae Bunge. Previous studies have demonstrated that SAA is a multi-target agent and has various pharmacological activities. The pleiotropic properties of SAA predict its potential in the treatment of NS. The study investigated the effect of SAA on doxorubicin-induced nephropathy. The kidney function related-biochemical changes, hemorheological parameters and oxidative stress status were determined, and histological examination using light and transmission electron microcopies and western blot analysis were also performed. Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology. Furthermore, SAA restored podocin expression, down-regulated the expression of NF-κB p65 and p-IκBα while up-regulating IκBα protein expression. Overall, as a multifunctional agent, SAA has a favorable renoprotection in doxorubicin-induced nephropathy. The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects. All these indicate that SAA is likely to be a promising agent for NS. PMID:26194431

  11. Hyaluronic acid and its use as a "rejuvenation" agent in cosmetic dermatology.

    PubMed

    Andre, Pierre

    2004-12-01

    Since 1996, hyaluronic acid (HA) has been launched onto the market in Europe. Since then, different companies proposed their HAs. Biomatrix (NJ, USA) proposes an animal-derived HA (from rooster comb). Q-Med AB (Uppsala, Sweden) and LEA-DERM (Paris, France) are the main companies to have a nonanimal HA. HA is produced by bacterial fermentation from a specific strain of streptococci. HA has no species specificity and theoretically has no risk of allergy. No skin testing is necessary before injecting because HA is a biodegradable agent. To be utilized as a filler agent for improving wrinkles, scars, or increasing volumes, HA must be stabilized to obtain a sufficient half-life. Process of stabilization varies, according to each manufacturer. This explains the differences in longevity and in viscosity of the different products. Several HAs are suitable to fine lines, to deep wrinkles/folds, or to increase volume. A new indication for "rejuvenation" is injection into the superficial dermis and epidermis. The HA (stabilized or not) is not used to fill in but rather to hydrate and finally to rejuvenate the skin. This procedure must be repeated at intervals of a few weeks or months. If HA is the safest filler agent in cosmetic indications today, some rare side effects may appear and must be known to inform patients. Most of these complications are not severe and will disappear when the product is degraded.

  12. α-Mangostin, a Natural Agent, Enhances the Response of NRAS Mutant Melanoma to Retinoic Acid

    PubMed Central

    Xia, Yun; Chen, Jing; Gong, Chongwen; Chen, Hongxiang; Sun, Jiaming

    2016-01-01

    Background The identification and use of novel compounds alone or in combination hold promise for the fight against NRAS mutant melanoma. Material/Methods We screened a kinase-specific inhibitor library through combining it with α-Mangostin in NRAS mutant melanoma cell line, and verified the enhancing effect of α-Mangostin through inhibition of the tumorigenesis pathway. Results Within the kinase inhibitors, retinoic acid showed a significant synergistic effect with α-Mangostin. α-Mangostin also can reverse the drug resistance of retinoic acid in RARa siRNA-transduced sk-mel-2 cells. Colony assay, TUNEL staining, and the expressions of several apoptosis-related genes revealed that α-Mangostin enhanced the effect of retinoic acid-induced apoptosis. The combination treatment resulted in marked induction of ROS generation and inhibition of the AKT/S6 pathway. Conclusions These results indicate that the combination of these novel natural agents with retinoid acid may be clinically effective in NRAS mutant melanoma. PMID:27104669

  13. A new source of whitening agent from a Thai Mulberry plant and its betulinic acid quantitation.

    PubMed

    Nattapong, Snitmatjaro; Omboon, Luanratana

    2008-06-15

    Protection of human body against the harmful ultraviolet exposure is nowadays more important and interesting. Melanin, a group of bio-pigments, acts as a natural solar filter absorbing and reflecting most of the UV radiation passing through the layer of skin. Over production of the pigments can create a health problem, hyperpigmentation. Tyrosinase is a key enzyme, which catalyzes the conversion of L-tyrosine to L-dihydroxyalanine (L-Dopa), therefore tyrosinase inhibitors are used in various skin preparations due to its pronounced effect on anti-hyperpigment. In this study, an in vitro anti-tyrosinase activity study of the extracts from a hybrid Mulberry plant obtained from Morus alba L. and Morus rotundiloba Koidz, is shown to prove as new source of Thai whitening agent. The presence of betulinic acid, as an anti-inflammatory and anti-tyrosinase activity agent, is also reported. The study develops the technique of HPLC quantitation of betulinic acid and its relation to anti-tyrosinase activity of the whole parts of Thai Mulberry.

  14. Lactic acid bacteria from fresh fruit and vegetables as biocontrol agents of phytopathogenic bacteria and fungi.

    PubMed

    Trias, Rosalia; Bañeras, Lluís; Montesinos, Emilio; Badosa, Esther

    2008-12-01

    This study evaluated the efficacy of lactic acid bacteria (LAB) isolated from fresh fruits and vegetables as biocontrol agents against the phytopathogenic and spoilage bacteria and fungi, Xanthomonas campestris, Erwinia carotovora, Penicillium expansum, Monilinia laxa, and Botrytis cinerea. The antagonistic activity of 496 LAB strains was tested in vitro and all tested microorganisms except P. expansum were inhibited by at least one isolate. The 496 isolates were also analyzed for the inhibition of P. expansum infection in wounds of Golden Delicious apples. Four strains (TC97, AC318, TM319, and FF441) reduced the fungal rot diameter of the apples by 20%; only Weissella cibaria strain TM128 decreased infection levels by 50%. Cell-free supernatants of selected antagonistic bacteria were studied to determine the nature of the antimicrobial compounds produced. Organic acids were the preferred mediators of inhibition but hydrogen peroxide was also detected when strains BC48, TM128, PM141 and FF441 were tested against E. carotovora. While previous reports of antifungal activity by LAB are scarce, our results support the potential of LAB as biocontrol agents against postharvest rot.

  15. Lactic acid bacteria from fresh fruit and vegetables as biocontrol agents of phytopathogenic bacteria and fungi.

    PubMed

    Trias, Rosalia; Bañeras, Lluís; Montesinos, Emilio; Badosa, Esther

    2008-12-01

    This study evaluated the efficacy of lactic acid bacteria (LAB) isolated from fresh fruits and vegetables as biocontrol agents against the phytopathogenic and spoilage bacteria and fungi, Xanthomonas campestris, Erwinia carotovora, Penicillium expansum, Monilinia laxa, and Botrytis cinerea. The antagonistic activity of 496 LAB strains was tested in vitro and all tested microorganisms except P. expansum were inhibited by at least one isolate. The 496 isolates were also analyzed for the inhibition of P. expansum infection in wounds of Golden Delicious apples. Four strains (TC97, AC318, TM319, and FF441) reduced the fungal rot diameter of the apples by 20%; only Weissella cibaria strain TM128 decreased infection levels by 50%. Cell-free supernatants of selected antagonistic bacteria were studied to determine the nature of the antimicrobial compounds produced. Organic acids were the preferred mediators of inhibition but hydrogen peroxide was also detected when strains BC48, TM128, PM141 and FF441 were tested against E. carotovora. While previous reports of antifungal activity by LAB are scarce, our results support the potential of LAB as biocontrol agents against postharvest rot. PMID:19204894

  16. Aquatic photodegradation of sunscreen agent p-aminobenzoic acid in the presence of dissolved organic matter.

    PubMed

    Zhou, Lei; Ji, Yuefei; Zeng, Chao; Zhang, Ya; Wang, Zunyao; Yang, Xi

    2013-01-01

    Dissolved organic matter (DOM) is an important photosensitizer for the phototransformation of organic contaminants in sunlit natural waters. This article focuses on the photolysis kinetics and mechanism of sunscreen agent p-aminobenzoic acid (PABA) in the presence of four kinds of DOM; Suwannee River fulvic acid (SRFA), Suwannee River humic acid (SRHA), Nordic Lake fulvic acid (NOFA) and Nordic Lake humic acid (NOHA). It is evident that direct photolysis of PABA is highly pH-dependent because different species of PABA have different electrical densities on the ring system. The presence of four kinds of DOM inhibits the photolysis of PABA primarily due to their light screening effect. Meanwhile, a complex interaction involving energy transfer, triplet carbonyl group induced electron transfer, and amino acid induced proton abstraction between PABA and DOM is verified by competition kinetics experiments and density functional theory (DFT) computation. In addition, DOM-induced singlet oxygen ((1)O(2)) and hydroxyl radical (OH) are determined to play an insignificant role in PABA photolysis by competition dynamics method. Photoproducts identification using solid phase extraction-liquid chromatography-mass spectrometry (SPE-LC-MS) techniques reveals that the distribution of the photoproducts could not be affected by the addition of DOM. Two photodegradation pathways of PABA are temporarily proposed, in which the di(tri)-polymerization of intermediates are the dominant pathway whereas the oxidation of amino group to nitryl followed by hydroxylation is a minor process. Our findings reveal that direct photolysis is the dominant transformation pathway of PABA in natural sunlit waters, while the presence of DOM could evidently influence such process by light screening effect, energy transfer, electron transfer and proton abstraction mechanism. The findings in this study provide useful information for understanding of interaction between DOM and organic contaminants. PMID

  17. Comparatve uric acid lowering studies of allopurinol with an indigenous medicinal plant in rabbits.

    PubMed

    Mohammad, Imran Shair; Latif, Sana; Yar, Muhammad; Nasar, Faiza; Ahmad, Irshad; Naeem, Muhammad

    2014-01-01

    The aim of this research was to carry out a comparative study of lowering of uric acid by the use of dried powder of Colchicum luteum and allopathic drug (allopurinol) in rabbits, to determine whether herbal drugs can be used by patients instead of allopathic drugs. The herbal medicine, dried corm powder of Colchicum luteum 2.5 mg/kg/day and dried powder of allopurinol 2 mg/kg/day an allopathic medicine, was used in the study. The results of these medicines were observed in animal model, using 12 adult rabbits, which were divided into three groups A, B and C, respectively, where group C was taken as control. The SPSS version 17 was used for statistical analysis and analysis of variance (ANOVA) was used for comparing the data in different groups and the level of significance was 5%. It was resulted that dried corm of Colchicum luteum significantly reduced the uric acid in adult rabbits as reduced by allopathic medicine--allopurinol. In the light of present research we concluded that the herbal medicines can be used in lieu of allopathic drugs. Thus, the risk of side effects that are associated with the prolonged use of allopathic drugs can be minimized.

  18. Biodegradable DNA-Brush Block Copolymer Spherical Nucleic Acids Enable Transfection Agent-Free Intracellular Gene Regulation.

    PubMed

    Zhang, Chuan; Hao, Liangliang; Calabrese, Colin M; Zhou, Yu; Choi, Chung Hang J; Xing, Hang; Mirkin, Chad A

    2015-10-28

    By grafting multiple DNA strands onto one terminus of a polyester chain, a DNA-brush block copolymer that can assemble into micelle structure is constructed. These micelle spherical nucleic acids have a density of nucleic acids that is substantively higher than linear DNA block copolymer structures, which makes them effective cellular transfection and intracellular gene regulation agents.

  19. High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells.

    PubMed

    Pellis, Linette; Dommels, Yvonne; Venema, Dini; Polanen, Ab van; Lips, Esther; Baykus, Hakan; Kok, Frans; Kampman, Ellen; Keijer, Jaap

    2008-04-01

    Folate, a water-soluble B vitamin, is a cofactor in one-carbon metabolism and is essential for DNA synthesis, amino acid interconversion, methylation and, consequently, normal cell growth. In animals with existing pre-neoplastic and neoplastic lesions, folic acid supplementation increases the tumour burden. To identify processes that are affected by increased folic acid levels, we compared HT29 human colon cancer cells exposed to a chronic supplemental (100 ng/ml) level of folic acid to cells exposed to a normal (10 ng/ml) level of folic acid, in the presence of vitamin B12 and other micronutrients involved in the folate-methionine cycle. In addition to higher intracellular folate levels, HT29 cells at 100 ng folic acid/ml displayed faster growth and higher metabolic activity. cDNA microarray analysis indicated an effect on cell turnover and Fe metabolism. We fully confirmed these effects at the physiological level. At 100 ng/ml, cell assays showed higher proliferation and apoptosis, while gene expression analysis and a lower E-cadherin protein expression indicated decreased differentiation. These results are in agreement with the promoting effect of folic acid supplementation on established colorectal neoplasms. The lower expression of genes related to Fe metabolism at 100 ng folic acid/ml was confirmed by lower intracellular Fe levels in the cells exposed to folic acid at 100 ng/ml. This suggests an effect of folate on Fe metabolism.

  20. Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia

    PubMed Central

    Jenkins, David J.A.; Chiavaroli, Laura; Wong, Julia M.W.; Kendall, Cyril; Lewis, Gary F.; Vidgen, Edward; Connelly, Philip W.; Leiter, Lawrence A.; Josse, Robert G.; Lamarche, Benoît

    2010-01-01

    Background Higher intake of monounsaturated fat may raise high-density lipoprotein (HDL) cholesterol without raising low-density lipoprotein (LDL) cholesterol. We tested whether increasing the monounsaturated fat content of a diet proven effective for lowering LDL cholesterol (dietary portfolio) also modified other risk factors for cardiovascular disease, specifically by increasing HDL cholesterol, lowering serum triglyceride and further reducing the ratio of total to HDL cholesterol. Methods Twenty-four patients with hyperlipidemia consumed a therapeutic diet very low in saturated fat for one month and were then randomly assigned to a dietary portfolio low or high in monounsaturated fatty acid for another month. We supplied participants’ food for the two-month period. Calorie intake was based on Harris–Benedict estimates for energy requirements. Results For patients who consumed the dietary portfolio high in monounsaturated fat, HDL cholesterol rose, whereas for those consuming the dietary portfolio low in monounsaturated fat, HDL cholesterol did not change. The 12.5% treatment difference was significant (0.12 mmol/L, 95% confidence interval [CI] 0.05 to 0.21, p = 0.003). The ratio of total to HDL cholesterol was reduced by 6.5% with the diet high in monounsaturated fat relative to the diet low in monounsaturated fat (−0.28, 95% CI −0.59 to −0.04, p = 0.025). Patients consuming the diet high in monounsaturated fat also had significantly higher concentrations of apolipoprotein AI, and their C-reactive protein was significantly lower. No treatment differences were seen for triglycerides, other lipids or body weight, and mean weight loss was similar for the diets high in monounsaturated fat (−0.8 kg) and low in monounsaturated fat (−1.2 kg). Interpretation Monounsaturated fat increased the effectiveness of a cholesterol-lowering dietary portfolio, despite statin-like reductions in LDL cholesterol. The potential benefits for cardiovascular risk were

  1. Targeted delivery of 5-fluorouracil to cholangiocarcinoma cells using folic acid as a targeting agent.

    PubMed

    Ngernyuang, Nipaporn; Seubwai, Wunchana; Daduang, Sakda; Boonsiri, Patcharee; Limpaiboon, Temduang; Daduang, Jureerut

    2016-03-01

    There are limits to the standard treatment for cholangiocarcinoma (CCA) including drug resistance and side effects. The objective of this study was to develop a new technique for carrying drugs by conjugation with gold nanoparticles and using folic acid as a targeting agent in order to increase drug sensitivity. Gold nanoparticles (AuNPs) were functionalized with 5-fluorouracil (5FU) and folic acid (FA) using polyethylene glycol (PEG) shell as a linker (AuNPs-PEG-5FU-FA). Its cytotoxicity was tested in CCA cell lines (M139 and M213) which express folic acid receptor (FA receptor). The results showed that AuNPs-PEG-5FU-FA increased the cytotoxic effects in the M139 and M213 cells by 4.76% and 7.95%, respectively compared to those treated with free 5FU+FA. It is found that the cytotoxicity of the AuNPs-PEG-5FU-FA correlates with FA receptor expression suggested the use of FA as a targeted therapy. The mechanism of cytotoxicity was mediated via mitochondrial apoptotic pathway as determined by apoptosis array. In conclusion, our findings shed some light on the use of gold nanoparticles for conjugation with potential compounds and FA as targeted therapy which contribute to the improvement of anti-cancer drug efficacy. In vivo study should be warranted for its effectiveness of stability, biosafety and side effect reduction.

  2. Natural fatty acid synthase inhibitors as potent therapeutic agents for cancers: A review.

    PubMed

    Zhang, Jia-Sui; Lei, Jie-Ping; Wei, Guo-Qing; Chen, Hui; Ma, Chao-Ying; Jiang, He-Zhong

    2016-09-01

    Context Fatty acid synthase (FAS) is the only mammalian enzyme to catalyse the synthesis of fatty acid. The expression level of FAS is related to cancer progression, aggressiveness and metastasis. In recent years, research on natural FAS inhibitors with significant bioactivities and low side effects has increasingly become a new trend. Herein, we present recent research progress on natural fatty acid synthase inhibitors as potent therapeutic agents. Objective This paper is a mini overview of the typical natural FAS inhibitors and their possible mechanism of action in the past 10 years (2004-2014). Method The information was collected and compiled through major databases including Web of Science, PubMed, and CNKI. Results Many natural products induce cancer cells apoptosis by inhibiting FAS expression, with fewer side effects than synthetic inhibitors. Conclusion Natural FAS inhibitors are widely distributed in plants (especially in herbs and foods). Some natural products (mainly phenolics) possessing potent biological activities and stable structures are available as lead compounds to synthesise promising FAS inhibitors.

  3. Facile synthesis of graphene from graphite using ascorbic acid as reducing agent

    NASA Astrophysics Data System (ADS)

    Andrijanto, Eko; Shoelarta, Shoerya; Subiyanto, Gatot; Rifki, Sadur

    2016-04-01

    Graphene has attracted a tremendous attention in recent years due to its unique properties such as mechanical, thermal, optical and electrical properties. However, a large scale production of this material is still an issue and subjected to intense research efforts. Here, we show a simple and green approach of the graphene synthesis from graphene oxide using ascorbic acid as reduction agent. A facile synthesis of graphene (rGO) through chemical oxidation of graphite into graphene oxide (GO) was described using modified Hummers method (Improved Tour Method/ITM). The ITM method does not produce toxic gas and the temperature of the oxidation is easily controlled using ice bath. The synthesized of graphene oxide was highly soluble and stable in water. The reduction of graphene oxide into graphene was performed using ascorbic acid (AA) in mild condition. The combined ITM method and green reduction using ascorbic acid open the avenue of replacing hydrazine in the reduction of graphite oxide into graphene and may be very important step for bulk production of graphene.

  4. Targeted delivery of 5-fluorouracil to cholangiocarcinoma cells using folic acid as a targeting agent.

    PubMed

    Ngernyuang, Nipaporn; Seubwai, Wunchana; Daduang, Sakda; Boonsiri, Patcharee; Limpaiboon, Temduang; Daduang, Jureerut

    2016-03-01

    There are limits to the standard treatment for cholangiocarcinoma (CCA) including drug resistance and side effects. The objective of this study was to develop a new technique for carrying drugs by conjugation with gold nanoparticles and using folic acid as a targeting agent in order to increase drug sensitivity. Gold nanoparticles (AuNPs) were functionalized with 5-fluorouracil (5FU) and folic acid (FA) using polyethylene glycol (PEG) shell as a linker (AuNPs-PEG-5FU-FA). Its cytotoxicity was tested in CCA cell lines (M139 and M213) which express folic acid receptor (FA receptor). The results showed that AuNPs-PEG-5FU-FA increased the cytotoxic effects in the M139 and M213 cells by 4.76% and 7.95%, respectively compared to those treated with free 5FU+FA. It is found that the cytotoxicity of the AuNPs-PEG-5FU-FA correlates with FA receptor expression suggested the use of FA as a targeted therapy. The mechanism of cytotoxicity was mediated via mitochondrial apoptotic pathway as determined by apoptosis array. In conclusion, our findings shed some light on the use of gold nanoparticles for conjugation with potential compounds and FA as targeted therapy which contribute to the improvement of anti-cancer drug efficacy. In vivo study should be warranted for its effectiveness of stability, biosafety and side effect reduction. PMID:26706547

  5. Relationship between High-Performance Liquid Chromatography Fingerprints and Uric Acid-Lowering Activities of Cichorium intybus L.

    PubMed

    Zhu, Chun-Sheng; Zhang, Bing; Lin, Zhi-Jian; Wang, Xue-Jie; Zhou, Yue; Sun, Xiao-Xia; Xiao, Ming-Liang

    2015-01-01

    This study aimed to explore the spectrum-effect relationships between high-performance liquid chromatography fingerprints and the uric acid-lowering activities of chicory. Chemical fingerprints of chicory samples from ten different sources were determined by high-performance liquid chromatography, and then investigated by similarity analysis and hierarchical clustering analysis. Pharmacodynamics experiments were conducted in animals to obtain the uric acid-lowering activity information of each chicory sample. The spectrum-effect relationships between chemical fingerprints and the uric acid-lowering activities of chicory were established by canonical correlation analysis. The structures of potential effective peaks were identified by liquid chromatography with tandem mass spectrometry. The results showed that a close correlation existed between the spectrum and effect of chicory. Aesculin, chlorogenic acid, chicoric acid, isochlorogenic acid A/B/C and 13,14-seco-stigma5(6),14(15)-diene-3α-ol might be the main effective constituents. This work provides a general model of the combination of high-performance liquid chromatography and uric acid-lowering activities to study the spectrum-effect relationships of chicory, which can be used to discover the principle components responsible for the bioactivity. PMID:26007193

  6. Relationship between High-Performance Liquid Chromatography Fingerprints and Uric Acid-Lowering Activities of Cichorium intybus L.

    PubMed

    Zhu, Chun-Sheng; Zhang, Bing; Lin, Zhi-Jian; Wang, Xue-Jie; Zhou, Yue; Sun, Xiao-Xia; Xiao, Ming-Liang

    2015-05-22

    This study aimed to explore the spectrum-effect relationships between high-performance liquid chromatography fingerprints and the uric acid-lowering activities of chicory. Chemical fingerprints of chicory samples from ten different sources were determined by high-performance liquid chromatography, and then investigated by similarity analysis and hierarchical clustering analysis. Pharmacodynamics experiments were conducted in animals to obtain the uric acid-lowering activity information of each chicory sample. The spectrum-effect relationships between chemical fingerprints and the uric acid-lowering activities of chicory were established by canonical correlation analysis. The structures of potential effective peaks were identified by liquid chromatography with tandem mass spectrometry. The results showed that a close correlation existed between the spectrum and effect of chicory. Aesculin, chlorogenic acid, chicoric acid, isochlorogenic acid A/B/C and 13,14-seco-stigma5(6),14(15)-diene-3α-ol might be the main effective constituents. This work provides a general model of the combination of high-performance liquid chromatography and uric acid-lowering activities to study the spectrum-effect relationships of chicory, which can be used to discover the principle components responsible for the bioactivity.

  7. Trapping of organophosphorus chemical nerve agents in water with amino acid functionalized baskets.

    PubMed

    Ruan, Yian; Dalkiliç, Erdin; Peterson, Paul W; Pandit, Aroh; Dastan, Arif; Brown, Jason D; Polen, Shane M; Hadad, Christopher M; Badjić, Jovica D

    2014-04-01

    We prepared eleven amino-acid functionalized baskets and used (1) H NMR spectroscopy to quantify their affinity for entrapping dimethyl methylphosphonate (DMMP, 118 Å(3) ) in aqueous phosphate buffer at pH=7.0±0.1; note that DMMP guest is akin in size to chemical nerve agent sarin (132 Å(3) ). The binding interaction (Ka ) was found to vary with the size of substituent groups at the basket's rim. In particular, the degree of branching at the first carbon of each substituent had the greatest effect on the host-guest interaction, as described with the Verloop's B1 steric parameter. The branching at the remote carbons, however, did not perturb the encapsulation, which is important for guiding the design of more effective hosts and catalysts in future. PMID:24616086

  8. Novel molecular hybrids of cinnamic acids and guanylhydrazones as potential antitubercular agents.

    PubMed

    Bairwa, Ranjeet; Kakwani, Manoj; Tawari, Nilesh R; Lalchandani, Jaya; Ray, M K; Rajan, M G R; Degani, Mariam S

    2010-03-01

    In an attempt to identify potential new agents active against tuberculosis, 20 novel phenylacrylamide derivatives incorporating cinnamic acids and guanylhydrazones were synthesized using microwave assisted synthesis. Activity of the synthesized compounds was evaluated using resazurin microtitre plate assay (REMA) against Mycobacterium tuberculosis H37Rv. Based on empirical structure-activity relationship data it was observed that both steric and electronic parameters play major role in the activity of this series of compounds. Compound 7s (2E)-N-((-2-(3,4-dimethoxybenzylidene) hydrazinyl) (imino) methyl)-3-(4-methoxyphenyl) acrylamide showed MIC of 6.49microM along with good safety profile of >50-fold in VERO cell line. Thus, this compound could act as a potential lead for further antitubercular studies.

  9. Application and appreciation of chemical sand fixing agent-poly (aspartic acid) and its composites.

    PubMed

    Yang, Jun; Cao, Hui; Wang, Fang; Tan, Tianwei

    2007-12-01

    The sand fixing agent-poly (aspartic acid) (PASP) and its composites were applied in the field by two forms (spraying around by PASP solution and PASP powder directly). It was found that the sand fixing effect in powder form was not as good as in solution form, but it was more practical in dry region. It needed 9, 6 and 7 days for PASP, xanthan gum-PASP (X2) and ethyl cellulose-PASP (E3) to attain the maximal mechanical strength after they were applied, respectively. The sand fixing effect decreased when the material was subjected to repeated hydration-dehydration cycles and the material had no negative influence on plant growth. The PASP and its composites had water-retaining ability and could reduce the water evaporation. PMID:17628237

  10. Evolution in medicinal chemistry of ursolic acid derivatives as anticancer agents.

    PubMed

    Chen, Haijun; Gao, Yu; Wang, Ailan; Zhou, Xiaobin; Zheng, Yunquan; Zhou, Jia

    2015-03-01

    Currently, there is a renewed interest in common dietaries and plant-based traditional medicines for the prevention and treatment of cancer. In the search for potential anticancer agents from natural sources, ursolic acid (UA), a pentacyclic triterpenoid widely found in various medicinal herbs and fruits, exhibits powerful biological effects including its attractive anticancer activity against various types of cancer cells. However, the limited solubility, rapid metabolism and poor bioavailability of UA restricted its further clinical applications. In the past decade, with substantial progress toward the development of new chemical entities for the treatment of cancer, numerous UA derivatives have been designed and prepared to overcome its disadvantages. Despite extensive effort, discovery of effective UA derivatives has so far met with only limited success. This review summarizes the current status of the structural diversity and evolution in medicinal chemistry of UA analogues and provides a detailed discussion of future direction for further research in the chemical modifications of UA.

  11. Plasma sterilization of poly lactic acid ultrasound contrast agents: surface modification and implications for drug delivery.

    PubMed

    Eisenbrey, John R; Hsu, Jennifer; Wheatley, Margaret A

    2009-11-01

    Poly lactic acid (PLA) ultrasound contrast agents (CA) have been developed previously in our laboratory for ultrasound (US) imaging, as well as surface coated with doxorubicin to create a potential targeted platform of chemotherapeutic delivery using focused US. However, we have previously found it impossible to sterilize these agents while at the same time maintaining their acoustic properties, a task that would probably require fabrication within a clean facility. The purpose of this paper is to investigate the feasibility of using plasma to sterilize these CA while maintaining maximum echogenicity, a step that would greatly facilitate in vivo investigations. Effects of plasma exposure time (1, 3 and 6 min) and intensity (low-10 mA, 6.8 W; medium-15 mA, 10.5 W; and high-25 mA, 18 W) on the CAs' acoustic properties, surface morphology, zeta potential, capacity to carry chemotherapeutics and overall sterility are described. Both increases in plasma intensity and exposure time increased CA zeta potential and also significantly increased drug payload. High-intensity plasma exposure for 3 min was found to be an optimal sterilization protocol for maximal (100%) preservation of CA echogenicity. Plasma exposure resulted in sterile samples and maintained original CA enhancement of 20 dB and acoustic half-life over 75 min, while increasing CA zeta potential by 11 mV and doxorubicin loading efficiency by 10%. This study not only shows how a highly temperature- and pressure-sensitive agent can be sterilized using plasma, but also that surface modification can be used to increase surface binding of the drug. PMID:19766380

  12. Material characterization of poly-lactic acid shelled ultrasound contrast agent and their dynamics

    NASA Astrophysics Data System (ADS)

    Paul, Shirshendu; Russakow, Daniel; Rodgers, Tyler; Sarkar, Kausik; Cochran, Michael; Wheatley, Margaret

    2011-11-01

    Micron-size gas bubbles encapsulated with lipids and proteins are used as contrast enhancing agents for ultrasound imaging. Biodegradable polymer poly-lactic acid (PLA) has recently been suggested as a possible means of encapsulation. Here, we report in vitro measurement of attenuation and scattering of ultrasound through an emulsion of PLA agent as well as theoretical modeling of the encapsulated bubble dynamics. The attenuation measured with three different transducers of central frequencies 2.25, 3.5 and 5 MHz, shows a peak around 2-3 MHz. These bubbles also show themselves to possess excellent scattering characteristics including strong non-linear response that can be used for harmonic and sub-harmonic contrast imaging. Our recently developed interfacial rheological models are applied to describe the dynamics of these bubbles; rheological model properties are estimated using measured attenuation data. The model is then applied to predict nonlinear scattered response, and the prediction is compared against experimental observation. Partially supported by NSF and NIH.

  13. Photochemical degradation of sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid in different water matrices.

    PubMed

    Ji, Yuefei; Zhou, Lei; Zhang, Ya; Ferronato, Corinne; Brigante, Marcello; Mailhot, Gilles; Yang, Xi; Chovelon, Jean-Marc

    2013-10-01

    The occurrence of sunscreen agents in natural environment is of scientific concern recently due to their potential risk to ecology system and human beings as endocrine disrupting chemicals (EDCs). In this work the photodegradation mechanism and pathways of sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid (PBSA) were investigated under artificial solar irradiation with the goal of assessing the potential of photolysis as a transformation mechanism in aquatic environments. The quantum yield of PBSA direct photolysis in pH 6.8 buffer solution under filtered mercury lamp irradiation was determined as 2.70 × 10(-4). Laser flash photolysis (LFP) experiments confirmed the involvement of PBSA radical cation (PBSA(·+)) during direct photolysis. Acidic or basic condition facilitated PBSA direct photolysis in aqueous solution. Indirect photolysis out-competes direct photolysis as a major process for PBSA attenuation only at higher level of photosensitizers (e.g., NO3(-) > 2 mM). Thus, direct photolysis is likely to be the major loss pathway responsible for the elimination of PBSA in natural sunlit surface waters, while indirect photolysis (e.g., mediated by HO·) appeared to be less important due to a general low level of steady-state concentration of HO· ([HO·]ss) in natural surface waters. Direct photolysis pathways of PBSA includes desulfonation and benzimidazole ring cleavage, which are probably initiated by the excited triplet state ((3)PBSA*) and radical cation (PBSA(·+)). Conversely, hydroxylation products of PBSA and 2-phenyl-1H-benzimidazole as well as their ring opening intermediates were found in nitrate-induced PBSA photolysis, suggesting the indirect photodegradation was primarily mediated by HO and followed a different mechanism.

  14. Myotoxic reactions to lipid-lowering therapy are associated with altered oxidation of fatty acids.

    PubMed

    Phillips, Paul S; Ciaraldi, Theodore P; Kim, Dong-Lim; Verity, M Anthony; Wolfson, Tanya; Henry, Robert R

    2009-02-01

    Despite exceptional efficacy and safety, fear of muscle toxicity remains a major reason statins are underutilized. Evidence suggests that statin muscle toxicity may be mediated by abnormalities in lipid metabolism. To test the hypothesis that myotubes from patients intolerant of lipid-lowering therapies have abnormal fatty acid oxidation (FAO) responses we compared muscle from 11 subjects with statin intolerance (Intolerant) with muscle from seven statin-naive volunteers undergoing knee arthroplasty (Comparator). Gross muscle pathology was graded and skeletal muscle cell cultures were produced from each subject. FAO was assessed following treatment with increasing statin concentrations. There was no difference in muscle biopsy myopathy scores between the groups. Basal octanoate oxidation was greater in Intolerant than in Comparator subjects (P = 0.03). Lovastatin-stimulated palmitate oxidation tended to be greater for Intolerant compared to Control subjects' myotubes (P = 0.07 for 5 microM and P = 0.06 for 20 microM lovastatin). In conclusion abnormalities in FAO of Intolerant subjects appear to be an intrinsic characteristic of these subjects that can be measured in their cultured myotubes.

  15. Calixarene based chiral solvating agents for α-hydroxy carboxylic acids

    NASA Astrophysics Data System (ADS)

    Bozkurt, Selahattin

    2013-09-01

    Novel chiral calix[4]arene derivatives functionalized at the lower rim have been prepared from the reaction of p-tert-butylcalix[4]arene diamine derivative with N-Phthaloyl-L-phenylalanine or (2S)-2-((benzyloxy)carbonyl)amino)-3-hydroxypropanoic acid or (2S,3R)-2-((benzyloxy)carbonyl)amino-3-hydroxybutanoic acid in 63-81% yield. The structures of these receptors were characterized by FTIR, 1H, 13C and 2D COSY NMR spectroscopy. The enantioselective recognition of these receptors towards the enantiomers of racemic carboxylic acids was studied by 1H NMR spectroscopy. The molar ratios of the chiral compounds with each of the enantiomers of guests were determined by using Job plots. The Job plots indicate that the hosts form 1:2 instantaneous complexes with all guests. The receptors exhibited different chiral recognition abilities toward the enantiomers of racemic guests. NMR studies demonstrated that the receptors function as highly effective chiral shift reagents for determining the enantiomeric purity of a series of carboxylic acids.

  16. Inactivation of Matrix-bound MMPs by Cross-linking Agents in Acid Etched Dentin

    PubMed Central

    Scheffel, Débora Lopes Salles; Hebling, Josimeri; Scheffel, Régis Henke; Agee, Kelly A.; Turco, Gianluca; de Souza Costa, Carlos Alberto; Pashley, David H.

    2014-01-01

    Objectives Published TEM analysis of in vivo resin-dentin bonds shows that in 44 months almost 70% of collagen fibrils from the hybrid layer disappear. Matrix metalloproteinases (MMPs) play an important role in that process and are thought to be the main factor responsible for the solubitization of dentin collagen. Therefore, this study aimed to evaluate the inactivation of matrix-bound MMPs by carbodiimide (EDC) or proanthocyanidin (PA) both cross-linking agents, or the MMP-inhibitor, chlorhexidine (CHX), on acid-etched dentin using a simplified MMP assay method. Methods Dentin beams (1×1×6mm) were obtained from mid-coronal dentin of sound third molars and randomly divided into 6 groups (G) according to the dentin treatment: G1: Deionized water (control), G2: 0.1M EDC, G3: 0.5M EDC, G4: 0.5M EDC+35% HEMA, G5: 5% Proanthocyanidin (PA) and G6: 2% CHX. The beams were etched for 15s with 37% phosphoric acid, rinsed and then immersed for 60s in one of the treatment solutions. The total MMP activity of dentin was analyzed for 1 h by colorimetric assay (Sensolyte). Data were submitted to Wilcoxon non-parametric test and Mann-Whitney tests (p>0.05). Results All experimental cross-linking solutions significantly reduced MMP activity compared to control, except 0.1M EDC (53.6% ±16.1). No difference was observed between cross-linking agents and 2% CHX 0.5M EDC + 35% HEMA (92.3% ±8.0) was similar to 0.5M EDC (89.1% ±6.4), 5% PA (100.8% ±10.9) and 2% CHX (83.4% ±10.9). Conclusion Dentin treatment with cross-linking agents is effective to significantly reduce MMP activity. Mixing 0.5M EDC and 35% HEMA did not influence EDC inhibitor potential. PMID:23786610

  17. Solubilizing properties of new surface-active agents, products of catalytic oxyethylation of cholic acid.

    PubMed

    Kołodziejczyk, Michał Krzysztof; Nachajski, Michal Jakub; Lukosek, Marek; Zgoda, Marian Mikołaj

    2013-01-01

    Solubilizing properties of aqueous solutions of a series of surface-active agents, products of oxyethylation of cholic acid, were examined in the present study. The content of oxyethylated segments determined by means of the 1H NMR method enabled the verification of the molecular mass of surfactants along with the calculation of the structural hydrophilic-lipophilic balance (HLB), the solubility parameter delta1/2, and the required solubility level of balance HLB(R). Viscosimetric measurements enabled the calculation of the limiting viscosity number, the content-average molecular mass, the effective volume, the hydrodynamic radius of the surfactant micelle and their equilibrium adducts with rutin, diclofenac and loratadine (BCS Class II and III). By means of the spectrophotometric method (UV) the amount of the solubilized diclofenac, loratadine and rutin (rutoside) was determined in the equilibrium system (saturated solution) in the environment of aqueous solutions of cholic acid derivatives of n(TE) = 20-70. The obtained results serve as a basis for determining the solubilization mechanism of lipophilic therapeutic products and indirectly for estimating the influence of the above process on pharmaceutical as well as biological availability of a micellar adduct from model drug forms (Lindbladt lithogenolitic index).

  18. Synthesis and biological evaluation of pyrazolylthiazole carboxylic acids as potent anti-inflammatory-antimicrobial agents.

    PubMed

    Khloya, Poonam; Kumar, Satish; Kaushik, Pawan; Surain, Parveen; Kaushik, Dhirender; Sharma, Pawan K

    2015-03-15

    Current Letter presents design, synthesis and biological evaluation of a novel series of pyrazolylthiazole carboxylates 1a-1p and corresponding acid derivatives 2a-2p. All 32 novel compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema method as well as for in vitro antimicrobial activity. All the tested compounds exhibited excellent AI activity profile. Three compounds 1p (R=Cl, R(1)=Cl), 2c (R=H, R(1)=F) and 2n (R=Cl, R(1)=OCH3) were identified as potent anti-inflammatory agents exhibiting edema inhibition of 93.06-89.59% which is comparable to the reference drug indomethacin (91.32%) after 3h of carrageenan injection while most of the other compounds displayed inhibition ⩾80%. In addition, pyrazolylthiazole carboxylic acids (2a-2p) also showed good antimicrobial profile. Compound 2h (R=OCH3, R(1)=Cl) showed excellent antimicrobial activity (MIC 6.25μg/mL) against both Gram positive bacteria comparable with the reference drug ciprofloxacin (MIC 6.25μg/mL).

  19. [Folic acid and cobalamine intake in daily food rations of women from the region of Lower Silesia].

    PubMed

    Bronkowska, Monika; Biernat, Jadwiga

    2008-01-01

    The aim of paper was to assess the folic acid and cobalamine women (n = 960). The information about vitamins intake were collected using 24-hour recall and diet history questionnaire. The intake of vitamins folic acid and cobalamine was too low. The mean folic acid content in the diets of 100 women from Lower Silesia was 221.5 mcg and complied in 79% recommended level. The mean cobalamine content in the diets of 100 women from Lower Silesia was 2.9 mcg and complied in 97% recommended level. In examined group low knowledge about importance role of folic acid and cobalamine in health was noticed. Educational interventions are required to inform women and to increase its intake among them.

  20. Synthesis and Biological Evaluation of Novel Dehydroabietic Acid Derivatives Conjugated with Acyl-Thiourea Peptide Moiety as Antitumor Agents

    PubMed Central

    Jin, Le; Qu, Hong-En; Huang, Xiao-Chao; Pan, Ying-Ming; Liang, Dong; Chen, Zhen-Feng; Wang, Heng-Shan; Zhang, Ye

    2015-01-01

    A series of dehydroabietic acid (DHAA) acyl-thiourea derivatives were designed and synthesized as potent antitumor agents. The in vitro pharmacological screening results revealed that the target compounds exhibited potent cytotoxicity against HeLa, SK-OV-3 and MGC-803 tumor cell lines, while they showed lower cytotoxicity against HL-7702 normal human river cells. Compound 9n (IC50 = 6.58 ± 1.11 μM) exhibited the best antitumor activity against the HeLa cell line and even displayed more potent inhibitory activity than commercial antitumor drug 5-FU (IC50 = 36.58 ± 1.55 μM). The mechanism of representative compound 9n was then studied by acridine orange/ethidium bromide staining, Hoechst 33,258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay and flow cytometry, which illustrated that this compound could induce apoptosis in HeLa cells. Cell cycle analysis indicated that compound 9n mainly arrested HeLa cells in the S phase stage. Further investigation demonstrated that compound 9n induced apoptosis of HeLa cells through a mitochondrial pathway. PMID:26132564

  1. A randomized phase II trial of azacitidine +/− epoetin-β in lower-risk myelodysplastic syndromes resistant to erythropoietic stimulating agents

    PubMed Central

    Thépot, Sylvain; Ben Abdelali, Raouf; Chevret, Sylvie; Renneville, Aline; Beyne-Rauzy, Odile; Prébet, Thomas; Park, Sophie; Stamatoullas, Aspasia; Guerci-Bresler, Agnes; Cheze, Stéphane; Tertian, Gérard; Choufi, Bachra; Legros, Laurence; Bastié, Jean Noel; Delaunay, Jacques; Chaury, Marie Pierre; Sanhes, Laurence; Wattel, Eric; Dreyfus, Francois; Vey, Norbert; Chermat, Fatiha; Preudhomme, Claude; Fenaux, Pierre; Gardin, Claude

    2016-01-01

    The efficacy of azacitidine in patients with anemia and with lower-risk myelodysplastic syndromes, if relapsing after or resistant to erythropoietic stimulating agents, and the benefit of combining these agents to azacitidine in this setting are not well known. We prospectively compared the outcomes of patients, all of them having the characteristics of this subset of lower-risk myelodysplastic syndrome, if randomly treated with azacitidine alone or azacitidine combined with epoetin-β. High-resolution cytogenetics and gene mutation analysis were performed at entry. The primary study endpoint was the achievement of red blood cell transfusion independence after six cycles. Ninety-eight patients were randomised (49 in each arm). Median age was 72 years. In an intention to treat analysis, transfusion independence was obtained after 6 cycles in 16.3% versus 14.3% of patients in the azacitidine and azacitidine plus epoetin-β arms, respectively (P=1.00). Overall erythroid response rate (minor and major responses according to IWG 2000 criteria) was 34.7% vs. 24.5% in the azacitidine and azacitidine plus epoetin-β arms, respectively (P=0.38). Mutations of the SF3B1 gene were the only ones associated with a significant erythroid response, 29/59 (49%) versus 6/27 (22%) in SF3B1 mutated and unmutated patients, respectively, P=0.02. Detection of at least one “epigenetic mutation” and of an abnormal single nucleotide polymorphism array profile were the only factors associated with significantly poorer overall survival by multivariate analysis. The transfusion independence rate observed with azacitidine in this lower-risk population, but resistant to erythropoietic stimulating agents, was lower than expected, with no observed benefit of added epoetin, (clinicaltrials.gov identifier: 01015352). PMID:27229713

  2. Tolfenamic acid inhibits neuroblastoma cell proliferation and induces apoptosis: a novel therapeutic agent for neuroblastoma.

    PubMed

    Eslin, Don; Sankpal, Umesh T; Lee, Chris; Sutphin, Robert M; Maliakal, Pius; Currier, Erika; Sholler, Giselle; Khan, Moeez; Basha, Riyaz

    2013-05-01

    Current therapeutic options for recurrent neuroblastoma have poor outcomes that warrant the development of novel therapeutic strategies. Specificity protein (Sp) transcription factors regulate several genes involved in cell proliferation, survival, and angiogenesis. Sp1 regulates genes believed to be important determinants of the biological behavior of neuroblastoma. Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to induce the degradation of Sp proteins and may serve as a novel anti-cancer agent. The objective of this investigation was to examine the anti-cancer activity of TA using established human neuroblastoma cell lines. We tested the anti-proliferative effect of TA using SH-SY5Y, CHLA90, LA1 55n, SHEP, Be2c, CMP 13Y, and SMS KCNR cell lines. Cells were treated with TA (0/25/50/100 µM) and cell viability was measured at 24, 48, and 72 h post-treatment. Selected neuroblastoma cell lines were treated with 50 µM TA for 24 and 48 h and tested for cell apoptosis using Annexin-V staining. Caspase activity was measured with caspase 3/7 Glo kit. Cell lysates were prepared and the expression of Sp1, survivin, and c-PARP were evaluated through Western blot analysis. TA significantly inhibited the growth of neuroblastoma cells in a dose/time-dependent manner and significantly decreased Sp1 and survivin expression. Apart from cell cycle (G0/G1) arrest, TA caused significant increase in the apoptotic cell population, caspase 3/7 activity, and c-PARP expression. These results show that TA effectively inhibits neuroblastoma cell growth potentially through suppressing mitosis, Sp1, and survivin expression, and inducing apoptosis. These results show TA as a novel therapeutic agent for neuroblastoma.

  3. Investigating the use of coupling agents to improve the interfacial properties between a resorbable phosphate glass and polylactic acid matrix.

    PubMed

    Hasan, Muhammad Sami; Ahmed, Ifty; Parsons, Andrew J; Rudd, Chris D; Walker, Gavin S; Scotchford, Colin A

    2013-09-01

    Eight different chemicals were investigated as potential candidate coupling agents for phosphate glass fibre reinforced polylactic acid composites. Evidence of reaction of the coupling agents with phosphate glass and their effect on surface wettability and glass degradation were studied along with their principle role of improving the interface between glass reinforcement and polymer matrix. It was found that, with an optimal amount of coupling agent on the surface of the glass/polymer, interfacial shear strength improved by a factor of 5. Evidence of covalent bonding between agent and glass was found for three of the coupling agents investigated, namely: 3-aminopropyltriethoxysilane; etidronic acid and hexamethylene diisocyanate. These three coupling agents also improved the interfacial shear strength and increased the hydrophobicity of the glass surface. It is expected that this would provide an improvement in the macroscopic properties of full-scale composites fabricated from the same materials which may also help to retain these properties for the desired length of time by retarding the breakdown of the fibre/matrix interface within these composites.

  4. Investigating the use of coupling agents to improve the interfacial properties between a resorbable phosphate glass and polylactic acid matrix.

    PubMed

    Hasan, Muhammad Sami; Ahmed, Ifty; Parsons, Andrew J; Rudd, Chris D; Walker, Gavin S; Scotchford, Colin A

    2013-09-01

    Eight different chemicals were investigated as potential candidate coupling agents for phosphate glass fibre reinforced polylactic acid composites. Evidence of reaction of the coupling agents with phosphate glass and their effect on surface wettability and glass degradation were studied along with their principle role of improving the interface between glass reinforcement and polymer matrix. It was found that, with an optimal amount of coupling agent on the surface of the glass/polymer, interfacial shear strength improved by a factor of 5. Evidence of covalent bonding between agent and glass was found for three of the coupling agents investigated, namely: 3-aminopropyltriethoxysilane; etidronic acid and hexamethylene diisocyanate. These three coupling agents also improved the interfacial shear strength and increased the hydrophobicity of the glass surface. It is expected that this would provide an improvement in the macroscopic properties of full-scale composites fabricated from the same materials which may also help to retain these properties for the desired length of time by retarding the breakdown of the fibre/matrix interface within these composites. PMID:22781920

  5. ALPHA SARCIN, A NEW ANTITUMOR AGENT. I. ISOLATION, PURIFICATION, CHEMICAL COMPOSITION, AND THE IDENTITY OF A NEW AMINO ACID.

    PubMed

    OLSON, B H; GOERNER, G L

    1965-05-01

    Isolation and purification procedures are given for the new antitumor agent, alpha sarcin. These procedures include the use of column ion exchange with a carboxylic resin (Amberlite IRC50), dialysis, decolorization with activated charcoal, gradient salt chromatography, salt removal, and drying from the frozen state. The final product has an activity of 800 sarcoma 180 mouse dilution units per mg. The amino acid composition of the purified material is reported. All of the usual amino acids found in proteins were present except methionine. In addition to the usual amino acids, an unknown amino acid was present in the acid hydrolysate. The latter was isolated, and was found to yield phenylalanine and kynurenine. This compound, which has been named "sarcinine," is extremely stable in 6 n hydrochloric acid in the absence of air, and is unstable in alkali. Sarcinine has also been found in two other antitumor peptides produced by aspergilli, and so may relate significantly to the antitumor properties of these peptides.

  6. Increase in complexation ability of humic acids with the addition of ligneous bulking agents during sewage sludge composting.

    PubMed

    Xiong, Xiong; Yan-Xia, Li; Ming, Yang; Feng-Song, Zhang; Wei, Li

    2010-12-01

    Wood sawdust and maize straw were selected to co-compost sewage sludge to investigate the effects of organic bulking agents on the formation and molecular transformation of humic substances. The results showed that composting process increased humic acids (HA) while decreased fulvic acids (FA), and the wood sawdust and maize straw promoted the formation of HA by 25.6% and 16.1%, respectively. Results from fluorescence titration demonstrated that organic bulking agents also increased the binding ability of HA with the heavy metal ions, Cu(II) and Cd(II), but had little influence on that of FA. These findings indicate that organic materials especially wood sawdust may be used as bulking agents to reduce the mobility and bioavailability of toxic metals in solid waste composts.

  7. A combination of omega-3 fatty acids, folic acid and B-group vitamins is superior at lowering homocysteine than omega-3 alone: A meta-analysis.

    PubMed

    Dawson, Samantha Loren; Bowe, Steven John; Crowe, Timothy Charles

    2016-06-01

    The aim of the study was to assess whether omega-3 polyunsaturated fatty acid supplementation alone or in combination with folic acid and B-group vitamins is effective in lowering homocysteine. The Medline Ovid, Embase and Cochrane databases were searched for randomized-controlled trial studies that intervened with omega-3 supplementation (with or without folic acid) and measured changes in homocysteine concentration. Studies were pooled using a random effects model for meta-analysis. Three different models were analyzed: all trials combined, omega-3 polyunsaturated fatty acid trials, and omega-3 polyunsaturated fatty acids with folic acid and B-group vitamin trials. Nineteen studies were included, consisting of 3267 participants completing 21 trials. Studies were heterogeneous; varying by dose, duration and participant health conditions. Across all trials, omega-3 supplementation was effective in lowering homocysteine by an average of 1.18μmol/L (95%CI: (-1.89, -0.48), P=.001). The average homocysteine-lowering effect was greater when omega-3 supplementation was combined with folic acid and B-group vitamins (-1.37μmol/L, 95%CI: (-2.38, -0.36), P<.01) compared to omega-3 supplementation alone (-1.09μmol/L 95%CI: (-2.04, -0.13), P=.03). Omega-3 polyunsaturated fatty acid supplementation was associated with a modest reduction in homocysteine. For the purposes of reducing homocysteine, a combination of omega-3s (0.2-6g/day), folic acid (150 - 2500μg/day) and vitamins B6 and B12 may be more effective than omega-3 supplementation alone.

  8. A combination of omega-3 fatty acids, folic acid and B-group vitamins is superior at lowering homocysteine than omega-3 alone: A meta-analysis.

    PubMed

    Dawson, Samantha Loren; Bowe, Steven John; Crowe, Timothy Charles

    2016-06-01

    The aim of the study was to assess whether omega-3 polyunsaturated fatty acid supplementation alone or in combination with folic acid and B-group vitamins is effective in lowering homocysteine. The Medline Ovid, Embase and Cochrane databases were searched for randomized-controlled trial studies that intervened with omega-3 supplementation (with or without folic acid) and measured changes in homocysteine concentration. Studies were pooled using a random effects model for meta-analysis. Three different models were analyzed: all trials combined, omega-3 polyunsaturated fatty acid trials, and omega-3 polyunsaturated fatty acids with folic acid and B-group vitamin trials. Nineteen studies were included, consisting of 3267 participants completing 21 trials. Studies were heterogeneous; varying by dose, duration and participant health conditions. Across all trials, omega-3 supplementation was effective in lowering homocysteine by an average of 1.18μmol/L (95%CI: (-1.89, -0.48), P=.001). The average homocysteine-lowering effect was greater when omega-3 supplementation was combined with folic acid and B-group vitamins (-1.37μmol/L, 95%CI: (-2.38, -0.36), P<.01) compared to omega-3 supplementation alone (-1.09μmol/L 95%CI: (-2.04, -0.13), P=.03). Omega-3 polyunsaturated fatty acid supplementation was associated with a modest reduction in homocysteine. For the purposes of reducing homocysteine, a combination of omega-3s (0.2-6g/day), folic acid (150 - 2500μg/day) and vitamins B6 and B12 may be more effective than omega-3 supplementation alone. PMID:27188895

  9. Awareness and Use of Folic Acid among Women in the Lower Mississippi Delta

    ERIC Educational Resources Information Center

    Robbins, James M.; Hopkins, Sarah E.; Mosley, Bridget S.; Casey, Patrick H.; Cleves, Mario A.; Hobbs, Charlotte A.

    2006-01-01

    Context: National and state efforts to increase folic acid awareness and use may not be reaching large segments of the population. Purpose: This study examines folic acid awareness and use among women of childbearing age in a representative, economically at-risk rural sample and identifies factors that influence awareness and use. Methods: A…

  10. Process for lowering the dielectric constant of polyimides using diamic acid additives

    NASA Technical Reports Server (NTRS)

    Stoakley, Diane M. (Inventor); St.clair, Anne K. (Inventor)

    1990-01-01

    Linear aromatic polyimides with low dielectric constants are produced by adding a diamic acid additive to the polyamic acid resin formed by the condensation of an aromatic dianhydride with an aromatic diamine. The resulting modified polyimide is a better electrical insulator than state-of-the-art commercially available polyimides.

  11. Development and assessment of an innovative soil-washing process based on the use of cholic acid-derivatives as pollutant-mobilizing agents.

    PubMed

    Berselli, Sara; Benitez, Emilio; Fedi, Stefano; Zannoni, Davide; Medici, Alessandro; Marchetti, Leonardo; Fava, Fabio

    2006-03-01

    Surfactant-aided soil washing is often proposed for the restoration of aged organic pollutant-contaminated soils. As many of commercial surfactants have been found to be toxic and recalcitrant, the opportunity to use in this process cheap, non-toxic, and biodegradable pollutant-mobilizing agents, such as deoxycholic acid (DA), bovine bile (BB), and the residue resulting from DA extraction from BB (BBR), was studied in this work. A soil historically contaminated by chlorinated anilines and benzenes, thiophenes, and several polycyclic aromatic hydrocarbons was suspended at 15% w/v and washed in water or water amended at 1.0% (w/v) with DA, BB, BBR, or Triton X-100 (TX). The resulting effluents were supplemented with nutrients and subjected to aerobic bioremediation. The biogenic agents enhanced the water pollutant elution potential by 230/440%. TX enhanced the same parameter by about 540%; however, it mediated a lower depletion of the initial soil ecotoxicity and a more extensive mobilization of soil constituents with respect to the biogenic agents. Furthermore, TX adversely affected the biotreatability of resulting effluents, by adversely affecting the growth of cultivable bacterial biomass and the structure of eubacterial community of the effluent. On the contrary, the biogenic agents, and in particular DA and BB, enhanced the effluents bioremediation, by sustaining the growth and increasing the complexity of the effluent eubacterial communities. Thus, DA and BB are very promising additives for an effective and environmental friendly soil washing treatment of aged (chloro)organics contaminated soils.

  12. [Extraction of Heavy Metals from Sludge Using Biodegradable Chelating Agent N,N-bis(carboxymethyl) Glutamic Acid Tetrasodium].

    PubMed

    Wu, Qing; Cui, Yan-rui; Tang, Xiao-xiao; Yang, Hui-juan; Sun, Jian-hui

    2015-05-01

    N, N-bis (carboxymethyl) glutamic acid tetrasodium (GLDA), a novel biodegradable and green chelating agent, has excellent metal chelating ability. Batch experiment was conducted to study the extraction process of Cd, Ni, Cu and Zn in industrial sludge using GLDA. The effects of contact time, pH of the system, content of chelating agent were investigated, and the forms of heavy metals in sludge pre- and post-extraction using the modified BCR sequential extraction procedure were studied. The results showed that GLDA was effective for cadmium extraction in sludge. Several heavy metals could be effectively extracted under the condition of pH 4 and molar ratio of chelating agent to total heavy metal 3:1. Residual fraction took the largest fraction in Zn, which caused the low extraction efficiency of this metal. Chelating properties were related not only to contact time, pH, chelating agent's concentration, and stability constant but also to species distribution of metals.

  13. Omega-3 fatty acid is a potential preventive agent for recurrent colon cancer.

    PubMed

    Vasudevan, Anita; Yu, Yingjie; Banerjee, Sanjeev; Woods, James; Farhana, Lulu; Rajendra, Sindhu G; Patel, Aamil; Dyson, Gregory; Levi, Edi; Maddipati, Krishna Rao; Majumdar, Adhip P N; Nangia-Makker, Pratima

    2014-11-01

    Increasing evidence supports the contention that many malignancies, including sporadic colorectal cancer, are driven by the self-renewing, chemotherapy-resistant cancer stem/stem-like cells (CSC/CSLC), underscoring the need for improved preventive and therapeutic strategies targeting CSCs/CSLCs. Omega-3 polyunsaturated fatty acids (ω-3 PUFA), have been reported to inhibit the growth of primary tumors, but their potential as a preventive agent for recurring cancers is unexplored. The primary objectives of this investigation are (i) to examine whether eicosapentaenoic acid (EPA; one of the ω-3 PUFA) synergizes with FuOx (5-FU+Oxaliplatin), the backbone of colon cancer chemotherapy, and (ii) whether EPA by itself or in combination with conventional chemotherapy prevents the recurrence of colon cancer via eliminating/suppressing CSCs/CSLCs. FuOx-resistant (chemoresistant; CR) colon cancer cells, highly enriched in CSCs, were used for this study. Although EPA alone was effective, combination of EPA and FuOx was more potent in (i) inhibiting cell growth, colonosphere formation, and sphere-forming frequency, (ii) increasing sphere disintegration, (iii) suppressing the growth of SCID mice xenografts of CR colon cancer cells, and (iv) decreasing proinflammatory metabolites in mice. In addition, EPA + FuOx caused a reduction in CSC/CSLC population. The growth reduction by this regimen is the result of increased apoptosis as evidenced by PARP cleavage. Furthermore, increased pPTEN, decreased pAkt, normalization of β-catenin expression, localization, and transcriptional activity by EPA suggests a role for the PTEN-Akt axis and Wnt signaling in regulating this process. Our data suggest that EPA by itself or in combination with FuOx could be an effective preventive strategy for recurring colorectal cancer.

  14. Natural selection for 2,4,5-trichlorophenoxyacetic acid mineralizing bacteria in agent orange contaminated soil.

    PubMed

    Rice, J F; Menn, F M; Hay, A G; Sanseverino, J; Sayler, G S

    2005-12-01

    Agent Orange contaminated soils were utilized in direct enrichment culture studies to isolate 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4-dichlorophenoxyacetic acid (2,4-D) mineralizing bacteria. Two bacterial cultures able to grow at the expense of 2,4,5-T and/or 2,4-D were isolated. The 2,4,5-T degrading culture was a mixed culture containing two bacteria, Burkholderia species strain JR7B2 and Burkholderia species strain JR7B3. JR7B3 was able to metabolize 2,4,5-T as the sole source of carbon and energy, and demonstrated the ability to affect metabolism of 2,4-D to a lesser degree. Strain JR7B3 was able to mineralize 2,4,5-T in pure culture and utilized 2,4,5-T in the presence of 0.01% yeast extract. Subsequent characterization of the 2,4-D degrading culture showed that one bacterium, Burkholderia species strain JRB1, was able to utilize 2,4-D as a sole carbon and energy source in pure culture. Polymerase chain reaction (PCR) experiments utilizing known genetic sequences from other 2,4-D and 2,4,5-T degrading bacteria demonstrated that these organisms contain gene sequences similar to tfdA, B, C, E, and R (Strain JRB1) and the tftA, C, and E genes (Strain JR7B3). Expression analysis confirmed that tftA, C, and E and tfdA, B, and C were transcribed during 2,4,5-T and 2,4-D dependent growth, respectively. The results indicate a strong selective pressure for 2,4,5-T utilizing strains under field condition. PMID:15865343

  15. Natural selection for 2,4,5-trichlorophenoxyacetic acid mineralizing bacteria in agent orange contaminated soil.

    PubMed

    Rice, J F; Menn, F M; Hay, A G; Sanseverino, J; Sayler, G S

    2005-12-01

    Agent Orange contaminated soils were utilized in direct enrichment culture studies to isolate 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4-dichlorophenoxyacetic acid (2,4-D) mineralizing bacteria. Two bacterial cultures able to grow at the expense of 2,4,5-T and/or 2,4-D were isolated. The 2,4,5-T degrading culture was a mixed culture containing two bacteria, Burkholderia species strain JR7B2 and Burkholderia species strain JR7B3. JR7B3 was able to metabolize 2,4,5-T as the sole source of carbon and energy, and demonstrated the ability to affect metabolism of 2,4-D to a lesser degree. Strain JR7B3 was able to mineralize 2,4,5-T in pure culture and utilized 2,4,5-T in the presence of 0.01% yeast extract. Subsequent characterization of the 2,4-D degrading culture showed that one bacterium, Burkholderia species strain JRB1, was able to utilize 2,4-D as a sole carbon and energy source in pure culture. Polymerase chain reaction (PCR) experiments utilizing known genetic sequences from other 2,4-D and 2,4,5-T degrading bacteria demonstrated that these organisms contain gene sequences similar to tfdA, B, C, E, and R (Strain JRB1) and the tftA, C, and E genes (Strain JR7B3). Expression analysis confirmed that tftA, C, and E and tfdA, B, and C were transcribed during 2,4,5-T and 2,4-D dependent growth, respectively. The results indicate a strong selective pressure for 2,4,5-T utilizing strains under field condition.

  16. In vitro cytotoxic and genotoxic effects of diphenylarsinic acid, a degradation product of chemical warfare agents.

    PubMed

    Ochi, Takafumi; Suzuki, Toshihide; Isono, Hideo; Kaise, Toshikazu

    2004-10-01

    Diphenylarsinic acid [DPAs(V)], a degradation product of diphenylcyanoarsine or diphenylchloroarsine, both of which were developed as chemical warfare agents, was investigated in terms of its capacity to induce cytotoxic effects, numerical and structural changes of chromosomes, and abnormalities of centrosome integrity and spindle organizations in conjunction with the effects of glutathione (GSH) depletion. DPAs(V) had toxic effects on cultured human hepatocarcinoma HepG2 cells at concentrations more than 0.5 mM. Depletion of GSH reduced the toxic effects of DPAs(V) as well as dimethylarsinic acid [DMAs(V)] toxicity, while toxicity by arsenite [iAs(III)] was enhanced. Exogenously added sulfhydryl (SH) compounds, such as dimercapropropane sulfonate (DMPS), GSH, and dithiothreitol (DTT), enhanced the toxic effects of DPAs(V) while they suppressed iAs(III) toxicity. DPAs(V) caused an increase in the mitotic index, and also structural and numerical changes in chromosomes in V79 Chinese hamster cells. Abnormality of centrosome integrity in mitotic V79 cells and multipolar spindles was also induced by DPAs(V) in a time- and concentration-dependent manner. These results suggested that highly toxic chemicals were generated by the interaction of DPAs(V) with SH compounds. Moreover, enhancements of toxicity by a combination of DPAs(V) and SH compounds suggested a risk in the use of SH compounds as a remedy for intoxication by diphenylarsenic compounds. Investigations on the effects of SH compounds on animals intoxicated with DPAs(V) are warranted.

  17. Cholesterol-lowering effects and mechanisms in view of bile acid pathway of resveratrol and resveratrol-glucuronides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Resveratrol (Res) was previously reported to be capable of lowering plasma TC and LDL-C. The mechanism behind Res is not clearly understood, although it is presumed to have an effect on bile acid metabolism in the liver: a significant way in eliminating cholesterol from the body. As one of the major...

  18. Development and Optimization of a Doxorubicin Loaded Poly Lactic Acid Contrast Agent for Ultrasound Directed Drug Delivery

    PubMed Central

    Eisenbrey, J.R.; Burstein, O. Mualem; Kambhampati, R.; Forsberg, F.; Liu, J-B.; Wheatley, M.A.

    2010-01-01

    An echogenic, intravenous drug delivery platform is proposed in which an encapsulated chemotherapeutic can travel to a desired location and drug delivery can be triggered using external, focused ultrasound at the area of interest. Three methods of loading poly lactic acid (PLA) shelled ultrasound contrast agents (UCA) with doxorubicin are presented. Effects on encapsulation efficiency, in vitro enhancement, stability, particle size, morphology and release during UCA rupture are compared by loading method and drug concentration. An agent containing doxorubicin within the shell was selected as an ideal candidate for future hepatocellular carcinoma studies. The agent achieved a maximal drug load of 6.2 mg Dox/g PLA with an encapsulation efficiency of 20.5%, showed a smooth surface morphology and tight size distribution (poly dispersity index = 0.309) with a peak size of 1865 nm. Acoustically, the agent provided 19 dB of enhancement in vitro at a dosage of 10 µg/ml, with a half life of over 15 mins. In vivo, the agent provided ultrasound enhancement of 13.4 ± 1.6 dB within the ascending aorta of New Zealand rabbits at a dose of 0.15 ml/kg. While the drug-incorporated agent is thought to be well suited for future drug delivery experiments, this study has shown that agent properties can be tailored for specific applications based on choice of drug loading method. PMID:20060024

  19. Drug-drug interactions with sodium-glucose cotransporters type 2 (SGLT2) inhibitors, new oral glucose-lowering agents for the management of type 2 diabetes mellitus.

    PubMed

    Scheen, André J

    2014-04-01

    Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment.

  20. Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting MRI contrast agent

    PubMed Central

    Hou, Lin; Zhang, Huijuan; Wang, Yating; Wang, Lili; Yang, Xiaomin; Zhang, Zhenzhong

    2015-01-01

    A tumor-targeting carrier, hyaluronic acid (HA)-functionalized single-walled carbon nanotubes (SWCNTs), was explored to deliver magnetic resonance imaging (MRI) contrast agents (CAs) targeting to the tumor cells specifically. In this system, HA surface modification for SWCNTs was simply accomplished by amidation process and could make this nanomaterial highly hydrophilic. Cellular uptake was performed to evaluate the intracellular transport capabilities of HA-SWCNTs for tumor cells and the uptake rank was HA-SWCNTs> SWCNTs owing to the presence of HA, which was also evidenced by flow cytometry. The safety evaluation of this MRI CAs was investigated in vitro and in vivo. It revealed that HA-SWCNTs could stand as a biocompatible nanocarrier and gadolinium (Gd)/HA-SWCNTs demonstrated almost no toxicity compared with free GdCl3. Moreover, GdCl3 bearing HA-SWCNTs could significantly increase the circulation time for MRI. Finally, to investigate the MRI contrast enhancing capabilities of Gd/HA-SWCNTs, T1-weighted MR images of tumor-bearing mice were acquired. The results suggested Gd/HA-SWCNTs had the highest tumor-targeting efficiency and T1-relaxivity enhancement, indicating HA-SWCNTs could be developed as a tumor-targeting carrier to deliver the CAs, GdCl3, for the identifiable diagnosis of tumor. PMID:26213465

  1. Potassium fulvate as co-interpenetrating agent during graft polymerization of acrylic acid from cellulose.

    PubMed

    Ghazy, Mohamed B M; El-Hai, Farag Abd; Mohamed, Magdy F; Essawy, Hisham A

    2016-10-01

    Grafting polymerization of acrylic acid onto cellulose in presence of potassium fulvate (KF) as a co-interpenetrating agent results enhanced water sorption compared to materials prepared similarly in its absence. The insertion of potassium fulvate (KF) did not affect the grafting process and is thought to proceed in parallel to the graft polymerization via intensive polycondensation reactions of its function groups (-COOH and OH) with COOH of the monomer and OH groups of cellulose. The combination of graft copolymerization and polycondensation reactions is assumed to produce interpenetrating network structure. Fourier transform infrared (FTIR) confirmed successful incorporation within the network structure which is an evidence for formation of interpenetrating network. The obtained structures showed homogeneous uniform surface as revealed by scanning electron microscopy (SEM). The obtained superabsorbent possessed high water absorbency 422 and 48.8g/g in distilled water and saline (0.9wt.% NaCl solution), respectively, and enhanced water retention even at elevated temperatures as revealed by thermogravimetric analysis (TGA). This could be explained by the high content of hydrophilic groups. The new superabsorbents proved to be efficient devices for controlled release of fertilizers which expands their use in agricultural applications. PMID:27370745

  2. Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting MRI contrast agent.

    PubMed

    Hou, Lin; Zhang, Huijuan; Wang, Yating; Wang, Lili; Yang, Xiaomin; Zhang, Zhenzhong

    2015-01-01

    A tumor-targeting carrier, hyaluronic acid (HA)-functionalized single-walled carbon nanotubes (SWCNTs), was explored to deliver magnetic resonance imaging (MRI) contrast agents (CAs) targeting to the tumor cells specifically. In this system, HA surface modification for SWCNTs was simply accomplished by amidation process and could make this nanomaterial highly hydrophilic. Cellular uptake was performed to evaluate the intracellular transport capabilities of HA-SWCNTs for tumor cells and the uptake rank was HA-SWCNTs> SWCNTs owing to the presence of HA, which was also evidenced by flow cytometry. The safety evaluation of this MRI CAs was investigated in vitro and in vivo. It revealed that HA-SWCNTs could stand as a biocompatible nanocarrier and gadolinium (Gd)/HA-SWCNTs demonstrated almost no toxicity compared with free GdCl3. Moreover, GdCl3 bearing HA-SWCNTs could significantly increase the circulation time for MRI. Finally, to investigate the MRI contrast enhancing capabilities of Gd/HA-SWCNTs, T1-weighted MR images of tumor-bearing mice were acquired. The results suggested Gd/HA-SWCNTs had the highest tumor-targeting efficiency and T1-relaxivity enhancement, indicating HA-SWCNTs could be developed as a tumor-targeting carrier to deliver the CAs, GdCl3, for the identifiable diagnosis of tumor.

  3. Butoxyethoxyacetic acid, a biomarker of exposure to water-based cleaning agents.

    PubMed

    Göen, Thomas; Korinth, Gintautas; Drexler, Hans

    2002-08-01

    The aim of the study was to investigate the suitability of butoxyethoxyacetic acid (BEAA) as a biomarker of exposure to water-based cleaning agents containing diethylene glycol mono butyl ether (DEGBE). The study was performed in two printing plants where water-based products containing 10-15% DEGBE were used for rubber and blanket washes. Thirty nine newspaper pressroom workers (exposed) and 19 employees of newspaper despatch departments (controls) were investigated. By questionnaire, the workers were asked about the use of personal protective measures. BEAA was determined in post-shift urine using GC-MS. The BEAA concentration in the urine of exposed workers ranged up to 75.1 mg/l (median 6.3 mg/l), whereas in urine samples of the controls the BEAA level was below or around the determination limit of 0.5 mg/l. A protective effect on DEGBE uptake was observed with the use of protective gloves. This observation implies that dermal penetration of DEGBE may be important in exposure monitoring. PMID:12191891

  4. Resource recycling through artificial lightweight aggregates from sewage sludge and derived ash using boric acid flux to lower co-melting temperature.

    PubMed

    Hu, Shao-Hua; Hu, Shen-Chih; Fu, Yen-Pei

    2012-02-01

    This study focuses on artificial lightweight aggregates (ALWAs) formed from sewage sludge and ash at lowered co-melting temperatures using boric acid as the fluxing agent. The weight percentages of boric acid in the conditioned mixtures of sludge and ash were 13% and 22%, respectively. The ALWA derived from sewage sludge was synthesized under the following conditions: preheating at 400 degrees C 0.5 hr and a sintering temperature of 850 degrees C 1 hr. The analytical results of water adsorption, bulk density, apparent porosity, and compressive strength were 3.88%, 1.05 g/cm3, 3.93%, and 29.7 MPa, respectively. Scanning electron microscope (SEM) images of the ALWA show that the trends in water adsorption and apparent porosity were opposite to those of bulk density. This was due to the inner pores being sealed off by lower-melting-point material at the aggregates'surface. In the case of ash-derived aggregates, water adsorption, bulk density, apparent porosity, and compressive strength were 0.82%, 0.91 g/cm3, 0.82%, and 28.0 MPa, respectively. Both the sludge- and ash-derived aggregates meet the legal standards for ignition loss and soundness in Taiwan for construction or heat insulation materials.

  5. Activation of Short and Long Chain Fatty Acid Sensing Machinery in the Ileum Lowers Glucose Production in Vivo.

    PubMed

    Zadeh-Tahmasebi, Melika; Duca, Frank A; Rasmussen, Brittany A; Bauer, Paige V; Côté, Clémence D; Filippi, Beatrice M; Lam, Tony K T

    2016-04-15

    Evidence continues to emerge detailing the myriad of ways the gut microbiota influences host energy homeostasis. Among the potential mechanisms, short chain fatty acids (SCFAs), the byproducts of microbial fermentation of dietary fibers, exhibit correlative beneficial metabolic effects in humans and rodents, including improvements in glucose homeostasis. The underlying mechanisms, however, remain elusive. We here report that one of the main bacterially produced SCFAs, propionate, activates ileal mucosal free fatty acid receptor 2 to trigger a negative feedback pathway to lower hepatic glucose production in healthy rats in vivo We further demonstrate that an ileal glucagon-like peptide-1 receptor-dependent neuronal network is necessary for ileal propionate and long chain fatty acid sensing to regulate glucose homeostasis. These findings highlight the potential to manipulate fatty acid sensing machinery in the ileum to regulate glucose homeostasis.

  6. Increase in the ozone decay time in acidic ozone water and its effects on sterilization of biological warfare agents.

    PubMed

    Uhm, Han S; Hong, Yi F; Lee, Han Y; Park, Yun H

    2009-09-15

    The sterilization properties of ozone in acidic water are investigated in this study. Acidification of water increases the ozone decay time by several times compared to the decay time in neutral water, thereby enhancing the sterilization strength of ozone in acidic water. A simple analytical model involving the viable microbial counts after contact with acidic ozone water was derived, and a sterilization experiment was conducted on bacterial cells using the acidic ozone water. The acidic ozone water was found to kill very effectively endospores of Bacillus atrophaeus ATCC 9372, thereby demonstrating the potential for disinfection of a large surface area in a very short time and for reinstating the contaminated environment as free from toxic biological agents.

  7. The fatty acid synthase inhibitor triclosan: repurposing an anti-microbial agent for targeting prostate cancer

    PubMed Central

    Sadowski, Martin C.; Pouwer, Rebecca H.; Gunter, Jennifer H.; Lubik, Amy A.; Quinn, Ronald J.; Nelson, Colleen C.

    2014-01-01

    Inhibition of FASN has emerged as a promising therapeutic target in cancer, and numerous inhibitors have been investigated. However, severe pharmacological limitations have challenged their clinical testing. The synthetic FASN inhibitor triclosan, which was initially developed as a topical antibacterial agent, is merely affected by these pharmacological limitations. Yet, little is known about its mechanism in inhibiting the growth of cancer cells. Here we compared the cellular and molecular effects of triclosan in a panel of eight malignant and non-malignant prostate cell lines to the well-known FASN inhibitors C75 and orlistat, which target different partial catalytic activities of FASN. Triclosan displayed a superior cytotoxic profile with a several-fold lower IC50 than C75 or orlistat. Structure-function analysis revealed that alcohol functionality of the parent phenol is critical for inhibitory action. Rescue experiments confirmed that end product starvation was a major cause of cytotoxicity. Importantly, triclosan, C75 and orlistat induced distinct changes to morphology, cell cycle, lipid content and the expression of key enzymes of lipid metabolism, demonstrating that inhibition of different partial catalytic activities of FASN activates different metabolic pathways. These finding combined with its well-documented pharmacological safety profile make triclosan a promising drug candidate for the treatment of prostate cancer. PMID:25313139

  8. The fatty acid synthase inhibitor triclosan: repurposing an anti-microbial agent for targeting prostate cancer.

    PubMed

    Sadowski, Martin C; Pouwer, Rebecca H; Gunter, Jennifer H; Lubik, Amy A; Quinn, Ronald J; Nelson, Colleen C

    2014-10-15

    Inhibition of FASN has emerged as a promising therapeutic target in cancer, and numerous inhibitors have been investigated. However, severe pharmacological limitations have challenged their clinical testing. The synthetic FASN inhibitor triclosan, which was initially developed as a topical antibacterial agent, is merely affected by these pharmacological limitations. Yet, little is known about its mechanism in inhibiting the growth of cancer cells. Here we compared the cellular and molecular effects of triclosan in a panel of eight malignant and non-malignant prostate cell lines to the well-known FASN inhibitors C75 and orlistat, which target different partial catalytic activities of FASN. Triclosan displayed a superior cytotoxic profile with a several-fold lower IC50 than C75 or orlistat. Structure-function analysis revealed that alcohol functionality of the parent phenol is critical for inhibitory action. Rescue experiments confirmed that end product starvation was a major cause of cytotoxicity. Importantly, triclosan, C75 and orlistat induced distinct changes to morphology, cell cycle, lipid content and the expression of key enzymes of lipid metabolism, demonstrating that inhibition of different partial catalytic activities of FASN activates different metabolic pathways. These finding combined with its well-documented pharmacological safety profile make triclosan a promising drug candidate for the treatment of prostate cancer.

  9. Development of novel radiogallium-labeled bone imaging agents using oligo-aspartic acid peptides as carriers.

    PubMed

    Ogawa, Kazuma; Ishizaki, Atsushi; Takai, Kenichiro; Kitamura, Yoji; Kiwada, Tatsuto; Shiba, Kazuhiro; Odani, Akira

    2013-01-01

    (68)Ga (T 1/2 = 68 min, a generator-produced nuclide) has great potential as a radionuclide for clinical positron emission tomography (PET). Because poly-glutamic and poly-aspartic acids have high affinity for hydroxyapatite, to develop new bone targeting (68)Ga-labeled bone imaging agents for PET, we used 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a chelating site and conjugated aspartic acid peptides of varying lengths. Subsequently, we compared Ga complexes, Ga-DOTA-(Asp)n (n = 2, 5, 8, 11, or 14) with easy-to-handle (67)Ga, with the previously described (67)Ga-DOTA complex conjugated bisphosphonate, (67)Ga-DOTA-Bn-SCN-HBP. After synthesizing DOTA-(Asp)n by a Fmoc-based solid-phase method, complexes were formed with (67)Ga, resulting in (67)Ga-DOTA-(Asp)n with a radiochemical purity of over 95% after HPLC purification. In hydroxyapatite binding assays, the binding rate of (67)Ga-DOTA-(Asp)n increased with the increase in the length of the conjugated aspartate peptide. Moreover, in biodistribution experiments, (67)Ga-DOTA-(Asp)8, (67)Ga-DOTA-(Asp)11, and (67)Ga-DOTA-(Asp)14 showed high accumulation in bone (10.5 ± 1.5, 15.1 ± 2.6, and 12.8 ± 1.7% ID/g, respectively) but were barely observed in other tissues at 60 min after injection. Although bone accumulation of (67)Ga-DOTA-(Asp)n was lower than that of (67)Ga-DOTA-Bn-SCN-HBP, blood clearance of (67)Ga-DOTA-(Asp)n was more rapid. Accordingly, the bone/blood ratios of (67)Ga-DOTA-(Asp)11 and (67)Ga-DOTA-(Asp)14 were comparable with those of (67)Ga-DOTA-Bn-SCN-HBP. In conclusion, these data provide useful insights into the drug design of (68)Ga-PET tracers for the diagnosis of bone disorders, such as bone metastases. PMID:24391942

  10. Detection of lower limb deep venous thrombosis in asymptomatic high risk patients using a new radiolabelled thrombus specific agent

    SciTech Connect

    Butler, S.P.; Rahman, T.; Boyd S.J.

    1995-05-01

    Deep venous thrombosis is a serious consequence of major orthopaedic surgery and non invasive screening with either venous ultrasound or impedance plethysmography is unreliable for detecting or excluding DVT in this group. A new method of thrombus detection has been devised using Tc-99m labelled inhibited recombinant tissue plasminogen activator. The accuracy of scanning with this new radiopharmaceutical in asymptomatic high risk patients was evaluated using venography as the gold standard. 36 consecutive asymptomatic high risk patients (17 total hip, 19 total knee replacements) underwent both a contrast venogram on the operated leg and scintigraphic scan 7 days following operation. Scintigraphic imaging was performed at 4 hours post injection. For the purpose of this analysis, each venogram was divided into a proximal and a distal segment. Venograms were interpreted as being positive, negative or uninterpretable in each segment. Similar analysis of the scintigraphic scans was performed except that all segments were considered to be of diagnostic quality. 57 segments were able to be analysed. Of the 13 thrombosed segments (1 proximal, 12 calf), 12 had positive scans; in the 44 non thrombosed segments, 40 had negative scans. Thus in detecting lower limb thrombosis, scanning had a sensitivity of 92% and a specificity of 91%. Scintigraphic scanning with this new radiopharmaceutical permits accurate detection of thrombus in high risk patients.

  11. High Folic Acid Intake during Pregnancy Lowers Body Weight and Reduces Femoral Area and Strength in Female Rat Offspring

    PubMed Central

    Huot, Pedro S. P.; Dodington, David W.; Mollard, Rebecca C.; Reza-López, Sandra A.; Sánchez-Hernández, Diana; Cho, Clara E.; Kuk, Justin; Ward, Wendy E.; Anderson, G. Harvey

    2013-01-01

    Rats fed gestational diets high in multivitamin or folate produce offspring of altered phenotypes. We hypothesized that female rat offspring born to dams fed a gestational diet high in folic acid (HFol) have compromised bone health and that feeding the offspring the same HFol diet attenuates these effects. Pregnant rats were fed diets with either recommended folic acid (RFol) or 10-fold higher folic acid (HFol) amounts. Female offspring were weaned to either the RFol or HFol diet for 17 weeks. HFol maternal diet resulted in lower offspring body weights (6%, P = 0.03) and, after adjusting for body weight and femoral length, smaller femoral area (2%, P = 0.03), compared to control diet. After adjustments, HFol pup diet resulted in lower mineral content (7%, P = 0.01) and density (4%, P = 0.002) of lumbar vertebra 4 without differences in strength. An interaction between folate content of the dam and pup diets revealed that a mismatch resulted in lower femoral peak load strength (P = 0.01) and stiffness (P = 0.002). However, the match in folate content failed to prevent lower weight gain. In conclusion, HFol diets fed to rat dams and their offspring affect area and strength of femurs and mineral quantity but not strength of lumbar vertebrae in the offspring. PMID:23781391

  12. The botanical molecule p-hydroxycinnamic acid as a new osteogenic agent: insight into the treatment of cancer bone metastases.

    PubMed

    Yamaguchi, Masayoshi

    2016-10-01

    Bone homeostasis is maintained through a balance between osteoblastic bone formation and osteoclastic bone resorption. Bone loss with aging is induced by decreasing in osteoblastic bone formation and increasing in osteoclastic bone resorption, thereby leading to osteoporosis. Osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public heath problem. Pharmacologic and nutritional factors may play a role in the prevention and treatment of bone loss with aging. p-Hydroxycinnamic acid (HCA), which stimulates bone mineralization in mouse bone tissues in vitro, has been found to be present in the leafstalk of wasabi (Wasabi japonica MATSUM) among various food and plants. Other phenolic acids including cinnamic acid, ferulic acid, caffeic acid and 3,4-dimethoxycinnamic acid did not have osteogenic effects. HCA was demonstrated to stimulate osteoblastic bone formation and suppresses osteoclastic bone resorption in vitro by antagonizing activation of the nuclear factor kappa B. Oral administration of HCA was found to exhibit restorative effects on bone loss induced by ovariectomy and diabetic states, supporting a role in the treatment of osteoporosis. Moreover, HCA was demonstrated to prevent the suppressed osteoblastic mineralization and the enhanced osteoclastogenesis in mouse bone marrow cells cocultured with bone metastatic MDA-MB-231 human breast cancer cells in vitro. The botanical molecule HCA, as a new osteogenic agent, is suggested to play a role in the treatment of cancer bone metastases. This review will discuss an advanced recent finding that HCA may be a useful agent to treat bone metabolic disorder. PMID:27573001

  13. Lactic Acid as a New Therapeutic Peeling Agent in the Treatment of Lifa Disease (Frictional Dermal Melanosis)

    PubMed Central

    Sharquie, Khalifa E; Al-Dhalimi, Muhsin A; Noaimi, Adil A; Al-Sultany, Hussein A

    2012-01-01

    Background: Lifa disease (frictional dermal melanosis) is a common dermatological problem. Full strength lactic acid has been proved to be effective and safe peeling agent in the treatment of melasma. Objective: To assess the effectiveness and the safety of lactic acid chemical peeling in the treatment of lifa disease. Materials and Methods: This open label therapeutic trial was conducted in Department of Dermatology in Najaf and Baghdad Teaching Hospitals, from March 2007-October 2008. Full strength lactic acid (92%, pH 3.5) was used as a peeling agent. The treatment sessions were done every 2 weeks until the desired response was achieved (but not more than 6 sessions). The response to therapy was evaluated by objective and subjective methods. All patients were followed monthly for 3 months after the last treatment session. Results: 52 patients with typical clinical features of lifa disease were included. All patients were slim with prominent bones and low body mass index, and gave history of using the lifa (washing agent) during bathing. The number of sessions ranged from 2-6 sessions. The pigmentation was improved in all patients as revealed by objective and subjective methods, and this response was statistically highly significant. No significant side effects were recorded in all treated patients. The improvement has been sustained without any obvious relapse throughout the follow-up period. Conclusion: Lactic acid peel is a new, non-costly mode of therapy in treating dermal melanosis in patients with lifa disease. PMID:23248362

  14. Sulfuric acid as an agent of carbonate weathering constrained by δ13C DIC: Examples from Southwest China

    NASA Astrophysics Data System (ADS)

    Li, Si-Liang; Calmels, Damien; Han, Guilin; Gaillardet, Jérôme; Liu, Cong-Qiang

    2008-06-01

    Rock weathering by carbonic acid is thought to play an important role in the global carbon cycle because it can geologically sequestrate atmospheric CO 2. Current model of carbon cycle evolution usually assumes that carbonic acid is the major weathering agent and that other acids are not important. Here, we use carbon isotopic evidence and water chemistry of springs and rivers from the Beipanjiang River basin (Guizhou Province, Southwest China) to demonstrate that sulfuric acid is also an important agent of rock weathering. The δ13C of dissolved inorganic carbon (DIC) in the water samples ranges from - 13.1‰ to - 2.4‰, and correlates negatively to [HCO 3-]/([Ca 2+] + [Mg 2+]) ratios and positively to [SO 42-]/([Ca 2+] + [Mg 2+]) ratios. These relationships are interpreted as mixing diagrams between two reactions of carbonate weathering, using carbonic acid and sulfuric acid as a proton donor, respectively. Mixing proportions show that around 42% of the divalent cations in the spring water from Guizhou are originated from the interaction between carbonate minerals and sulfuric acid. It is shown that 40% of this sulfuric acid is derived from the atmosphere and has an anthropogenic origin. The remaining 60% are derived from the oxidative weathering of sulfide minerals in sedimentary rocks. Our results show the positive action of sulfuric acid on the chemical weathering of carbonate. Particularly, we show that sulfuric acid generated by coal combustion has increased by almost 20% the weathering rates of carbonate in Southwest China. This is a clear evidence that human activities are changing the weathering rates of rocks and demonstrates a negative feedback on the acidification of the ocean by greenhouse gases. Because of the involvement of sulfuric acid in weathering reactions, 63% of the alkalinity exported by rivers is derived from carbonate, instead of 50% when atmospheric CO 2 is the only acid involved in chemical weathering of carbonate. In the Guizhou

  15. Higher Dietary Acidity is Associated with Lower Bone Mineral Density in Postmenopausal Iranian Women, Independent of Dietary Calcium Intake.

    PubMed

    Shariati-Bafghi, Seyedeh-Elaheh; Nosrat-Mirshekarlou, Elaheh; Karamati, Mohsen; Rashidkhani, Bahram

    2014-01-01

    Findings of studies on the link between dietary acid-base balance and bone mass are relatively mixed. We examined the association between dietary acid-base balance and bone mineral density (BMD) in a sample of Iranian women, hypothesizing that a higher dietary acidity would be inversely associated with BMD, even when dietary calcium intake is adequate. In this cross-sectional study, lumbar spine and femoral neck BMDs of 151 postmenopausal women aged 50-85 years were measured using dual-energy x-ray absorptiometry. Dietary intakes were assessed using a validated food frequency questionnaire. Renal net acid excretion (RNAE), an estimate of acid-base balance, was then calculated indirectly from the diet using the formulae of Remer (based on dietary intakes of protein, phosphorus, potassium, and magnesium; RNAERemer) and Frassetto (based on dietary intakes of protein and potassium; RNAEFrassetto), and was energy adjusted by the residual method. After adjusting for potential confounders, multivariable adjusted means of the lumbar spine BMD of women in the highest tertiles of RNAERemer and RNAEFrassetto were significantly lower than those in the lowest tertiles (for RNAERemer: mean difference -0.084 g/cm2; P=0.007 and for RNAEFrassetto: mean difference -0.088 g/cm2; P=0.004). Similar results were observed in a subgroup analysis of subjects with dietary calcium intake of >800 mg/day. In conclusion, a higher RNAE (i. e. more dietary acidity), which is associated with greater intake of acid-generating foods and lower intake of alkali-generating foods, may be involved in deteriorating the bone health of postmenopausal Iranian women, even in the context of adequate dietary calcium intake.

  16. Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure.

    PubMed

    de Bortoli, N; Martinucci, I; Savarino, E; Franchi, R; Bertani, L; Russo, S; Ceccarelli, L; Costa, F; Bellini, M; Blandizzi, C; Savarino, V; Marchi, S

    2016-01-01

    Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty-five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity.

  17. Bonding of a cobalt-chromium alloy with acidic primers and tri-n-butylborane-initiated luting agents.

    PubMed

    Matsumura, H; Tanaka, T; Taira, Y; Atsuta, M

    1996-08-01

    Limited information is available about chemical bonding of cobalt-chromium alloys for resin-retained fixed partial dentures. This study evaluated the effect of acidic primers on the bonding of luting agents joined to a cobalt-chromium alloy. Disk alloy specimens were bonded with eight combinations of five primers and two luting agents. Shear bond strengths were determined before and after thermocycling. The effect of priming on bond strength varied among the combinations of primer and luting agent. In particular, after thermocycling three groups demonstrated greater bond strengths than the other groups did. These were (1) specimens treated with a phosphate-methacrylate primer (Cesead Opaque Primer), (2) specimens bonded with an adhesive resin (Super-Bond Opaque), or (3) a combination of both.

  18. Gallic Acid as a Complexing Agent for Copper Chemical Mechanical Polishing Slurries at Neutral pH

    NASA Astrophysics Data System (ADS)

    Kim, Yung Jun; Kang, Min Cheol; Kwon, Oh Joong; Kim, Jae Jeong

    2011-05-01

    Gallic acid was investigated as a new complexing agent for copper (Cu) chemical mechanical polishing slurries at neutral pH. Addition of 0.03 M gallic acid and 1.12 M H2O2 at pH 7 resulted in a Cu removal rate of 560.73±17.49 nm/min, and the ratio of the Cu removal rate to the Cu dissolution rate was 14.8. Addition of gallic acid improved the slurry performance compared to glycine addition. X-ray photoelectron spectroscopy analysis and contact angle measurements showed that addition of gallic acid enhanced the Cu polishing behavior by suppressing the formation of surface Cu oxide.

  19. An in vitro comparison of acid etched vs. nonacid etched dentin bonding agents/composite interfaces over primary dentin.

    PubMed

    Donly, K J; Keprta, M; Stratmann, R G

    1991-01-01

    The purpose of this study was to evaluate acid etchant penetration on dentin bonding agents and its effect on the composite resin bond strength. Forty primary molars were mounted, then the buccal and lingual surfaces were prepared into dentin. The teeth were divided into four groups of 10, and four dentin bonding agents were placed on the buccal and lingual surfaces of exposed dentin, as recommended by the manufacturers. One surface of each tooth was etched randomly for 60 sec with 35% phosphoric acid. A standardized tube of composite resin was placed on each dentin surface and polymerized for 60 sec. The tubes were sheared off with an Instron Testing Machine. The specimens then were sectioned to be examined by a scanning electron microscope (SEM). Results demonstrated shear strengths (kg/cm2) of etched (e) and unetched (u) bonding agents to be: Scotchbond (3M Dental Products, St. Paul, MN) (e) 116.7 +/- 37.7, (u) 116.7 +/- 63.0; Scotchbond 2 (3M Dental Products, St. Paul, MN) (e) 112.0 +/- 40.6, (u) 127.0 +/- 38.7; Gluma (Bayer Dental, Leverkusen, Federal Republic of Germany) (e) 80.1 +/- 21.7, (u) 107.0 +/- 16.6; Bondlite (Kerr Manufacturing Co., Romulus, MI) (e) 53.4 +/- 34.7, (u) 79.1 +/- 26.3. The analysis of variance (ANOVA) demonstrated a statistical significance in variance at the P less than 0.001 level. Scheffe's Test indicated no statistically significant differences between the bond strengths of etched vs. nonetched dentin bonding agents and composite resin. SEM evaluation indicated that the acid etchant penetrated none of the dentin bonding agents. PMID:1886824

  20. Data of thermal degradation and dynamic mechanical properties of starch-glycerol based films with citric acid as crosslinking agent.

    PubMed

    González Seligra, Paula; Medina Jaramillo, Carolina; Famá, Lucía; Goyanes, Silvia

    2016-06-01

    Interest in biodegradable edible films as packaging or coating has increased because their beneficial effects on foods. In particular, food products are highly dependents on thermal stability, integrity and transition process temperatures of the packaging. The present work describes a complete data of the thermal degradation and dynamic mechanical properties of starch-glycerol based films with citric acid (CA) as crosslinking agent described in the article titled: "Biodegradable and non-retrogradable eco-films based on starch-glycerol with citric acid as crosslinking agent" González Seligra et al. (2016) [1]. Data describes thermogravimetric and dynamical mechanical experiences and provides the figures of weight loss and loss tangent of the films as a function of the temperature.

  1. Data of thermal degradation and dynamic mechanical properties of starch-glycerol based films with citric acid as crosslinking agent.

    PubMed

    González Seligra, Paula; Medina Jaramillo, Carolina; Famá, Lucía; Goyanes, Silvia

    2016-06-01

    Interest in biodegradable edible films as packaging or coating has increased because their beneficial effects on foods. In particular, food products are highly dependents on thermal stability, integrity and transition process temperatures of the packaging. The present work describes a complete data of the thermal degradation and dynamic mechanical properties of starch-glycerol based films with citric acid (CA) as crosslinking agent described in the article titled: "Biodegradable and non-retrogradable eco-films based on starch-glycerol with citric acid as crosslinking agent" González Seligra et al. (2016) [1]. Data describes thermogravimetric and dynamical mechanical experiences and provides the figures of weight loss and loss tangent of the films as a function of the temperature. PMID:27158645

  2. In vitro activities of enoxacin, ticarcillin plus clavulanic acid, aztreonam, piperacillin, and imipenem and comparison with commonly used antimicrobial agents.

    PubMed Central

    Henry, D; Skidmore, A G; Ngui-Yen, J; Smith, A; Smith, J A

    1985-01-01

    A total of 745 gram-negative and 313 gram-positive clinical isolates were tested against enoxacin, ticarcillin plus clavulanic acid, aztreonam, imipenem, and piperacillin and compared with commonly used antimicrobial agents. Ticarcillin plus clavulanic acid, imipenem, and piperacillin were active against Pseudomonas aeruginosa and Acinetobacter spp. and most Pseudomonas spp. Aztreonam was active against members of the family Enterobacteriaceae but was less effective against the nonfermenters. Enoxacin was active against the Enterobacteriaceae, P. aeruginosa, the staphylococci, and most Acinetobacter spp. but was less active against Pseudomonas spp. and streptococci. Imipenem was very active against all gram-positive and -negative organisms tested except for Pseudomonas maltophilia. PMID:3869433

  3. Zwitterion/Brønsted Acid Mixtures Showing Controlled Lower Critical Solution Temperature-Type Phase Changes with Water.

    PubMed

    Mieno, Yuki; Kohno, Yuki; Saita, Shohei; Ohno, Hiroyuki

    2016-08-22

    A new ammonium-type zwitterion (ZI), N,N-dihexyl-N-monopentyl-3-sulfonyl-1-propaneammonium (N665 C3S) with adequate hydrophobicity showed reversible and highly temperature-sensitive lower critical solution temperature (LCST)-type phase transitions after being mixed with pure water. Generally for such compounds, those with longer alkyl chains were immiscible with water and those with shorter chains were miscible with water, regardless of temperature. A slightly more hydrophobic ZI than N665 C3S showed LCST-type phase behavior with water when it was mixed with equimolar amounts of a Brønsted acid such as trifluoromethanesulfonic acid (HTfO). The phase-transition temperature of the ZI/Brønsted acid mixed aqueous solution was controllable by water content. PMID:27310140

  4. Omega-3 PUFAs Lower the Propensity for Arachidonic Acid Cascade Overreactions.

    PubMed

    Lands, Bill

    2015-01-01

    A productive view of the benefits from omega-3 (n-3) nutrients is that the dietary essential omega-6 (n-6) linoleic acid has a very narrow therapeutic window which is widened by n-3 nutrients. The benefit from moderate physiological actions of the arachidonic acid cascade can easily shift to harm from excessive pathophysiological actions. Recognizing the factors that predispose the cascade to an unwanted overactivity gives a rational approach for arranging beneficial interactions between the n-3 and n-6 essential nutrients that are initial components of the cascade. Much detailed evidence for harmful cascade actions was collected by pharmaceutical companies as they developed drugs to decrease those actions. A remaining challenge is to understand the factors that predispose the cascade toward unwanted outcomes and create the need for therapeutic interventions. Such understanding involves recognizing the similar dynamics for dietary n-3 and n-6 nutrients in forming the immediate precursors of the cascade plus the more vigorous actions of the n-6 precursor, arachidonic acid, in forming potent mediators that amplify unwanted cascade outcomes. Tools have been developed to aid deliberate day-to-day quantitative management of the propensity for cascade overactivity in ways that can decrease the need for drug treatments.

  5. Omega-3 PUFAs Lower the Propensity for Arachidonic Acid Cascade Overreactions

    PubMed Central

    Lands, Bill

    2015-01-01

    A productive view of the benefits from omega-3 (n-3) nutrients is that the dietary essential omega-6 (n-6) linoleic acid has a very narrow therapeutic window which is widened by n-3 nutrients. The benefit from moderate physiological actions of the arachidonic acid cascade can easily shift to harm from excessive pathophysiological actions. Recognizing the factors that predispose the cascade to an unwanted overactivity gives a rational approach for arranging beneficial interactions between the n-3 and n-6 essential nutrients that are initial components of the cascade. Much detailed evidence for harmful cascade actions was collected by pharmaceutical companies as they developed drugs to decrease those actions. A remaining challenge is to understand the factors that predispose the cascade toward unwanted outcomes and create the need for therapeutic interventions. Such understanding involves recognizing the similar dynamics for dietary n-3 and n-6 nutrients in forming the immediate precursors of the cascade plus the more vigorous actions of the n-6 precursor, arachidonic acid, in forming potent mediators that amplify unwanted cascade outcomes. Tools have been developed to aid deliberate day-to-day quantitative management of the propensity for cascade overactivity in ways that can decrease the need for drug treatments. PMID:26301244

  6. Synthesis and Evaluation of Novel Triterpene Analogues of Ursolic Acid as Potential Antidiabetic Agent.

    PubMed

    Wu, Panpan; Zheng, Jie; Huang, Tianming; Li, Dianmeng; Hu, Qingqing; Cheng, Anming; Jiang, Zhengyun; Jiao, Luoying; Zhao, Suqing; Zhang, Kun

    2015-01-01

    Ursolic acid (UA) is a naturally bioactive compound that possesses potential anti-diabetic activity. The relatively safe and effective molecule intrigued us to further explore and to improve its anti-diabetic activity. In the present study, a series of novel UA analogues was synthesized and their structures were characterized. Their bioactivities against the α-glucosidase from baker's yeast were determined in vitro. The results suggested that most of the analogues exhibited significant inhibitory activity, especially analogues 8b and 9b with the IC50 values of 1.27 ± 0.27 μM (8b) and 1.28 ± 0.27 μM (9b), which were lower than the other analogues and the positive control. The molecular docking and 2D-QSAR studies were carried out to prove that the C-3 hydroxyl could interact with the hydrophobic region of the active pocket and form hydrogen bonds to increase the binding affinity of ligand and the homology modelling protein. Thus, these results will be helpful for understanding the relationship between binding mode and bioactivity and for designing better inhibitors from UA analogues. PMID:26406581

  7. Synthesis and Evaluation of Novel Triterpene Analogues of Ursolic Acid as Potential Antidiabetic Agent

    PubMed Central

    Wu, Panpan; Zheng, Jie; Huang, Tianming; Li, Dianmeng; Hu, Qingqing; Cheng, Anming; Jiang, Zhengyun; Jiao, Luoying; Zhao, Suqing; Zhang, Kun

    2015-01-01

    Ursolic acid (UA) is a naturally bioactive compound that possesses potential anti-diabetic activity. The relatively safe and effective molecule intrigued us to further explore and to improve its anti-diabetic activity. In the present study, a series of novel UA analogues was synthesized and their structures were characterized. Their bioactivities against the α-glucosidase from baker's yeast were determined in vitro. The results suggested that most of the analogues exhibited significant inhibitory activity, especially analogues 8b and 9b with the IC50 values of 1.27 ± 0.27 μM (8b) and 1.28 ± 0.27 μM (9b), which were lower than the other analogues and the positive control. The molecular docking and 2D-QSAR studies were carried out to prove that the C-3 hydroxyl could interact with the hydrophobic region of the active pocket and form hydrogen bonds to increase the binding affinity of ligand and the homology modelling protein. Thus, these results will be helpful for understanding the relationship between binding mode and bioactivity and for designing better inhibitors from UA analogues. PMID:26406581

  8. New formulation of chemical peeling agent: 30% salicylic acid in polyethylene glycol. Absorption and distribution of 14C-salicylic acid in polyethylene glycol applied topically to skin of hairless mice.

    PubMed

    Ueda, Setsuko; Mitsugi, Koichi; Ichige, Kazumi; Yoshida, Kenji; Sakuma, Tomoko; Ninomiya, Shin-ichi; Sudou, Tetsuji

    2002-04-01

    Salicylic acid is used in chemical peeling procedures. However, they have caused many side effects, even salicylism. To achieve a salicylic acid peeling that would be safer for topical use, we recently developed a new formulation consisting of 30% salicylic acid in polyethylene glycol (PEG) vehicle. In an extension of our previous research, we studied the absorption of 30% salicylic acid labeled with 14C in PEG vehicle applied topically to the intact and damaged skin of male hairless mice. An ointment containing 3 mg salicylic acid in 10 mg vehicle was applied to both groups. In animals with intact skin, 1 h after application the plasma concentration of radioactivity was 1665.1 ng eq/ml, significantly lower than the 21437.6 ng eq/ml observed in mice with damaged skin. Microautoradiograms of intact skin showed that the level of radioactivity in the cornified cell layer was similar at 6 h after application. However, in damaged skin, the overall level of radioactivity showed a decrease by 3 h after application. In the carcasses remaining after the treated intact and damaged skin had been removed, 0.09 and 11.38% of the applied radioactivity remained, respectively. These findings confirm that 30% salicylic acid in PEG vehicle is little absorbed through the intact skin of hairless mice, and suggest that salicylism related to absorption through the skin of quantities of topically applied salicylic acid is not likely to occur in humans with intact skin during chemical peeling with this preparation. This new preparation of 30% salicylic acid in PEG vehicle is believed to be safe for application as a chemical peeling agent.

  9. Phosphate Stability in Diagenetic Fluids Constrains the Acidic Alteration Model for Lower Mt. Sharp Sedimentary Rocks in Gale Crater, Mars

    NASA Technical Reports Server (NTRS)

    Berger, J. A.; Schmidt, M. E.; Izawa, M. R. M.; Gellert, R.; Ming, D. W.; Rampe, E. B.; VanBommel, S. J.; McAdam, A. C.

    2016-01-01

    The Mars rover Curiosity has encountered silica-enriched bedrock (as strata and as veins and associated halos of alteration) in the largely basaltic Murray Fm. of Mt. Sharp in Gale Crater. Alpha Particle X-ray Spectrometer (APXS) investigations of the Murray Fm. revealed decreasing Mg, Ca, Mn, Fe, and Al, and higher S, as silica increased (Fig. 1). A positive correlation between SiO2 and TiO2 (up to 74.4 and 1.7 wt %, respectively) suggests that these two insoluble elements were retained while acidic fluids leached more soluble elements. Other evidence also supports a silica-retaining, acidic alteration model for the Murray Fm., including low trace element abundances consistent with leaching, and the presence of opaline silica and jarosite determined by CheMin. Phosphate stability is a key component of this model because PO4 3- is typically soluble in acidic water and is likely a mobile ion in diagenetic fluids (pH less than 5). However, the Murray rocks are not leached of P; they have variable P2O5 (Fig. 1) ranging from average Mars (0.9 wt%) up to the highest values in Gale Crater (2.5 wt%). Here we evaluate APXS measurements of Murray Fm. bedrock and veins with respect to phosphate stability in acidic fluids as a test of the acidic alteration model for the Lower Mt. Sharp rocks.

  10. Amino acid sequences of lower vertebrate parvalbumins and their evolution: parvalbumins of boa, turtle, and salamander.

    PubMed

    Maeda, N; Zhu, D X; Fitch, W M

    1984-11-01

    One major parvalbumin each was isolated from the skeletal muscle of two reptiles, a boa snake, Boa constrictor, and a map turtle, Graptemys geographica, while two parvalbumins were isolated from an amphibian, the salamander Amphiuma means. The amino acid sequences of all four parvalbumins were determined from the sequences of their tryptic peptides, which were ordered partially by homology to other parvalbumins. Phylogenetic study of these and 16 other parvalbumin sequences revealed that the turtle parvalbumin belongs to beta lineage, while the salamander sequences belong, one each, to the alpha and beta lineages defined by Goodman and Pechère (1977). Boa parvalbumin, however, while belonging to the beta lineage, clusters within the fish in all reasonably parsimonious trees. The most parsimonious trees show many parallel or back mutations in the evolution of many parvalbumin residues, although the residues responsible for Ca2+ binding are very well conserved. These most parsimonious trees show an actinopterygian rather than a crossoptyrigian origin of the tetrapods in both the alpha and beta groups. One of two electric eel parvalbumins is evolving more than 10 times faster than its paralogous partner, suggesting it may be on its way to becoming a pseudogene. It is concluded that varying rates of amino acid replacement, much homoplasy, considerable gene duplication, plus complicated lineages make the set of parvalbumin sequences unsuitable for systematic study of the origin of the tetrapods and other higher-taxa divergence, although it may be suitable within a genus or family.

  11. Impact of Glucose-Lowering Agents on the Risk of Cancer in Type 2 Diabetic Patients. The Barcelona Case-Control Study

    PubMed Central

    Simó, Rafael; Plana-Ripoll, Oleguer; Puente, Diana; Morros, Rosa; Mundet, Xavier; Vilca, Luz M.; Hernández, Cristina; Fuentes, Inmaculada; Procupet, Adriana; Tabernero, Josep M.; Violán, Concepción

    2013-01-01

    Background The aim of the present study is to evaluate the impact of glucose-lowering agents in the risk of cancer in a large type 2 diabetic population. Methods A nested case-control study was conducted within a defined cohort (275,164 type 2 diabetic patients attending 16 Primary Health Care Centers of Barcelona). Cases (n = 1,040) comprised those subjects with any cancer diagnosed between 2008 and 2010, registered at the Cancer Registry of Hospital Vall d'Hebron (Barcelona). Three control subjects for each case (n = 3,120) were matched by age, sex, diabetes duration, and geographical area. The treatments analyzed (within 3 years prior to cancer diagnosis) were: insulin glargine, insulin detemir, human insulin, fast-acting insulin and analogues, metformin, sulfonylureas, repaglinide, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and alpha glucosidase inhibitors. Conditional logistic regressions were used to calculate the risk of cancer associated with the use of each drug adjusted by age, BMI, dose and duration of treatment, alcohol use, smoking habit, and diabetes duration. Results No differences were observed between case and control subjects for the proportion, dose or duration of exposure to each treatment. None of the types of insulin and oral agents analyzed showed a significant increase in the risk of cancer. Moreover, no cancer risk was observed when glargine was used alone or in combination with metformin. Conclusions Our results suggest that diabetes treatment does not influence the risk of cancer associated with type 2 diabetes. Therefore, an eventual increase of cancer should not be a reason for biasing the selection of any glucose-lowering treatment in type 2 diabetic population. PMID:24278227

  12. Natural flavonoids as antidiabetic agents. The binding of gallic and ellagic acids to glycogen phosphorylase b.

    PubMed

    Kyriakis, Efthimios; Stravodimos, George A; Kantsadi, Anastassia L; Chatzileontiadou, Demetra S M; Skamnaki, Vassiliki T; Leonidas, Demetres D

    2015-07-01

    We present a study on the binding of gallic acid and its dimer ellagic acid to glycogen phosphorylase (GP). Ellagic acid is a potent inhibitor with Kis of 13.4 and 7.5 μM, in contrast to gallic acid which displays Kis of 1.7 and 3.9 mM for GPb and GPa, respectively. Both compounds are competitive inhibitors with respect to the substrate, glucose-1-phoshate, and non-competitive to the allosteric activator, AMP. However, only ellagic acid functions with glucose in a strongly synergistic mode. The crystal structures of the GPb-gallic acid and GPb-ellagic acid complexes were determined at high resolution, revealing that both ligands bind to the inhibitor binding site of the enzyme and highlight the structural basis for the significant difference in their inhibitory potency.

  13. "Click" Chemistry-Tethered Hyaluronic Acid-Based Contact Lens Coatings Improve Lens Wettability and Lower Protein Adsorption.

    PubMed

    Deng, Xudong; Korogiannaki, Myrto; Rastegari, Banafsheh; Zhang, Jianfeng; Chen, Mengsu; Fu, Qiang; Sheardown, Heather; Filipe, Carlos D M; Hoare, Todd

    2016-08-31

    Improving the wettability of and reducing the protein adsorption to contact lenses may be beneficial for improving wearer comfort. Herein, we describe a simple "click" chemistry approach to surface functionalize poly(2-hydroxyethyl methacrylate) (pHEMA)-based contact lenses with hyaluronic acid (HA), a carbohydrate naturally contributing to the wettability of the native tear film. A two-step preparation technique consisting of laccase/TEMPO-mediated oxidation followed by covalent grafting of hydrazide-functionalized HA via simple immersion resulted in a model lens surface that is significantly more wettable, more water retentive, and less protein binding than unmodified pHEMA while maintaining the favorable transparency, refractive, and mechanical properties of a native lens. The dipping/coating method we developed to covalently tether the HA wetting agent is simple, readily scalable, and a highly efficient route for contact lens modification. PMID:27509015

  14. Mechanisms of cholesterol and saturated fatty acid lowering by Quillaja saponaria extract, studied by in vitro digestion model.

    PubMed

    Vinarova, Liliya; Vinarov, Zahari; Damyanova, Borislava; Tcholakova, Slavka; Denkov, Nikolai; Stoyanov, Simeon

    2015-04-01

    Quillaja saponin extracts are known to reduce plasma cholesterol levels in humans. Here we study the mechanism of this effect with Quillaja Dry saponin extract (QD). In vitro model of triglyceride lipolysis is used to quantify the effect of QD on the solubilization of cholesterol and of the lipolysis products (fatty acids and monoglycerides) in the dietary mixed micelles (DMM). We found that QD extract decreases significantly both the cholesterol (from 80% to 20%) and saturated fatty acids (SFA, from 70% to 10%) solubilised in DMM. Series of dedicated experiments prove that QD may act by two mechanisms: (1) direct precipitation of cholesterol and (2) displacement of cholesterol from the DMM. Both mechanisms lead to increased cholesterol precipitation and, thus, render cholesterol bio-inaccessible. We prove also that the saponin molecules are not the active component of QD, because highly purified Quillaja extract with very similar saponin composition does not exhibit cholesterol-lowering or SFA-lowering effect. The effect of QD extract on cholesterol solubilisation is most probably caused by the high-molecular weight polyphenol molecules, present in this extract. The reduced SFA solubilisation is caused by Ca(2+) ions of relatively high concentration (1.25 wt%), also present in QD extract, which precipitate the fatty acids into calcium soaps. PMID:25773645

  15. Using high dose omega-3 fatty acid supplements to lower triglyceride levels in 10–19 year-olds

    PubMed Central

    de Ferranti, Sarah D.; Milliren, Carly E.; Denhoff, Erica R.; Steltz, Sarah K.; Selamet Tierney, Elif Seda; Feldman, Henry A.; Osganian, Stavroula K.

    2015-01-01

    Background Omega-3 fatty acids (FA) supplements lower triglyceride (TG) levels in adults; little pediatric information is available. We evaluated their effect in hypertriglyceridemic adolescents. Methods 25 patients ages 10–19 years with TG levels 150–1000 mg/dL were randomized to 6 months double-blind trial of Lovaza [∼3360 mg docosahexaenoic acid + eicosapentaenoic acid/day] vs. Placebo. Results Baseline mean TG levels were 227 mg/dl (SD 49). TG levels declined at 3 months in the Lovaza group by 54 ± 27 mg/dL [mean ± standard error (SE)] (p=0.02) and by 34 ± 26 mg/dL (p=0.16) in the Placebo group. The difference in TG lowering between groups was not significant (p=0.52). There were no between-group differences in endothelial function, blood pressure, body mass index, C-reactive protein or side effects. Conclusions High dose omega-3 FA supplements are well tolerated in adolescents. However, declines in TG levels did not differ significantly from Placebo in this small study. PMID:24707021

  16. ALPHA SARCIN, A NEW ANTITUMOR AGENT. I. ISOLATION, PURIFICATION, CHEMICAL COMPOSITION, AND THE IDENTITY OF A NEW AMINO ACID.

    PubMed

    OLSON, B H; GOERNER, G L

    1965-05-01

    Isolation and purification procedures are given for the new antitumor agent, alpha sarcin. These procedures include the use of column ion exchange with a carboxylic resin (Amberlite IRC50), dialysis, decolorization with activated charcoal, gradient salt chromatography, salt removal, and drying from the frozen state. The final product has an activity of 800 sarcoma 180 mouse dilution units per mg. The amino acid composition of the purified material is reported. All of the usual amino acids found in proteins were present except methionine. In addition to the usual amino acids, an unknown amino acid was present in the acid hydrolysate. The latter was isolated, and was found to yield phenylalanine and kynurenine. This compound, which has been named "sarcinine," is extremely stable in 6 n hydrochloric acid in the absence of air, and is unstable in alkali. Sarcinine has also been found in two other antitumor peptides produced by aspergilli, and so may relate significantly to the antitumor properties of these peptides. PMID:14325268

  17. Folic acid supplementation at lower doses increases oxidative stress resistance and longevity in Caenorhabditis elegans.

    PubMed

    Rathor, Laxmi; Akhoon, Bashir Akhlaq; Pandey, Swapnil; Srivastava, Swati; Pandey, Rakesh

    2015-12-01

    Folic acid (FA) is an essential nutrient that the human body needs but cannot be synthesized on its own. Fortified foods and plant food sources such as green leafy vegetables, beans, fruits, and juices are good sources of FA to meet the daily requirements of the body. The aim was to evaluate the effect of dietary FA levels on the longevity of well-known experimental aging model Caenorhabditis elegans. Here, we show for first time that FA extends organism life span and causes a delay in aging. We observed that FA inhibits mechanistic target of rapamycin (mTOR) and insulin/insulin growth factor 1 (IGF-1) signaling pathways to control both oxidative stress levels and life span. The expression levels of stress- and life span-relevant gerontogenes, viz. daf-16, skn-1, and sir. 2.1, and oxidative enzymes, such as glutathione S-transferase 4 (GST-4) and superoxide dismutase 3 (SOD-3), were also found to be highly enhanced to attenuate the intracellular reactive oxygen species (ROS) damage and to delay the aging process. Our study promotes the use of FA to mitigate abiotic stresses and other aging-related ailments. PMID:26546011

  18. Folic acid supplementation at lower doses increases oxidative stress resistance and longevity in Caenorhabditis elegans.

    PubMed

    Rathor, Laxmi; Akhoon, Bashir Akhlaq; Pandey, Swapnil; Srivastava, Swati; Pandey, Rakesh

    2015-12-01

    Folic acid (FA) is an essential nutrient that the human body needs but cannot be synthesized on its own. Fortified foods and plant food sources such as green leafy vegetables, beans, fruits, and juices are good sources of FA to meet the daily requirements of the body. The aim was to evaluate the effect of dietary FA levels on the longevity of well-known experimental aging model Caenorhabditis elegans. Here, we show for first time that FA extends organism life span and causes a delay in aging. We observed that FA inhibits mechanistic target of rapamycin (mTOR) and insulin/insulin growth factor 1 (IGF-1) signaling pathways to control both oxidative stress levels and life span. The expression levels of stress- and life span-relevant gerontogenes, viz. daf-16, skn-1, and sir. 2.1, and oxidative enzymes, such as glutathione S-transferase 4 (GST-4) and superoxide dismutase 3 (SOD-3), were also found to be highly enhanced to attenuate the intracellular reactive oxygen species (ROS) damage and to delay the aging process. Our study promotes the use of FA to mitigate abiotic stresses and other aging-related ailments.

  19. Development and in-vitro characterization of fish oil oleogels containing benzoyl peroxide and salicylic acid as keratolytic agents.

    PubMed

    Rehman, K; Tan, C M; Zulfakar, M H

    2014-03-01

    Topical keratolytic agents such as benzoyl peroxide (BP) and salicylic acid (SA) are one of the common treatments for inflammatory skin diseases. However, the amount of drug delivery through the skin is limited due to the stratum corneum. The purposes of this study were to investigate the ability of fish oil to act as penetration enhancer for topical keratolytic agents and to determine the suitable gelator for formulating stable fish oil oleogels. 2 types of gelling agents, beeswax and sorbitan monostearate (Span 60), were used to formulate oleogels. To investigate the efficacy of fish oil oleogel permeation, commercial hydrogels of benzoyl peroxide (BP) and salicylic acid (SA) were used as control, and comparative analysis was performed using Franz diffusion cell. Stability of oleogels was determined by physical assessments at 20°C and 40°C storage. Benzoyl peroxide (BP) fish oil oleogels containing beeswax were considered as better formulations in terms of drug permeation and cumulative drug release. All the results were found to be statistically significant (p<0.05, ANOVA) and it was concluded that the beeswax-fish oil combination in oleogel can prove to be beneficial in terms of permeation across the skin and stability.

  20. Cytocompatibility and Mechanical Properties of Short Phosphate Glass Fibre Reinforced Polylactic Acid (PLA) Composites: Effect of Coupling Agent Mediated Interface

    PubMed Central

    Hasan, Muhammad Sami; Ahmed, Ifty; Parsons, Andrew; Walker, Gavin; Scotchford, Colin

    2012-01-01

    In this study three chemical agents Amino-propyl-triethoxy-silane (APS), sorbitol ended PLA oligomer (SPLA) and Hexamethylene diisocyanate (HDI) were identified to be used as coupling agents to react with the phosphate glass fibre (PGF) reinforcement and the polylactic acid (PLA) polymer matrix of the composite. Composites were prepared with short chopped strand fibres (l = 20 mm, ϕ = 20 µm) in a random arrangement within PLA matrix. Improved, initial composite flexural strength (~20 MPa) was observed for APS treated fibres, which was suggested to be due to enhanced bonding between the fibres and polymer matrix. Both APS and HDI treated fibres were suggested to be covalently linked with the PLA matrix. The hydrophobicity induced by these coupling agents (HDI, APS) helped to resist hydrolysis of the interface and thus retained their mechanical properties for an extended period of time as compared to non-treated control. Approximately 70% of initial strength and 65% of initial modulus was retained by HDI treated fibre composites in contrast to the control, where only ~50% of strength and modulus was retained after 28 days of immersion in PBS at 37 °C. All coupling agent treated and control composites demonstrated good cytocompatibility which was comparable to the tissue culture polystyrene (TCP) control, supporting the use of these materials as coupling agent’s within medical implant devices. PMID:24955744

  1. Valproic acid increases expression of methylenetetrahydrofolate reductase (MTHFR) and induces lower teratogenicity in MTHFR deficiency.

    PubMed

    Roy, Marc; Leclerc, Daniel; Wu, Qing; Gupta, Sapna; Kruger, Warren D; Rozen, Rima

    2008-10-01

    Valproate (VPA) treatment in pregnancy leads to congenital anomalies, possibly by disrupting folate or homocysteine metabolism. Since methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate interconversion and homocysteine metabolism, we addressed the possibility that VPA might have different teratogenicity in Mthfr(+/+) and Mthfr(+/-) mice and that VPA might interfere with folate metabolism through MTHFR modulation. Mthfr(+/+) and Mthfr(+/-) pregnant mice were injected with VPA on gestational day 8.5; resorption rates and occurrence of neural tube defects (NTDs) were examined on gestational day 14.5. We also examined the effects of VPA on MTHFR expression in HepG2 cells and on MTHFR activity and homocysteine levels in mice. Mthfr(+/+) mice had increased resorption rates (36%) after VPA treatment, compared to saline treatment (10%), whereas resorption rates were similar in Mthfr(+/-) mice with the two treatments (25-27%). NTDs were only observed in one group (VPA-treated Mthfr(+/+)). In HepG2 cells, VPA increased MTHFR promoter activity and MTHFR mRNA and protein (2.5- and 3.7-fold, respectively). Consistent with cellular MTHFR upregulation by VPA, brain MTHFR enzyme activity was increased and plasma homocysteine was decreased in VPA-treated pregnant mice compared to saline-treated animals. These results underscore the importance of folate interconversion in VPA-induced teratogenicity, since VPA increases MTHFR expression and has lower teratogenic potential in MTHFR deficiency. PMID:18615588

  2. Particulate organic matter distribution along the lower Amazon River: addressing aquatic ecology concepts using fatty acids.

    PubMed

    Mortillaro, Jean-Michel; Rigal, François; Rybarczyk, Hervé; Bernardes, Marcelo; Abril, Gwenaël; Meziane, Tarik

    2012-01-01

    One of the greatest challenges in understanding the Amazon basin functioning is to ascertain the role played by floodplains in the organic matter (OM) cycle, crucial for a large spectrum of ecological mechanisms. Fatty acids (FAs) were combined with environmental descriptors and analyzed through multivariate and spatial tools (asymmetric eigenvector maps, AEM and principal coordinates of neighbor matrices, PCNM). This challenge allowed investigating the distribution of suspended particulate organic matter (SPOM), in order to trace its seasonal origin and quality, along a 800 km section of the Amazon river-floodplain system. Statistical analysis confirmed that large amounts of saturated FAs (15:0, 18:0, 24:0, 25:0 and 26:0), an indication of refractory OM, were concomitantly recorded with high pCO(2) in rivers, during the high water season (HW). Contrastingly, FAs marker which may be attributed in this ecosystem to aquatic plants (18:2ω6 and 18:3ω3) and cyanobacteria (16:1ω7), were correlated with higher O(2), chlorophyll a and pheopigments in floodplains, due to a high primary production during low waters (LW). Decreasing concentrations of unsaturated FAs, that characterize labile OM, were recorded during HW, from upstream to downstream. Furthermore, using PCNM and AEM spatial methods, FAs compositions of SPOM displayed an upstream-downstream gradient during HW, which was attributed to OM retention and the extent of flooded forest in floodplains. Discrimination of OM quality between the Amazon River and floodplains corroborate higher autotrophic production in the latter and transfer of OM to rivers at LW season. Together, these gradients demonstrate the validity of FAs as predictors of spatial and temporal changes in OM quality. These spatial and temporal trends are explained by 1) downstream change in landscape morphology as predicted by the River Continuum Concept; 2) enhanced primary production during LW when the water level decreased and its residence time

  3. Particulate Organic Matter Distribution along the Lower Amazon River: Addressing Aquatic Ecology Concepts Using Fatty Acids

    PubMed Central

    Mortillaro, Jean-Michel; Rigal, François; Rybarczyk, Hervé; Bernardes, Marcelo; Abril, Gwenaël; Meziane, Tarik

    2012-01-01

    One of the greatest challenges in understanding the Amazon basin functioning is to ascertain the role played by floodplains in the organic matter (OM) cycle, crucial for a large spectrum of ecological mechanisms. Fatty acids (FAs) were combined with environmental descriptors and analyzed through multivariate and spatial tools (asymmetric eigenvector maps, AEM and principal coordinates of neighbor matrices, PCNM). This challenge allowed investigating the distribution of suspended particulate organic matter (SPOM), in order to trace its seasonal origin and quality, along a 800 km section of the Amazon river-floodplain system. Statistical analysis confirmed that large amounts of saturated FAs (15:0, 18:0, 24:0, 25:0 and 26:0), an indication of refractory OM, were concomitantly recorded with high pCO2 in rivers, during the high water season (HW). Contrastingly, FAs marker which may be attributed in this ecosystem to aquatic plants (18:2ω6 and 18:3ω3) and cyanobacteria (16:1ω7), were correlated with higher O2, chlorophyll a and pheopigments in floodplains, due to a high primary production during low waters (LW). Decreasing concentrations of unsaturated FAs, that characterize labile OM, were recorded during HW, from upstream to downstream. Furthermore, using PCNM and AEM spatial methods, FAs compositions of SPOM displayed an upstream-downstream gradient during HW, which was attributed to OM retention and the extent of flooded forest in floodplains. Discrimination of OM quality between the Amazon River and floodplains corroborate higher autotrophic production in the latter and transfer of OM to rivers at LW season. Together, these gradients demonstrate the validity of FAs as predictors of spatial and temporal changes in OM quality. These spatial and temporal trends are explained by 1) downstream change in landscape morphology as predicted by the River Continuum Concept; 2) enhanced primary production during LW when the water level decreased and its residence time

  4. Particulate organic matter distribution along the lower Amazon River: addressing aquatic ecology concepts using fatty acids.

    PubMed

    Mortillaro, Jean-Michel; Rigal, François; Rybarczyk, Hervé; Bernardes, Marcelo; Abril, Gwenaël; Meziane, Tarik

    2012-01-01

    One of the greatest challenges in understanding the Amazon basin functioning is to ascertain the role played by floodplains in the organic matter (OM) cycle, crucial for a large spectrum of ecological mechanisms. Fatty acids (FAs) were combined with environmental descriptors and analyzed through multivariate and spatial tools (asymmetric eigenvector maps, AEM and principal coordinates of neighbor matrices, PCNM). This challenge allowed investigating the distribution of suspended particulate organic matter (SPOM), in order to trace its seasonal origin and quality, along a 800 km section of the Amazon river-floodplain system. Statistical analysis confirmed that large amounts of saturated FAs (15:0, 18:0, 24:0, 25:0 and 26:0), an indication of refractory OM, were concomitantly recorded with high pCO(2) in rivers, during the high water season (HW). Contrastingly, FAs marker which may be attributed in this ecosystem to aquatic plants (18:2ω6 and 18:3ω3) and cyanobacteria (16:1ω7), were correlated with higher O(2), chlorophyll a and pheopigments in floodplains, due to a high primary production during low waters (LW). Decreasing concentrations of unsaturated FAs, that characterize labile OM, were recorded during HW, from upstream to downstream. Furthermore, using PCNM and AEM spatial methods, FAs compositions of SPOM displayed an upstream-downstream gradient during HW, which was attributed to OM retention and the extent of flooded forest in floodplains. Discrimination of OM quality between the Amazon River and floodplains corroborate higher autotrophic production in the latter and transfer of OM to rivers at LW season. Together, these gradients demonstrate the validity of FAs as predictors of spatial and temporal changes in OM quality. These spatial and temporal trends are explained by 1) downstream change in landscape morphology as predicted by the River Continuum Concept; 2) enhanced primary production during LW when the water level decreased and its residence time

  5. Terpolymers of ethyl acrylate/methacrylic acid/unsaturated acid ester of alcohols and acids as anti-settling agents in coal water slurries

    SciTech Connect

    Savoly, A.; Villa, J.L.; Grinstein, R.H.; Nachfolger, S.J.

    1988-05-17

    This patent describes a pumpable stabilized coal water slurry, having a coal content of at least about 50% by weight wherein at least 80% of the coal particles are about 200 mesh or finer, containing from about 0.01% to about 1% by weight of the slurry of a water soluble terpolymer of ethylacrylate (A), metacrylic acid (B) and a third monomer (C) selected from the group consisting of an unsaturated carboxylic acid ester of an alcohol and an ethoxylated carboxylic acid. The unsaturated carboxylic acid is a mono- or di- basic unsaturated carboxylic acid of 3 to 10 carbon atoms selected from the group consisting of acrylic acid, methacrylic acid, itaconic acid, fumaric acid, and maleic acid.

  6. Recent advances in inhibitors of bacterial fatty acid synthesis type II (FASII) system enzymes as potential antibacterial agents.

    PubMed

    Wang, Yi; Ma, Shutao

    2013-10-01

    Bacterial infections are a constant and serious threat to human health. With the increase of multidrug resistance of clinically pathogenic bacteria, common antibiotic therapies have been less effective. Fatty acid synthesis type II (FASII) system enzymes are essential for bacterial membrane lipid biosynthesis and represent increasingly promising targets for the discovery of antibacterial agents with new mechanisms of action. This review highlights recent advances in inhibitors of bacterial FASII as potential antibacterial agents, paying special attention to the activities, mechanisms, and structure-activity relationships of those inhibitors that mainly target β-ketoacyl-ACP synthase, β-ketoacyl-ACP reductase, β-hydroxyacyl-ACP dehydratase, and enoyl-ACP reductase. Although inhibitors with low nanomolar and selective activity against various bacterial FASII have entered clinical trials, further research is needed to expand upon both available and yet unknown scaffolds to identify new FASII inhibitors that may have antibacterial potential, particularly against resistant bacterial strains.

  7. Synthesis, characterization and application of a novel chemical sand-fixing agent-poly(aspartic acid) and its composites.

    PubMed

    Yang, Jun; Wang, Fang; Fang, Li; Tan, Tianwei

    2007-09-01

    A novel sand-fixing agent-poly(aspartic acid) and its composites were synthesized to improve sand particles compressive strength and anti-wind erosion properties. The relationship between the concentration of sand-fixing agent and the sand-fixing properties was studied by three kinds of aging tests. Some composites were choose to improve the sand-fixing property and the composition of 40% xanthan gum and 60% ethyl cellulose were chosen to compare sand-fixing property with lignosulfonate. The results showed that the sand-fixing and water-retaining properties of xanthan gum and ethyl cellulose composites were better than that of lignosulfonate. The biodegradability experiment showed that the PASP and its composites were environment-friendly products and the field test showed that the PASP composites could improve wind erosion disturbance.

  8. Metabolism in rats and man of piromidic acid, a new antibacterial agent.

    PubMed

    Sekine, Y; Miyamoto, M; Hashimoto, M; Nakamura, K

    1976-03-01

    1. Metabolism of the antibacterial, piromidic acid (5,8-dihydro-8-ethyl-5-oxo-2-pyrrolidinopyrido[2,3-d]pyrimidine-6-carboxylic acid) was investigated in rats and human subjects. Ten metabolites and the unchanged drug were found in the urine and the bile of both species after oral administration. 2. Metabolites were identified by comparison with authentic materials, except for the unstable metabolite, M-VI, for which a probable structure is proposed. The metabolic pathway of piromidic acid involved hydroxylation in the pyrrolidine ring to give the 2- and 3-hydroxy-derivatives (M-II and M-V). M-II was further metabolized to the corresponding gamma-aminobutyric acid derivative (M-IV) and the 2-5-dihydroxypyrrolidine derivative (M-VI) which was further metabolized to the 2-amino-pyridopyrimidine carboxylic acid (M-III). Piromidic acid, M-V, M-II, M-III and M-IV were partly excreted as respective glucuronides. 3. Metabolites, except glucuronides, exhibited antibacterial activity; M-V and M-II showed greater activity than piromidic acid. 4. The metabolism of piromidic acid is discussed in relation to the physicochemical properties of the drug and its metabolites.

  9. Amphiphilic calixresorcinarene associates as effective solubilizing agents for hydrophobic organic acids: construction of nano-aggregates.

    PubMed

    Morozova, Ju E; Syakaev, V V; Kazakova, E Kh; Shalaeva, Ya V; Nizameev, I R; Kadirov, M K; Voloshina, A D; Zobov, V V; Konovalov, A I

    2016-07-01

    Here we represent the first example of the formation of mixed nanoscale associates, constructed from amphiphilic calixresorcinarenes and hydrophobic carboxylic acids including drugs. The amidoamino-calixresorcinarene self-associates effectively solubilize hydrophobic carboxylic acids - drugs such as naproxen, ibuprofen, ursodeoxycholic acid and aliphatic dodecanoic acid - with the formation of the mixed aggregates with the macrocycle/substrate stoichiometry from 1/1 to 1/7. The ionization of organic acids and the peripheral nitrogen atoms of the macrocycles with the subsequent inclusion of hydrophobic acids into the macrocycle self-associates is the driving force of solubilization. In some cases, this leads to the co-assembly of the macrocycle polydisperse associates into supramolecular monodisperse nanoparticles with the diameter of about 100 nm. The efficiency of drug loading into the nanoparticles is up to 45% and depends on the structure of organic acid. The dissociation of the mixed aggregates and release of organic acid are attained by decreasing pH. PMID:27252123

  10. Copolymer of methacrylic acid with its diethylammonium salt: Effective waterproofing agent for oil wells

    SciTech Connect

    Kuznetsova, O.N.; Avvakumova, N.I.

    1992-08-10

    In the development of technology for the copolymerization of methacrylic acid with its diethylammonium salt (MAA-MAA{center_dot}DEA), the polymer-like reaction of polymethacrylic acid (PMAA) with diethylamine (DEA) and the polymerization of MAA in the presence of DEA have been studied. 13 refs., 3 figs., 4 tabs.

  11. EMPA-REG and Other Cardiovascular Outcome Trials of Glucose-lowering Agents: Implications for Future Treatment Strategies in Type 2 Diabetes Mellitus.

    PubMed

    Schernthaner, Guntram; Schernthaner-Reiter, Marie Helene; Schernthaner, Gerit-Holger

    2016-06-01

    During the last decade, the armamentarium for glucose-lowering drugs has increased enormously by the development of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors, allowing individualization of antidiabetic therapy for patients with type 2 diabetes (T2DM). Some combinations can now be used without an increased risk for severe hypoglycemia and weight gain. Following a request of the US Food and Drug Administration, many large cardiovascular (CV) outcome studies have been performed in patients with longstanding disease and established CV disease. In the majority of CV outcome studies, CV risk factors were well controlled and a high number of patients were already treated with ACE inhibitors/angiotensin receptor blockers, statins and antiplatelet drugs. Most studies with insulin glargine and newer glucose-lowering drugs (saxagliptin, alogliptin, sitagliptin, lixisenatide) demonstrated safety of newer glucose-lowering agents but did not show superiority in the CV outcomes compared with placebo. By contrast, in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study, CV death, all-cause mortality, and hospitalization for heart failure were significantly decreased when empagliflozin was added instead of placebo to therapy for patients with high CV risk and T2DM already well treated with statins, glucose-lowering drugs, and blood pressure-lowering drugs as well as antiplatelet agents. In addition, renal endpoints including endstage renal disease were also significantly reduced when empagliflozin was added instead of placebo. Interestingly, the reduction of these clinically relevant end points was observed after a few months, making antiatherogenic effects an unlikely cause. The fact that the incidence of myocardial infarction (MI) and stroke were not reduced is in line with the hypothesis that hemodynamic factors in particular have contributed to the impressive improvement of the prognosis. To

  12. Aldol Condensation Products and Polyacetals in Organic Films Formed from Reactions of Propanal in Sulfuric Acid at Upper Troposphere/Lower Stratosphere (UT/LS) Aerosol Acidities

    NASA Astrophysics Data System (ADS)

    Bui, J. V. H.; Perez-Montano, S.; Li, E. S. W.; Nelson, T. E.; Ha, K. T.; Leong, L.; Iraci, L. T.; Van Wyngarden, A. L.

    2015-12-01

    Aerosols in the upper troposphere and lower stratosphere (UT/LS) consist mostly of concentrated sulfuric acid (40-80 wt. %) which is highly reflective towards UV and visible radiation. However, airborne measurements have shown that these particles may also contain a significant amount of organic material. Experiments combining organics (propanal, glyoxal and/or methylglyoxal) with sulfuric acid at concentrations typical of UT/LS aerosols produced highly colored surface films (and solutions) that have the potential to impact chemical, optical and/or cloud-forming properties of aerosols. In order to assess the potential for such films to impact aerosol chemistry or climate properties, experiments were performed to identify the chemical processes responsible for film formation. Surface films were analyzed via Attenuated Total Reflectance-FTIR and Nuclear Magnetic Resonance spectroscopies and are shown to consist primarily of aldol condensation products and cyclic and linear polyacetals, the latter of which are likely responsible for separation from the aqueous phase.

  13. Synthesis and Biological Evaluation of Novel Phosphatidylcholine Analogues Containing Monoterpene Acids as Potent Antiproliferative Agents

    PubMed Central

    Gliszczyńska, Anna; Niezgoda, Natalia; Gładkowski, Witold; Czarnecka, Marta; Świtalska, Marta; Wietrzyk, Joanna

    2016-01-01

    The synthesis of novel phosphatidylcholines with geranic and citronellic acids in sn-1 and sn-2 positions is described. The structured phospholipids were obtained in high yields (59–87%) and evaluated in vitro for their cytotoxic activity against several cancer cell lines of different origin: MV4-11, A-549, MCF-7, LOVO, LOVO/DX, HepG2 and also towards non-cancer cell line BALB/3T3 (normal mice fibroblasts). The phosphatidylcholines modified with monoterpene acid showed a significantly higher antiproliferative activity than free monoterpene acids. The highest activity was observed for the terpene-phospholipids containing the isoprenoid acids in sn-1 position of phosphatidylcholine and palmitic acid in sn-2. PMID:27310666

  14. Nucleic acid approaches for detection and identification of biological warfare and infectious disease agents.

    PubMed

    Ivnitski, Dmitri; O'Neil, Daniel J; Gattuso, Anthony; Schlicht, Roger; Calidonna, Michael; Fisher, Rodney

    2003-10-01

    Biological warfare agents are the most problematic of the weapons of mass destruction and terror. Both civilian and military sources predict that over the next decade the threat from proliferation of these agents will increase significantly. In this review we summarize the state of the art in detection and identification of biological threat agents based on PCR technology with emphasis on the new technology of microarrays. The advantages and limitations of real-time PCR technology and a review of the literature as it applies to pathogen and virus detection are presented. The paper covers a number of issues related to the challenges facing biological threat agent detection technologies and identifies critical components that must be overcome for the emergence of reliable PCR-based DNA technologies as bioterrorism countermeasures and for environmental applications. The review evaluates various system components developed for an integrated DNA microchip and the potential applications of the next generation of fully automated DNA analyzers with integrated sample preparation and biosensing elements. The article also reviews promising devices and technologies that are near to being, or have been, commercialized.

  15. Poly(Lactic-co-Glycolic) Acid as a Carrier for Imaging Contrast Agents

    PubMed Central

    Doiron, Amber L.; Homan, Kimberly A.; Emelianov, Stanislav; Brannon-Peppas, Lisa

    2010-01-01

    Purpose With the broadening field of nanomedicine poised for future molecular level therapeutics, nano-and microparticles intended for the augmentation of either single- or multimodal imaging are created with PLGA as the chief constituent and carrier. Methods Emulsion techniques were used to encapsulate hydrophilic and hydrophobic imaging contrast agents in PLGA particles. The imaging contrast properties of these PLGA particles were further enhanced by reducing silver onto the PLGA surface, creating a silver cage around the polymeric core. Results The MRI contrast agent Gd-DTPA and the exogenous dye rhodamine 6G were both encapsulated in PLGA and shown to enhance MR and fluorescence contrast, respectively. The silver nanocage built around PLGA nanoparticles exhibited strong near infrared light absorbance properties, making it a suitable contrast agent for optical imaging strategies such as photoacoustic imaging. Conclusions The biodegradable polymer PLGA is an extremely versatile nano- and micro-carrier for several imaging contrast agents with the possibility of targeting diseased states at a molecular level. PMID:19034628

  16. Nucleic acid approaches for detection and identification of biological warfare and infectious disease agents.

    PubMed

    Ivnitski, Dmitri; O'Neil, Daniel J; Gattuso, Anthony; Schlicht, Roger; Calidonna, Michael; Fisher, Rodney

    2003-10-01

    Biological warfare agents are the most problematic of the weapons of mass destruction and terror. Both civilian and military sources predict that over the next decade the threat from proliferation of these agents will increase significantly. In this review we summarize the state of the art in detection and identification of biological threat agents based on PCR technology with emphasis on the new technology of microarrays. The advantages and limitations of real-time PCR technology and a review of the literature as it applies to pathogen and virus detection are presented. The paper covers a number of issues related to the challenges facing biological threat agent detection technologies and identifies critical components that must be overcome for the emergence of reliable PCR-based DNA technologies as bioterrorism countermeasures and for environmental applications. The review evaluates various system components developed for an integrated DNA microchip and the potential applications of the next generation of fully automated DNA analyzers with integrated sample preparation and biosensing elements. The article also reviews promising devices and technologies that are near to being, or have been, commercialized. PMID:14579752

  17. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines.

    PubMed

    Choi, Sujean; Disilvio, Briana; Fernstrom, Madelyn H; Fernstrom, John D

    2013-11-01

    Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.

  18. Pyridine hydroxamic acids are specific anti-HCV agents affecting HDAC6.

    PubMed

    Kozlov, Maxim V; Kleymenova, Alla A; Romanova, Lyudmila I; Konduktorov, Konstantin A; Kamarova, Kamila A; Smirnova, Olga A; Prassolov, Vladimir S; Kochetkov, Sergey N

    2015-06-01

    Recently we reported benzohydroxamic acids (BHAs) as potent and selective inhibitors of hepatitis C virus (HCV) replicon propagation. In this work 12 pyridine hydroxamic acids (PHAs) were synthesized and tested in full-genome replicon assay. It was found that PHAs possessed very similar anti-HCV properties compared to BHAs. Both classes of hydroxamic acids caused hyperacetylation of α-tubulin pointing to inhibition of histone deacetylase 6 (HDAC6) as part of their antiviral activity. The tested compounds did not inhibit the growth of poliovirus, displaying high selectivity against HCV.

  19. Amino acid, mineral, and polyphenolic profiles of black vinegar, and its lipid lowering and antioxidant effects in vivo.

    PubMed

    Chou, Chung-Hsi; Liu, Cheng-Wei; Yang, Deng-Jye; Wu, Yi-Hsieng Samuel; Chen, Yi-Chen

    2015-02-01

    Black vinegar (BV) contains abundant essential and hydrophobic amino acids, and polyphenolic contents, especially catechin and chlorogenic acid via chemical analyses. K and Mg are the major minerals in BV, and Ca, Fe, Mn, and Se are also measured. After a 9-week experiment, high-fat/cholesterol-diet (HFCD) fed hamsters had higher (p<0.05) weight gains, relative visceral-fat sizes, serum/liver lipids, and serum cardiac indices than low-fat/cholesterol diet (LFCD) fed ones, but BV supplementation decreased (p<0.05) them which may resulted from the higher (p<0.05) faecal TAG and TC contents. Serum ALT value, and hepatic thiobarbituric acid reactive substances (TBARS), and hepatic TNF-α and IL-1β contents in HFCD-fed hamsters were reduced (p<0.05) by supplementing BV due to increased (p<0.05) hepatic glutathione (GSH) and trolox equivalent antioxidant capacity (TEAC) levels, and catalase (CAT) and glutathione peroxidase (GPx) activities. Taken together, the component profiles of BV contributed the lipid lowering and antioxidant effects on HFCD fed hamsters.

  20. Screening of Cholesterol-lowering Bifidobacterium from Guizhou Xiang Pigs, and Evaluation of Its Tolerance to Oxygen, Acid, and Bile.

    PubMed

    Zhang, Rujiao; He, Laping; Zhang, Ling; Li, Cuiqin; Zhu, Qiujin

    2016-01-01

    Cardiovascular and cerebrovascular diseases seriously harm human health, and Bifidobacterium is the most beneficial probiotic in the gastrointestinal tract of humans. This work aimed to screen cholesterol-lowering Bifidobacterium from Guizhou Xiang Pig and evaluate its tolerance to oxygen, acid, and bile. Twenty-seven aerotolerant strains with similar colony to Bifidobacterium were isolated through incubation at 37℃ in 20% (v/v) CO2-80% (v/v) atmospheric air by using Mupirocin lithium modified MRS agar medium, modified PTYG with added CaCO3, and modified PTYG supplemented with X-gal. Ten strains with cholesterol-lowering rates above 20% (w/w) were used for further screening. The selected strains' tolerance to acid and bile was then determined. A combination of colony and cell morphology, physiological, and biochemical experiments, as well as 16S rRNA gene-sequence analysis, was performed. Results suggested that BZ25 with excellent characteristics of high cholesterol-removal rate of 36.32% (w/w), as well as tolerance to acid and bile, was identified as Bifidobacterium animalis subsp. lactis. To further evaluate Bifidobacterium BZ25's growth characteristic and tolerance to oxygen, culture experiments were performed in liquid medium and an agar plate. Findings suggested that BZ25 grew well both in environmental 20% (v/v) CO2-80% (v/v) atmospheric air and in 100% atmospheric air because BZ25 reached an absorbance of 1.185 at 600 nm in 100% atmospheric air. Moreover, BZ25 was aerotolerant and can grow in an agar medium under the environmental condition of 100% atmospheric air. This study can lay a preliminary foundation for the potential industrial applications of BZ25. PMID:27499662

  1. Screening of Cholesterol-lowering Bifidobacterium from Guizhou Xiang Pigs, and Evaluation of Its Tolerance to Oxygen, Acid, and Bile

    PubMed Central

    Zhang, Rujiao; He, Laping; Zhang, Ling; Li, Cuiqin; Zhu, Qiujin

    2016-01-01

    Cardiovascular and cerebrovascular diseases seriously harm human health, and Bifidobacterium is the most beneficial probiotic in the gastrointestinal tract of humans. This work aimed to screen cholesterol-lowering Bifidobacterium from Guizhou Xiang Pig and evaluate its tolerance to oxygen, acid, and bile. Twenty-seven aerotolerant strains with similar colony to Bifidobacterium were isolated through incubation at 37℃ in 20% (v/v) CO2-80% (v/v) atmospheric air by using Mupirocin lithium modified MRS agar medium, modified PTYG with added CaCO3, and modified PTYG supplemented with X-gal. Ten strains with cholesterol-lowering rates above 20% (w/w) were used for further screening. The selected strains’ tolerance to acid and bile was then determined. A combination of colony and cell morphology, physiological, and biochemical experiments, as well as 16S rRNA gene-sequence analysis, was performed. Results suggested that BZ25 with excellent characteristics of high cholesterol-removal rate of 36.32% (w/w), as well as tolerance to acid and bile, was identified as Bifidobacterium animalis subsp. lactis. To further evaluate Bifidobacterium BZ25’s growth characteristic and tolerance to oxygen, culture experiments were performed in liquid medium and an agar plate. Findings suggested that BZ25 grew well both in environmental 20% (v/v) CO2-80% (v/v) atmospheric air and in 100% atmospheric air because BZ25 reached an absorbance of 1.185 at 600 nm in 100% atmospheric air. Moreover, BZ25 was aerotolerant and can grow in an agar medium under the environmental condition of 100% atmospheric air. This study can lay a preliminary foundation for the potential industrial applications of BZ25. PMID:27499662

  2. Uptake measurements of acetic acid on ice and nitric acid-doped thin ice films over upper troposphere/lower stratosphere temperatures.

    PubMed

    Romanias, Manolis N; Zogka, Antonia G; Papadimitriou, Vassileios C; Papagiannakopoulos, Panos

    2012-03-01

    The adsorption of gaseous acetic acid (CH(3)C(O)OH) on thin ice films and on ice doped with nitric acid (1.96 and 7.69 wt %) was investigated over upper troposphere and lower stratosphere (UT/LS) temperatures (198-208 K), and at low gas concentrations. Experiments were performed in a Knudsen flow reactor coupled to a quadrupole mass spectrometer. The initial uptake coefficients, γ(0), on thin ice films or HNO(3)-doped ice films were measured at low surface coverage. In all cases, γ(0) showed an inverse temperature dependence, and for pure thin ice films, it was given by the expression γ(0)(T) = (4.73 ± 1.13) × 10(-17) exp[(6496 ± 1798)/T]; the quoted errors are the 2σ precision of the linear fit, and the estimated systematic uncertainties are included in the pre-exponential factor. The inverse temperature dependence suggests that the adsorption process occurs via the formation of an intermediate precursor state. Uptakes were well represented by the Langmuir adsorption model, and the saturation surface coverage, N(max), on pure thin ice films was (2.11 ± 0.16) × 10(14) molecules cm(-2), independent of temperature in the range 198-206 K. Light nitration (1.96 and 7.69 wt %) of ice films resulted in more efficient CH(3)C(O)OH uptakes and larger N(max) values that may be attributed to in-bulk diffusion or change in nature of the gas-ice surface interaction. Finally, it was estimated that the rate of adsorption of acetic acid on high-density cirrus clouds in the UT/LS is fast, and this is reflected in the short atmospheric lifetimes (2-8 min) of acetic acid; however, the extent of this uptake is minor resulting in at most a 5% removal of acetic acid in UT/LS cirrus clouds.

  3. Analogs of the antituberculous agent pyrazinamide are competitive inhibitors of NADPH binding to M. tuberculosis fatty acid synthase I.

    PubMed

    Sayahi, Halimah; Pugliese, Kaitlin M; Zimhony, Oren; Jacobs, William R; Shekhtman, Alexander; Welch, John T

    2012-11-01

    Analogs of pyrazinamide (=pyrazine-2-carboxamide; PZA), an essential component of short-course antituberculous chemotherapy, such as 5-chloropyrazinamide (5-Cl-PZA) act as competitive inhibitors of NADPH binding to purified mycobacterial fatty acid synthase I (FAS I) as shown by Saturation Transfer Difference (STD) NMR studies. In addition, pyrazinoic acid esters (POE) and 5-Cl-POE reversibly bind to FAS I with the relatively greater affinity of longer-chain esters for FAS I, clear from the STD amplification factors. The competitive binding of PZA and 5-Cl-PZA clearly illustrates that both agents bind FAS. In contrast to PZA, at low NADPH concentrations 5-Cl-PZA is a cooperative inhibitor of NADPH binding.

  4. Amino acids as chiral auxiliaries in cyanuric chloride-based chiral derivatizing agents for enantioseparation by liquid chromatography.

    PubMed

    Batra, Sonika; Bhushan, Ravi

    2014-11-01

    This review summarizes and critically evaluates the recent research on application of amino acids and amino acid amides as chiral auxiliaries in cyanuric chloride (CC) based chiral derivatizing agents (CDRs), used in the indirect approach for enantiomeric resolution. Methods of synthesis of such CDRs, methods for synthesis of diastereomers of a variety of racemic compounds and parameters of liquid chromatographic separation, along with their prospects and their limitations in indirect enantioresolution, are discussed. Application of the said CDR(s) and the technical approach to be used that are discussed should be beneficial for control of enantiomeric purity in pharmaceutical industry, verification of enantiomeric ratio of commercial formulations and the development of methods for indirect resolution of a variety of chiral compounds. Derivatization methods are particularly required when a chromophore is to be introduced in low UV absorbing molecules, for their detection.

  5. Data of thermal degradation and dynamic mechanical properties of starch–glycerol based films with citric acid as crosslinking agent

    PubMed Central

    González Seligra, Paula; Medina Jaramillo, Carolina; Famá, Lucía; Goyanes, Silvia

    2016-01-01

    Interest in biodegradable edible films as packaging or coating has increased because their beneficial effects on foods. In particular, food products are highly dependents on thermal stability, integrity and transition process temperatures of the packaging. The present work describes a complete data of the thermal degradation and dynamic mechanical properties of starch–glycerol based films with citric acid (CA) as crosslinking agent described in the article titled: “Biodegradable and non-retrogradable eco-films based on starch–glycerol with citric acid as crosslinking agent” González Seligra et al. (2016) [1]. Data describes thermogravimetric and dynamical mechanical experiences and provides the figures of weight loss and loss tangent of the films as a function of the temperature. PMID:27158645

  6. Ferulic acid-carbazole hybrid compounds: Combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents.

    PubMed

    Fang, Lei; Chen, Mohao; Liu, Zhikun; Fang, Xubin; Gou, Shaohua; Chen, Li

    2016-02-15

    In order to search for novel multifunctional anti-Alzheimer agents, a series of ferulic acid-carbazole hybrid compounds were designed and synthesized. Ellman's assay revealed that the hybrid compounds showed moderate to potent inhibitory activity against the cholinesterases. Particularly, the AChE inhibition potency of compound 5k (IC50 1.9μM) was even 5-fold higher than that of galantamine. In addition, the target compounds showed pronounced antioxidant ability and neuroprotective property, especially against the ROS-induced toxicity. Notably, the neuroprotective effect of 5k was obviously superior to that of the mixture of ferulic acid and carbazole, indicating the therapeutic effect of the hybrid compound is better than the combination administration of the corresponding mixture.

  7. Ferulic acid-carbazole hybrid compounds: Combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents.

    PubMed

    Fang, Lei; Chen, Mohao; Liu, Zhikun; Fang, Xubin; Gou, Shaohua; Chen, Li

    2016-02-15

    In order to search for novel multifunctional anti-Alzheimer agents, a series of ferulic acid-carbazole hybrid compounds were designed and synthesized. Ellman's assay revealed that the hybrid compounds showed moderate to potent inhibitory activity against the cholinesterases. Particularly, the AChE inhibition potency of compound 5k (IC50 1.9μM) was even 5-fold higher than that of galantamine. In addition, the target compounds showed pronounced antioxidant ability and neuroprotective property, especially against the ROS-induced toxicity. Notably, the neuroprotective effect of 5k was obviously superior to that of the mixture of ferulic acid and carbazole, indicating the therapeutic effect of the hybrid compound is better than the combination administration of the corresponding mixture. PMID:26795115

  8. Lower ω-6/ω-3 Polyunsaturated Fatty Acid Ratios Decrease Fat Deposition by Inhibiting Fat Synthesis in Gosling.

    PubMed

    Yu, Lihuai; Wang, Shunan; Ding, Luoyang; Liang, Xianghuan; Wang, Mengzhi; Dong, Li; Wang, Hongrong

    2016-10-01

    The objective of the current study was to investigate the effects of dietary ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratios on lipid metabolism in goslings. One hundred and sixty 21-day-old Yangzhou geese of similar weight were randomly divided into 4 groups. They were fed different PUFA-supplemented diets (the 4 diets had ω-6/ω-3 PUFA ratios of 12:1, 9:1, 6:1, or 3:1). The geese were slaughtered and samples of liver and muscle were collected at day 70. The activities and the gene expression of enzymes involved in lipid metabolism were measured. The results show that the activities of acetyl coenzyme A carboxylase (ACC), malic enzyme (ME), and fatty acid synthase (FAS) were lower (p<0.05), but the activities of hepatic lipase (HL) and lipoprotein lipase (LPL) were higher (p<0.05), in the liver and the muscle from the 3:1 and 6:1 groups compared with those in the 9:1 and 12:1 groups. Expression of the genes for FAS (p<0.01), ME (p<0.01) and ACC (p<0.05) were higher in the muscle of groups fed diets with higher ω-6/ω-3 PUFA ratios. Additionally, in situ hybridization tests showed that the expression intensities of the high density lipoprotein (HDL-R) gene in the 12:1 and 9:1 groups were significantly lower (p<0.01) than that of the 3:1 group in the muscle of goslings. In conclusion, diets containing lower ω-6/ω-3 PUFA ratios (3:1 or 6:1) could decrease fat deposition by inhibiting fat synthesis in goslings. PMID:27189638

  9. Lower ω-6/ω-3 Polyunsaturated Fatty Acid Ratios Decrease Fat Deposition by Inhibiting Fat Synthesis in Gosling.

    PubMed

    Yu, Lihuai; Wang, Shunan; Ding, Luoyang; Liang, Xianghuan; Wang, Mengzhi; Dong, Li; Wang, Hongrong

    2016-10-01

    The objective of the current study was to investigate the effects of dietary ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratios on lipid metabolism in goslings. One hundred and sixty 21-day-old Yangzhou geese of similar weight were randomly divided into 4 groups. They were fed different PUFA-supplemented diets (the 4 diets had ω-6/ω-3 PUFA ratios of 12:1, 9:1, 6:1, or 3:1). The geese were slaughtered and samples of liver and muscle were collected at day 70. The activities and the gene expression of enzymes involved in lipid metabolism were measured. The results show that the activities of acetyl coenzyme A carboxylase (ACC), malic enzyme (ME), and fatty acid synthase (FAS) were lower (p<0.05), but the activities of hepatic lipase (HL) and lipoprotein lipase (LPL) were higher (p<0.05), in the liver and the muscle from the 3:1 and 6:1 groups compared with those in the 9:1 and 12:1 groups. Expression of the genes for FAS (p<0.01), ME (p<0.01) and ACC (p<0.05) were higher in the muscle of groups fed diets with higher ω-6/ω-3 PUFA ratios. Additionally, in situ hybridization tests showed that the expression intensities of the high density lipoprotein (HDL-R) gene in the 12:1 and 9:1 groups were significantly lower (p<0.01) than that of the 3:1 group in the muscle of goslings. In conclusion, diets containing lower ω-6/ω-3 PUFA ratios (3:1 or 6:1) could decrease fat deposition by inhibiting fat synthesis in goslings.

  10. Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation

    NASA Astrophysics Data System (ADS)

    Lee, Dong-Wook; Jin, Min-Ho; Lee, Young-Joo; Park, Ju-Hyoung; Lee, Chun-Boo; Park, Jong-Soo

    2016-05-01

    The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room-temperature formic acid decomposition than those prepared by the incipient wetness method.

  11. Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation.

    PubMed

    Lee, Dong-Wook; Jin, Min-Ho; Lee, Young-Joo; Park, Ju-Hyoung; Lee, Chun-Boo; Park, Jong-Soo

    2016-05-20

    The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room-temperature formic acid decomposition than those prepared by the incipient wetness method.

  12. Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation

    PubMed Central

    Lee, Dong-Wook; Jin, Min-Ho; Lee, Young-Joo; Park, Ju-Hyoung; Lee, Chun-Boo; Park, Jong-Soo

    2016-01-01

    The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room-temperature formic acid decomposition than those prepared by the incipient wetness method. PMID:27198855

  13. Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation.

    PubMed

    Lee, Dong-Wook; Jin, Min-Ho; Lee, Young-Joo; Park, Ju-Hyoung; Lee, Chun-Boo; Park, Jong-Soo

    2016-01-01

    The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room-temperature formic acid decomposition than those prepared by the incipient wetness method. PMID:27198855

  14. Research on the interaction of hydrogen-bond acidic polymer sensitive sensor materials with chemical warfare agents simulants by inverse gas chromatography.

    PubMed

    Yang, Liu; Han, Qiang; Cao, Shuya; Huang, Feng; Qin, Molin; Guo, Chenghai; Ding, Mingyu

    2015-01-01

    Hydrogen-bond acidic polymers are important high affinity materials sensitive to organophosphates in the chemical warfare agent sensor detection process. Interactions between the sensor sensitive materials and chemical warfare agent simulants were studied by inverse gas chromatography. Hydrogen bonded acidic polymers, i.e., BSP3, were prepared for micro-packed columns to examine the interaction. DMMP (a nerve gas simulant) and 2-CEES (a blister agent simulant) were used as probes. Chemical and physical parameters such as heats of absorption and Henry constants of the polymers to DMMP and 2-CEES were determined by inverse gas chromatography. Details concerning absorption performance are also discussed in this paper.

  15. Study of photo-oxidative reactivity of sunscreening agents based on photo-oxidation of uric acid by kinetic Monte Carlo simulation.

    PubMed

    Moradmand Jalali, Hamed; Bashiri, Hadis; Rasa, Hossein

    2015-05-01

    In the present study, the mechanism of free radical production by light-reflective agents in sunscreens (TiO2, ZnO and ZrO2) was obtained by applying kinetic Monte Carlo simulation. The values of the rate constants for each step of the suggested mechanism have been obtained by simulation. The effect of the initial concentration of mineral oxides and uric acid on the rate of uric acid photo-oxidation by irradiation of some sun care agents has been studied. The kinetic Monte Carlo simulation results agree qualitatively with the existing experimental data for the production of free radicals by sun care agents.

  16. Research on the Interaction of Hydrogen-Bond Acidic Polymer Sensitive Sensor Materials with Chemical Warfare Agents Simulants by Inverse Gas Chromatography

    PubMed Central

    Yang, Liu; Han, Qiang; Cao, Shuya; Huang, Feng; Qin, Molin; Guo, Chenghai; Ding, Mingyu

    2015-01-01

    Hydrogen-bond acidic polymers are important high affinity materials sensitive to organophosphates in the chemical warfare agent sensor detection process. Interactions between the sensor sensitive materials and chemical warfare agent simulants were studied by inverse gas chromatography. Hydrogen bonded acidic polymers, i.e., BSP3, were prepared for micro-packed columns to examine the interaction. DMMP (a nerve gas simulant) and 2-CEES (a blister agent simulant) were used as probes. Chemical and physical parameters such as heats of absorption and Henry constants of the polymers to DMMP and 2-CEES were determined by inverse gas chromatography. Details concerning absorption performance are also discussed in this paper. PMID:26043177

  17. Reduced Oxidative Stress Contributes to the Lipid Lowering Effects of Isoquercitrin in Free Fatty Acids Induced Hepatocytes

    PubMed Central

    Rongyin, Gao; Daoud, Abdelkader; Ding, Lin; Wang, Lulu; Liu, Jun

    2014-01-01

    Oxidative stress interferes with hepatic lipid metabolism at various levels ranging from benign lipid storage to so-called second hit of inflammation activation. Isoquercitrin (IQ) is widely present flavonoid but its effects on hepatic lipid metabolism remain unknown. We used free fatty acids (FFA) induced lipid overload and oxidative stress model in two types of liver cells and measured cell viability, intracellular lipids, and reactive oxygen species (ROS) within hepatocytes. In addition, Intracellular triglycerides (TG), superoxide dismutase (SOD), and malondialdehyde (MDA) were examined. A novel in vitro model was used to evaluate correlation between lipid lowering and antioxidative activities. Furthermore, 34 major cytokines and corresponding ROS levels were analyzed in FFA/LPS induced coculture model between hepatocytes and Kupffer cells. At molecular level AMPK pathway was elucidated. We showed that IQ attenuated FFA induced lipid overload and ROS within hepatocytes. Further, IQ reversed FFA induced increase in intracellular TG SOD and MDA. It was shown that antioxidative activity of IQ correlates with its lipid lowering potentials. IQ reversed major proinflammatory cytokines and oxidative stress in FFA/LPS induced coculture model. Finally, AMPK pathway was found responsible for metabolic benefits at molecular level. IQ strikingly manifests antioxidative and related lipid lowering activities in hepatocytes. PMID:25404990

  18. A new facile route for synthesizing of graphene oxide using mixture of sulfuric-nitric-phosphoric acids as intercalating agent

    NASA Astrophysics Data System (ADS)

    Panwar, Vinay; Chattree, Ananya; Pal, Kaushik

    2015-09-01

    In this work, graphene oxide (GO) has been prepared through three different processes namely, eco-friendly Hummers method, modification in improved Hummers method and a new approach. This new approach has been designed by changing some processing parameters and intercalating agent for significant reduction in processing time and to improve the quantity of GO in comparison to the other two methods. This has been achieved through better oxidization of graphite using nitric-sulfuric acid (HNO3-H2SO4) as intercalating agent. X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Energy-dispersive X-ray spectroscopy (EDX), Raman spectroscopy, Atomic Force Microscopy (AFM), X-ray photoelectron spectroscopy (XPS), UV-visible spectroscopy, and Thermogravimetric analysis (TGA) are used to characterize the GO prepared through different processes. These characterizations have confirmed an improved exfoliation of graphite, using addition of HNO3 in intercalating agent, in a short processing time and bring on higher yield of GO via this new process.

  19. Citrus Flavanones Affect Hepatic Fatty Acid Oxidation in Rats by Acting as Prooxidant Agents

    PubMed Central

    Constantin, Rodrigo Polimeni; do Nascimento, Gilson Soares; Constantin, Renato Polimeni; Salgueiro, Clairce Luzia; Bracht, Adelar; Ishii-Iwamoto, Emy Luiza; Yamamoto, Nair Seiko

    2013-01-01

    Citrus flavonoids have a wide range of biological activities and positive health effects on mammalian cells because of their antioxidant properties. However, they also act as prooxidants and thus may interfere with metabolic pathways. The purpose of this work was to evaluate the effects of three citrus flavanones, hesperidin, hesperetin, and naringenin, on several parameters linked to fatty acid oxidation in mitochondria, peroxisomes, and perfused livers of rats. When exogenous octanoate was used as substrate, hesperetin and naringenin reduced the mitochondrial NADH/NAD+ ratio and stimulated the citric acid cycle without significant changes on oxygen uptake or ketogenesis. When fatty acid oxidation from endogenous sources was evaluated, hesperetin and naringenin strongly reduced the mitochondrial NADH/NAD+ ratio. They also inhibited both oxygen uptake and ketogenesis and stimulated the citric acid cycle. Hesperidin, on the other hand, had little to no effect on these parameters. These results confirm the hypothesis that citrus flavanones are able to induce a more oxidised state in liver cells, altering parameters related to hepatic fatty acid oxidation. The prooxidant effect is most likely a consequence of the ability of these substances to oxidise NADH upon production of phenoxyl radicals in the presence of peroxidases and hydrogen peroxide. PMID:24288675

  20. New ionic derivatives of betulinic acid as highly potent anti-cancer agents.

    PubMed

    Suresh, Challa; Zhao, Hua; Gumbs, Angelique; Chetty, Chellu S; Bose, Himangshu S

    2012-02-15

    Betulinic acid is a natural compound with high in vitro cytotoxicity toward many cancer cells. However, the poor water solubility of this compound hampers an effective in vivo cancer study. We prepared new ionic derivatives of betulinic acid with higher water solubilities, without losing the structural integrity and functionality of this compound. As a result, these new ionic derivatives have shown much higher inhibitory effects against different cancer cell lines such as melanoma A375, neuroblastoma SH-SY5Y and breast adenocarcinoma MCF7. For A375 cell lines, the derivative 5 exhibited a low IC(50) value of 36 μM (vs 154 μM for betulinic acid); for MCF7 cell lines, the derivative 5 also exhibited a low IC(50) value of 25 μM (vs 112 μM for betulinic acid). The high cytotoxicity of these new derivatives can be linked to their greatly improved water solubility. Our assay method used little DMSO in aiding the dissolution of these derivatives to demonstrate the advantage of improved water solubility and to mimic the in vivo study conditions. The cell viability studies based on both MTT and LDH assay methods have confirmed the high inhibitory effect of our ionic derivatives of betulinic acid (particularly 4 and 5) against different cancer cells.

  1. Synthesis and performance evaluation of the new thickening agent of acidizing fluid

    NASA Astrophysics Data System (ADS)

    Tian, Zhenxing; Lv, Tong; Ren, Yanmei

    2010-07-01

    An acid thickener, poly (AMPS-co-DMC) was synthesized using water aqueous solution polymerization of these monomers such as 2-acrylamide-2-methylpropanesulfonic acid (AMPS) and [2-(Methacryloyloxy) ethyl] trimethylammonium chloride (DMC), with ammonium persulfate and sodium sulfite redox system as initiator, while at 65°C, 25% of the total concentration of monomer, initiator dosage of 1.6% for the monomer mass and nitrogen protection condition. The paper discussed the property evaluation of poly(AMPS-co-DMC), it was shown that poly (AMPS-co-DMC) had good acid solubility (time for dissolving in acid is 21 min); acid containing 5.0% of poly(AMPSco-DMC) had a viscosity of greater than 25.0mPa•s the shearing stability and heat resistance of the system was good and over 90% at a shear rate of 170s-1; poly(AMPS-co-DMC) performed well in the presence of standard saline at a total concentration of 40000mg/L.

  2. Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments

    PubMed Central

    Nwe, Kido; Huang, Ching-Hui; Tsourkas, Andrew

    2013-01-01

    Neoplastic lesions can create a hostile tumor microenvironment with low extracellular pH. It is commonly believed that these conditions can contribute to tumor progression and resistance to therapy. We report the development and characterization of a pH-responsive magnetic resonance imaging contrast agent, for imaging the acidic tumor microenvironment. The preparation included conjugation of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid 1-(2,5-dioxo-1-pyrrolidinyl) ester (DOTA-NHS) to the surface of a water soluble glycol chitosan (GC) polymer, which contains pH titrable primary amines, followed by gadolinium complexation (GC-NH2-GdDOTA). GC-NH2-GdDOTA had a chelate to polymer ratio of approximately1:24 and a molar relaxivity of 9.1 mM−1s−1. GC-NH2-GdDOTA demonstrated pH-dependent cellular association in vitro compared to the control. It also generated a 2.4-fold enhancement in signal in tumor bearing mice 2 h post-injection. These findings suggest that glycol chitosan coupled with contrast agents can provide important diagnostic information about the tumor microenvironment. PMID:24044414

  3. Aminolevulinic Acid-Photodynamic Therapy Combined with Topically Applied Vascular Disrupting Agent Vadimezan Led to Enhanced Antitumor Responses

    PubMed Central

    Marrero, Allison; Becker, Theresa; Sunar, Ulas; Morgan, Janet; Bellnier, David

    2011-01-01

    The tumor-vascular disrupting agent (VDA) vadimezan (5,6-dimethylxanthenone-4-acetic acid, DMXAA) has been shown to potentiate the antitumor activity of photodynamic therapy (PDT) using systemically administered photosensitizers. Here, we characterized the response of subcutaneous syngeneic Colon26 murine colon adenocarcinoma tumors to PDT using the locally applied photosensitizer precursor aminolevulinic acid (ALA) in combination with a topical formulation of vadimezan. Diffuse correlation spectroscopy (DCS), a non-invasive method for monitoring blood flow, was utilized to determine tumor vascular response to treatment. Additionally, correlative CD31-immunohistochemistry to visualize endothelial damage, ELISA assays to measure induction of tumor necrosis factor-alpha (TNF-α) and tumor weight measurements were also examined in separate animals. In our previous work, DCS revealed a selective decrease in tumor blood flow over time following topical vadimezan. ALA-PDT treatment also induced a decrease in tumor blood flow. The onset of blood flow reduction was rapid in tumors treated with both ALA-PDT and vadimezan. CD31-immunostaining of tumor sections confirmed vascular damage following topical application of vadimezan. Tumor weight measurements revealed enhanced tumor growth inhibition with combination treatment compared to ALA-PDT or vadimezan treatment alone. In conclusion, vadimezan as a topical agent enhances treatment efficacy when combined with ALA-PDT. This combination could be useful in clinical applications. PMID:21575001

  4. Synthesis and characterization of a new retinoic acid ECPIRM as potential chemotherapeutic agent for human cutaneous squamous carcinoma.

    PubMed

    Zhang, Mengli; Tao, Yue; Ma, Pengcheng; Wang, Dechuan; He, Chundi; Cao, Yuping; Wei, Jun; Li, Lingjun; Tao, Lei

    2015-01-01

    Cutaneous squamous cell carcinoma (CSCC) is one of the most common cancers worldwide, requiring effective therapeutic interventions. Retinoids are important chemopreventive and therapeutic agents for a variety of human cancers including CSCC. In this study we synthesized a novel retinoic derivative N-(4-ethoxycarbonylphenyl) isoretinamide (ECPIRM) and evaluated its biological activities and possible mechanisms in human cutaneous squamous cell lines. ECPIRM had better inhibitory effect on the proliferation of squamous carcinoma cells SCL-1 and colo-16, compared with All-trans retinoic acid and 13-cis retinoic acid. ECPIRM had less toxicity to normal keratinocyte cell line HaCaT. Mechanistically, ECPIRM induced G1 cell cycle arrest in SCL-1 cells, via the downregulation of CDK2, CDK4, cycling D1 and cyclin E expression and upregulation of p21. In addition, these effects were at least partially due to the inhibition of JNK/ ERK-AP-1 signaling pathway by ECPIRM. Importantly, these effects of ECPIRM are independent of the classical retinoid receptor pathway, suggesting that the novel compound will have less side-effects in chemotherapy. These findings demonstrate that ECPIRM is a potential inhibitor of MPAK-AP-1 pathway, and is a potential therapeutic agent against CSCC.

  5. Synthesis and characterization of a new retinoic acid ECPIRM as potential chemotherapeutic agent for human cutaneous squamous carcinoma.

    PubMed

    Zhang, Mengli; Tao, Yue; Ma, Pengcheng; Wang, Dechuan; He, Chundi; Cao, Yuping; Wei, Jun; Li, Lingjun; Tao, Lei

    2015-01-01

    Cutaneous squamous cell carcinoma (CSCC) is one of the most common cancers worldwide, requiring effective therapeutic interventions. Retinoids are important chemopreventive and therapeutic agents for a variety of human cancers including CSCC. In this study we synthesized a novel retinoic derivative N-(4-ethoxycarbonylphenyl) isoretinamide (ECPIRM) and evaluated its biological activities and possible mechanisms in human cutaneous squamous cell lines. ECPIRM had better inhibitory effect on the proliferation of squamous carcinoma cells SCL-1 and colo-16, compared with All-trans retinoic acid and 13-cis retinoic acid. ECPIRM had less toxicity to normal keratinocyte cell line HaCaT. Mechanistically, ECPIRM induced G1 cell cycle arrest in SCL-1 cells, via the downregulation of CDK2, CDK4, cycling D1 and cyclin E expression and upregulation of p21. In addition, these effects were at least partially due to the inhibition of JNK/ ERK-AP-1 signaling pathway by ECPIRM. Importantly, these effects of ECPIRM are independent of the classical retinoid receptor pathway, suggesting that the novel compound will have less side-effects in chemotherapy. These findings demonstrate that ECPIRM is a potential inhibitor of MPAK-AP-1 pathway, and is a potential therapeutic agent against CSCC. PMID:25991427

  6. Persistent induction of nitric oxide synthase in tumours from mice treated with the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid.

    PubMed

    Moilanen, E; Thomsen, L L; Miles, D W; Happerfield, D W; Knowles, R G; Moncada, S

    1998-01-01

    An anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA) induced nitric oxide synthase (NOS) in the tumour, spleen, thymus and small intestine, but not in the lung, liver, kidney, heart or skeletal muscle in B6D2F1 mice bearing subcutaneous colon 38 tumours. This pattern of induction is distinct from that caused by agents such as endotoxin, muramyl dipeptide or Corynebacterium parvum. The induction of NOS (iNOS) in the tumour was more persistent (maximal at 3 days) than in other tissues (maximal at 12 h). Immunohistochemical staining suggested that iNOS was located in macrophages and endothelial cells within and around the tumour. Treatment with 5,6-MeXAA also caused substantial increases in plasma nitrite and nitrate (NOx) concentrations that peaked at 8-12 h after 5,6-MeXAA. The increase in plasma NOx was prevented by a NOS inhibitor N-iminoethyl-L-ornithine (L-NIO), indicating that it was due to enhanced production of NO. Tumour-bearing mice were more responsive than controls to 5,6-MeXAA both in their plasma NOx increase and in their lower maximally tolerated dose. L-NIO was unable to prevent the complete tumour necrosis and regression caused by 5,6-MeXAA at a dose that substantially inhibited the increase of plasma NOx. In conclusion, the experimental anti-tumour agent 5,6-MeXAA induced NO synthesis in tumour-associated macrophages and in immunologically active tissues in parallel with its effects on tumour growth. The experiments with a non-selective NOS inhibitor L-NIO, however, suggest that NO is not a significant component in the mechanism of the anti-tumour action of 5,6-MeXAA in this particular model. PMID:9472639

  7. Cost benefit analysis of the use of tranexamic acid in primary lower limb arthroplasty: A retrospective cohort study

    PubMed Central

    McGoldrick, Niall P; O’Connor, Eabhann M; Davarinos, Nikos; Galvin, Rose; Quinlan, John F

    2015-01-01

    AIM: To examine the cost benefit conferred by the perioperative administration of intravenous tranexamic acid (TXA) in lower limb arthroplasty. METHODS: This study evaluates the use of TXA in 200 consecutive lower limb arthroplasties performed in a single surgeon series. The initial 100 patients (control group) underwent surgery without perioperative administration of TXA while the subsequent 100 patients (TXA group) all received 1 g TXA at the time of induction of anaesthesia. Pre- and post-operative haemoglobin, platelet count, haematocrit, the use of blood product post-operatively, length of stay were examined. A financial analysis of both groups was then undertaken. RESULTS: The mean age of patients in both groups was 63 ± 13 years. There were no significant differences between groups in terms of gender (P = 0.47), proportion of total hip replacement to total knee replacement (P = 0.25) or pre-operative haemoglobin (P = 0.43). In the control group, the transfusion rate was 22%. In the TXA group, the transfusion rate dropped to 2% (P < 0.001). The mean post-operative haemoglobin was 10.82 ± 1.55 g/dL in the control group vs 11.33 ± 1.27 g/dL in the TXA group (P = 0.01). The total cost of transfused blood products was €11055 and €603 respectively. The mean length of stay in the control group was 6.53 ± 5.93 d vs 5.47 ± 4.26 d in the TXA group (P = 0.15) leading to an estimated financial saving of €114586. There was one pulmonary embolus in the control group and one deep venous thrombosis in the TXA group. CONCLUSION: Intravenous TXA reduces blood loss in lower limb arthroplasty. This leads to lower transfusion rates, shorter length of stay in hospital and significant financial savings. PMID:26716094

  8. Label-free functional nucleic acid sensors for detecting target agents

    SciTech Connect

    Lu, Yi; Xiang, Yu

    2015-01-13

    A general methodology to design label-free fluorescent functional nucleic acid sensors using a vacant site approach and an abasic site approach is described. In one example, a method for designing label-free fluorescent functional nucleic acid sensors (e.g., those that include a DNAzyme, aptamer or aptazyme) that have a tunable dynamic range through the introduction of an abasic site (e.g., dSpacer) or a vacant site into the functional nucleic acids. Also provided is a general method for designing label-free fluorescent aptamer sensors based on the regulation of malachite green (MG) fluorescence. A general method for designing label-free fluorescent catalytic and molecular beacons (CAMBs) is also provided. The methods demonstrated here can be used to design many other label-free fluorescent sensors to detect a wide range of analytes. Sensors and methods of using the disclosed sensors are also provided.

  9. Effect of sweetening agents in acidic beverages on associated erosion lesions.

    PubMed

    Bassiouny, Mohamed A

    2012-01-01

    Accurate diagnosis of erosion defects caused by acidic beverages is essential when designing a comprehensive management strategy that includes combating possible recurrence. The manifestations of erosion lesions associated with acidic beverages are diverse, as seen in the differences and similarities of lesions associated with various regular and diet varieties of beverages. Erosion lesions caused by regular sugar-sweetened beverages display signs similar to dental caries, while lesions resulting from diet, non-sugar-sweetened soft drinks have defects similar to mechanical wear of the dentition. Aggravating factors such as toothbrushing or compromised oral home care could influence the features of erosion lesions. These diverse characteristics of erosion lesions could make identification difficult. This article describes pertinent signs of erosion defects associated with the regular and diet varieties of acidic beverages and discusses their causative factors. This information is designed to avert an improper diagnosis that would derail any restorative intervention and alter a proper preventive management course.

  10. Citric acid and ethylene diamine tetra-acetic acid as effective washing agents to treat sewage sludge for agricultural reuse.

    PubMed

    Ren, Xianghao; Yan, Rui; Wang, Hong-Cheng; Kou, Ying-Ying; Chae, Kyu-Jung; Kim, In S; Park, Yong-Jin; Wang, Ai-Jie

    2015-12-01

    This paper presents the effects of different concentrations of citric acid (CA) and ethylene diamine tetra-acetic acid (EDTA) when used as additive reagents for the treatment of sewage sludge for agricultural use. Herein, both the retention of nutrients and removal of metals from the sewage sludge are examined. The average removal rate for the metals after treatment by CA decreased in the order Cu>Pb>Cd>Cr>Zn, while the rates after treatment by EDTA decreased in the order of Pb>Cu>Cr>Cd>Zn. After treatment with CA and EDTA, total nitrogen and total phosphorus concentrations in the sludge decreased, while the content of available nitrogen and Olsen-P increased. In addition, a multi-criteria analysis model-fuzzy analytic network process method (with 3 main factors and 12 assessment sub-factors) was adopted to evaluate the effectiveness of different treatment methods. The results showed that the optimal CA and EDTA concentrations for sewage sludge treatment were 0.60 and 0.125 mol/L, respectively.

  11. Citric acid and ethylene diamine tetra-acetic acid as effective washing agents to treat sewage sludge for agricultural reuse.

    PubMed

    Ren, Xianghao; Yan, Rui; Wang, Hong-Cheng; Kou, Ying-Ying; Chae, Kyu-Jung; Kim, In S; Park, Yong-Jin; Wang, Ai-Jie

    2015-12-01

    This paper presents the effects of different concentrations of citric acid (CA) and ethylene diamine tetra-acetic acid (EDTA) when used as additive reagents for the treatment of sewage sludge for agricultural use. Herein, both the retention of nutrients and removal of metals from the sewage sludge are examined. The average removal rate for the metals after treatment by CA decreased in the order Cu>Pb>Cd>Cr>Zn, while the rates after treatment by EDTA decreased in the order of Pb>Cu>Cr>Cd>Zn. After treatment with CA and EDTA, total nitrogen and total phosphorus concentrations in the sludge decreased, while the content of available nitrogen and Olsen-P increased. In addition, a multi-criteria analysis model-fuzzy analytic network process method (with 3 main factors and 12 assessment sub-factors) was adopted to evaluate the effectiveness of different treatment methods. The results showed that the optimal CA and EDTA concentrations for sewage sludge treatment were 0.60 and 0.125 mol/L, respectively. PMID:26235448

  12. Boronated Unnatural Cyclic Amino Acids as Potential Delivery Agents for Neutron Capture Therapy

    PubMed Central

    Kabalka, George W.; Shaikh, Aarif L.; Barth, Rolf F.; Huo, Tianyao; Yang, Weilian; Gordnier, Pamela M.; Chandra, Subhash

    2011-01-01

    Boron delivery characteristics of cis and trans isomers of a boronated unnatural amino acid, 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC) were tested in B16 mouse model for human melanoma. Both ABCPC isomers delivered comparable boron to B16 melanoma tumor cells as L-p-boronophenylalanine (BPA). Secondary ion mass spectrometry (SIMS) analysis revealed the presence of boron throughout the tumor from these compounds, and a near homogeneous distribution between the nucleus and cytoplasm of B16 cells grown in vitro. These encouraging observations support further studies of these new boron carriers in BNCT. PMID:21481596

  13. Activatable hyaluronic acid nanoparticle as a theranostic agent for optical/photoacoustic image-guided photothermal therapy.

    PubMed

    Zhang, Liwen; Gao, Shi; Zhang, Fan; Yang, Kai; Ma, Qingjie; Zhu, Lei

    2014-12-23

    Photothermal therapy (PTT) is an emerging treatment modality that is under intensive preclinical investigations for the treatment of various medical conditions, including cancer. However, the lack of targeting function of PTT agents hampers its clinical application. An effective and nontoxic delivery vehicle that can carry PTT agents into tumor areas is still needed urgently. In this study, we developed a multifunctional nanocomposite by loading copper sulfide (CuS) into Cy5.5-conjugated hyaluronic acid nanoparticles (HANP), obtaining an activatable Cy5.5-HANP/CuS (HANPC) nanocomposite. In this system, Cy5.5 fluorescent signal is quenched by CuS inside the particle until the whole nanocomposite is degraded by hyaluronidase present in tumor, giving strong fluorescence signals delineating the tumor. Importantly, CuS with strong NIR absorbance appears to be an excellent contrast agent for photoacoustic (PA) imaging and an effective PTT agent. After intravenous administration of HANPC into SCC7 tumor-bearing mice, high fluorescence and PA signals were observed in the tumor area over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.25±0.25 for optical imaging and 3.8±0.42 for PA imaging). The tumors were then irradiated with a laser, and a good tumor inhibition rate (89.74% on day 5) was observed. Our studies further encourage application of this HA-based multifunctional nanocomposite for image-guided PTT in biomedical applications, especially in cancer theranostics. PMID:25402600

  14. Effects of six anaesthetic agents on UDP-glucuronic acid and other nucleotides in rat liver.

    PubMed

    Christensson, P I; Eriksson, G

    1985-08-01

    Anaesthesia affects the liver nucleotide pool. It was the aim of the present study to examine how anaesthesia for 60 min with pentobarbital, ketamin + diazepam, halothane, enflurane and isoflurane may influence the nucleotide pool in the rat liver, studied with isotachophoresis. It was found that none of the agents gave both safe and reproducible anaesthesia without affecting the nucleotide pools or affecting the experiments in some other way. Halothane and isoflurane were the two best alternatives with respect to both efficiency and safety. Isoflurane may be preferable since it gives a higher energy charge.

  15. The blood pressure-lowering effect and safety of chlorogenic acid from green coffee bean extract in essential hypertension.

    PubMed

    Watanabe, Takuya; Arai, Yoichi; Mitsui, Yuki; Kusaura, Tatsuya; Okawa, Wataru; Kajihara, Yasushi; Saito, Ikuo

    2006-07-01

    Chlorogenic acids (CGA) in green coffee bean extract (GCE) reduce blood pressure in spontaneously hypertensive rats and humans. The authors examined the blood pressure-lowering effect and safety of CGA in patients with mild hypertension through a placebo-controlled, randomized clinical trial. Subjects (n = 28) were randomized to receive treatment with CGA (140 mg/day) from GCE or placebo. Blood pressure, pulse rate, body mass index, routine blood test, hematochemistry, urinalysis, and subjective symptoms were recorded throughout the study. In the CGA group, but not the placebo group, blood pressure (systolic and diastolic) decreased significantly during the ingestion period. There was no difference in body mass index and pulse rate between groups, nor were there any apparent side effects. Thus, CGA from GCE is effective in decreasing blood pressure and safe for patients with mild hypertension.

  16. Barbituric acid-based magnetic N-halamine nanoparticles as recyclable antibacterial agents.

    PubMed

    Dong, Alideertu; Sun, Yue; Lan, Shi; Wang, Qin; Cai, Qian; Qi, Xiuzhen; Zhang, Yanling; Gao, Ge; Liu, Fengqi; Harnoode, Chokto

    2013-08-28

    Novel recyclable bactericidal materials, barbituric acid-based magnetic N-halamine nanoparticles (BAMNH NPs), were fabricated by coating of magnetic silica nanoparticles (MS NPs) with barbituric acid-based N-halamine by the aid of the radical polymerization. The sterilizing effect on the bacterial strain is investigated by incubating Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis). The as-prepared BAMNH NPs exhibit higher biocidal activity than the bulk powder barbituric acid-based N-halamine due to the high activated surface area. The structural effect of N-halamine on antimicrobial performance was fully clarified through the comparison between BAMNH NPs and hydantoin-based magnetic N-halamine nanoparticles (HMNH NPs). BAMNH NPs exhibited promising stability toward repeated washing and long-term storage. BAMNH NPs with different chlorine content were comparatively chosen to investigate the influence of chlorine content on the antimicrobial activity. An antibacterial recycle experiment revealed that no significant change occurred in the structure and antibacterial efficiency of BAMNH NPs after five recycle experiments. The combination of barbituric acid-based N-halamine with magnetic component results in an obvious synergistic effect and facilitates the repeated antibacterial applications, providing potential and ideal candidates for sterilization or even for the control of disease.

  17. Dimercaptosuccinic acid: A multifunctional cost effective agent for imaging and therapy

    PubMed Central

    Shukla, Jaya; Mittal, Bhagwant Rai

    2015-01-01

    Dimercaptosuccinic acid (DMSA) is an analog of dimercaprol used as metal chelating moiety in variety of conditions. In nuclear medicine itself two types of Tc-99m DMSA complexes are used, trivalent and pentavalent forms. In this review, we have discussed the mechanism of uptake of both complexes as well as diagnostic and therapeutic application in a clinical scenario. PMID:26430311

  18. Novel cinnamic acid derivatives as antioxidant and anticancer agents: design, synthesis and modeling studies.

    PubMed

    Pontiki, Eleni; Hadjipavlou-Litina, Dimitra; Litinas, Konstantinos; Geromichalos, George

    2014-07-07

    Cinnamic acids have been identified as interesting compounds with antioxidant, anti-inflammatory and cytotoxic properties. In the present study, simple cinnamic acids were synthesized by Knoevenagel condensation reactions and evaluated for the above biological activities. Compound 4ii proved to be the most potent LOX inhibitor. Phenyl- substituted acids showed better inhibitory activity against soybean LOX, and it must be noted that compounds 4i and 3i with higher lipophilicity values resulted less active than compounds 2i and 1i. The compounds have shown very good activity in different antioxidant assays. The antitumor properties of these derivatives have been assessed by their 1/IC50 inhibitory values in the proliferation of HT-29, A-549, OAW-42, MDA-MB-231, HeLa and MRC-5 normal cell lines. The compounds presented low antitumor activity considering the IC50 values attained for the cell lines, with the exception of compound 4ii. Molecular docking studies were carried out on cinnamic acid derivative 4ii and were found to be in accordance with our experimental biological results.

  19. Boric acid: a potential chemoprotective agent against aflatoxin b1 toxicity in human blood

    PubMed Central

    Geyikoglu, Fatime

    2010-01-01

    Aflatoxin B1 is the most potent pulmonary and hepatic carcinogen. Since the eradication of Aflatoxin B1 contamination in agricultural products has been difficult, the use of natural or synthetic free radical scavengers could be a potential chemopreventive strategy. Boric acid is the major component of industry and its antioxidant role has recently been reported. The present study assessed, for the first time, the effectiveness of boric acid following exposure to Aflatoxin B1 on human whole blood cultures. The biochemical characterizations of glutathione and some enzymes have been carried out in erythrocytes. Alterations in malondialdehyde level were determined as an index of oxidative stress. The sister-chromatid exchange and micronucleus tests were performed to assess DNA damages in lymphocytes. Aflatoxin B1 treatment significantly reduced the activities of antioxidants by increasing malondialdehyde level (30.53 and 51.43%) of blood, whereas, the boric acid led to an increased resistance of DNA to oxidative damage induced by Aflatoxin B1 in comparison with control values (P < 0.05). In conclusion, the support of boric acid was especially useful in Aflatoxin-toxicated blood. Thus the risk on tissue targeting of Aflatoxin B1 could be reduced ensuring early recovery from its toxicity. PMID:20431944

  20. Augmenting antifungal activity of oxidizing agent with kojic acid: Control of Penicillium strains infecting crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative treatment is a strategy for preventing Penicillium contamination in foods or crops. Antifungal efficacy of oxidant [hydrogen peroxide (H2O2)], biotic effector [kojic acid (KA)] and abiotic stress (heat), alone or in combination, was investigated in Penicillium. The levels of antifungal int...

  1. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines.

    PubMed

    Choi, Sujean; Disilvio, Briana; Fernstrom, Madelyn H; Fernstrom, John D

    2013-11-01

    Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge. PMID:23904096

  2. Complementary Cholesterol-Lowering Response of a Phytosterol/α-Lipoic Acid Combination in Obese Zucker Rats.

    PubMed

    Rideout, Todd C; Carrier, Bradley; Wen, Shin; Raslawsky, Amy; Browne, Richard W; Harding, Scott V

    2016-01-01

    To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (-55%) than either the PS (-24%) or the αLA (-25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (-47%) or in combination with PS (-54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21-22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (+52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone.

  3. Magnesium hydroxide as the neutralizing agent for radioactive hydrochloric acid solutions

    SciTech Connect

    Palmer, M.J.; Fife, K.W.

    1995-10-01

    The current technology at Los Alamos for removing actinides from acidic chloride waste streams is precipitation with approximately 10 M potassium hydroxide. Although successful, there are many inherent drawbacks to this precipitation technique which will be detailed in this paper. Magnesium hydroxide (K{sub sp} = 1.3 x 10{sup -11}) has limited solubility in water and as a result of the common ion effect, cannot generate a filtrate with a pH greater than 9. At a pH of 9, calcium (K{sub sp} = 5.5 x 10{sup -6}) will not coprecipitate as the hydroxide. This is an important factor since many acidic chloride feeds to hydroxide precipitation contain significant amounts of calcium. In addition, neutralization with Mg(OH){sub 2} produces a more filterable precipitate because neutralization occurs as the Mg(OH){sub 2} is dissolved by the acid rather than as a result of the much faster liquid/liquid reaction of KOH with the waste acid. This slower solid/liquid reaction allows time for crystal growth to occur and produces more easily filterable precipitates. On the other hand, neutralization of spent acid with strong KOH that yields numerous hydroxide ions in solution almost instantaneously forming a much larger volume of small crystallites that result in gelatinous, slow-filtering precipitates. Magnesium hydroxide also offers a safety advantage. Although mildly irritating, it is a weak base and safe and easy to handle. From a waste minimization perspective, Mg(OH){sub 2} offers many advantages. First, the magnesium hydroxide is added as a solid. This step eliminates the diluent water used in KOH neutralizations. Secondly, because the particle size of the precipitate is larger, more actinides are caught on the filter paper resulting in a smaller amount of actinide being transferred to the TA-50 Liquid Waste Treatment Facility. Third, the amount of solids that must be reprocessed is significantly smaller resulting in less waste generation from the downstream processes.

  4. Salts of hexamethylenetetramine with organic acids: Enhanced anomeric interactions with a lowering of molecular symmetry revealed by crystal structures

    NASA Astrophysics Data System (ADS)

    Chandrasekhar, Sosale; Mukherjee, Somnath

    2015-02-01

    The hexamethylenetetramine (HMT) framework displays interesting stereoelectronic interactions of the anomeric type. In the highly symmetrical parent system, the nitrogen centres act as both donors and acceptors. Protonation lowers symmetry and also leads to an enhancement of the anomeric interaction around the protonated centre. X-ray diffraction crystal structures of four derivatives of HMT - with succinic, (DL)-malic, phthalic and 4-hydroxybenzoic acids - reveal significant trends. (The first three form well-defined salts, 4-hydroxybenzoic acid forming a co-crystalline compound.) Each molecular structure is essentially characterised by a major anomeric interaction involving the protonated centre as acceptor. In two cases (succinic and 4-hydroxybenzoic), secondary protonation leads to a weaker anomeric interaction site that apparently competes with the dominant one. Bond length changes indicate that the anomeric interaction decreases as malic > phthalic > succinic > 4-hydroxybenzoic, which correlates with the degree of proton transfer to the nitrogen centre. Along with other bond length and angle changes, the results offer insight into the applicability of the antiperiplanar lone pair hypothesis (ALPH) in a rigid system.

  5. Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models.

    PubMed

    Diekman, Eugene F; van Weeghel, Michel; Wanders, Ronald J A; Visser, Gepke; Houten, Sander M

    2014-07-01

    Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited disorder of mitochondrial long-chain fatty acid β-oxidation (FAO). Patients with VLCAD deficiency may present with hypoglycemia, hepatomegaly, cardiomyopathy, and myopathy. Although several mouse models have been developed to aid in the study of the pathogenesis of long-chain FAO defects, the muscular phenotype is underexposed. To address the muscular phenotype, we used a newly developed mouse model on a mixed genetic background with a more severe defect in FAO (LCAD(-/-); VLCAD(+/-)) in addition to a validated mouse model (LCAD(-/-); VLCAD(+/+)) and compared them with wild-type (WT) mice. We found that both mouse models show a 20% reduction in energy expenditure (EE) and a 3-fold decrease in locomotor activity in the unfed state. In addition, we found a 1.7°C drop in body temperature in unfed LCAD(-/-); VLCAD(+/+) mice compared with WT body temperature. We conclude that food withdrawal-induced inactivity, hypothermia, and reduction in EE are novel phenotypes associated with FAO deficiency in mice. Unexpectedly, inactivity was not explained by rhabdomyolysis, but rather reflected the overall reduced capacity of these mice to generate heat. We suggest that mice are partly protected against the negative consequence of an FAO defect.-Diekman, E. F., van Weeghel, M., Wanders, R. J. A., Visser, G., Houten, S. M. Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models.

  6. Lower vegetable protein intake and higher dietary acid load associated with lower carbohydrate intake are risk factors for metabolic syndrome in patients with type 2 diabetes: Post-hoc analysis of a cross-sectional study

    PubMed Central

    Iwase, Hiroya; Tanaka, Muhei; Kobayashi, Yukiko; Wada, Sayori; Kuwahata, Masashi; Kido, Yasuhiro; Hamaguchi, Masahide; Asano, Mai; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto; Fukui, Michiaki

    2015-01-01

    Aims/Introduction A low-carbohydrate diet based on animal sources is associated with higher all-cause mortality, whereas a vegetable-based low-carbohydrate diet is associated with lower cardiovascular disease mortality. It has been suggested that acid/base imbalance might play an important role in some cardiometabolic abnormalities. The aims of the present study were to evaluate whether carbohydrate intake is associated with quality of dietary protein and acid load, and whether these are related to metabolic syndrome in patients with type 2 diabetes. Materials and Methods The present cross-sectional study involved 149 patients with type 2 diabetes. Dietary intake was assessed using a validated self-administered diet history questionnaire. Dietary acid load was assessed by potential renal acid load and net endogenous acid production. Results Mean daily total energy intake, carbohydrate intake, animal protein intake and vegetable protein intake were 1821.5 kcal, 248.8 g, 36.1 g and 31.1 g, respectively. Carbohydrate energy/total energy was negatively correlated with animal protein energy/total energy, potential renal acid load or net endogenous acid production score, and was positively correlated with vegetable protein energy/total energy. Logistic regression analyses showed that the subgroup of patients with a lower vegetable protein energy/total energy or higher potential renal acid load or net endogenous acid production score was significantly associated with the prevalence of metabolic syndrome. Conclusions The present study showed that carbohydrate intake was associated with the quality of dietary protein and dietary acid load. Furthermore, decreased vegetable protein intake and increased dietary acid load were associated with the prevalence of metabolic syndrome. PMID:26221526

  7. Lower Serum Levels of Uric Acid in Uterine Fibroids and Fibrocystic Breast Disease Patients in Dongying City, China

    PubMed Central

    CHEN, Qicai; XIAO, Juan; ZHANG, Pengpeng; CHEN, Lili; CHEN, Xiaoxiao; WANG, Shumei

    2016-01-01

    Background: Increasing serum levels of uric acid (SUA) after menopause in women brought up a hypothesis that estrogenic effect may protectively regulate SUA. Estrogenic effect is a major etiology of uterine fibroids and fibrocystic breast disease. The study aimed to explore SUA among patients suffering from these diseases to enhance the hypothesis. Methods: Overall, 1349 female participants were selected into three cases: Case I having uterine fibroids (n=568), Case II having fibrocycstic breast disease (n=608) and Case III having uterine fibroids combining with fibrocycstic breast disease (n=173); 4206 participants without these diseases were selected as controls. Based on health check-up data from 2011 to 2012, in Dongying Shengli Oilfield Central Hospital, a cross-sectional study was conducted to examine the difference in SUA between the case and control. We adjusted covariates by generalized linear regression mode. Results: From 19 to 44 yr, SUA of Case I to Case III were lower than controls by 8.46 umol/L (P=0.011), 5.88umol/L (P=0.014) and 9.39 umol/L (P=0.059), respectively. From 45–54 yr, no significant differences were between three cases and controls. In Case I and its control: from 54–59 yr, differences were not significant; from 60 to 72 yr, SUA in Case I was lower than the control by 32.02umol/L (P=0.003). Conclusion: Participants of uterine fibroids and fibrocystic breast disease had a lower SUA except the stage of menopause, which indirectly supported that estrogenic effect, may protectively decrease SUA. PMID:27398332

  8. Complex chemical composition of colored surface films formed from reactions of propanal in sulfuric acid at upper troposphere/lower stratosphere aerosol acidities

    PubMed Central

    Van Wyngarden, A. L.; Pérez-Montaño, S.; Bui, J. V. H.; Li, E. S. W.; Nelson, T. E.; Ha, K. T.; Leong, L.; Iraci, L. T.

    2016-01-01

    Particles in the upper troposphere and lower stratosphere (UT/LS) consist mostly of concentrated sulfuric acid (40–80 wt %) in water. However, airborne measurements have shown that these particles also contain a significant fraction of organic compounds of unknown chemical composition. Acid-catalyzed reactions of carbonyl species are believed to be responsible for significant transfer of gas phase organic species into tropospheric aerosols and are potentially more important at the high acidities characteristic of UT/LS particles. In this study, experiments combining sulfuric acid (H2SO4) with propanal and with mixtures of propanal with glyoxal and/or methylglyoxal at acidities typical of UT/LS aerosols produced highly colored surface films (and solutions) that may have implications for aerosol properties. In order to identify the chemical processes responsible for the formation of the surface films, attenuated total reflectance–Fourier transform infrared (ATR-FTIR) and 1H nuclear magnetic resonance (NMR) spectroscopies were used to analyze the chemical composition of the films. Films formed from propanal were a complex mixture of aldol condensation products, acetals and propanal itself. The major aldol condensation products were the dimer (2-methyl-2-pentenal) and 1,3,5-trimethylbenzene that was formed by cyclization of the linear aldol condensation trimer. Additionally, the strong visible absorption of the films indicates that higher-order aldol condensation products must also be present as minor species. The major acetal species were 2,4,6-triethyl-1,3,5-trioxane and longer-chain linear polyacetals which are likely to separate from the aqueous phase. Films formed on mixtures of propanal with glyoxal and/or methylglyoxal also showed evidence of products of cross-reactions. Since cross-reactions would be more likely than self-reactions under atmospheric conditions, similar reactions of aldehydes like propanal with common aerosol organic species like glyoxal and

  9. Complex chemical composition of colored surface films formed from reactions of propanal in sulfuric acid at upper troposphere/lower stratosphere aerosol acidities

    NASA Astrophysics Data System (ADS)

    Van Wyngarden, A. L.; Pérez-Montaño, S.; Bui, J. V. H.; Li, E. S. W.; Nelson, T. E.; Ha, K. T.; Leong, L.; Iraci, L. T.

    2014-11-01

    Particles in the upper troposphere and lower stratosphere (UT/LS) consist mostly of concentrated sulfuric acid (40-80 wt %) in water. However, airborne measurements have shown that these particles also contain a significant fraction of organic compounds of unknown chemical composition. Acid-catalyzed reactions of carbonyl species are believed to be responsible for significant transfer of gas phase organic species into tropospheric aerosols and are potentially more important at the high acidities characteristic of UT/LS particles. In this study, experiments combining sulfuric acid (H2SO4) with propanal and with mixtures of propanal with glyoxal and/or methylglyoxal at acidities typical of UT/LS aerosols produced highly colored surface films (and solutions) that may have implications for aerosol properties. In order to identify the chemical processes responsible for the formation of the surface films, Attenuated Total Reflectance-Fourier Transform Infrared and 1H Nuclear Magnetic Resonance spectroscopies were used to analyze the chemical composition of the films. Films formed from propanal were a complex mixture of aldol condensation products, acetals and propanal itself. The major aldol condensation products were the dimer (2-methyl-2-pentenal) and 1,3,5-trimethylbenzene, which was formed by cyclization of the linear aldol condensation trimer. Additionally, the strong visible absorption of the films indicates that higher order aldol condensation products must also be present as minor species. The major acetal species were 2,4,6-triethyl-1,3,5-trioxane and longer-chain linear polyacetals which are likely to separate from the aqueous phase. Films formed on mixtures of propanal with glyoxal and/or methylglyoxal also showed evidence for products of cross-reactions. Since cross-reactions would be more likely than self-reactions under atmospheric conditions, similar reactions of aldehydes like propanal with common aerosol organic species like glyoxal and methylglyoxal

  10. Complex chemical composition of colored surface films formed from reactions of propanal in sulfuric acid at upper troposphere/lower stratosphere aerosol acidities

    NASA Astrophysics Data System (ADS)

    Van Wyngarden, A. L.; Pérez-Montaño, S.; Bui, J. V. H.; Li, E. S. W.; Nelson, T. E.; Ha, K. T.; Leong, L.; Iraci, L. T.

    2015-04-01

    Particles in the upper troposphere and lower stratosphere (UT/LS) consist mostly of concentrated sulfuric acid (40-80 wt%) in water. However, airborne measurements have shown that these particles also contain a significant fraction of organic compounds of unknown chemical composition. Acid-catalyzed reactions of carbonyl species are believed to be responsible for significant transfer of gas phase organic species into tropospheric aerosols and are potentially more important at the high acidities characteristic of UT/LS particles. In this study, experiments combining sulfuric acid (H2SO4) with propanal and with mixtures of propanal with glyoxal and/or methylglyoxal at acidities typical of UT/LS aerosols produced highly colored surface films (and solutions) that may have implications for aerosol properties. In order to identify the chemical processes responsible for the formation of the surface films, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) and 1H nuclear magnetic resonance (NMR) spectroscopies were used to analyze the chemical composition of the films. Films formed from propanal were a complex mixture of aldol condensation products, acetals and propanal itself. The major aldol condensation products were the dimer (2-methyl-2-pentenal) and 1,3,5-trimethylbenzene that was formed by cyclization of the linear aldol condensation trimer. Additionally, the strong visible absorption of the films indicates that higher-order aldol condensation products must also be present as minor species. The major acetal species were 2,4,6-triethyl-1,3,5-trioxane and longer-chain linear polyacetals which are likely to separate from the aqueous phase. Films formed on mixtures of propanal with glyoxal and/or methylglyoxal also showed evidence of products of cross-reactions. Since cross-reactions would be more likely than self-reactions under atmospheric conditions, similar reactions of aldehydes like propanal with common aerosol organic species like glyoxal and

  11. Potential cerebral perfusion agents: synthesis and evaluation of a radioiodinated vinylalkylbarbituric acid analogue

    SciTech Connect

    Srivastava, P.C.; Callahan, A.P.; Cunningham, E.B.; Knapp, F.F. Jr.

    1983-05-01

    A new iodinated barbiturate has been prepared. Treatment of 5-chloropentyne and propargyl bromide with diethyl 2-ethyl-2-sodiomalonate (DESM) provided diethyl 2-ethyl-2-(1-pentyn-5-yl)malonate (3) and diethyl 2-ethyl-2-propargylmalonate (4), respectively. Similar condensation of DESM with (E)-(5-iodo-1-penten-1-yl)boronic acid (9) or the reaction of catecholborane with 3 provided diethyl (E)-2-ethyl-2-(1-borono-1-penten-5-yl)malonate (8). The direct sodium iodide-chloramine-T iodination of 8 or the treatment of (E)-1,5-diiodo-1-pentene (10) with DESM provided diethyl (E)-2-ethyl-2-(1-iodo-1-penten-5-yl)malonate (11). The condensation of functionalized malonates 3, 4, and 11 with urea in the presence of a base provided the corresponding barbiturates, 5-ethyl-5-(1-pentyn-5-yl)-(5), 5-ethyl-5-propargyl- (6), and (E)-5-ethyl-5-(1-iodo-1-penten-5-yl)barbituric acid (12), respectively. (E)-6-(Ethoxycarbonyl)-1-iodo-1-octene-6-carboxylic acid (13) was isolated as the hydrolytic byproduct of 11. Compound 13 decarboxylated under vacuum to provide ethyl (E)-1-iodo-1-octene-6-carboxylate (14). The /sup 125/I-labeled congeners of 12 and 13 were synthesized in the same manner and evaluated in rats. The barbiturate 12 exhibited significant brain uptake (approximately 1% dose after 5 min), demonstrating that iodinated barbiturates freely cross the intact blood-brain barrier.

  12. Carboxylic Acid-Functionalized Conducting-Polymer Nanotubes as Highly Sensitive Nerve-Agent Chemiresistors.

    PubMed

    Kwon, Oh Seok; Park, Chul Soon; Park, Seon Joo; Noh, Seonmyeong; Kim, Saerona; Kong, Hye Jeong; Bae, Joonwon; Lee, Chang-Soo; Yoon, Hyeonseok

    2016-09-21

    Organophosphates are powerful inhibitors of acetylcholinesterase, which is critical to nerve function. Despite continuous research for detecting the highly toxic organophosphates, a new and improved methodology is still needed. Herein we demonstrate simple-to-fabricate chemiresistive gas sensors using conducting-polymer polypyrrole (PPy) nanotube transducers, which are chemically specific and capable of recognizing sub-ppb concentrations (ca. 0.5 ppb) of dimethyl methylphosphonate (DMMP), a simulant of nerve agent sarin. Interestingly, the introduction of carboxylic groups on the surface of PPy nanotube transistors resulted in enhanced sensitivity to DMMP via intermolecular hydrogen bonding. Furthermore, it was found that the sensitivity of the nanotube transducer depended on the degree of the carboxylic group introduced. Finally, a sensor array composed of 5 different transducers including the carboxylated nanotubes exhibited excellent selectivity to DMMP in 16 vapor species.

  13. Carboxylic Acid-Functionalized Conducting-Polymer Nanotubes as Highly Sensitive Nerve-Agent Chemiresistors

    PubMed Central

    Kwon, Oh Seok; Park, Chul Soon; Park, Seon Joo; Noh, Seonmyeong; Kim, Saerona; Kong, Hye Jeong; Bae, Joonwon; Lee, Chang-Soo; Yoon, Hyeonseok

    2016-01-01

    Organophosphates are powerful inhibitors of acetylcholinesterase, which is critical to nerve function. Despite continuous research for detecting the highly toxic organophosphates, a new and improved methodology is still needed. Herein we demonstrate simple-to-fabricate chemiresistive gas sensors using conducting-polymer polypyrrole (PPy) nanotube transducers, which are chemically specific and capable of recognizing sub-ppb concentrations (ca. 0.5 ppb) of dimethyl methylphosphonate (DMMP), a simulant of nerve agent sarin. Interestingly, the introduction of carboxylic groups on the surface of PPy nanotube transistors resulted in enhanced sensitivity to DMMP via intermolecular hydrogen bonding. Furthermore, it was found that the sensitivity of the nanotube transducer depended on the degree of the carboxylic group introduced. Finally, a sensor array composed of 5 different transducers including the carboxylated nanotubes exhibited excellent selectivity to DMMP in 16 vapor species. PMID:27650635

  14. Carboxylic Acid-Functionalized Conducting-Polymer Nanotubes as Highly Sensitive Nerve-Agent Chemiresistors.

    PubMed

    Kwon, Oh Seok; Park, Chul Soon; Park, Seon Joo; Noh, Seonmyeong; Kim, Saerona; Kong, Hye Jeong; Bae, Joonwon; Lee, Chang-Soo; Yoon, Hyeonseok

    2016-01-01

    Organophosphates are powerful inhibitors of acetylcholinesterase, which is critical to nerve function. Despite continuous research for detecting the highly toxic organophosphates, a new and improved methodology is still needed. Herein we demonstrate simple-to-fabricate chemiresistive gas sensors using conducting-polymer polypyrrole (PPy) nanotube transducers, which are chemically specific and capable of recognizing sub-ppb concentrations (ca. 0.5 ppb) of dimethyl methylphosphonate (DMMP), a simulant of nerve agent sarin. Interestingly, the introduction of carboxylic groups on the surface of PPy nanotube transistors resulted in enhanced sensitivity to DMMP via intermolecular hydrogen bonding. Furthermore, it was found that the sensitivity of the nanotube transducer depended on the degree of the carboxylic group introduced. Finally, a sensor array composed of 5 different transducers including the carboxylated nanotubes exhibited excellent selectivity to DMMP in 16 vapor species. PMID:27650635

  15. Targeted LC–MS derivatization for aldehydes and carboxylic acids with a new derivatization agent 4-APEBA

    PubMed Central

    Eggink, Mark; Wijtmans, Maikel; Kretschmer, Ansgar; Kool, Jeroen; Lingeman, Henk; de Esch, Iwan J. P.; Irth, Hubertus

    2010-01-01

    Based on the template of a recently introduced derivatization reagent for aldehydes, 4-(2-(trimethylammonio)ethoxy)benzeneaminium dibromide (4-APC), a new derivatization agent was designed with additional features for the analysis and screening of biomarkers of lipid peroxidation. The new derivatization reagent, 4-(2-((4-bromophenethyl)dimethylammonio)ethoxy)benzenaminium dibromide (4-APEBA) contains a bromophenethyl group to incorporate an isotopic signature to the derivatives and to add additional fragmentation identifiers, collectively enhancing the abilities for detection and screening of unknown aldehydes. Derivatization can be achieved under mild conditions (pH 5.7, 10 °C). By changing the secondary reagent (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide instead of sodium cyanoborohydride), 4-APEBA is also applicable to the selective derivatization of carboxylic acids. Synthesis of the new label, exploration of the derivatization conditions, characterization of the fragmentation of the aldehyde and carboxylic acid derivatives in MS/MS, and preliminary applications of the labeling strategy for the analysis of aldehydes in urine and plasma are described. Figure Structure and MS/MS fragmentation spectrum of 4-APEBA reagents derivatized with octanoic acid Electronic supplementary material The online version of this article (doi:10.1007/s00216-010-3575-1) contains supplementary material, which is available to authorized users. PMID:20238107

  16. Bioprospecting the Curculigoside-Cinnamic Acid-Rich Fraction from Molineria latifolia Rhizome as a Potential Antioxidant Therapeutic Agent.

    PubMed

    Ooi, Der Jiun; Chan, Kim Wei; Sarega, Nadarajan; Alitheen, Noorjahan Banu; Ithnin, Hairuszah; Ismail, Maznah

    2016-06-17

    Increasing evidence from both experimental and clinical studies depicts the involvement of oxidative stress in the pathogenesis of various diseases. Specifically, disruption of homeostatic redox balance in accumulated body fat mass leads to obesity-associated metabolic syndrome. Strategies for the restoration of redox balance, potentially by exploring potent plant bioactives, have thus become the focus of therapeutic intervention. The present study aimed to bioprospect the potential use of the curculigoside-cinnamic acid-rich fraction from Molineria latifolia rhizome as an antioxidant therapeutic agent. The ethyl acetate fraction (EAF) isolated from M. latifolia rhizome methanolic extract (RME) contained the highest amount of phenolic compounds, particularly curculigoside and cinnamic acid. EAF demonstrated glycation inhibitory activities in both glucose- and fructose-mediated glycation models. In addition, in vitro chemical-based and cellular-based antioxidant assays showed that EAF exhibited high antioxidant activities and a protective effect against oxidative damage in 3T3-L1 preadipocytes. Although the efficacies of individual phenolics differed depending on the structure and concentration, a correlational study revealed strong correlations between total phenolic contents and antioxidant capacities. The results concluded that enriched phenolic contents in EAF (curculigoside-cinnamic acid-rich fraction) contributed to the overall better reactivity. Our data suggest that this bioactive-rich fraction warrants therapeutic potential against oxidative stress-related disorders.

  17. Bioprospecting the Curculigoside-Cinnamic Acid-Rich Fraction from Molineria latifolia Rhizome as a Potential Antioxidant Therapeutic Agent.

    PubMed

    Ooi, Der Jiun; Chan, Kim Wei; Sarega, Nadarajan; Alitheen, Noorjahan Banu; Ithnin, Hairuszah; Ismail, Maznah

    2016-01-01

    Increasing evidence from both experimental and clinical studies depicts the involvement of oxidative stress in the pathogenesis of various diseases. Specifically, disruption of homeostatic redox balance in accumulated body fat mass leads to obesity-associated metabolic syndrome. Strategies for the restoration of redox balance, potentially by exploring potent plant bioactives, have thus become the focus of therapeutic intervention. The present study aimed to bioprospect the potential use of the curculigoside-cinnamic acid-rich fraction from Molineria latifolia rhizome as an antioxidant therapeutic agent. The ethyl acetate fraction (EAF) isolated from M. latifolia rhizome methanolic extract (RME) contained the highest amount of phenolic compounds, particularly curculigoside and cinnamic acid. EAF demonstrated glycation inhibitory activities in both glucose- and fructose-mediated glycation models. In addition, in vitro chemical-based and cellular-based antioxidant assays showed that EAF exhibited high antioxidant activities and a protective effect against oxidative damage in 3T3-L1 preadipocytes. Although the efficacies of individual phenolics differed depending on the structure and concentration, a correlational study revealed strong correlations between total phenolic contents and antioxidant capacities. The results concluded that enriched phenolic contents in EAF (curculigoside-cinnamic acid-rich fraction) contributed to the overall better reactivity. Our data suggest that this bioactive-rich fraction warrants therapeutic potential against oxidative stress-related disorders. PMID:27322226

  18. Evaluation of physicochemical properties, skin permeation and accumulation profiles of salicylic acid amide prodrugs as sunscreen agent.

    PubMed

    Yan, Yi-Dong; Sung, Jun Ho; Lee, Dong Won; Kim, Jung Sun; Jeon, Eun-Mi; Kim, Dae-Duk; Kim, Dong Wuk; Kim, Jong Oh; Piao, Ming Guan; Li, Dong Xun; Yong, Chul Soon; Choi, Han Gon

    2011-10-31

    Various amide prodrugs of salicylic acid were synthesised, and their physicochemical properties including lipophilicity, chemical stability and enzymatic hydrolysis were investigated. In vivo skin permeation and accumulation profiles were also evaluated using a combination of common permeation enhancing techniques such as the use of a supersaturated solution of permeants in an enhancer vehicle, a lipophilic receptor solution, removal of the stratum corneum and delipidisation of skin. Their capacity factor values were proportional to the degree of carbon-carbon saturation in the side chain. All these amides were highly stable in acetonitrile and glycerine. Amide prodrugs were converted to salicylic acid both in hairless mouse liver and skin homogenates. N-dodecyl salicylamide (C12SM) showed the lowest permeation of salicylic acid in skin compared to the other prodrugs, probably due to its low aqueous solubility. It had a high affinity for the stratum corneum and its accumulation was restricted to only the uppermost layer of skin. Thus, this amide prodrug could be a safer topical sunscreen agent with minimum potential for systemic absorption.

  19. Can propolis and caffeic acid phenethyl ester be promising agents against cyclophosphamide toxicity?

    PubMed Central

    Akyol, Sumeyya; Gulec, Mehmet Akif; Erdemli, Haci Kemal; Akyol, Omer

    2016-01-01

    Propolis is a mixture having hundreds of polyphenols including caffeic acid phenethyl ester (CAPE). They have been using in several medical conditions/diseases in both in vitro and in vivo experimental setup. Cyclophosphamide (CP) has been used to treat a broad of malignancies including Hodgkin’s and non-Hodgkin’s lymphoma, Burkitt’s lymphoma, chronic lymphocytic leukemia, Ewing’s sarcoma, breast cancer, testicular cancer, etc. It may cause several side effects after treatment. In this mini review, the protective effects of propolis and CAPE were compared each other in terms of effectiveness against CP-induced injuries. PMID:27069732

  20. Can propolis and caffeic acid phenethyl ester be promising agents against cyclophosphamide toxicity?

    PubMed

    Akyol, Sumeyya; Gulec, Mehmet Akif; Erdemli, Haci Kemal; Akyol, Omer

    2016-01-01

    Propolis is a mixture having hundreds of polyphenols including caffeic acid phenethyl ester (CAPE). They have been using in several medical conditions/diseases in both in vitro and in vivo experimental setup. Cyclophosphamide (CP) has been used to treat a broad of malignancies including Hodgkin's and non-Hodgkin's lymphoma, Burkitt's lymphoma, chronic lymphocytic leukemia, Ewing's sarcoma, breast cancer, testicular cancer, etc. It may cause several side effects after treatment. In this mini review, the protective effects of propolis and CAPE were compared each other in terms of effectiveness against CP-induced injuries. PMID:27069732

  1. Lipoic acid as a potential first agent for protection from mycotoxins and treatment of mycotoxicosis.

    PubMed

    Rogers, Sherry A

    2003-08-01

    Mycotoxins--toxic substances produced by fungi or molds--are ubiquitous in the environment and are capable of damaging multiple biochemical mechanisms, resulting in a variety of human symptoms referred to collectively as "mycotoxicosis." In fact, mycotoxins mimic multiple xenobiotics, not only with respect to their ultimate damage, but also in their routes of detoxification. This suggests potential therapeutic options for the challenging treatment of mycotoxicosis. In this brief review, the author examines the use of lipoic acid as an example of an inexpensive and available nutrient that has been shown to protect against, or reverse, the adverse health effects of mycotoxins. PMID:15259433

  2. Design, synthesis and evaluation of PEGylated lipoic acid derivatives with functionality as potent anti-melanogenic agents.

    PubMed

    Lu, Chichong; Kim, Bo-Mi; Chai, Kyu Yun

    2011-10-01

    The novel PEGylated lipoic acid (LA) derivatives with functionality were synthesized in satisfactory yield by simple procedures and evaluated about its anti-melanogenic activity on the B16F10 melanoma cells. Grafting a PEG moiety onto the carboxyl group of LA has reduced the cell cytotoxicity and provided the water solubility and functionality to incorporate the other bioactive moieties. We have found that derivatives showed inhibition of melanin formation by up to 36.5% at 0.1 mM, whereas LA decreased the melanin formation by 8.6%. In addition, it also inhibits at least 86.4% UV-induced MMP-1 expression at 0.1 mM which is higher than LA. These data suggest that the novel PEGylated LA derivatives with functionality may thus serve as a potentially effective anti-melanogenic and anti-aging agent. PMID:21890247

  3. [Determination of antidangdruff agent salicylic acid, zinc pyrithione, octopirox, climbazole and ketoconazole in shampoo by high performance liquid chromatography].

    PubMed

    Yang, Yan-Wei; Zhu, Ying; Su, Xiao-Qing

    2005-09-01

    A high performance liquid chromatography method was established for determination of antidangdruff agent salicylic acid,zinc pyrithione, octopirox, climbazole and ketoconazole in shampoo on a C18 column using acetonitrile-metholaqueous solution (10 mmol/L KH2 PO4 and 5 mmol/L EDTANa2, pH is adjusted to 4.0 with H3 PO4) (50:10:40) as mobile phase at a flow rate of 1.0 ml/min, with the column temperature 25 degrees C and detection wave 230nm. The precision was less than 3.8% and recovery varied from 92.7% to 104.9%. The experimental results showed that the method was simple, precise and accurate. PMID:16329615

  4. The sensitization of near-ultraviolet radiation killing of mammalian cells by the sunscreen agent para-aminobenzoic acid

    SciTech Connect

    Osgood, P.J.; Moss, S.H.; Davies, D.J.

    1982-12-01

    The wavelengths of sunlight considered to be responsible for erythema and skin cancer formation are in the range 290-340 nm. Formulated sunscreens usually contain an agent that absorbs in this wavelength region, and one of the most widely used is para-aminobenzoic acid (PABA). Previous work has demonstrated the sensitization by PABA of the lethal and mutagenic effects of near-ultraviolet (UV) radiation in a model bacterial system. Experiments with the mouse lymphoma L5178Y cell line have now demonstrated sensitization by PABA of the lethal effect of near-UV radiation, the extent of which, after correction for absorption of UV radiation by PABA, bears a direct relationship to PABA concentration. The limitations of these results in predicting the response of human skin to the presence of PABA during exposure to UV radiation is emphasized.

  5. Synthesis and biological evaluation of quinic acid derivatives as anti-inflammatory agents.

    PubMed

    Zeng, Kui; Thompson, Karin Emmons; Yates, Charles R; Miller, Duane D

    2009-09-15

    Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. cat's claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappaB). Herein, we describe the synthesis and biological testing of novel QA derivatives. Inhibition of NF-kappaB was assessed using A549 (Type II alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-kappaB response element. A549-NF-kappaB cells were stimulated with TNF-alpha (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at the carboxylic acid position yielded potent inhibitors of NF-kappaB. A variety of modifications to the amide substitution were tolerated with the N-propyl amide derivative being the most potent. Further examination of the SAR demonstrated that acetylation of the hydroxyl groups reduced NF-kappaB inhibitory activity. QA amide derivatives lacked anti-oxidant activity and were found to be neither anti-proliferative nor cytotoxic at concentrations up to 100 microM. In conclusion, we have discovered a novel series of non-toxic QA amides that potently inhibit NF-kappaB, despite their lack of anti-oxidant activity. Mechanistic studies and pre-clinical efficacy studies in various inflammatory animal models are on-going.

  6. Novel 3,4-seco bile acid diamides as selective anticancer proliferation and migration agents.

    PubMed

    Mao, Shi-Wei; Chen, Huang; Yu, Li-Fang; Lv, Fang; Xing, Ya-Jing; Liu, Ting; Xie, Jia; Tang, Jie; Yi, Zhengfang; Yang, Fan

    2016-10-21

    A series of new seco-A ring bile acid diamides were synthesized, and their antiproliferative activities against PC3M (prostate), HT29 (colon) and ES-2 (ovarian) cancer cell lines were investigated using SRB assays. Most synthesized compounds presented improved antiproliferative activities compared to the parent bile acids (IC50 > 80 μM), especially the piperazine conjugated compound 27 with IC50 values of 1.07, 4.58 and 3.86 μM against PC3M, HT29 and ES-2 cancer cell lines, respectively. In addition, all the tested compounds showed less cytotoxic activity on a noncancerous cell line (HAF), and the most active compound 27 exhibited the highest selectivity (Selectivity Index, SI(PC3M) = 26.3). Furthermore, 27 could also enhance G1 arrest in PC3M cell, revealed by cell cycle analysis, and increase anti-migration activity on PC3M cells, confirmed by transwell migration assay. PMID:27448915

  7. Interactions of Phenolic Acids, Metallic Ions and Chelating Agents on Auxin-Induced Growth

    PubMed Central

    Tomaszewski, Miroslaw; Thimann, Kenneth V.

    1966-01-01

    By growth experiments in indoleacetic acid-1-14C (IAA), and determination of the 14CO2 evolved, it has been shown directly that polyphenols synergize IAA-induced growth by counteracting IAA decarboxylation. Sinapic and ferulic acids act like polyphenols. Endogenous polyphenols doubtless exert the same influence in intact plants. Monophenols stimulate the decarboxylation of IAA under conditions where they depress growth. When Mn++ is present as well, this effect is enhanced. All these growth effects are paralleled by effects on the isolated IAA oxidizing enzyme of Avena. EDTA acts like the polyphenols in depressing the decarboxylation of IAA, and not synergizing with the growth induced by naphthalene-acetic acid (NAA) and 2,4-D. However, since EDTA synergizes with IAA for growth even at optimal IAA concentrations, its growth promotion probably involves an additional effect. DIECA inhibits powerfully the destruction of IAA, but without causing much growth promotion, apparently because its decomposition products inhibit respiration. Mn++ aloné stimulates the decarboxylation of IAA, i.e. this ion promotes the IAA oxidase in vivo as it does in vitro. Nevertheless, it does not inhibit elongation, but at relatively high concentrations even stimulates it, both at low and high IAA levels. Since Mn++ also promotes the growth induced by NAA and 2,4-D, its growth action cannot rest primarily on modifying the metabolism of the auxins. Cobalt somewhat decreases the decarboxylation of IAA, but this cannot explain its growth promotion, since Co++, like Mn++, stimulates elongation even at optimal IAA concentrations, and acts with NAA just as well as with IAA. Ferrous ion, on the other hand, acts like the polyphenols. Floating pea stem sections exude enough organic matter to support bacteria which after 7 hours cause considerable decarboxylation of IAA. Avena coleoptile sections have a comparable though smaller effect after 12 hours. The present experiments, with those of others

  8. Replacement of dietary fish oils by alpha-linolenic acid-rich oils lowers omega 3 content in tilapia flesh.

    PubMed

    Karapanagiotidis, Ioannis T; Bell, Michael V; Little, David C; Yakupitiyage, Amararatne

    2007-06-01

    A 20-week feeding trial was conducted to determine whether increasing linolenic acid (18:3n-3) in vegetable oil (VO) based diets would lead to increased tissue deposition of 22:6n-3 in Nile tilapia (Oreochromis niloticus). Five isonitrogenous and isoenergetic diets were supplemented with 3% of either linseed oil (LO), a mixture of linseed oil with refined palm olein oil (PO) (LO-PO 2:1) and a mixture of refined palm olein oil with linseed oil (PO-LO 3:2) or with fish oil (FO) or corn oil (CO) as controls. The PO-LO, LO-PO and LO diets supplied a similar amount of 18:2n-6 (0.5% of diet by dry weight) and 0.5, 0.7 and 1.1% of 18:3n-3, respectively. Increased dietary 18:3n-3 caused commensurate increases in longer-chain n-3 PUFA and decreases in longer-chain n-6 PUFA in the muscle lipids of tilapia. However, the biosynthetic activities of fish fed the LO-based diets were not sufficient to raise the tissue concentrations of 20:5n-3, 22:5n-3 and 22:6n-3 to those of fish fed FO. The study suggests that tilapia (O. niloticus) has a limited capacity to synthesise 20:5n-3 and 22:6n-3 from dietary 18:3n-3. The replacement of FO in the diet of farmed tilapia with vegetable oils could therefore lower tissue concentrations of 20:5n-3 and 22:6n-3, and consequently produce an aquaculture product of lower lipid nutritional value for the consumer.

  9. HPLC and 31P NMR characterization of the reaction between antitumor platinum agents and the phosphorothioate chemoprotective agent S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721).

    PubMed

    Thompson, D C; Wyrick, S D; Holbrook, D J; Chaney, S G

    1995-10-26

    In prior studies, we examined the effects of the radioprotective and chemoprotective agent WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] on the in vivo biotransformation of the cisplatin [cis-diamminedichloroplatinum(II)] analog ormaplatin [(d,I)trans-1,2-diaminocyclohexanetetrachloroplatinum(IV), Pt(dach)Cl4, (formerly called tetraplatin)]. Those data suggested that a direct interaction between WR-2721 and ormaplatin and/or the corresponding Pt(II) drug, Pt(dach)Cl2, may be occurring in vivo. This would be in contrast to the generally accepted hypothesis that WR-2721 is a prodrug that must first be converted by alkaline phosphatase to a free thiol compound, WR-1065, before any appreciable reactivity would be evident. However, the major biotransformation product observed in the peritoneal fluid, plasma, and all tissues was Pt(dach)(WR-1065). We report here on further investigations into the in vitro reactivity of Pt(dach) compounds with WR-2721 and WR-1065. Separation of reaction products resulting from incubation of Pt(dach)(malonato) with either WR-2721 or WR-1065 under physiological conditions gave profiles that were indistinguishable by reverse phase HPLC and cation exchange HPLC at two different pHs. 31P NMR characterization of the dephosphorylation of WR-2721 revealed essentially no loss of inorganic phosphate for up to 24 hr when incubated in unbuffered water at 30 degrees. In contrast, when incubated with a 1:1 molar ratio of cisplatin under the same conditions, the WR-2721 signal was decreased markedly in the first 5 min, and had disappeared almost completely by 1 hr. The signal corresponding to inorganic phosphate increased in parallel to the decrease in the WR-2721 signal. No intermediate formation of a complex containing both platinum and phosphate could be detected at any time. These data suggest that the reaction between WR-2721 and platinum complexes results in rapid dephosphorylation of WR-2721, and, consequently, that the reaction

  10. Oleic Acid Produced by a Marine Vibrio spp. Acts as an Anti-Vibrio parahaemolyticus Agent

    PubMed Central

    Leyton, Yanett; Borquez, Jorge; Darias, José; Cueto, Mercedes; Díaz-Marrero, Ana R.; Riquelme, Carlos

    2011-01-01

    It is known that some strains of Vibrio parahaemolyticus are responsible for gastroenteric diseases caused by the ingestion of marine organisms contaminated with these bacterial strains. Organic products that show inhibitory activity on the growth of the pathogenic V. parahaemolyticus were extracted from a Vibrio native in the north of Chile. The inhibitory organic products were isolated by reverse phase chromatography and permeation by Sephadex LH20, and were characterized by spectroscopic and spectrometric techniques. The results showed that the prevailing active product is oleic acid, which was compared with standards by gas chromatography and high-performance liquid chromatography (HPLC). These active products might be useful for controlling the proliferation of pathogenic clones of V. parahaemolyticus. PMID:22073014

  11. Synthesis of some novel D-glucuronic acid acetylated derivatives as potential anti-tumor agents.

    PubMed

    El-Nezhawy, Ahmed O H; Adly, Frady G; Eweas, Ahmed F; Hanna, Atef G; El-Kholy, Yehya M; El-Sayed, Shahenaz H; El-Naggar, Tarek B A

    2011-10-01

    A structurally diverse series of Δ(4,5) -uronamide derivatives have been chemically synthesized starting from D-glucuronic acid itself by means of acetylation, activation, amide bond formation and base-catalyzed elimination protocols. Structure elucidation for all products along with optimization of the synthetic steps is described. The synthesized compounds were evaluated for their in-vitro anti-tumor activity against MCF-7, TK-10 and UACC-62 cell lines. The compounds 5, 11, 13, 15 and 16 were the most active against TK-10 cell line. On the other hand, the most active compounds against the MCF-7 cell line were 11 and 15. However, compounds 5, 7, 11, 13, 15 and 16 were the most active against the UACC-62 cell line.

  12. Synthesis, evaluation and molecular docking studies of amino acid derived N-glycoconjugates as antibacterial agents.

    PubMed

    Baig, Noorullah; Singh, Rajnish Prakash; Chander, Subhash; Jha, Prabhat Nath; Murugesan, Sankaranarayanan; Sah, Ajay K

    2015-12-01

    Six amino acid derived N-glycoconjugates of d-glucose were synthesized, characterized and tested for antibacterial activity against G(+)ve (Bacillus cereus) as well as G(-)ve (Escherichia coli and Klebsiella pneumoniae) bacterial strains. All the tested compounds exhibited moderate to good antibacterial activity against these bacterial strains. The results were compared with the antibacterial activity of standard drug Chloramphenicol, where results of A5 (Tryptophan derived glycoconjugates) against E. coli and A4 (Isoleucine derived glycoconjugates) against K. pneumoniae bacterial strains are comparable with the standard drug molecule. In silico docking studies were also performed in order to understand the mode of action and binding interactions of these molecules. The docking studies revealed that, occupation of compound A5 at the ATP binding site of subunit GyrB (DNA gyrase, PDB ID: 3TTZ) via hydrophobic and hydrogen bonding interactions may be the reason for its significant in vitro antibacterial activity.

  13. Concentrated Phosphatidic Acid in Cereal Brans as Potential Protective Agents against Indomethacin-Induced Stomach Ulcer.

    PubMed

    Afroz, Sheuli; Ikoma, Teru; Yagi, Ayano; Kogure, Kentaro; Tokumura, Akira; Tanaka, Tamotsu

    2016-09-21

    One of complications associated with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is peptic ulcer. Recently, we found that orally administered phosphatidic acid (PA) ameliorated aspirin-induced stomach lesions in mice. In this study, we identified PA-rich food sources and examined the effects of the food materials on indomethacin-induced stomach ulcer. Among examined, buckwheat (Fagopyrum esculentum) bran contained the highest level of PA (188 mg/100 g). PA was the richest phospholipid (25%) in the lipid fraction of the buckwheat bran. Administration of the lipid extracts of buckwheat bran significantly ameliorated indomethacin-induced stomach lesions in mice. In contrast, wheat (Triticum durum) bran lipids (PA, 4%) and soybean (Glycine max) lipids (PA, 3%) were not associated with ameliorative effects. These results indicated that PA-rich lipids can be used as an effective supplement for prevention of NSAID-induced stomach ulcer. PMID:27561232

  14. Sulfone and phosphinic acid analogs of decaprenolphosphoarabinose as potential anti-tuberculosis agents.

    PubMed

    Centrone, Charla A; Lowary, Todd L

    2004-11-01

    Mycobacteria biosynthesize a cell wall structure that is rich in polysaccharides containing arabinofuranose residues. The source of these arabinofuranose residues is decaprenolphosphoarabinose (1), the donor substrate for mycobacterial arabinosyltransferases. We have previously demonstrated that an analog of 1, C-phosphonate 7, prevented the growth of mycobacteria and this compound is currently undergoing testing for efficacy in tuberculosis-infected mice. We describe here the synthesis and testing of additional analogs of 1 that contain either a sulfone (8-14) or phosphinic acid (15-19) moiety in place of the phosphodiester functionality. Screening of these compounds in vitro against Mycobacterium tuberculosis strain H(37)Rv revealed that while some of these compounds possessed low to modest activity, none was as potent as 7.

  15. Concentrated Phosphatidic Acid in Cereal Brans as Potential Protective Agents against Indomethacin-Induced Stomach Ulcer.

    PubMed

    Afroz, Sheuli; Ikoma, Teru; Yagi, Ayano; Kogure, Kentaro; Tokumura, Akira; Tanaka, Tamotsu

    2016-09-21

    One of complications associated with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is peptic ulcer. Recently, we found that orally administered phosphatidic acid (PA) ameliorated aspirin-induced stomach lesions in mice. In this study, we identified PA-rich food sources and examined the effects of the food materials on indomethacin-induced stomach ulcer. Among examined, buckwheat (Fagopyrum esculentum) bran contained the highest level of PA (188 mg/100 g). PA was the richest phospholipid (25%) in the lipid fraction of the buckwheat bran. Administration of the lipid extracts of buckwheat bran significantly ameliorated indomethacin-induced stomach lesions in mice. In contrast, wheat (Triticum durum) bran lipids (PA, 4%) and soybean (Glycine max) lipids (PA, 3%) were not associated with ameliorative effects. These results indicated that PA-rich lipids can be used as an effective supplement for prevention of NSAID-induced stomach ulcer.

  16. Influence of pH, bleaching agents, and acid etching on surface wear of bovine enamel

    PubMed Central

    Soares, Ana Flávia; Bombonatti, Juliana Fraga Soares; Alencar, Marina Studart; Consolmagno, Elaine Cristina; Honório, Heitor Marques; Mondelli, Rafael Francisco Lia

    2016-01-01

    ABSTRACT Development of new materials for tooth bleaching justifies the need for studies to evaluate the changes in the enamel surface caused by different bleaching protocols. Objective The aim of this study was to evaluate the bovine dental enamel wear in function of different bleaching gel protocols, acid etching and pH variation. Material and Methods Sixty fragments of bovine teeth were cut, obtaining a control and test areas. In the test area, one half received etching followed by a bleaching gel application, and the other half, only the bleaching gel. The fragments were randomly divided into six groups (n=10), each one received one bleaching session with five hydrogen peroxide gel applications of 8 min, activated with hybrid light, diode laser/blue LED (HL) or diode laser/violet LED (VHL) (experimental): Control (C); 35% Total Blanc Office (TBO35HL); 35% Lase Peroxide Sensy (LPS35HL); 25% Lase Peroxide Sensy II (LPS25HL); 15% Lase Peroxide Lite (LPL15HL); and 10% hydrogen peroxide (experimental) (EXP10VHL). pH values were determined by a pHmeter at the initial and final time periods. Specimens were stored, subjected to simulated brushing cycles, and the superficial wear was determined (μm). ANOVA and Tukey´s tests were applied (α=0.05). Results The pH showed a slight decrease, except for Group LPL15HL. Group LPS25HL showed the highest degree of wear, with and without etching. Conclusion There was a decrease from the initial to the final pH. Different bleaching gels were able to increase the surface wear values after simulated brushing. Acid etching before bleaching increased surface wear values in all groups. PMID:27008254

  17. Biocontrol agents-mediated suppression of oxalic acid induced cell death during Sclerotinia sclerotiorum-pea interaction.

    PubMed

    Jain, Akansha; Singh, Akanksha; Singh, Surendra; Sarma, Birinchi Kumar; Singh, Harikesh Bahadur

    2015-05-01

    Oxalic acid (OA) is an important pathogenic factor during early Sclerotinia sclerotiorum-host interaction and might work by reducing hydrogen peroxide production (H2 O2 ). In the present investigation, oxalic acid-induced cell death in pea was studied. Pea plants treated with biocontrol agents (BCAs) viz., Pseudomonas aeruginosa PJHU15, Bacillus subtilis BHHU100, and Trichoderma harzianum TNHU27 either singly and/or in consortium acted on S. sclerotiorum indirectly by enabling plants to inhibit the OA-mediated suppression of oxidative burst via induction of H2 O2 . Our results showed that BCA treated plants upon treatment with culture filtrate of the pathogen, conferred the resistance via. significantly decreasing relative cell death of pea against S. sclerotiorum compared to control plants without BCA treatment but treated with the culture filtrate of the pathogen. The results obtained from the present study indicate that the microbes especially in consortia play significant role in protection against S. sclerotiorum by modulating oxidative burst and partially enhancing tolerance by increasing the H2 O2 generation, which is otherwise suppressed by OA produced by the pathogen.

  18. Thermal inactivation of rabies and other rhabdoviruses: stabilization by the chelating agent ethylenediaminetetraacetic acid at physiological temperatures.

    PubMed

    Michalski, F; Parks, N F; Sokol, F; Clark, H F

    1976-07-01

    Thermal inactivation of rabies and several other rhabdoviruses was studied using virus suspended in several different diluents. Rabies serogroup viruses were more stable than Kern Canyon or vesicular stomatitis viruses. Limited studies of two fish rhabdoviruses requiring low temperatures (less than 33 C) for replication indicated that they were not markedly more thermolabile than rabies virus. Bovine serum protein components in complex cell culture media stabilized virus at 56 C, but at temperatures of less than or equal to 37 C, sodium tris (hydroxymethyl)-aminomethane (NT) buffer containing ethylenediaminetetraacetic acid (EDTA) (NTE) was a much more efficient stabilizer of virus infectivity. Chelating agents EDTA and ethyleneglycol-bis-(beta-aminoethyl ether)tetraacetic acid were equally efficient in protection of rabies virus infectivity; the effect of each was lost when excess Ca2+ was added. Bovine serum in NT or NTE buffers produced a thermostabilizing effect at 37 C not provided by the same serum concentration in complex cell culture media. Bovine serum was more efficient than EDTA in stabilizing virus infectivity during repeated cycles of freezing and thawing. PMID:181323

  19. Biodegradable and non-retrogradable eco-films based on starch-glycerol with citric acid as crosslinking agent.

    PubMed

    Seligra, Paula González; Medina Jaramillo, Carolina; Famá, Lucía; Goyanes, Silvia

    2016-03-15

    Biodegradable and non-retrogradable starch-glycerol based films were obtained using citric acid (CA) as crosslinking agent at 75°C. This material allowed decreasing water vapor permeability (WVP) more than 35%, remained amorphous for at least 45 days as a result of the network formed by the CA that avoided starch retrogradation and maintained the degradability in compost, occurring only six days after the films without citric acid. A simulation of the gelatinization process of starch-glycerol with and without CA, using a differential thermal analysis device, showed that the system with CA completed the gelatinization 5°C before than the other and, CA first reacted with glycerol and then starch-glycerol-CA reaction occurred. The temperature at which the gelatinization process was carried out was critical to obtain the best results. An increase of gelatinization process temperature at 85°C in system with CA, led to a worsening on WVP and its integrity after a swelling process with dimethylsulphoxide (DMSO), compared to the films processed at 75°C.

  20. Production of L-lactic acid by a thermophilic Bacillus mutant using sodium hydroxide as neutralizing agent.

    PubMed

    Qin, Jiayang; Wang, Xiuwen; Zheng, Zhaojuan; Ma, Cuiqing; Tang, Hongzhi; Xu, Ping

    2010-10-01

    A sodium lactate tolerant mutant strain named Bacillus sp. Na-2 was obtained and applied to sodium hydroxide-based L-lactic acid (LA) production process. The influences of aeration and pH were investigated to further improve the resistance of strain Na-2 against sodium lactate stress and to obtain the most efficient L-LA production process. Although mild aeration was favorable for cell growth and L-LA production, vigorous aeration resulted in a metabolic shift from homolactic to mixed-acid/acetoin fermentation. Therefore, a two-stage aeration control strategy was employed. Optimum pH was found to be 6.0. A total of 106.0 g/l L-LA was produced in 30 h by Bacillus sp. Na-2 using sodium hydroxide as neutralizing agent. Productivity, conversion rate and optical purity were 3.53 g/l/h, 94% and 99.5%, respectively. The remarkable fermentation traits of Bacillus sp. Na-2 and the environment-friendly characteristics of NaOH-based process represent new insight for industrial scale production of L-LA.

  1. Biodegradable and non-retrogradable eco-films based on starch-glycerol with citric acid as crosslinking agent.

    PubMed

    Seligra, Paula González; Medina Jaramillo, Carolina; Famá, Lucía; Goyanes, Silvia

    2016-03-15

    Biodegradable and non-retrogradable starch-glycerol based films were obtained using citric acid (CA) as crosslinking agent at 75°C. This material allowed decreasing water vapor permeability (WVP) more than 35%, remained amorphous for at least 45 days as a result of the network formed by the CA that avoided starch retrogradation and maintained the degradability in compost, occurring only six days after the films without citric acid. A simulation of the gelatinization process of starch-glycerol with and without CA, using a differential thermal analysis device, showed that the system with CA completed the gelatinization 5°C before than the other and, CA first reacted with glycerol and then starch-glycerol-CA reaction occurred. The temperature at which the gelatinization process was carried out was critical to obtain the best results. An increase of gelatinization process temperature at 85°C in system with CA, led to a worsening on WVP and its integrity after a swelling process with dimethylsulphoxide (DMSO), compared to the films processed at 75°C. PMID:26794739

  2. Caffeic Acid phenethyl ester is a potential therapeutic agent for oral cancer.

    PubMed

    Kuo, Ying-Yu; Jim, Wai-Tim; Su, Liang-Cheng; Chung, Chi-Jung; Lin, Ching-Yu; Huo, Chieh; Tseng, Jen-Chih; Huang, Shih-Han; Lai, Chih-Jen; Chen, Bo-Chih; Wang, Bi-Juan; Chan, Tzu-Min; Lin, Hui-Ping; Chang, Wun-Shaing Wayne; Chang, Chuang-Rung; Chuu, Chih-Pin

    2015-01-01

    Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients. PMID:25984601

  3. Synthesis of heterocycle-modified betulinic acid derivatives as antitumor agents.

    PubMed

    Cui, Hai-Wei; He, Yuan; Wang, Jinhua; Gao, Wei; Liu, Ting; Qin, Min; Wang, Xue; Gao, Cheng; Wang, Yan; Liu, Ming-Yao; Yi, Zhengfang; Qiu, Wen-Wei

    2015-05-01

    A series of novel heterocycle-modified betulinic acid (BA) derivatives were synthesized and investigated for their activity against the growth of eight non-drug resistant and one multidrug-resistant tumor cell line using a sulforhodamine B (SRB) assay. The most active compound 17 showed an average IC50 1.19 μM, which was about 20 times more potent than the lead compound BA. It is amazing that for most synthetic saturated N-heterocycle derivatives, MCF-7/ADR was the most sensitive tumor cells, especially 17 showed the most potent antitumor activity (IC50 = 0.33 μM) on this multidrug-resistant tumor cell line, that was 117 times more potent than BA. Most of the tested compounds displayed less toxic on human fibroblasts (HAF) in comparison with the tumor cell lines. The cytometry and transwell migration assays were used to test the ability of 17 to induce apoptosis and inhibit metastasis on tumor cell lines respectively.

  4. Preliminary Appraisal of Ferrocene as an Igniting Agent for JP-4 Fuel and Fuming Nitric Acid

    NASA Technical Reports Server (NTRS)

    Miller, RIley O.

    1953-01-01

    A preliminary experimental study was made of the properties of ferrocene as a solute and as a suspension in JP-4 fuel, and of the ignition delays of ferrocene - JP-4 mixture with A.F. specification 14104 white fuming nitric acid (WFNA). The investigation covered concentrations of 4 to 10 percent by weight ferrocene, and a temperature range of -40 to 80 F. The solubility of ferrocene in JP-4 is about 5 percent at room temperature and about 1 percent (extrapolated) at -80 F. The solubility is increased somewhat by increased aromatics content. Undissolved ferrocene particles of 100 mesh and smaller settle rapidly in JP-4. Clear solutions of 4 and 5 percent ferrocene in JP-4 fuels containing 10 and 25 percent by volume aromatics, respectively, do not ignite with WFNA at room temperature. Mixtures containing 10 percent ferrocene (100- mesh and smaller undissolved particles in suspension) ignited with vigorous persistent flames at room temperature, but did not ignite at -38 F. The ignition delays at room temperature, however, were widely varied; the range from 85 milliseconds to over 1 second perhaps reflected differences in degree of sedimentation.

  5. Development of antiproliferative nanohybrid compound with controlled release property using ellagic acid as the active agent.

    PubMed

    Hussein, Mohd Zobir; Al Ali, Samer Hasan; Zainal, Zulkarnain; Hakim, Muhammad Nazrul

    2011-01-01

    An ellagic acid (EA)-zinc layered hydroxide (ZLH) nanohybrid (EAN) was synthesized under a nonaqueous environment using EA and zinc oxide (ZnO) as the precursors. Powder X-ray diffraction showed that the basal spacing of the nanohybrid was 10.4 Å, resulting in the spatial orientation of EA molecules between the interlayers of 22.5° from z-axis with two negative charges at 8,8' position of the molecules pointed toward the ZLH interlayers. FTIR study showed that the intercalated EA spectral feature is generally similar to that of EA, but with bands slightly shifted. This indicates that some chemical bonding of EA presence between the nanohybrid interlayers was slightly changed, due to the formation of host-guest interaction. The nanohybrid is of mesopores type with 58.8% drug loading and enhanced thermal stability. The release of the drug active, EA from the nanohybrid was found to be sustained and therefore has good potential to be used as a drug controlled-release formulation. In vitro bioassay study showed that the EAN has a mild effect on the hepatocytes cells, similar to its counterpart, free EA.

  6. Development of antiproliferative nanohybrid compound with controlled release property using ellagic acid as the active agent

    PubMed Central

    Hussein, Mohd Zobir; Al Ali, Samer Hasan; Zainal, Zulkarnain; Hakim, Muhammad Nazrul

    2011-01-01

    An ellagic acid (EA)–zinc layered hydroxide (ZLH) nanohybrid (EAN) was synthesized under a nonaqueous environment using EA and zinc oxide (ZnO) as the precursors. Powder X-ray diffraction showed that the basal spacing of the nanohybrid was 10.4 Å, resulting in the spatial orientation of EA molecules between the interlayers of 22.5° from z-axis with two negative charges at 8,8′ position of the molecules pointed toward the ZLH interlayers. FTIR study showed that the intercalated EA spectral feature is generally similar to that of EA, but with bands slightly shifted. This indicates that some chemical bonding of EA presence between the nanohybrid interlayers was slightly changed, due to the formation of host–guest interaction. The nanohybrid is of mesopores type with 58.8% drug loading and enhanced thermal stability. The release of the drug active, EA from the nanohybrid was found to be sustained and therefore has good potential to be used as a drug controlled-release formulation. In vitro bioassay study showed that the EAN has a mild effect on the hepatocytes cells, similar to its counterpart, free EA. PMID:21796241

  7. Surface Engineered Protein Nanoparticles With Hyaluronic Acid Based Multilayers For Targeted Delivery Of Anticancer Agents.

    PubMed

    Pulakkat, Sreeranjini; Balaji, Sai A; Rangarajan, Annapoorni; Raichur, Ashok M

    2016-09-14

    Layer-by-layer (LbL) technique was employed to modify the surface of doxorubicin (Dox)-loaded bovine serum albumin (BSA) nanoparticles using hyaluronic acid (HA) to enable targeted delivery to overexpressed CD44 receptors in metastatic breast cancer cells. LbL technique offers a versatile approach to modify the surface of colloidal nanoparticles without any covalent modification. Dox-loaded BSA (Dox Ab) nanoparticles optimized for their size, zeta potential, and drug encapsulation efficiency were prepared by modified desolvation technique. The cellular uptake and cytotoxicity of the LbL coated Dox Ab nanoparticles were analyzed in CD44 overexpressing breast cancer cell line MDA-MB-231. Nanoparticles with HA as the final layer (Dox Ab HA) showed maximum cellular uptake in MDA-MB-231 cells owing to the CD44 receptor-mediated endocytosis and hence, exhibited more cytotoxicity as compared to free Dox. Further, luciferase-transfected MDA-MB-231 cells were used to induce tumor in BALB/c female nude mice to enable whole body tumor imaging. The mice were imaged before and after Dox treatment to visualize the tumor growth. The in vivo biodistribution of Dox Ab HA nanoparticles in nude mice showed maximum accumulation in tumor, and importantly, better tumor reduction in comparison with free Dox, thus paving the way for improved drug delivery into tumors. PMID:27560126

  8. Molecular interaction studies of amorphous solid dispersions of the antimelanoma agent betulinic acid.

    PubMed

    Yu, Meiki; Ocando, Joseph E; Trombetta, Louis; Chatterjee, Parnali

    2015-04-01

    Betulinic acid (BA), a novel natural product with antimelanoma activity, has poor aqueous solubility (<0.1 μg/mL) and therefore exhibits poor bioavailability. The purpose of this study was to explore the feasibility of preparing BA solid dispersions (BA-SDs) with hydrophilic polymers to enhance the aqueous solubility of BA. Melt-quenched solid dispersions (MQ-SDs) of BA were prepared at various ratios with the hydrophilic polymers including Soluplus, HPMCAS-HF, Kollidon VA64, Kollidon K90, and Eudragit RLPO. BA was found to be miscible in all polymers at a 1:4 (w/w) ratio by modulated differential scanning calorimetry (MDSC). BA/Soluplus MQ-SD exhibited the highest solubility in simulated body fluids followed by BA/Kollidon VA64 MQ-SD. The MQ-SDs of BA/Soluplus, BA/HPMCAS-HF, and BA/Kollidon VA64 were found to be amorphous as indicated by X-ray powder diffraction (XRPD) studies. Fourier transform infra-red (FT-IR) studies indicated molecular interactions between BA and Soluplus. Our preliminary screening of polymers indicates that Soluplus and Kollidon VA64 exhibit the greatest potential to form BA-SDs. PMID:25331193

  9. Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer

    PubMed Central

    Kuo, Ying-Yu; Jim, Wai-Tim; Su, Liang-Cheng; Chung, Chi-Jung; Lin, Ching-Yu; Huo, Chieh; Tseng, Jen-Chih; Huang, Shih-Han; Lai, Chih-Jen; Chen, Bo-Chih; Wang, Bi-Juan; Chan, Tzu-Min; Lin, Hui-Ping; Chang, Wun-Shaing Wayne; Chang, Chuang-Rung; Chuu, Chih-Pin

    2015-01-01

    Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients. PMID:25984601

  10. Surface Engineered Protein Nanoparticles With Hyaluronic Acid Based Multilayers For Targeted Delivery Of Anticancer Agents.

    PubMed

    Pulakkat, Sreeranjini; Balaji, Sai A; Rangarajan, Annapoorni; Raichur, Ashok M

    2016-09-14

    Layer-by-layer (LbL) technique was employed to modify the surface of doxorubicin (Dox)-loaded bovine serum albumin (BSA) nanoparticles using hyaluronic acid (HA) to enable targeted delivery to overexpressed CD44 receptors in metastatic breast cancer cells. LbL technique offers a versatile approach to modify the surface of colloidal nanoparticles without any covalent modification. Dox-loaded BSA (Dox Ab) nanoparticles optimized for their size, zeta potential, and drug encapsulation efficiency were prepared by modified desolvation technique. The cellular uptake and cytotoxicity of the LbL coated Dox Ab nanoparticles were analyzed in CD44 overexpressing breast cancer cell line MDA-MB-231. Nanoparticles with HA as the final layer (Dox Ab HA) showed maximum cellular uptake in MDA-MB-231 cells owing to the CD44 receptor-mediated endocytosis and hence, exhibited more cytotoxicity as compared to free Dox. Further, luciferase-transfected MDA-MB-231 cells were used to induce tumor in BALB/c female nude mice to enable whole body tumor imaging. The mice were imaged before and after Dox treatment to visualize the tumor growth. The in vivo biodistribution of Dox Ab HA nanoparticles in nude mice showed maximum accumulation in tumor, and importantly, better tumor reduction in comparison with free Dox, thus paving the way for improved drug delivery into tumors.

  11. Peracetic Acid: A Practical Agent for Sterilizing Heat-Labile Polymeric Tissue-Engineering Scaffolds

    PubMed Central

    Yoganarasimha, Suyog; Trahan, William R.; Best, Al M.; Bowlin, Gary L.; Kitten, Todd O.; Moon, Peter C.

    2014-01-01

    Advanced biomaterials and sophisticated processing technologies aim at fabricating tissue-engineering scaffolds that can predictably interact within a biological environment at the cellular level. Sterilization of such scaffolds is at the core of patient safety and is an important regulatory issue that needs to be addressed before clinical translation. In addition, it is crucial that meticulously engineered micro- and nano- structures are preserved after sterilization. Conventional sterilization methods involving heat, steam, and radiation are not compatible with engineered polymeric systems because of scaffold degradation and loss of architecture. Using electrospun scaffolds made from polycaprolactone, a low melting polymer, and employing spores of Bacillus atrophaeus as biological indicators, we compared ethylene oxide, autoclaving and 80% ethanol to a known chemical sterilant, peracetic acid (PAA), for their ability to sterilize as well as their effects on scaffold properties. PAA diluted in 20% ethanol to 1000 ppm or above sterilized electrospun scaffolds in 15 min at room temperature while maintaining nano-architecture and mechanical properties. Scaffolds treated with PAA at 5000 ppm were rendered hydrophilic, with contact angles reduced to 0°. Therefore, PAA can provide economical, rapid, and effective sterilization of heat-sensitive polymeric electrospun scaffolds that are used in tissue engineering. PMID:24341350

  12. Peracetic acid: a practical agent for sterilizing heat-labile polymeric tissue-engineering scaffolds.

    PubMed

    Yoganarasimha, Suyog; Trahan, William R; Best, Al M; Bowlin, Gary L; Kitten, Todd O; Moon, Peter C; Madurantakam, Parthasarathy A

    2014-09-01

    Advanced biomaterials and sophisticated processing technologies aim at fabricating tissue-engineering scaffolds that can predictably interact within a biological environment at the cellular level. Sterilization of such scaffolds is at the core of patient safety and is an important regulatory issue that needs to be addressed before clinical translation. In addition, it is crucial that meticulously engineered micro- and nano- structures are preserved after sterilization. Conventional sterilization methods involving heat, steam, and radiation are not compatible with engineered polymeric systems because of scaffold degradation and loss of architecture. Using electrospun scaffolds made from polycaprolactone, a low melting polymer, and employing spores of Bacillus atrophaeus as biological indicators, we compared ethylene oxide, autoclaving and 80% ethanol to a known chemical sterilant, peracetic acid (PAA), for their ability to sterilize as well as their effects on scaffold properties. PAA diluted in 20% ethanol to 1000 ppm or above sterilized electrospun scaffolds in 15 min at room temperature while maintaining nano-architecture and mechanical properties. Scaffolds treated with PAA at 5000 ppm were rendered hydrophilic, with contact angles reduced to 0°. Therefore, PAA can provide economical, rapid, and effective sterilization of heat-sensitive polymeric electrospun scaffolds that are used in tissue engineering. PMID:24341350

  13. Molecular interaction studies of amorphous solid dispersions of the antimelanoma agent betulinic acid.

    PubMed

    Yu, Meiki; Ocando, Joseph E; Trombetta, Louis; Chatterjee, Parnali

    2015-04-01

    Betulinic acid (BA), a novel natural product with antimelanoma activity, has poor aqueous solubility (<0.1 μg/mL) and therefore exhibits poor bioavailability. The purpose of this study was to explore the feasibility of preparing BA solid dispersions (BA-SDs) with hydrophilic polymers to enhance the aqueous solubility of BA. Melt-quenched solid dispersions (MQ-SDs) of BA were prepared at various ratios with the hydrophilic polymers including Soluplus, HPMCAS-HF, Kollidon VA64, Kollidon K90, and Eudragit RLPO. BA was found to be miscible in all polymers at a 1:4 (w/w) ratio by modulated differential scanning calorimetry (MDSC). BA/Soluplus MQ-SD exhibited the highest solubility in simulated body fluids followed by BA/Kollidon VA64 MQ-SD. The MQ-SDs of BA/Soluplus, BA/HPMCAS-HF, and BA/Kollidon VA64 were found to be amorphous as indicated by X-ray powder diffraction (XRPD) studies. Fourier transform infra-red (FT-IR) studies indicated molecular interactions between BA and Soluplus. Our preliminary screening of polymers indicates that Soluplus and Kollidon VA64 exhibit the greatest potential to form BA-SDs.

  14. Novel Type II Fatty Acid Biosynthesis (FAS II) Inhibitors as Multistage Antimalarial Agents

    PubMed Central

    Schrader, Florian C.; Glinca, Serghei; Sattler, Julia M.; Dahse, Hans-Martin; Afanador, Gustavo A.; Prigge, Sean T.; Lanzer, Michael; Mueller, Ann-Kristin; Klebe, Gerhard; Schlitzer, Martin

    2013-01-01

    Malaria is a potentially fatal disease caused by Plasmodium parasites and poses a major medical risk in large parts of the world. The development of new, affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics. In addition, most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood. At this point, a patient might already be suffering from the symptoms associated with the disease and could additionally be infectious to an Anopheles mosquito. These insects act as a vector, subsequently spreading the disease to other humans. In order to cure not only malaria but prevent transmission as well, a drug must target both the blood- and pre-erythrocytic liver stages of the parasite. P. falciparum (Pf) enoyl acyl carrier protein (ACP) reductase (ENR) is a key enzyme of plasmodial type II fatty acid biosynthesis (FAS II). It has been shown to be essential for liver-stage development of Plasmodium berghei and is therefore qualified as a target for true causal chemoprophylaxis. Using virtual screening based on two crystal structures of PfENR, we identified a structurally novel class of FAS inhibitors. Subsequent chemical optimization yielded two compounds that are effective against multiple stages of the malaria parasite. These two most promising derivatives were found to inhibit blood-stage parasite growth with IC50 values of 1.7 and 3.0 µm and lead to a more prominent developmental attenuation of liver-stage parasites than the gold-standard drug, primaquine. PMID:23341167

  15. Managing potential drug-drug interactions between gastric acid-reducing agents and antiretroviral therapy: experience from a large HIV-positive cohort.

    PubMed

    Lewis, J M; Stott, K E; Monnery, D; Seden, K; Beeching, N J; Chaponda, M; Khoo, S; Beadsworth, M B J

    2016-02-01

    Drug-drug interactions between antiretroviral therapy and other drugs are well described. Gastric acid-reducing agents are one such class. However, few data exist regarding the frequency of and indications for prescription, nor risk assessment in the setting of an HIV cohort receiving antiretroviral therapy. To assess prevalence of prescription of gastric acid-reducing agents and drug-drug interaction within a UK HIV cohort, we reviewed patient records for the whole cohort, assessing demographic data, frequency and reason for prescription of gastric acid-reducing therapy. Furthermore, we noted potential drug-drug interaction and whether risk had been documented and mitigated. Of 701 patients on antiretroviral therapy, 67 (9.6%) were prescribed gastric acid-reducing therapy. Of these, the majority (59/67 [88.1%]) were prescribed proton pump inhibitors. We identified four potential drug-drug interactions, which were appropriately managed by temporally separating the administration of gastric acid-reducing agent and antiretroviral therapy, and all four of these patients remained virally suppressed. Gastric acid-reducing therapy, in particular proton pump inhibitor therapy, appears common in patients prescribed antiretroviral therapy. Whilst there remains a paucity of published data, our findings are comparable to those in other European cohorts. Pharmacovigilance of drug-drug interactions in HIV-positive patients is vital. Education of patients and staff, and accurate data-gathering tools, will enhance patient safety.

  16. Influence of different acid and alkaline cleaning agents on the effects of irrigation of synthetic dairy factory effluent on soil quality, ryegrass growth and nutrient uptake.

    PubMed

    Liu, Y-Y; Haynes, R J

    2013-01-01

    The aim of this study was to examine the effects of replacement of phosphoric acid with nitric or acetic acid, and replacement of NaOH with KOH, as cleaning agents in dairy factories, on the effects that irrigation of dairy factory effluent (DFE) has on the soil-plant system. A 16-week greenhouse study was carried out in which the effects of addition of synthetic dairy factory effluent containing (a) milk residues alone or milk residues plus (b) H(3)PO(4)/NaOH, (c) H(3)PO(4)/HNO(3)/NaOH or (d) CH(3)COOH/KOH, on soil's chemical, physical and microbial properties and perennial ryegrass growth and nutrient uptake were investigated. The cumulative effect of DFE addition was to increase exchangeable Na, K, Ca, Mg, exchangeable sodium percentage, microbial biomass C and N and basal respiration in the soil. Dry matter yields of ryegrass were increased by additions of DFE other than that containing CH(3)COOH. Plant uptake of P, Ca and Mg was in the same order as their inputs in DFE but for Na; inputs were an order of magnitude greater than plant uptake. Replacement of NaOH by KOH resulted in increased accumulation of exchangeable K. The effects of added NaOH and KOH on promoting breakdown of soil aggregates during wet sieving (and formation of a < 0.25 mm size class) were similar. Replacement of H(2)PO(4) by HNO(3) is a viable but CH(3)COOH appears to have detrimental effects on plant growth. Replacement of NaOH by KOH lowers the likelihood of phytotoxic effects of Na, but K and Na have similar effects on disaggregation. PMID:22707204

  17. Influence of different acid and alkaline cleaning agents on the effects of irrigation of synthetic dairy factory effluent on soil quality, ryegrass growth and nutrient uptake.

    PubMed

    Liu, Y-Y; Haynes, R J

    2013-01-01

    The aim of this study was to examine the effects of replacement of phosphoric acid with nitric or acetic acid, and replacement of NaOH with KOH, as cleaning agents in dairy factories, on the effects that irrigation of dairy factory effluent (DFE) has on the soil-plant system. A 16-week greenhouse study was carried out in which the effects of addition of synthetic dairy factory effluent containing (a) milk residues alone or milk residues plus (b) H(3)PO(4)/NaOH, (c) H(3)PO(4)/HNO(3)/NaOH or (d) CH(3)COOH/KOH, on soil's chemical, physical and microbial properties and perennial ryegrass growth and nutrient uptake were investigated. The cumulative effect of DFE addition was to increase exchangeable Na, K, Ca, Mg, exchangeable sodium percentage, microbial biomass C and N and basal respiration in the soil. Dry matter yields of ryegrass were increased by additions of DFE other than that containing CH(3)COOH. Plant uptake of P, Ca and Mg was in the same order as their inputs in DFE but for Na; inputs were an order of magnitude greater than plant uptake. Replacement of NaOH by KOH resulted in increased accumulation of exchangeable K. The effects of added NaOH and KOH on promoting breakdown of soil aggregates during wet sieving (and formation of a < 0.25 mm size class) were similar. Replacement of H(2)PO(4) by HNO(3) is a viable but CH(3)COOH appears to have detrimental effects on plant growth. Replacement of NaOH by KOH lowers the likelihood of phytotoxic effects of Na, but K and Na have similar effects on disaggregation.

  18. Regeneration of Three-Way Automobile Catalysts using Biodegradable Metal Chelating Agent – S, S-Ethylenediamine Disuccinic Acid (S, S-EDDS)

    EPA Science Inventory

    Regeneration of the activity of three-way catalytic converters (TWCs) was tested for the first time using a biodegradable metal chelating agent (S, S. Ethylenediamine disuccinic acid (S, S-EDDS). The efficiency of this novel environmentally friendly solvent in removing various c...

  19. Quantitative High-Pressure Liquid Chromatography-Fluorescence Determination of Some Important Lower Fatty Acids in Lake Sediments

    PubMed Central

    Hordijk, Kees A.; Cappenberg, Thomas E.

    1983-01-01

    For the quantitative determination of traces of fatty acids in pore water, several gas and liquid chromatographic methods were tested and discussed. Direct determination by gas-liquid chromatography with the use of formic acid-saturated carrier gas was found to be the least laborious method, but it is only recommended for the determination of volatile acids such as acetate and higher homologs. For the determination of lactate and formate, a derivatization procedure is necessary. The determination of these acids as phenacyl or benzyl esters was complicated by contaminants in the reagents. For this reason, a high-pressure liquid chromatography procedure with 4-bromomethyl-7-methoxycoumarin as a fluorescent labeling reagent is preferred. With this method, lactic, acetic, and formic acids could be demonstrated simultaneously at the nanogram level in 5-ml samples. Profiles of these acids in the sediment of Lake Vechten were measured, and they showed correlations with sulfate-reducing and methanogenic bacterial activities. PMID:16346362

  20. Solid phase nucleic acid extraction technique in a microfluidic chip using a novel non-chaotropic agent: dimethyl adipimidate.

    PubMed

    Shin, Yong; Perera, Agampodi Promoda; Wong, Chee Chung; Park, Mi Kyoung

    2014-01-21

    Here, we present a silicon microfluidic system for the purification and extraction of nucleic acids from human body fluid samples utilizing a dimethyl adipimidate (DMA)-based solid-phase extraction method. We propose DMA, which has been used as an amino-reactive cross-linking agent within cells and proteins, as a non-chaotropic reagent for the capture of nucleic acids to overcome the limitations of existing chaotropic and non-chaotropic techniques such as low binding efficiency, PCR inhibition and so on. DMA contains bi-functional imidoesters that form reversible cross-linking structures with DNA therefore providing a high surface-area to volume ratio for capturing DNA without structurally modifying microfluidic channels. In this work, we have first demonstrated highly efficient capture and purification of genomic DNA (T24 cell line) with DMA using a label-free silicon microring resonator sensor device. In addition, we observed the improvement of the DNA amplification efficiency by using the proposed technique for both the genetic (HRAS) and epigenetic (RARβ) analysis of DNA biomarkers. Particularly, we confirmed that the DMA-based solid-phase extraction technique can be applied for the extraction of genomic DNA with higher purity (p < 0.001) using human body fluids (blood and urine) in silicon microfluidic devices compared to other chaotropic methods. Therefore, the proposed technique would be able to harmonize with a micro-total analysis system platform for the analysis of genetic and epigenetic DNA biomarkers related to human diseases in the field of point-of-care (POC) diagnostic applications. PMID:24263404

  1. Both the Jasmonic Acid and the Salicylic Acid Pathways Contribute to Resistance to the Biotrophic Clubroot Agent Plasmodiophora brassicae in Arabidopsis.

    PubMed

    Lemarié, Séverine; Robert-Seilaniantz, Alexandre; Lariagon, Christine; Lemoine, Jocelyne; Marnet, Nathalie; Jubault, Mélanie; Manzanares-Dauleux, Maria J; Gravot, Antoine

    2015-11-01

    The role of salicylic acid (SA) and jasmonic acid (JA) signaling in resistance to root pathogens has been poorly documented. We assessed the contribution of SA and JA to basal and partial resistance of Arabidopsis to the biotrophic clubroot agent Plasmodiophora brassicae. SA and JA levels as well as the expression of the SA-responsive genes PR2 and PR5 and the JA-responsive genes ARGAH2 and THI2.1 were monitored in infected roots of the accessions Col-0 (susceptible) and Bur-0 (partially resistant). SA signaling was activated in Bur-0 but not in Col-0. The JA pathway was weakly activated in Bur-0 but was strongly induced in Col-0. The contribution of both pathways to clubroot resistance was then assessed using exogenous phytohormone application and mutants affected in SA or JA signaling. Exogenous SA treatment decreased clubroot symptoms in the two Arabidopsis accessions, whereas JA treatment reduced clubroot symptoms only in Col-0. The cpr5-2 mutant, in which SA responses are constitutively induced, was more resistant to clubroot than the corresponding wild type, and the JA signaling-deficient mutant jar1 was more susceptible. Finally, we showed that the JA-mediated induction of NATA1 drove N(δ)-acetylornithine biosynthesis in infected Col-0 roots. The 35S::NATA1 and nata1 lines displayed reduced or enhanced clubroot symptoms, respectively, thus suggesting that in Col-0 this pathway was involved in the JA-mediated basal clubroot resistance. Overall, our data support the idea that, depending on the Arabidopsis accession, both SA and JA signaling can play a role in partial inhibition of clubroot development in compatible interactions with P. brassicae.

  2. Using polyaspartic acid hydro-gel as water retaining agent and its effect on plants under drought stress.

    PubMed

    Wei, Jun; Yang, Haiyuan; Cao, Hui; Tan, Tianwei

    2016-09-01

    Polyaspartic acid (PASP) hydrogel is an important and widely applied water-retaining agent, thanks to its special space network structure which contains a carboxyl group attached on the side chain. In this study, the PASP hydrogel with high water absorption rate (300-350 g H2O/g hydrogel) was developed and adopted to transplant Xanthoceras sorbifolia seedlings in the ecological restoration project of Mount Daqing National Nature Reserve. Transplantation experiments showed that the survival rate and leaf water content index for X. sorbifolia seedlings were increased by 8-12% and 4-16%, respectively. Additionally, compared with the counterpart without PASP hydrogel, the value of chlorophyll fluorescence that was considered as one of the most important indicators of plant physiology, was significantly improved with the addition of PASP hydrogel. The PASP hydrogel displays a promising future for the applications of increasing the survival rate and simultaneously alleviating the drought stress effects on the pioneer plants in arid and semi-arid areas. PMID:27579017

  3. Degradation of sunscreen agent p-aminobenzoic acid using a combination system of UV irradiation, persulphate and iron(II).

    PubMed

    Xue, Yicen; Dong, Wenbo; Wang, Xiaoning; Bi, Wenlong; Zhai, Pingping; Li, Hongjing; Nie, Minghua

    2016-03-01

    Increased usage and discharge of sunscreens have led to ecological safety crisis, and people are developing the advanced oxidation processes (AOPs) to treat them. The present study aimed to determine the degradation efficiency and mechanism of the sunscreen agent p-aminobenzoic acid (PABA) using the UV/Fe(2+)/persulphate (PS) method. A series of irradiation experiments were conducted to optimise the system conditions and to study the impacts of the natural anion. Free radicals and degradation products were identified in order to clarify the degradation mechanism. Initial PS and Fe(2+) concentrations showed significant impacts on PABA degradation. Natural anions, such as Cl(-), NO3 (-), H2PO4 (-) and HCO3 (-), impeded PABA degradation because of ion (Fe(2+)) capture, radical scavenging or pH effects. Hydroxyl (HO·) and sulphate (SO4 (·-)) radicals were two main radicals observed in the UV/Fe(2+)/PS system; of these, SO4 (·-) showed greater effects on PABA degradation. Over 99 % of the available PABA was completely degraded into carbon dioxide (CO2) and water (H2O) by the UV/Fe(2+)/PS system, and the remaining PABA participated in complex radical reactions. By-products were identified by total ion chromatography and mass spectrometry. Our research provides a treatment process for PABA with high degradation efficiency and environmental safety and introduces a new strategy for sunscreen degradation. PMID:26517998

  4. Degradation of sunscreen agent p-aminobenzoic acid using a combination system of UV irradiation, persulphate and iron(II).

    PubMed

    Xue, Yicen; Dong, Wenbo; Wang, Xiaoning; Bi, Wenlong; Zhai, Pingping; Li, Hongjing; Nie, Minghua

    2016-03-01

    Increased usage and discharge of sunscreens have led to ecological safety crisis, and people are developing the advanced oxidation processes (AOPs) to treat them. The present study aimed to determine the degradation efficiency and mechanism of the sunscreen agent p-aminobenzoic acid (PABA) using the UV/Fe(2+)/persulphate (PS) method. A series of irradiation experiments were conducted to optimise the system conditions and to study the impacts of the natural anion. Free radicals and degradation products were identified in order to clarify the degradation mechanism. Initial PS and Fe(2+) concentrations showed significant impacts on PABA degradation. Natural anions, such as Cl(-), NO3 (-), H2PO4 (-) and HCO3 (-), impeded PABA degradation because of ion (Fe(2+)) capture, radical scavenging or pH effects. Hydroxyl (HO·) and sulphate (SO4 (·-)) radicals were two main radicals observed in the UV/Fe(2+)/PS system; of these, SO4 (·-) showed greater effects on PABA degradation. Over 99 % of the available PABA was completely degraded into carbon dioxide (CO2) and water (H2O) by the UV/Fe(2+)/PS system, and the remaining PABA participated in complex radical reactions. By-products were identified by total ion chromatography and mass spectrometry. Our research provides a treatment process for PABA with high degradation efficiency and environmental safety and introduces a new strategy for sunscreen degradation.

  5. Biodegradable chelating agent ethylenediaminedisuccinic acid reduces uptake of copper through alleviation of copper toxicity in hydroponically grown Chrysanthemum coronarium L.

    PubMed

    Wei, Lan; Luo, Chunling; Wang, Chunchun; Li, Xiangdong; Shen, Zhenguo

    2007-04-01

    Hydroponic cultures were conducted to investigate the effects of the biodegradable chelating agent S,S-ethylenediaminedisuccinic acid (EDDS) on the growth and copper uptake by garland chrysanthemum (Chrysanthemum coronarium L.), a plant species sensitive to soil chelate amendment. In the presence of 50 micromol/L Cu, the addition of EDDS increased shoot and root biomass and the vitality of cells in root tips and decreased the relative electrolyte leakage of root cells and the concentration of Cu in shoots. When the roots were pretreated with 65 degrees C hot water for 0.5 to 2 h or with 0.001 to 0.1 mol/L HCl for 24 h before the exposure to 50 micromol/L Cu + 100 micromol/L EDDS, the concentration of Cu in shoots increased considerably compared with the plants without any pretreatment. A statistically significant correlation was found between the Cu concentrations in shoots and the relative electrolyte leakage of root cells. These results indicated that Cu-EDDS might be a less bioavailable form to plants and that some physiological damage to the roots led to enhanced accumulation of Cu in plant shoots.

  6. First Chemical Feature Based Pharmacophore Modeling of Potent Retinoidal Retinoic Acid Metabolism Blocking Agents (RAMBAs): Identification of Novel RAMBA Scaffolds

    PubMed Central

    Purushottamachar, Puranik; Patel, Jyoti B.; Gediya, Lalji K; Clement, Omoshile O.; Njar, Vincent C. O.

    2011-01-01

    The first three-dimensional (3D) pharmacophore model was developed for potent retinoidal retinoic acid metabolism blocking agents (RAMBAs) with IC50 values ranging from 0.0009 to 5.84 nM. The seven common chemical features in these RAMBAs as deduced by the Catalyst/HipHop program include five hydrophobic groups (hydrophobes), one hydrogen bond acceptor (HBA) and one ring aromatic group. Using the pharmacophore model as a 3D search query against NCI and Maybridge conformational Catalyst formatted databases; we retrieved several compounds with different structures (scaffolds) as hits. Twenty one retrieved hits were tested for RAMBA activity at 100 nM concentration. The most potent of these compounds, NCI10308597 and HTS01914 showed inhibitory potencies less (54.7% and 53.2%, respectively, at 100 nM) than those of our best previously reported RAMBAs VN/12-1 and VN/14-1 (90% and 86%, respectively, at 100 nM). Docking studies using a CYP26A1 homology model revealed that our most potent RAMBAs showed similar binding to the one observed for a series of RAMBAs reported previously by others. Our data shows the potential of our pharmacophore model in identifying structurally diverse and potent RAMBAs. Further refinement of the model and searches of other robust databases is currently in progress with a view to identifying and optimizing new leads. PMID:22130607

  7. Enantioselective capillary electrophoresis-mass spectrometry of amino acids in cerebrospinal fluid using a chiral derivatizing agent and volatile surfactant.

    PubMed

    Prior, A; Moldovan, R C; Crommen, J; Servais, A C; Fillet, M; de Jong, G J; Somsen, G W

    2016-10-12

    The sensitivity of coupled enantioselective capillary electrophoresis-mass spectrometry (CE-MS) of amino acids (AAs) is often hampered by the chiral selectors in the background electrolyte (BGE). A new method is presented in which the use of a chiral selector is circumvented by employing (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC) as chiral AA derivatizing agent and ammonium perfluorooctanoate (APFO) as a volatile pseudostationary phase for separation of the formed diastereomers. Efficient AA derivatization with FLEC was completed within 10 min. Infusion experiments showed that the APFO concentration hardly affects the MS response of FLEC-AAs and presents significantly less ion suppression than equal concentrations of ammonium acetate. The effect of the pH and APFO concentration of the BGE and the capillary temperature were studied in order to achieve optimized enantioseparation. Optimization of CE-MS parameters, such as sheath-liquid composition and flow rate, ESI and MS settings was performed in order to prevent analyte fragmentation and achieve sensitive detection. Selective detection and quantification of 14 chiral proteinogenic AAs was achieved with chiral resolution between 1.2 and 8.6, and limits of detection ranging from 130 to 630 nM injected concentration. Aspartic acid and glutamic acid were detected, but not enantioseparated. The optimized method was applied to the analysis of chiral AAs in cerebrospinal fluid (CSF). Good linearity (R(2) > 0.99) and acceptable peak area and electrophoretic mobility repeatability (RSDs below 21% and 2.4%, respectively) were achieved for the chiral proteinogenic AAs, with sensitivity and chiral resolution mostly similar to obtained for standard solutions. Next to l-AAs, endogenous levels of d-serine and d-glutamine could be measured in CSF revealing enantiomeric ratios of 4.8%-8.0% and 0.34%-0.74%, respectively, and indicating the method's potential for the analysis of low concentrations of d-AAs in presence of

  8. Enantioselective capillary electrophoresis-mass spectrometry of amino acids in cerebrospinal fluid using a chiral derivatizing agent and volatile surfactant.

    PubMed

    Prior, A; Moldovan, R C; Crommen, J; Servais, A C; Fillet, M; de Jong, G J; Somsen, G W

    2016-10-12

    The sensitivity of coupled enantioselective capillary electrophoresis-mass spectrometry (CE-MS) of amino acids (AAs) is often hampered by the chiral selectors in the background electrolyte (BGE). A new method is presented in which the use of a chiral selector is circumvented by employing (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC) as chiral AA derivatizing agent and ammonium perfluorooctanoate (APFO) as a volatile pseudostationary phase for separation of the formed diastereomers. Efficient AA derivatization with FLEC was completed within 10 min. Infusion experiments showed that the APFO concentration hardly affects the MS response of FLEC-AAs and presents significantly less ion suppression than equal concentrations of ammonium acetate. The effect of the pH and APFO concentration of the BGE and the capillary temperature were studied in order to achieve optimized enantioseparation. Optimization of CE-MS parameters, such as sheath-liquid composition and flow rate, ESI and MS settings was performed in order to prevent analyte fragmentation and achieve sensitive detection. Selective detection and quantification of 14 chiral proteinogenic AAs was achieved with chiral resolution between 1.2 and 8.6, and limits of detection ranging from 130 to 630 nM injected concentration. Aspartic acid and glutamic acid were detected, but not enantioseparated. The optimized method was applied to the analysis of chiral AAs in cerebrospinal fluid (CSF). Good linearity (R(2) > 0.99) and acceptable peak area and electrophoretic mobility repeatability (RSDs below 21% and 2.4%, respectively) were achieved for the chiral proteinogenic AAs, with sensitivity and chiral resolution mostly similar to obtained for standard solutions. Next to l-AAs, endogenous levels of d-serine and d-glutamine could be measured in CSF revealing enantiomeric ratios of 4.8%-8.0% and 0.34%-0.74%, respectively, and indicating the method's potential for the analysis of low concentrations of d-AAs in presence of

  9. High intake of dietary long-chain ω-3 fatty acids is associated with lower blood pressure in children born with low birth weight: NHANES 2003-2008.

    PubMed

    Skilton, Michael R; Raitakari, Olli T; Celermajer, David S

    2013-05-01

    Reduced fetal growth is associated with increased systolic blood pressure. Recently, we found an inverse association between serum ω-3 fatty acids and systolic blood pressure in young adults born with impaired fetal growth. We investigated the associations of dietary intake in childhood of the long-chain ω-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid with blood pressure parameters in children born with reduced birth weight. We analyzed data from 3457 children aged 8 to 15 years participating in the continuous National Health and Nutrition Examination Survey 2003-2004, 2005-2006, and 2007-2008. Dietary intake was assessed by two 24-hour dietary recalls, birth weight by questionnaire, and blood pressure was measured. Systolic blood pressure was 1.1 mm Hg higher in those with reduced (<10th centile) compared with normal birth weight (≥ 10th centile), consistent with previous findings, although not statistically significant (P=0.40); however, pulse pressure was significantly higher in these children (3.4 mm Hg). In the 354 participants with reduced birth weight, when compared with children with the lowest tertile of intake, those who had the highest tertile of dietary eicosapentaenoic acid and docosahexaenoic acid intake had significantly lower systolic blood pressure (-4.9 mm Hg [95% confidence interval, -9.7 to -0.1]) and pulse pressure (-7.7 mm Hg [95% confidence interval, -15.0 to -0.4]). High-dietary intakes of eicosapentaenoic acid and docosahexaenoic acid are associated with lower systolic blood pressure and pulse pressure in children born with reduced birth weight. These data are consistent with the hypothesis that long-chain ω-3 fatty acids reduce blood pressure in those with impaired fetal growth. PMID:23460284

  10. Omega-3 Fatty Acid Enriched Chevon (Goat Meat) Lowers Plasma Cholesterol Levels and Alters Gene Expressions in Rats

    PubMed Central

    Rajion, Mohamed Ali; Meng, Goh Yong; Soleimani Farjam, Abdoreza

    2014-01-01

    In this study, control chevon (goat meat) and omega-3 fatty acid enriched chevon were obtained from goats fed a 50% oil palm frond diet and commercial goat concentrate for 100 days, respectively. Goats fed the 50% oil palm frond diet contained high amounts of α-linolenic acid (ALA) in their meat compared to goats fed the control diet. The chevon was then used to prepare two types of pellets (control or enriched chevon) that were then fed to twenty-male-four-month-old Sprague-Dawley rats (n = 10 in each group) for 12 weeks to evaluate their effects on plasma cholesterol levels, tissue fatty acids, and gene expression. There was a significant increase in ALA and docosahexaenoic acid (DHA) in the muscle tissues and liver of the rats fed the enriched chevon compared with the control group. Plasma cholesterol also decreased (P < 0.05) in rats fed the enriched chevon compared to the control group. The rat pellets containing enriched chevon significantly upregulated the key transcription factor PPAR-γ and downregulated SREBP-1c expression relative to the control group. The results showed that the omega-3 fatty acid enriched chevon increased the omega-3 fatty acids in the rat tissues and altered PPAR-γ and SREBP-1c genes expression. PMID:24719886

  11. Omega-3 fatty acid enriched chevon (goat meat) lowers plasma cholesterol levels and alters gene expressions in rats.

    PubMed

    Ebrahimi, Mahdi; Rajion, Mohamed Ali; Meng, Goh Yong; Soleimani Farjam, Abdoreza

    2014-01-01

    In this study, control chevon (goat meat) and omega-3 fatty acid enriched chevon were obtained from goats fed a 50% oil palm frond diet and commercial goat concentrate for 100 days, respectively. Goats fed the 50% oil palm frond diet contained high amounts of α-linolenic acid (ALA) in their meat compared to goats fed the control diet. The chevon was then used to prepare two types of pellets (control or enriched chevon) that were then fed to twenty-male-four-month-old Sprague-Dawley rats (n = 10 in each group) for 12 weeks to evaluate their effects on plasma cholesterol levels, tissue fatty acids, and gene expression. There was a significant increase in ALA and docosahexaenoic acid (DHA) in the muscle tissues and liver of the rats fed the enriched chevon compared with the control group. Plasma cholesterol also decreased (P < 0.05) in rats fed the enriched chevon compared to the control group. The rat pellets containing enriched chevon significantly upregulated the key transcription factor PPAR-γ and downregulated SREBP-1c expression relative to the control group. The results showed that the omega-3 fatty acid enriched chevon increased the omega-3 fatty acids in the rat tissues and altered PPAR-γ and SREBP-1c genes expression.

  12. Improve the Strength of PLA/HA Composite Through the Use of Surface Initiated Polymerization and Phosphonic Acid Coupling Agent

    PubMed Central

    Wang, Tongxin; Chow, Laurence C.; Frukhtbeyn, Stanislav A.; Ting, Andy Hai; Dong, Quanxiao; Yang, Mingshu; Mitchell, James W.

    2011-01-01

    Bioresorbable composite made from degradable polymers, e.g., polylactide (PLA), and bioactive calcium phosphates, e.g., hydroxyapatite (HA), are clinically desirable for bone fixation, repair and tissue engineering because they do not need to be removed by surgery after the bone heals. However, preparation of PLA/HA composite from non-modified HA usually results in mechanical strength reductions due to a weak interface between PLA and HA. In this study, a calcium-phosphate/phosphonate hybrid shell was developed to introduce a greater amount of reactive hydroxyl groups onto the HA particles. Then, PLA was successfully grafted on HA by surface-initiated polymerization through the non-ionic surface hydroxyl groups. Thermogravimetric analysis indiated that the amount of grafted PLA on HA can be up to 7 %, which is about 50 % greater than that from the literature. PLA grafted HA shows significantly different pH dependent ζ-potential and particle size profiles from those of uncoated HA. By combining the phosphonic acid coupling agent and surface initiated polymerization, PLA could directly link to HA through covalent bond so that the interfacial interaction in the PLA/HA composite can be significantly improved. The diametral tensile strength of PLA/HA composite prepared from PLA-grafted HA was found to be over twice that of the composite prepared from the non-modified HA. Moreover, the tensile strength of the improved composite was 23 % higher than that of PLA alone. By varying additional variables, this approach has the potential to produce bioresorbable composites with improved mechanical properties that are in the range of natural bones, and can have wide applications for bone fixation and repair in load-bearing areas. PMID:22399838

  13. Plant-bacteria bioremediation agents affect the response of plant bioindicators independent of 2-chlorobenzoic acid degradation

    SciTech Connect

    Siciliano, S.D.; Germida, J.J.

    1995-12-31

    Plants are known to degrade toxicants in soil and are potentially useful bioremediation agents. The authors developed plant-bacteria associations (e.g., Meadow brome [Bromus riparius] and Pseudomonas aeruginosa strain R75) that degrade 2-chlorobenzoic acid (2CBA) in soil, and assessed their success using Slender wheatgrass (Agropyron trachycaulum) germination as a bioindicator of 2CBA levels. Gas chromatography was used to chemically assess 2CBA levels. Specific plant-bacteria bioremediation treatments decreased soil 2CBA levels by 17 to 52%, but bioindicator response did not correspond to chemical analysis. Contaminated and uncontaminated soil was subjected to bioremediation treatments. After 42 days, uncontaminated soil was collected and amended to various 2CBA levels. This soil and the remediated soil were analyzed by the plant bioindicator and gas chromatography. Bioremediation treatments altered germination of Slender wheatgrass in both contaminated and noncontaminated soils to a similar extent. These treatments decreased the toxicity of 2CBA to Slender wheatgrass in both contaminated and noncontaminated soils to a similar extent. These treatments decreased the toxicity of 2CBA to Slender wheatgrass at low 2CBA levels, but increased the toxicity of 2CBA at high 2CBA levels. For example, germination in soil subjected to the Meadow brome and R75 treatment was increased by ca. 30% at 50 mg kg{sup {minus}1} 2CBA, but decreased by ca. 50% at 150 mg kg{sup {minus}1} 2CBA. The results indicate that specific plant-bacteria bioremediation treatments affect plant bioindicator response independent of 2CBA degradation, and may confound efforts to determine the toxicity of 2CBA in soil.

  14. Synthesis and Preclinical Evaluation of Radioiodinated Hypericin Dicarboxylic Acid as a Necrosis Avid Agent in Rat Models of Induced Hepatic, Muscular, and Myocardial Necroses.

    PubMed

    Li, Jindian; Zhang, Jian; Yang, Shengwei; Jiang, Cuihua; Zhang, DongJian; Jin, Qiaomei; Wang, Qin; Wang, Cong; Ni, Yicheng; Yin, Zhiqi; Song, Shaoli

    2016-01-01

    Myocardial infarction (MI) leads to substantial morbidity and mortality around the world. Accurate assessment of myocardial viability is essential to assist therapies and improve patient outcomes. (131)I-hypericin dicarboxylic acid ((131)I-HDA) was synthesized and evaluated as a potential diagnostic agent for earlier assessment of myocardium viability compared to its preceding counterpart (131)I-hypericin ((131)I-Hyp) with strong hydrophobic property, long plasma half-life, and high uptake in mononuclear phagocyte system (MPS). Herein, HDA was synthesized and characterized, and self-aggregation constant Kα was analyzed by spectrophotometry. Plasma half-life was determined in healthy rats by γ-counting. (131)I-HDA and (131)I-Hyp were prepared with iodogen as oxidant. In vitro necrosis avidity of (131)I-HDA and (131)I-Hyp was evaluated in necrotic cells induced by hyperthermia. Biodistribution was determined in rat models of induced necrosis using γ-counting, autoradiography, and histopathology. Earlier imaging of necrotic myocardium to assess myocardial viability was performed in rat models of reperfused myocardium infarction using single photon emission computed tomography/computed tomography (SPECT/CT). As a result, the self-aggregation constant Kα of HDA was lower than that of Hyp (105602 vs 194644, p < 0.01). (131)I-HDA displayed a shorter blood half-life compared with (131)I-Hyp (9.21 vs 31.20 h, p < 0.01). The necrotic-viable ratio in cells was higher with (131)I-HDA relative to that with (131)I-Hyp (5.48 vs 4.63, p < 0.05). (131)I-HDA showed a higher necrotic-viable myocardium ratio (7.32 vs 3.20, p < 0.01), necrotic myocardium-blood ratio (3.34 vs 1.74, p < 0.05), and necrotic myocardium-lung ratio (3.09 vs 0.61, p < 0.01) compared with (131)I-Hyp. (131)I-HDA achieved imaging of necrotic myocardium at 6 h postinjection (p.i.) with SPECT/CT, earlier than what (131)I-Hyp did. Therefore, (131)I-HDA may serve as a promising necrosis-avid diagnostic agent for

  15. Renal clearance of uric acid is linked to insulin resistance and lower excretion of sodium in gout patients.

    PubMed

    Perez-Ruiz, Fernando; Aniel-Quiroga, Maria Angeles; Herrero-Beites, Ana María; Chinchilla, Sandra Pamela; Erauskin, Gorka Garcia; Merriman, Toni

    2015-09-01

    Inefficient renal excretion of uric acid is the main pathophysiological mechanism for hyperuricemia in gout patients. Polymorphisms of renal tubular transporters linked with sodium and monosaccharide transport have yet to be demonstrated. We intended to evaluate the impact of insulin resistance, evaluated with the homeostasis model assessment (HOMA), through a transversal study of non-diabetic patients with gout, with normal renal function, not treated with any medication but colchicine as prophylaxis. One hundred and thirty-three patients were evaluated. Clearance of uric acid was inversely correlated with insulin resistance and directly correlated with fractional excretion of sodium. In multivariate analysis, hypertension and hyperlipidemia, in addition to insulin resistance and fractional excretion of sodium, were associated with renal clearance of uric acid. HOMA cutoff for efficient versus inefficient renal handling of uric acid was 2.72, close to that observed in studies of reference population. The impact of insulin resistance and renal handling of sodium on renal clearance of uric acid may help to explain why hyperuricemia is more commonly associated with diabetes and hypertension. PMID:25763991

  16. Nitric Acid Uptake and Decomposition on Black Carbon (Soot) Surfaces: Its Implications for the Upper Troposphere and Lower Stratosphere

    NASA Technical Reports Server (NTRS)

    Choi, W.; Leu, M. T.

    1998-01-01

    Black carbon particles (soot) are formed as a result of incomplete combustion processes and are ubiquitous in the atmosphere. The lower troposphere contains plenty of soot particles whose principal sources are fossil fuel and biomass combustion at the ground level.

  17. A new chiral derivatizing agent for the HPLC separation of α-amino acids on a standard reverse-phase column.

    PubMed

    Kotthaus, A F; Altenbach, H-J

    2011-02-01

    A new chiral derivatizing agent for α-amino acids is described which leads to diastereomers that can be separated by reverse-phase HPLC with direct detection by a diode array detector. The main advantage of the presented procedure is the fact that an excess of the derivatizing reagent can be employed as the product exhibits an absorption maximum at 360 nm, while the reagent has its absorption maximum at 260 nm. Therefore, it is possible to suppress the reagent signal by a detection wavelength of 400 nm leading to an easy and general method for the enantioseparation of a mixture of DL-amino acids and the determination of the enantiomeric purity of α-amino acid as exemplified by 16 different α-amino acids.

  18. Strategies for the design and synthesis of boronated nucleic acid and protein components as potential delivery agents for neutron capture therapy

    SciTech Connect

    Wyzlic, I.M.; Tjarks, W.; Soloway, A.H.; Anisuzzaman, A.K.M.; Rong, Feng-Guang; Barth, R.F. )

    1994-03-30

    Strategies for the design and synthesis of boronated nucleosides, amino acids, and peptides as potential delivery agents for boron neutron capture therapy (BNCT) are described. For BNCT to be a useful treatment modality, there is a need to design and synthesize nontoxic boron compounds that selectively target tumor cells, accumulate in sufficient amounts (20-30 [mu]g [sup 10]B/g of tumor) and persist at therapeutic levels for a sufficient time prior to neutron irradiation. Boronated nucleosides, amino acids and peptides are such promising target compounds. Such structures may be selectively used by proliferating neoplastic cells compared with mitotically less active normal cells and therefore achieve the tissue differentials necessary for BNCT. The rationale for synthesis of boronated nucleic acid and protein components is discussed. Results of biological and clinical studies of some boronated nucleosides, nucleotides, amino acids and peptides are presented. Boronated nucleosides, amino acids and peptides can be considered as potential targeting agents for BNCT. 96 refs., 4 figs.

  19. Lorenzo's oil inhibits ELOVL1 and lowers the level of sphingomyelin with a saturated very long-chain fatty acid.

    PubMed

    Sassa, Takayuki; Wakashima, Takeshi; Ohno, Yusuke; Kihara, Akio

    2014-03-01

    X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by impaired degradation of very long-chain fatty acids (VLCFAs) due to mutations in the ABCD1 gene responsible for VLCFA transport into peroxisomes. Lorenzo's oil, a 4:1 mixture of glyceryl trioleate and glyceryl trierucate, has been used to reduce the saturated VLCFA level in the plasma of X-ALD patients; however, the mechanism by which this occurs remains elusive. We report the biochemical characterization of Lorenzo's oil activity toward elongation of very long-chain fatty acid (ELOVL) 1, the primary enzyme responsible for the synthesis of saturated and monounsaturated VLCFAs. Oleic and erucic acids inhibited ELOVL1, and, moreover, their 4:1 mixture (the FA composition of Lorenzo's oil) exhibited the most potent inhibitory activity. The kinetics analysis revealed that this was a mixed (not a competitive) inhibition. At the cellular level, treatment with the 4:1 mixture reduced the level of SM with a saturated VLCFA accompanied by an increased level of SM with a monounsaturated VLCFA, probably due to the incorporation of erucic acid into the FA elongation cycle. These results suggest that inhibition of ELOVL1 may be an underlying mechanism by which Lorenzo's oil exerts its action.

  20. A pilot trial of the anti-angiogenic copper lowering agent tetrathiomolybdate in combination with irinotecan, 5-flurouracil, and leucovorin for metastatic colorectal cancer

    PubMed Central

    Griffith, Kent A.; Pan, Quintin; Brewer, George J.; Henja, Gwen F.; Merajver, Sofia D.; Zalupski, Mark M.

    2013-01-01

    Summary Tetrathiomolybdate (TM) is an oral copper chelator under development as an anti-angiogenic agent. We evaluated TM in combination with irinotecan, 5-fluorouracil, and leucovorin (IFL). Serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor, interleukin 6 (IL-6), and IL-8 were measured to evaluate the anti-angiogenic effect. Twenty-four patients with metastatic colorectal cancer were treated. The combination with IFL was well tolerated and dose intensity of IFL was maintained during combination therapy with TM. By intention to treat analysis, the overall response rate (RR) was 25% (95% CI 9.8–46.7) and the median time to progression (TTP) was 5.6 months (95% CI 2.7–7.7). VEGF levels were correlated with TTP, as were changes in VEGF, IL-8, and IL-6. TM can be safely added to IFL without compromising dose intensity or diminishing the expected RR. Changes in serum VEGF, IL-8, and IL-6 after treatment may directly reflect changes in CRC tissue angiogenesis. PMID:18712502

  1. Carotid Intima-Media Thickness in Indonesian Subjects with Cardiovascular Disease Risk Factors Who Were Not Receiving Lipid-Lowering Agents.

    PubMed

    Kaligis, Rinambaan W M; Adiarto, Suko; Nugroho, Johanes; Pradnyana, Bagus Ari; Lefi, Achmad; Rifqi, Sodiqur

    2016-09-01

    Carotid intima-media thickness (CIMT) is frequently utilized for detection of subclinical atherosclerosis. This study aims to investigate the association between the CIMT values and demographic characteristics, cardiovascular disease (CVD) risk factors, lipid biochemistry profiles, and high-sensitivity C-reactive protein (hs-CRP) levels among the Indonesian population. Subjects who had two or more CVD risk factors but were not receiving lipid-lowering therapy were recruited from six hospitals of Indonesia. Measurements of CIMT are obtained by ultrasonography of 12 sites within the common carotid artery. CVD risk factors, lipid and glucose profiles, and hs-CRP values were analyzed with respect to distribution of CIMT. The mean-max CIMT was 0.805 ± 0.190 mm (minimum, 0.268 mm; maximum, 1.652 mm) and the mean-mean CIMT was 0.614 ± 0.190 mm (minimum, 0.127 mm; maximum, 1.388 mm). Multivariate analyses confirmed an independent association between increasing CIMT and increasing age (regression coefficient = 0.004; p = 0.004). Our data show normative mean-mean CIMT data for Indonesian subjects with two or more CVD risk factors who are not receiving lipid-lowering therapy, which may guide CVD risk stratification of asymptomatic individuals in Indonesia. PMID:27574385

  2. Carotid Intima-Media Thickness in Indonesian Subjects with Cardiovascular Disease Risk Factors Who Were Not Receiving Lipid-Lowering Agents.

    PubMed

    Kaligis, Rinambaan W M; Adiarto, Suko; Nugroho, Johanes; Pradnyana, Bagus Ari; Lefi, Achmad; Rifqi, Sodiqur

    2016-09-01

    Carotid intima-media thickness (CIMT) is frequently utilized for detection of subclinical atherosclerosis. This study aims to investigate the association between the CIMT values and demographic characteristics, cardiovascular disease (CVD) risk factors, lipid biochemistry profiles, and high-sensitivity C-reactive protein (hs-CRP) levels among the Indonesian population. Subjects who had two or more CVD risk factors but were not receiving lipid-lowering therapy were recruited from six hospitals of Indonesia. Measurements of CIMT are obtained by ultrasonography of 12 sites within the common carotid artery. CVD risk factors, lipid and glucose profiles, and hs-CRP values were analyzed with respect to distribution of CIMT. The mean-max CIMT was 0.805 ± 0.190 mm (minimum, 0.268 mm; maximum, 1.652 mm) and the mean-mean CIMT was 0.614 ± 0.190 mm (minimum, 0.127 mm; maximum, 1.388 mm). Multivariate analyses confirmed an independent association between increasing CIMT and increasing age (regression coefficient = 0.004; p = 0.004). Our data show normative mean-mean CIMT data for Indonesian subjects with two or more CVD risk factors who are not receiving lipid-lowering therapy, which may guide CVD risk stratification of asymptomatic individuals in Indonesia.

  3. The cholesterol-lowering agent methyl-β-cyclodextrin promotes glucose uptake via GLUT4 in adult muscle fibers and reduces insulin resistance in obese mice.

    PubMed

    Llanos, Paola; Contreras-Ferrat, Ariel; Georgiev, Tihomir; Osorio-Fuentealba, Cesar; Espinosa, Alejandra; Hidalgo, Jorge; Hidalgo, Cecilia; Jaimovich, Enrique

    2015-02-15

    Insulin stimulates glucose uptake in adult skeletal muscle by promoting the translocation of GLUT4 glucose transporters to the transverse tubule (T-tubule) membranes, which have particularly high cholesterol levels. We investigated whether T-tubule cholesterol content affects insulin-induced glucose transport. Feeding mice a high-fat diet (HFD) for 8 wk increased by 30% the T-tubule cholesterol content of triad-enriched vesicular fractions from muscle tissue compared with triads from control mice. Additionally, isolated muscle fibers (flexor digitorum brevis) from HFD-fed mice showed a 40% decrease in insulin-stimulated glucose uptake rates compared with fibers from control mice. In HFD-fed mice, four subcutaneous injections of MβCD, an agent reported to extract membrane cholesterol, improved their defective glucose tolerance test and normalized their high fasting glucose levels. The preincubation of isolated muscle fibers with relatively low concentrations of MβCD increased both basal and insulin-induced glucose uptake in fibers from controls or HFD-fed mice and decreased Akt phosphorylation without altering AMPK-mediated signaling. In fibers from HFD-fed mice, MβCD improved insulin sensitivity even after Akt or CaMK II inhibition and increased membrane GLUT4 content. Indinavir, a GLUT4 antagonist, prevented the stimulatory effects of MβCD on glucose uptake. Addition of MβCD elicited ryanodine receptor-mediated calcium signals in isolated fibers, which were essential for glucose uptake. Our findings suggest that T-tubule cholesterol content exerts a critical regulatory role on insulin-stimulated GLUT4 translocation and glucose transport and that partial cholesterol removal from muscle fibers may represent a useful strategy to counteract insulin resistance.

  4. α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology.

    PubMed

    Piermartiri, Tetsade; Pan, Hongna; Figueiredo, Taiza H; Marini, Ann M

    2015-01-01

    α-Linolenic acid (ALA) is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP) nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE) that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders. PMID:26569216

  5. Changes in acidity and metal geochemistry in soils, groundwater, drain and river water in the Lower Murray River after a severe drought.

    PubMed

    Mosley, Luke M; Fitzpatrick, Rob W; Palmer, David; Leyden, Emily; Shand, Paul

    2014-07-01

    Acid sulfate soils with sulfuric material (pH<4) can have significant impacts on surface water quality and aquatic ecosystems due to low pH and high soluble metal concentrations in runoff and drainage discharges. There has been limited research on the complex geochemical transformations that occur along flow pathways from the soil acidity source to receiving waters. We studied the integrated geochemistry of metals in acid sulfate soils with sulfuric material, groundwater, drain and river water in the Lower Murray River (South Australia) over a 2 year period. The oxidation of an estimated 3500 ha of acid sulfate soils with sulfidic material (pH>4) underlying this former floodplain occurred due to falling river and groundwater levels during the 2006-2010 extreme "millennium" drought. A low pH (<4.5) soil layer was found approximately 1-2.5m below ground level with substantial amounts (up to 0.2 mol H(+)/kg dry weight) of available/soluble acidity and retained acidity in the form of the Fe oxyhydroxy sulfate mineral jarosite. The jarosite appears to be dissolving over time and buffering the sub-surface soil layers at pH≈4. Metal (Fe, Al, Mn) and metalloid (As) lability was greatly increased in the acidic soil layer. Highly acidic and metal rich groundwater (median pH 4.3, Fe, Al, Mn of 0.04-0.52 mmol/L) was observed at the same depths as the acidic soil layers. Nearly all of the dissolved Fe in the groundwater was present as Fe(2+). In the drains, increases in pH and redox potential promoted formation of the Fe oxyhydroxysulfate mineral schwertmannite. This mineral precipitation transferred a portion of the dissolved acidity to the drain sediments. Upon discharge to, and dilution of, the acid drainage in the river, pH neutralisation and rapid oxidation, hydrolysis, and precipitation of solid Al and Fe phases occurred in a localised area. Acidity is persisting (>3 years) following a return to pre-drought water levels.

  6. Anthocyanin-Rich Juice Lowers Serum Cholesterol, Leptin, and Resistin and Improves Plasma Fatty Acid Composition in Fischer Rats

    PubMed Central

    Graf, Daniela; Seifert, Stephanie; Jaudszus, Anke; Bub, Achim; Watzl, Bernhard

    2013-01-01

    Obesity and obesity-associated diseases e.g. cardiovascular diseases and type 2 diabetes are spread worldwide. Anthocyanins are supposed to have health-promoting properties, although convincing evidence is lacking. The aim of the present study was to investigate the effect of anthocyanins on several risk factors for obesity-associated diseases. Therefore, Fischer rats were fed anthocyanin-rich grape-bilberry juice or an anthocyanin-depleted control juice for 10 weeks. Intervention with anthocyanin-rich grape-bilberry juice reduced serum cholesterol and tended to decrease serum triglycerides. No effects were seen for serum non-esterified fatty acids, glucose, and insulin. Anthocyanin-rich grape-bilberry juice intervention reduced serum leptin and resistin, but showed no influence on serum adiponectin and secretion of adipokines from mesenteric adipose tissue. Furthermore, anthocyanin-rich grape-bilberry juice increased the proportion of polyunsaturated fatty acids and decreased the amount of saturated fatty acids in plasma. These results indicate that anthocyanins possess a preventive potential for obesity-associated diseases. PMID:23825152

  7. Lorenzo's oil inhibits ELOVL1 and lowers the level of sphingomyelin with a saturated very long-chain fatty acid[S

    PubMed Central

    Sassa, Takayuki; Wakashima, Takeshi; Ohno, Yusuke; Kihara, Akio

    2014-01-01

    X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by impaired degradation of very long-chain fatty acids (VLCFAs) due to mutations in the ABCD1 gene responsible for VLCFA transport into peroxisomes. Lorenzo's oil, a 4:1 mixture of glyceryl trioleate and glyceryl trierucate, has been used to reduce the saturated VLCFA level in the plasma of X-ALD patients; however, the mechanism by which this occurs remains elusive. We report the biochemical characterization of Lorenzo's oil activity toward elongation of very long-chain fatty acid (ELOVL) 1, the primary enzyme responsible for the synthesis of saturated and monounsaturated VLCFAs. Oleic and erucic acids inhibited ELOVL1, and, moreover, their 4:1 mixture (the FA composition of Lorenzo's oil) exhibited the most potent inhibitory activity. The kinetics analysis revealed that this was a mixed (not a competitive) inhibition. At the cellular level, treatment with the 4:1 mixture reduced the level of SM with a saturated VLCFA accompanied by an increased level of SM with a monounsaturated VLCFA, probably due to the incorporation of erucic acid into the FA elongation cycle. These results suggest that inhibition of ELOVL1 may be an underlying mechanism by which Lorenzo's oil exerts its action. PMID:24489110

  8. [In vivo toxicity, lipid peroxide lowering, and glutathione, ascorbic acid and copper elevation induced in mouse liver by low dose of oxine-copper, a fungicide].

    PubMed

    Hojo, Y; Hashimoto, I; Miyamoto, Y; Kawazoe, S; Mizutani, T

    2000-03-01

    While oxine-copper (OxCu) is generally used as an agricultural fungicide and induces a harmful effect on ecosystems, little information is available regarding a toxic effect of OxCu on mammals. In this article, we examined in vivo induction of toxicity and change of levels of glutathione and ascorbic acid, major biological antioxidants, lipid peroxide and copper (Cu) in liver and kidney 4 h and 24 h after intraperitoneal administration of OxCu at a low dose (0.05 mmol/kg) to mice. Increased hepatic ascorbic acid and Cu levels were found at 4 h after the treatment. In addition, body weight change was lowered and serum glutamic pyruvic transaminase activity was elevated significantly compared to control at 24 h after the treatment, suggesting induction of systemic and hepatic toxicity respectively. These were accompanied by lowered lipid peroxide level and enhanced glutathione, ascorbic acid and Cu levels in the mouse liver. On the other hand, OxCu induced no elevation in serum urea nitrogen concentration 4 h and 24 h after the treatment, suggesting no induction of nephrotoxicity, accompanied by no change in renal lipid peroxide, glutathione, ascorbic acid and Cu levels. These results suggest that hepatic Cu elevation may induce hepatotoxicity and no renal Cu elevation may lead to no induction of nephrotoxicity after the treatment with OxCu.

  9. D-amino acid peptide residualizing agents bearing N-hydroxysuccinimido-and maleimido- functional groups and their application for trastuzumab radioiodination

    PubMed Central

    Pruszynski, Marek; Koumarianou, Eftychia; Vaidyanathan, Ganesan; Chitneni, Satish; Zalutsky, Michael R.

    2014-01-01

    Introduction Proteins that undergo receptor-mediated endocytosis are subject to lysosomal degradation, requiring radioiodination methods that minimize loss of radioactivity from tumor cells after this process occurs. To accomplish this, we developed the residualizing radioiodination agent N∊-(3-[*I]iodobenzoyl)-Lys5-Nα-maleimido-Gly1-d-GEEEK (Mal-d-GEEEK-[*I]IB), which enhanced tumor uptake but also increased kidney activity and necessitates generation of sulfhydryl moieties on the protein. The purpose of the current study was to synthesize and evaluate a new d-amino acid based agent that might avoid these potential problems. Methods Nα-(3-iodobenzoyl)-(5-succinimidyloxycarbonyl)-d-EEEG (NHS-IB-d-EEEG), which contains 3 d-glutamates to provide negative charge and a N-hydroxysuccinimide function to permit conjugation to unmodified proteins, and the corresponding tin precursor were produced by solid phase peptide synthesis and subsequent conjugation with appropriate reagents. Radioiodination of the anti-HER2 antibody trastuzumab using NHS-IB-d-EEEG and Mal-d-GEEEK-IB were compared. Paired-label internalization assays on BT474 breast carcinoma cells and biodistribution studies in athymic mice bearing BT474M1 xenografts were performed to evaluate the two radioiodinated d-peptide trastuzumab conjugates. Results NHS-[131I]IB-d-EEEG was produced in 53.8 ± 13.4 % and conjugated to trastuzumab in 39.5 ± 7.6 % yield. Paired-label internalization assays with trastuzumab-NHS-[131I]IB-d-EEEG and trastuzumab-Mal-d-GEEEK-[125I]IB demonstrated similar intracellular trapping for both conjugates at 1 h (131I, 84.4 ± 6.1%; 125I, 88.6 ± 5.2%) through 24 h (131I, 60.7 ± 6.8%; 125I, 64.9 ± 6.9 %). In the biodistribution experiment, tumor uptake peaked at 48 h (trastuzumab-NHS-[131I]IB-d-EEEG, 29.8 ± 3.6 %ID/g; trastuzumab-Mal-d-GEEEK-[125I]IB, 45.3 ± 5.3 %ID/g) and was significantly higher for 125I at all time points. In general, normal tissue levels were lower for

  10. Enhanced intracellular accumulation of a non-nucleoside anti-cancer agent via increased uptake of its valine ester prodrug through amino acid transporters.

    PubMed

    Kwak, Eun-Young; Shim, Won-Sik; Chang, Ji-Eun; Chong, Saeho; Kim, Dae-Duk; Chung, Suk-Jae; Shim, Chang-Koo

    2012-07-01

    The phenomenon known as multiple-drug resistance, whereby anti-cancer agents are expelled from cancer cells, makes it necessary to develop methods that will reliably increase the accumulation of anti-cancer agents within cancer cells. To accomplish this goal, a new model compound, Val-SN-38, was synthesized by introducing valine to SN-38, an active ingredient of irinotecan. Val-SN-38 improved intracellular accumulation approximately 5-fold in MCF7 cells, compared with SN-38, and rather than changes in membrane permeability, the amino acid transporter ATB(0,+) played a role, whereas the dipeptide transporter PEPT1 did not. Other sodium-dependent amino acid transporters, namely ATA1, ATA2, and ASCT2, were unexpectedly involved in the uptake of Val-SN-38 as well. The efflux of Val-SN-38 by major efflux transporters was variably changed, but not significantly. In summary, the enhanced accumulation of Val-SN-38 in cancer cells was due to augmented uptake via various amino acid transporters. The results of the present study make a compelling argument in favour of a prodrug concept that can improve intracellular accumulation and take advantage of amino acid transporters without significantly inducing multiple-drug resistance.

  11. The formation of short-chain fatty acids is positively associated with the blood lipid-lowering effect of lupin kernel fiber in moderately hypercholesterolemic adults.

    PubMed

    Fechner, Anita; Kiehntopf, Michael; Jahreis, Gerhard

    2014-05-01

    Lupin kernel fiber beneficially modifies blood lipids because of its bile acid-binding capacity. The aim of this study was to evaluate the preventive effects of a lupin kernel fiber preparation on cardiovascular diseases and to clarify possible mechanisms. In a randomized, double-blind, controlled crossover trial, 60 moderately hypercholesterolemic adults (plasma total cholesterol: >5.2 mmol/L) passed 3 intervention periods in different orders with a 2-wk washout phase between each. Participants consumed either a high-fiber diet containing 25-g/d lupin kernel fiber (LF) or citrus fiber (CF), or a low-fiber control diet (CD) for 4 wk each. Anthropometric, plasma, and fecal variables were assessed at baseline and after the interventions. Contrary to the CF period, total (9%) and LDL (12%) cholesterol as well as triacylglycerols (10%) were lower after the LF period when compared with the CD period [P ≤ 0.02, adjusted for baseline, age, gender, and body mass index (BMI)]. HDL cholesterol remained unchanged. Moreover, the LF period reduced high-sensitivity C-reactive protein (P = 0.02) and systolic blood pressure (P = 0.01) when compared with baseline. Bile acid binding could not be shown because the excretion of total bile acids remained constant after the high-fiber diets. However, the LF period resulted in an enhanced formation of the main short-chain fatty acids in comparison with the CD period. During the CF period, only acetate increased significantly. Both high-fiber diets led to higher satiety and modified nutritional behavior, resulting in significantly lower body weight, BMI, and waist circumference compared with the CD period. The blood lipid-lowering effects of LF are apparently not a result of bile acid binding. Rather, we hypothesize for the first time, to our knowledge, that the blood lipid-lowering effects of LF may be mainly attributed to the formation of short-chain fatty acids, specifically propionate and acetate. This trial was registered at

  12. Effective methylation of phosphonic acids related to chemical warfare agents mediated by trimethyloxonium tetrafluoroborate for their qualitative detection and identification by gas chromatography-mass spectrometry.

    PubMed

    Valdez, Carlos A; Leif, Roald N; Alcaraz, Armando

    2016-08-24

    The effective methylation of phosphonic acids related to chemical warfare agents (CWAs) employing trimethyloxonium tetrafluoroborate (TMO·BF4) for their qualitative detection and identification by gas chromatography-mass spectrometry (GC-MS) is presented. The methylation occurs in rapid fashion (1 h) and can be conveniently carried out at ambient temperature, thus providing a safer alternative to the universally employed diazomethane-based methylation protocols. Optimization of the methylation parameters led us to conclude that methylene chloride was the ideal solvent to carry out the derivatization, and that even though methylated products can be observed surfacing after only 1 h, additional time was not found to be detrimental but beneficial to the process particularly when dealing with analytes at low concentrations (∼10 μg mL(-1)). Due to its insolubility in methylene chloride, TMO·BF4 conveniently settles to the bottom during the reaction and does not produce additional interfering by-products that may further complicate the GC-MS analysis. The method was demonstrated to successfully methylate a variety of Schedule 2 phosphonic acids, including their half esters, resulting in derivatives that were readily detected and identified using the instrument's spectral library. Most importantly, the method was shown to simultaneously methylate a mixture of the organophosphorus-based nerve agent hydrolysis products: pinacolyl methylphosphonate (PMPA), cyclohexyl methylphosphonate (CyMPA) and ethyl methylphosphonate (EMPA) (at a 10 μg mL(-1) concentration each) in a fatty acid ester-rich organic matrix (OPCW-PT-O3) featured in the 38th Organisation for the Prohibition of Chemical Weapons (OPCW) Proficiency Test. In addition, the protocol was found to effectively methylate N,N-diethylamino ethanesulfonic acid and N,N-diisopropylamino ethanesulfonic acid that are products arising from the oxidative degradation of the V-series agents VR and VX respectively. The

  13. Effective methylation of phosphonic acids related to chemical warfare agents mediated by trimethyloxonium tetrafluoroborate for their qualitative detection and identification by gas chromatography-mass spectrometry.

    PubMed

    Valdez, Carlos A; Leif, Roald N; Alcaraz, Armando

    2016-08-24

    The effective methylation of phosphonic acids related to chemical warfare agents (CWAs) employing trimethyloxonium tetrafluoroborate (TMO·BF4) for their qualitative detection and identification by gas chromatography-mass spectrometry (GC-MS) is presented. The methylation occurs in rapid fashion (1 h) and can be conveniently carried out at ambient temperature, thus providing a safer alternative to the universally employed diazomethane-based methylation protocols. Optimization of the methylation parameters led us to conclude that methylene chloride was the ideal solvent to carry out the derivatization, and that even though methylated products can be observed surfacing after only 1 h, additional time was not found to be detrimental but beneficial to the process particularly when dealing with analytes at low concentrations (∼10 μg mL(-1)). Due to its insolubility in methylene chloride, TMO·BF4 conveniently settles to the bottom during the reaction and does not produce additional interfering by-products that may further complicate the GC-MS analysis. The method was demonstrated to successfully methylate a variety of Schedule 2 phosphonic acids, including their half esters, resulting in derivatives that were readily detected and identified using the instrument's spectral library. Most importantly, the method was shown to simultaneously methylate a mixture of the organophosphorus-based nerve agent hydrolysis products: pinacolyl methylphosphonate (PMPA), cyclohexyl methylphosphonate (CyMPA) and ethyl methylphosphonate (EMPA) (at a 10 μg mL(-1) concentration each) in a fatty acid ester-rich organic matrix (OPCW-PT-O3) featured in the 38th Organisation for the Prohibition of Chemical Weapons (OPCW) Proficiency Test. In addition, the protocol was found to effectively methylate N,N-diethylamino ethanesulfonic acid and N,N-diisopropylamino ethanesulfonic acid that are products arising from the oxidative degradation of the V-series agents VR and VX respectively. The

  14. Agent-based model of Fecal Microbial Transplant effect on Bile Acid Metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection

    PubMed Central

    Peer, Xavier; An, Gary

    2014-01-01

    Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the Clostridium difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, Fecal Microbial Transplant (FMT). The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with

  15. Effects of dietary fats on plasma lipids and lipoproteins: an hypothesis for the lipid-lowering effect of unsaturated fatty acids

    PubMed Central

    Spritz, Norton; Mishkel, Maurice A.

    1969-01-01

    Several aspects of the effects of dietary fat on plasma lipids and lipoproteins were investigated in 12 subjects during the long-term feeding of formulas containing 40% of their calories as either saturated or unsaturated fats. The changes in fatty acid composition of plasma lipids, shown previously to occur after prolonged feedings of a dietary fat, required 10-14 days to be complete and were synchronous with the effect of the fat on plasma lipid concentrations. The change in lipid concentration occurred in low but not in high density lipoproteins. The effects on lipid levels of the low density lipoproteins were found to occur with little or no effect on the concentration of the protein moiety of these lipoproteins; as a result, cholesterol- and phospholipid to protein ratios in low density lipoproteins fell during unsaturated fat feeding. The effects of dietary fat on plasma phospholipids were studied in detail: the relative amounts of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and lysophosphatidylcholine were unaffected by the type of dietary fat. However, the molecular species of phosphatidylcholine were markedly affected. More than 90% of the fatty acids at the α-position were saturated during both saturated and unsaturated feedings. In contrast, during unsaturated feedings, linoleate at the β-position outnumbered oleate by approximately 4:1, whereas during saturated feedings these two types of fatty acids were present in nearly equal amounts. This paper also presents the following hypothesis for the lipid-lowering effect of unsaturated dietary fat: since unsaturated fatty acids occupy a greater area than saturated acids, they alter the spatial configuration of the lipids into which they are incorporated; as a result, fewer lipid molecules can be accommodated by the apoprotein of the low-density lipoproteins (LDL), and thus the lipid content of the lipoprotein is lowered. The experimental findings of this study, while not proving this

  16. The use of negative pressure therapy and hyaluronic acid for the management of post-traumatic lower limb injury.

    PubMed

    Cigna, Emanuele; Maruccia, Michele; Sorvillo, Valentina; Parisi, Paola; Palumbo, Francesca; Onesti, Maria Giuseppina

    2013-10-01

    Management of severe limb trauma continues to challenge surgeons. Suitable treatment should be individualised for each patient, taking into consideration not only the wound extremity but also the associated injuries, age and socioeconomic status of the patient with the goal to recover function and to improve patient quality of life. The aim of this report is to present a severe degloving multiplane lower limb injury case in which a conservative treatment of the wound was performed with negative pressure therapy and dermal substitute, avoiding amputation and restoring limb function.

  17. Polyphenols: well beyond the antioxidant capacity: gallic acid and related compounds as neuroprotective agents: you are what you eat!

    PubMed

    Daglia, Maria; Di Lorenzo, Arianna; Nabavi, Seyed F; Talas, Zeliha S; Nabavi, Seyed M

    2014-01-01

    Gallic acid (3,4,5-trihydroxybenzoic acid) is a phenolic acid widely distributed in many different families of higher plants, both in free state, and as a part of more complex molecules, such as ester derivatives or polymers. In nature, gallic acid and its derivatives are present in nearly every part of the plant, such as bark, wood, leaf, fruit, root and seed. They are present in different concentrations in common foodstuffs such as blueberry, blackberry, strawberry, plums, grapes, mango, cashew nut, hazelnut, walnut, tea, wine and so on. After consumption, about 70% of gallic acid is adsorbed and then excreted in the urine as 4-O-methylgallic acid. Differently, the ester derivatives of gallic acid, such as catechin gallate ester or gallotannins, are hydrolyzed to gallic acid before being metabolized to methylated derivatives. Gallic acid is a well known antioxidant compounds which has neuroprotective actions in different models of neurodegeneration, neurotoxicity and oxidative stress. In this review, we discuss about the neuroprotective actions of gallic acid and derivatives and their potential mechanisms of action.

  18. Polyphenols: well beyond the antioxidant capacity: gallic acid and related compounds as neuroprotective agents: you are what you eat!

    PubMed

    Daglia, Maria; Di Lorenzo, Arianna; Nabavi, Seyed F; Talas, Zeliha S; Nabavi, Seyed M

    2014-01-01

    Gallic acid (3,4,5-trihydroxybenzoic acid) is a phenolic acid widely distributed in many different families of higher plants, both in free state, and as a part of more complex molecules, such as ester derivatives or polymers. In nature, gallic acid and its derivatives are present in nearly every part of the plant, such as bark, wood, leaf, fruit, root and seed. They are present in different concentrations in common foodstuffs such as blueberry, blackberry, strawberry, plums, grapes, mango, cashew nut, hazelnut, walnut, tea, wine and so on. After consumption, about 70% of gallic acid is adsorbed and then excreted in the urine as 4-O-methylgallic acid. Differently, the ester derivatives of gallic acid, such as catechin gallate ester or gallotannins, are hydrolyzed to gallic acid before being metabolized to methylated derivatives. Gallic acid is a well known antioxidant compounds which has neuroprotective actions in different models of neurodegeneration, neurotoxicity and oxidative stress. In this review, we discuss about the neuroprotective actions of gallic acid and derivatives and their potential mechanisms of action. PMID:24938889

  19. Dietary linoleic acid requirements in the presence of α-linolenic acid are lower than the historical 2 % of energy intake value, study in rats.

    PubMed

    Choque, Benjamin; Catheline, Daniel; Delplanque, Bernadette; Guesnet, Philippe; Legrand, Philippe

    2015-04-14

    Previous studies on rats and human subjects have established that the linoleic acid (LA) requirement is 2 % of the total energy intake (en%), but is obtained in the absence of α-linolenic acid (ALA) and consequently appear to be overestimated. This raises questions since a recent study including ALA has suggested to divide the historical value by four. However, this recent study has remained inconclusive because the animals used were not totally LA-deficient animals. For the first time, the present study was especially designed using physiological and biochemical markers and performed in two steps: (1) to achieve a specific n-6 fatty acid deficiency model using growing male rats fed either a 0 en% from LA/0 en% from ALA (0LA/0ALA), 0LA/0·5ALA or 2LA/0·5ALA diet, born from female rats fed a 0LA/0·5ALA diet; and (2) to refine the required level of LA in the presence of ALA using rats fed either a 0LA/0ALA, 0·5LA/0·5ALA, 1LA/0·5ALA, 1·5LA/0·5ALA diet, born from female rats fed a 0LA/0·5ALA diet. The first step shows that the best LA deficiency model was obtained using rats fed the 0LA/0ALA diet, born from female rats fed the 0LA/0·5ALA diet. The second step demonstrates that in growing rats, LA deficiency was corrected with an intake of 1-1·5 en% from LA and 0·5 en% from ALA. These data suggest that the requirements in humans should be revisited, considering the presence of ALA to set up the recommendation for LA.

  20. Compatibilization of immiscible poly(lactic acid)/poly(ɛ-caprolactone) blend through electron-beam irradiation with the addition of a compatibilizing agent

    NASA Astrophysics Data System (ADS)

    Shin, Boo Young; Han, Do Hung

    2013-02-01

    The aim of this study was to compatibilize immiscible poly(lactic acid) (PLA)/poly(ɛ-caprolactone) (PCL) blend by using electron-beam radiation method with the addition of a compatibilizing agent. Glycidyl methacrylate (GMA) was chosen as the compatibilizing agent, in the expectation that the GMA plays a role as a monomeric compatibilizer and a reactive agent at the interface between the PLA and the PCL phases. Compatibilization process has been investigated through the melt mixing of the PLA/PCL and the GMA by using a twin-screw extruder and the exposure of the PLA/PCL/GMA mixture to electron-beam radiation at room temperature. The melt mixing process was performed to locate the GMA at the interface, thereby expecting a finer morphology due to the GMA as the monomeric plasticizer. The exposure process was carried out to induce definite interfacial adhesion at the interface through electron-beam initiated cross-copolymerization by the medium of the GMA as the reactive agent. To investigate the results of this compatibilization strategy, the morphological, mechanical, and rheological properties of the blend were analyzed. The morphological study clearly showed the reduced particle size of dispersed PCL domains and significantly improved interfacial adhesion by the electron-beam irradiation with the addition of the GMA. The stress-strain curves of the blends irradiated at less than 20 kGy showed the typical characteristics of ductile materials. The tensile properties of the blend were strongly affected by the dose of irradiation.

  1. Poly(acrylic acid) Bridged Gadolinium Metal-Organic Framework-Gold Nanoparticle Composites as Contrast Agents for Computed Tomography and Magnetic Resonance Bimodal Imaging

    PubMed Central

    Tian, Chixia; Zhu, Liping; Lin, Feng; Boyes, Stephen G.

    2015-01-01

    Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early-stage cancer diagnosis. Gadolinium (Gd) (III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high x-ray attenuation coefficient, is an ideal contrast agent candidate for x-ray based CT imaging. Gd metal organic framework (MOF) nanoparticles with tunable size, high Gd (III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multi-modal imaging probes. PMID:26147906

  2. Poly(acrylic acid) Bridged Gadolinium Metal-Organic Framework-Gold Nanoparticle Composites as Contrast Agents for Computed Tomography and Magnetic Resonance Bimodal Imaging.

    PubMed

    Tian, Chixia; Zhu, Liping; Lin, Feng; Boyes, Stephen G

    2015-08-19

    Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early stage cancer diagnosis. Gadolinium (Gd)(III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high X-ray attenuation coefficient, is an ideal contrast agent candidate for X-ray-based CT imaging. Gd metal-organic framework (MOF) nanoparticles with tunable size, high Gd(III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multimodal imaging probes.

  3. The effects of lowered extracellular sodium on gamma-aminobutyric acid (GABA)-induced currents of Muller (glial) cells of the skate retina.

    PubMed

    Qian, H; Malchow, R P; Ripps, H

    1993-04-01

    1. The effects of external sodium on GABA-induced chloride currents were examined with whole-cell voltage-clamp recordings obtained from enzymatically dissociated solitary Muller cells in culture. Our goal was to determine whether a sodium-dependent GABA uptake mechanism influences the GABAa-mediated responses of skate Muller cells. 2. At low concentrations of GABA (0.01 to 0.5 microM), removal of sodium from the external solution resulted in a marked increase in the ligand-gated currents mediated by activation of GABAa receptors. The enhancement by lowered sodium was greatest at hyperpolarizing potentials and decreased progressively as the cell was depolarized. 3. The reversal potential for the GABA-induced response was not significantly altered by the removal of sodium, suggesting that sodium ions did not directly contribute to the GABAa-mediated current. 4. Lowering external sodium had no effect on the currents induced by the GABAa-agonist muscimol, consistent with its much lower affinity for the GABA transport carrier. 5. Application of the GABA uptake blocker nipecotic acid also abolished the effects of lowered sodium. 6. These findings suggest that the effects of lowered external sodium resulted from a decrease in the uptake of GABA into the Muller cells, thus raising the effective concentration of GABA acting upon the GABAa receptors. PMID:8394215

  4. High-fat diet from perilla oil induces insulin resistance despite lower serum lipids and increases hepatic fatty acid oxidation in rats

    PubMed Central

    2014-01-01

    Background The purpose of this study is to investigate the effects of a high-fat diet from perilla oil on serum lipids, hepatic lipid metabolism and insulin sensitivity. Methods Male Sprague–Dawley (SD) rats were fed either a control (CT) diet or a diet high in perilla oil (HP). After 16 weeks of feeding, the serum lipids were measured, and the gene expressions involved in hepatic fatty acid oxidation and synthesis were determined. In addition, hepatic fat deposition was detected, and insulin sensitivity was evaluated by means of euglycemic-hyperinsulinemic clamp. Results Compared with the rats in the CT group, the HP-feeding significantly decreased the levels of triglyceride (TG), total cholesterol (TCH) and HDL-cholesterol (HDL-c). HP-feeding did not change the levels of LDL-cholesterol (LDL-c), free fatty acid (FFA), intrahepatic lipids or body weight. Moreover, the HP-feeding dramatically increased the mRNA expressions of fatty acid oxidation markers (PPAR-alpha, CPT1A) and fatty acid synthesis markers (SREBP-1, FASN and ACC) in the liver. The HP-feeding induced increased protein levels of CPT1A, while reducing the protein levels of FASN and ACC in the liver. However, the glucose infusion rate significantly increased in the HP group compared with the CT group. Conclusions Our data show that, in rats, excessive perilla oil intake may significantly lower serum lipids, strengthen hepatic fatty acid oxidation, and inhibit hepatic fatty acid synthesis, but at the same time may also lead to insulin resistance. PMID:24422660

  5. The effect of nitrate, bicarbonate and natural organic matter on the degradation of sunscreen agent p-aminobenzoic acid by simulated solar irradiation.

    PubMed

    Mao, Liang; Meng, Cui; Zeng, Chao; Ji, Yuefei; Yang, Xi; Gao, Shixiang

    2011-11-15

    Our experiments revealed that a model sunscreen agent, p-aminobenzoic acid (PABA), can be effectively transformed through reactions that are mediated by simulated solar irradiation. We systematically explored the effects of nitrate ions, bicarbonate and different types of natural organic matter (NOM) on the degradation of PABA by simulated solar irradiation. Experimental data suggest that these components ubiquitous in nature water have different influence on the rates of the photoinduced removal of PABA. Products were extracted and analyzed using LC/MS and a total of four products probably resulting from OH and NO2 radicals attack were identified and the possible reaction pathways were proposed. The findings in this study provide useful information for understanding the environmental transformation of sunscreen agent in aquatic system. PMID:21975008

  6. Geochemical behaviour of palladium in soils and Pd/PdO model substances in the presence of the organic complexing agents L-methionine and citric acid.

    PubMed

    Zereini, Fathi; Wiseman, Clare L S; Vang, My; Albers, Peter; Schneider, Wolfgang; Schindl, Roland; Leopold, Kerstin

    2016-01-01

    Risk assessments of platinum group metal (PGE) emissions, notably those of platinum (Pt), palladium (Pd) and rhodium (Rh), have been mostly based on data regarding the metallic forms used in vehicular exhaust converters, known to be virtually biologically inert and immobile. To adequately assess the potential impacts of PGE, however, data on the chemical behaviour of these metals under ambient conditions post-emission is needed. Complexing agents with a high affinity for metals in the environment are hypothesized to contribute to an increased bioaccessibility of PGE. The purpose of this study is to examine the modulating effects of the organic complexing agents, L-methionine and citric acid, on the geochemical behavior of Pd in soils and model substances (Pd black and PdO). Batch experimental tests were conducted with soils and model substances to examine the impacts of the concentration of complexing agents, pH and length of extraction period on Pd solubility and its chemical transformation. Particle surface chemistry was examined using X-ray photoelectron spectroscopy (XPS) on samples treated with solutions under various conditions, including low and high O2 levels. Pd was observed to be more soluble in the presence of organic complexing agents, compared to Pt and Rh. Pd in soils was more readily solubilized with organic complexing agents compared to the model substances. After 7 days of extraction, L-methionine (0.1 M) treated soil and Pd black samples, for instance, had mean soluble Pd fractions of 12.4 ± 5.9% and 0.554 ± 0.024%, respectively. Surface chemistry analyses (XPS) confirmed the oxidation of metallic Pd surfaces when treated with organic complexing agents. The type of organic complexing agent used for experimental purposes was observed to be the most important factor influencing solubility, followed by solution pH and time of extraction. The results demonstrate that metallic Pd can be transformed into more bioaccessible species in the presence of

  7. Acetyl salicylic acid (aspirin) improves synthesis of maspin and lowers incidence of metastasis in breast cancer patients [corrected].

    PubMed

    Bhattacharyya, Mau; Girish, Gannareddy V; Ghosh, Rajeshwary; Chakraborty, Somashree; Sinha, Asru K

    2010-10-01

    Maspin, a 42 kDa protein produced in normal breast cells, has been shown to inhibit the invasion and metastasis of breast cancer in an animal model. Ingestion of acetylsalicylic acid (aspirin) by breast cancer patients has been reported to restore the systemic synthesis of maspin through the stimulation of systemic nitric oxide production. Studies were carried out to determine the effect of aspirin on the incidence of breast cancer metastasis, which is reported to occur in 50% of patients who have previously received chemotherapy, radiation, and/or surgery. Thirty-five female patients (aged 41-65 years) with breast cancer who had previously received these therapies took one 75 mg/70 kg body weight enteric-coated aspirin tablet every 24 h, after an adequate meal, for 3 years. Their plasma nitric oxide and maspin levels were measured. The occurrence of metastasis was ascertained monthly by a qualified oncologist, and confirmed, if necessary, by biopsy. Daily ingestion of aspirin by participants resulted in an increase in maspin levels from 0.95 ± 0.04 to 4.63 ± 0.05 nM after 24 h. These levels were maintained for 3 years. These studies suggest that daily ingestion of aspirin might significantly reduce the incidence of breast cancer metastasis in patients who have previously received anticancer therapies.

  8. Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With or Without Ribavirin in HCV-Infected Patients Taking Concomitant Acid-Reducing Agents

    PubMed Central

    Shiffman, Mitchell L; Rustgi, Vinod; Bennett, Michael; Forns, Xavier; Asselah, Tarik; Planas Vila, Ramon; Liu, Li; Pedrosa, Marcos; Moller, Jonathan; Reau, Nancy

    2016-01-01

    OBJECTIVES: Acid-reducing agents (ARAs) and proton-pump inhibitors (PPIs) that increase gastric pH can alter the bioavailability of antiviral drugs, particularly relevant in patients with advanced liver disease caused by chronic hepatitis C virus (HCV) infection seeking therapy. Using integrated data from six phase 3 studies, we report the safety and efficacy of the 3-direct-acting antiviral (DAA) regimen containing ombitasvir (OBV, an NS5A inhibitor), ritonavir-boosted paritaprevir (PTV/r, an NS3/4A protease inhibitor), and dasabuvir (DSV, an NS5B polymerase inhibitor) with or without ribavirin (RBV) for HCV genotype 1 patients taking concomitant ARAs and PPIs. METHODS: Treatment-naïve or peginterferon/RBV treatment-experienced patients with or without compensated cirrhosis received OBV/PTV/r and DSV with or without weight-based RBV. Rates of sustained virologic response (SVR), defined as HCV RNA below the lower limit of quantification, 12 weeks post-treatment (SVR12) and safety were evaluated in patients who were receiving concomitant ARAs. RESULTS: Among 2,053 patients enrolled and dosed with study drug, 410 (20%) were receiving concomitant ARAs; of these, 308 (15%) were taking concomitant PPIs. Rates of SVR12 were 95.9% (95% confidence interval (CI) 93.5–97.4%) among patients receiving an ARA, and 96.3% (95% CI 95.3–97.2%) in patients not receiving a concomitant ARA. Similarly, among patients receiving a PPI or not, SVR12 was achieved in 95.1% (95% CI 92.1–97.0%) and 96.4% (95% CI 95.5–97.2%), respectively. Response rates were high regardless of treatment regimen (with or without RBV), and among patients receiving a standard or high dose of PPIs. Regarding safety, adverse events and serious adverse events were more frequently reported in patients taking concomitant ARAs, though baseline population differences may have played a role. CONCLUSIONS: In phase 3 trials of OBV/PTV/r plus DSV and RBV in HCV genotype 1-infected patients, SVR12 rates were high

  9. Synthesis and tissue biodistribution of [{omega}-{sup 11}C]palmitic acid. A novel PET imagining agent for cardiac fatty acid metabolism

    SciTech Connect

    Buckman, B.O.; VanBrocklin, H.F.; Katzenellenbogen, J.A.; Dence, C.S.; Bergmann, S.R.; Welch, M.J.

    1994-12-31

    In order to diagnose patients with medium-chain acyl-CoA dehydrogenase deficiency with a noninvasive diagnostic technique such as positron emission tomography, they have developed a synthesis of [{omega}-{sup 11}C]palmitic acid. The radiochemical synthesis was achieved by coupling an alkylfuran Grignard reagent (7) with [{sup 11}C]methyl iodide, followed by rapid oxidative cleavage of the furan ring to the carboxylate using ruthenium tetraoxide. Tissue biodistribution studies in rags comparing [{omega}-{sup 11}C]palmitic acid and [1-{sup 11}C]palmitic acid show that the %ID/g and %ID/organ in the heart tissue after administration of [{omega}-{sup 11}C]palmitic acid is approximately 50% greater than after administration of [1-{sup 11}C]palmitic acid, due to the diminished metabolism of the [{omega}-{sup 11}C]palmitic acid. These studies show as well, low uptake in nontarget tissues (blood, lung, kidney, and muscle). PET images of a dog heart obtained after administration of [{omega}-{sup 11}C]- and [1-{sup 11}C]palmitic acid show virtually identical uptake and distribution in the myocardium. The differing cardiac washout of labeled palmitates measured by dynamic PET studies may allow diagnosis of disorders in cardiac fatty acid metabolism.

  10. Assessment of boric acid and borax using the IEHR evaluative process for assessing human developmental and reproductive toxicity of agents

    SciTech Connect

    Moore, J.A.

    1995-03-01

    This document presents an evaluation of the reproductive and developmental effects of boric acid, H3BO3 (CAS Registry No. 10043-35-3) and disodium tetraborate decahydrate or borax, Na2B4O2O(CAS Registry No. 1303-96-4). The element, boron, does not exist naturally. In dilute aqueous solution and at physiological pH (7.4), the predominant species in undissociated boric acid (greater than 98%), irrespective of whether the initial material was boric acid of borax. Therefore, it is both useful and correct to compare exposures and dosages to boric acid and borax in terms of `boron equivalents`, since both materials form equivalent species in dilute aqueous solution with similar systemic effects. In order to be clear in this document, the term `boron` will refer to `boron equivalents` or percent boron in boric acid and borax.

  11. Identification of Retinoic Acid in a High Content Screen for Agents that Overcome the Anti-Myogenic Effect of TGF-Beta-1

    PubMed Central

    Krueger, Chateen; Hoffmann, F. Michael

    2010-01-01

    Background Transforming growth factor beta 1 (TGF-β1) is an inhibitor of muscle cell differentiation that is associated with fibrosis, poor regeneration and poor function in some diseases of muscle. When neutralizing antibodies to TGF-β1 or the angiotensin II inhibitor losartan were used to reduce TGF-β1 signaling, muscle morphology and function were restored in mouse models of Marfan Syndrome and muscular dystrophy. The goal of our studies was to identify additional agents that overcome the anti-myogenic effect of TGF-β1. Methodology/Principal Findings A high-content cell-based assay was developed in a 96-well plate format that detects the expression of myosin heavy chain (MHC) in C2C12 cells. The assay was used to quantify the dose-dependent responses of C2C12 cell differentiation to TGF-β1 and to the TGF-β1 Type 1 receptor kinase inhibitor, SB431542. Thirteen agents previously described as promoting C2C12 differentiation in the absence of TGF-β1 were screened in the presence of TGF-β1. Only all-trans retinoic acid and 9-cis retinoic acid allowed a maximal level of C2C12 cell differentiation in the presence of TGF-β1; the angiotensin-converting enzyme inhibitor captopril and 10 nM estrogen provided partial rescue. Vitamin D was a potent inhibitor of retinoic acid-induced myogenesis in the presence of TGF-β1. TGF-β1 inhibits myoblast differentiation through activation of Smad3; however, retinoic acid did not inhibit TGF-β1-induced activation of a Smad3-dependent reporter gene in C2C12 cells. Conclusions/Significance Retinoic acid alleviated the anti-myogenic effect of TGF-β1 by a Smad3-independent mechanism. With regard to the goal of improving muscle regeneration and function in individuals with muscle disease, the identification of retinoic acid is intriguing in that some retinoids are already approved for human therapy. However, retinoids also have well-described adverse effects. The quantitative, high-content assay will be useful to screen for

  12. Identification of linoleic acid, a main component of the n-hexane fraction from Dryopteris crassirhizoma, as an anti-Streptococcus mutans biofilm agent.

    PubMed

    Jung, Ji-Eun; Pandit, Santosh; Jeon, Jae-Gyu

    2014-01-01

    Dryopteris crassirhizoma is a semi-evergreen plant. Previous studies have shown the potential of this plant as an agent for the control of cariogenic biofilms. In this study, the main antibacterial components of the plant were identified by correlating gas chromatography-mass spectrometry data with the antibacterial activity of chloroform and n-hexane fractions and then evaluating the activity of the most potent antibacterial component against Streptococcus mutans UA159 biofilms. The most potent antibacterial component was linoleic acid, a main component of the n-hexane fraction. Linoleic acid reduced viability in a dose dependent manner and reduced biofilm accumulation during initial and mature biofilm formation. Furthermore, when the biofilms were briefly treated with linoleic acid (10 min/treatment, a total of six times), the dry weight of the biofilms was significantly diminished. In addition, the anti-biofilm activity of the n-hexane fraction was similar to that of linoleic acid. These results suggest that the n-hexane fraction of D. crassirhizoma and linoleic acid may be useful for controlling cariogenic biofilms.

  13. Investigation of the Prebiotic Synthesis of Amino Acids and RNA Bases from CO2 using FeS/H2S as a Reducing Agent

    NASA Technical Reports Server (NTRS)

    Keefe, Anthony D.; Miller, Stanley L.; McDonald, Gene; Bada, Jeffrey

    1995-01-01

    An autotrophic theory of the origin of metabolism and life has been proposed in which carbon dioxide is reduced by ferrous sulfide and hydrogen sulfide by means of a reversed citric acid cycle, leading to the production of amino acids. Similar processes have been proposed for purine synthesis. Ferrous sulfide is a strong reducing agent in the presence of hydrogen sulfide and can produce hydrogen as well as reduce alkenes, alkynes, and thiols to saturated hydrocarbons and reduce ketones to thiols. However, the reduction of carbon dioxide has not been demonstrated. We show here that no amino acids, purines, or pyrimidines are produced from carbon dioxide with the ferrous sulfide and hydrogen sulfide system. Furthermore, this system does not produce amino acids from carboxylic acids by reductive amination and carboxylation. Thus, the proposed autotrophic theory, using carbon dioxide, ferrous sulfide, and hydrogen sulfide, lacks the robustness needed to be a geological process and is, therefore, unlikely to have played a role in the origin of metabolism or the origin of life.

  14. Investigation of the Prebiotic Synthesis of Amino Acids and RNA Bases from CO2 Using FeS/H2S As a Reducing Agent

    NASA Technical Reports Server (NTRS)

    Keefe, Anthony D.; Miller, Stanley L.; McDonald, Gene; Bada, Jeffrey

    1995-01-01

    An autotrophic theory of the origin of metabolism and life has been proposed in which carbon dioxide is reduced by ferrous sulfide and hydrogen sulfide by means of a reversed citric acid cycle, leading to the production of amino acids. Similar processes have been proposed for purine synthesis. Ferrous sulfide is a strong reducing agent in the presence of hydrogen sulfide and can produce hydrogen as well as reduce alkenes, alkynes, and thiols to saturated hydrocarbons and reduce ketones to thiols. However, the reduction of carbon dioxide has not been demonstrated. We show here that no amino acids, purities, or pyrimidines are produced from carbon dioxide with the ferrous sulfide and hydrogen sulfide system. Furthermore, this system does not produce amino acids from carboxylic acids by reductive amination and carboxylation. Thus, the proposed autotrophic theory, using carbon dioxide, ferrous sulfide, and hydrogen sulfide, lacks the robustness needed to be a geological process and is, therefore, unlikely to have played a role In the origin of metabolism or the origin of life.

  15. The lower Miocene ignimbrite of Lesbos Island (Greece): an example for extreme K-rich acidic volcanism

    NASA Astrophysics Data System (ADS)

    Helbling, A.; Altherr, R.

    2003-04-01

    On Lesbos Island, Miocene volcanics overlie a metamorphic basement of late Palaeozoic to early Mesozoic age (e.g. [1]). The 17.0 ±0.5 Ma old [2] ignimbritic unit of Lesbos is over 100 m thick and covers approximately 190 km^2. Two vertical profiles through the ignimbrite were mapped and sampled. The deposit is extremely welded and dense. Relative amounts and character of pumice, fiamme, lithics, and crystals vary vertically and laterally. From bottom to top there is a continuous transition from a light grey, pumice-rich ash and lapilli deposit with approximately 5 vol.% lithics into an extremely dense, welded fiamme-rich ignimbrite. While the amout of lithics drecreases at first upwards, there is a notable lithic component of up to 20 vol.% at the top of the profiles. The matrix changes from a light grey ash at the bottom to an ever denser matrix of welded ash altering in colour from dark grey into pink, red and finally black. Crystals of alkali feldspar, plagioclase, biotite, and minor amounts of Fe-Ti-oxides, clinopyroxene, Ca-amphibole, apatite and zirkon are present. Electron microprobe and secondary ion mass spectrometer (SIMS) analysis have been carried out on polished thin sections. The glass components are acidic (SiO_2 approx. 69 wt %) and extremely rich in K_2O (6.6 to 7.9 wt %). The glass contains 3.6 wt % H_2O (determined by SIMS) consistent with analyses totals of approximately 95.5 wt %. Further investigations will focus on the question whether the observed transition in the profiles is due to a change in chemical composition and related magma chamber aspects (e.g. zonation) or differences in temperature and mechanisms of deposition. [1] Pe-Piper, G. (1980) Zeitschrift der Deutschen Geologischen Gesellschaft 131: 889-901 [2] Borsi, S. et al. (1973) Bulletin of Volcanology 36: 473-496

  16. Molecular recognition of CYP26A1 binding pockets and structure-activity relationship studies for design of potent and selective retinoic acid metabolism blocking agents.

    PubMed

    Sun, Bin; Song, Shuai; Hao, Chen-Zhou; Huang, Wan-Xu; Liu, Chun-Chi; Xie, Hong-Lei; Lin, Bin; Cheng, Mao-Sheng; Zhao, Dong-Mei

    2015-03-01

    All-trans-retinoic acid (ATRA), the biologically most active metabolite of vitamin A, plays a major role in the regulation of cellular differentiation and proliferation, and it is also an important pharmacological agent particularly used in the treatment of cancer, skin, neurodegenerative and autoimmune diseases. However, ATRA is very easy to be metabolized into 4-hydroxyl-RA in vivo by CYP26A1, an inducible cytochrome P450 enzyme, eventually into more polar metabolites. Therefore, it is vital to develop specific retinoic acid metabolism blocking agents (RAMBAs) to inhibit the metabolic enzyme CYP26A1 in the treatment of relevant diseases aforementioned. In this study, CYP26A1 and its interactions with retinoic acid-competitive metabolism blocking agents were investigated by a combined ligand- and structure-based approach. First, since the crystal structure of CYP26A1 protein has not been determined, we constructed the 3D structure of CYP26A1 using homology modeling. In order to achieve a deeper insight into the mode of action of RAMBAs in the active site, the molecular superimposition model and the common feature pharmacophore model were constructed, and molecular docking was performed. The molecular superimposition model is composed of three features: the main chain groups, side chain groups, and azole groups. The common feature pharmacophore model consists of five chemical features: four hydrophobic groups and one hydrogen acceptor (HHHHA). The results of molecular docking show that the characteristic groups of RAMBAs were mapped into three different active pockets, respectively. A structure-activity relationship (SAR) was obtained by a combination of the molecular superimposition and docking results with the pharmacophore model. This study gives more insight into the interaction model inside the CYP26A1 active site and provides guidance for the design of more potent and possibly more selective RAMBAs. PMID:25541526

  17. Molecular recognition of CYP26A1 binding pockets and structure-activity relationship studies for design of potent and selective retinoic acid metabolism blocking agents.

    PubMed

    Sun, Bin; Song, Shuai; Hao, Chen-Zhou; Huang, Wan-Xu; Liu, Chun-Chi; Xie, Hong-Lei; Lin, Bin; Cheng, Mao-Sheng; Zhao, Dong-Mei

    2015-03-01

    All-trans-retinoic acid (ATRA), the biologically most active metabolite of vitamin A, plays a major role in the regulation of cellular differentiation and proliferation, and it is also an important pharmacological agent particularly used in the treatment of cancer, skin, neurodegenerative and autoimmune diseases. However, ATRA is very easy to be metabolized into 4-hydroxyl-RA in vivo by CYP26A1, an inducible cytochrome P450 enzyme, eventually into more polar metabolites. Therefore, it is vital to develop specific retinoic acid metabolism blocking agents (RAMBAs) to inhibit the metabolic enzyme CYP26A1 in the treatment of relevant diseases aforementioned. In this study, CYP26A1 and its interactions with retinoic acid-competitive metabolism blocking agents were investigated by a combined ligand- and structure-based approach. First, since the crystal structure of CYP26A1 protein has not been determined, we constructed the 3D structure of CYP26A1 using homology modeling. In order to achieve a deeper insight into the mode of action of RAMBAs in the active site, the molecular superimposition model and the common feature pharmacophore model were constructed, and molecular docking was performed. The molecular superimposition model is composed of three features: the main chain groups, side chain groups, and azole groups. The common feature pharmacophore model consists of five chemical features: four hydrophobic groups and one hydrogen acceptor (HHHHA). The results of molecular docking show that the characteristic groups of RAMBAs were mapped into three different active pockets, respectively. A structure-activity relationship (SAR) was obtained by a combination of the molecular superimposition and docking results with the pharmacophore model. This study gives more insight into the interaction model inside the CYP26A1 active site and provides guidance for the design of more potent and possibly more selective RAMBAs.

  18. In Vitro Dissolution of Fluconazole and Dipyridamole in Gastrointestinal Simulator (GIS), Predicting in Vivo Dissolution and Drug-Drug Interaction Caused by Acid-Reducing Agents.

    PubMed

    Matsui, Kazuki; Tsume, Yasuhiro; Amidon, Gregory E; Amidon, Gordon L

    2015-07-01

    Weakly basic drugs typically exhibit pH-dependent solubility in the physiological pH range, displaying supersaturation or precipitation along the gastrointestinal tract. Additionally, their oral bioavailabilities may be affected by coadministration of acid-reducing agents that elevate gastric pH. The purpose of this study was to assess the feasibility of a multicompartmental in vitro dissolution apparatus, Gastrointestinal Simulator (GIS), in predicting in vivo dissolution of certain oral medications. In vitro dissolution studies of fluconazole, a BCS class I, and dipyridamole, a BCS class II weak bases (class IIb), were performed in the GIS as well as United States Pharmacopeia (USP) apparatus II and compared with the results of clinical drug-drug interaction (DDI) studies. In both USP apparatus II and GIS, fluconazole completely dissolved within 60 min regardless of pH, reflecting no DDI between fluconazole and acid-reducing agents in a clinical study. On the other hand, seven-fold and 15-fold higher concentrations of dipyridamole than saturation solubility were observed in the intestinal compartments in GIS with gastric pH 2.0. Precipitation of dipyridamole was also observed in the GIS, and the percentage of dipyridamole in solution was 45.2 ± 7.0%. In GIS with gastric pH 6.0, mimicking the coadministration of acid-reducing agents, the concentration of dipyridamole was equal to its saturation solubility, and the percentage of drug in solution was 9.3 ± 2.7%. These results are consistent with the clinical DDI study of dipyridamole with famotidine, which significantly reduced the Cmax and area under the curve. An In situ mouse infusion study combined with GIS revealed that high concentration of dipyridamole in the GIS enhanced oral drug absorption, which confirmed the supersaturation of dipyridamole. In conclusion, GIS was shown to be a useful apparatus to predict in vivo dissolution for BCS class IIb drugs.

  19. Newly designed Tc(V)-99m dimercaptosuccinic acid: An agent of high accuracy for the diagnosis of head and neck and soft tissue tumors

    SciTech Connect

    Endo, K.; Ohta, H.; Sakahara, H.; Nakashima, T.; Masuda, H.; Horiuchi, K.; Yokoyama, A.; Torizuka, K.

    1984-01-01

    Being aware of the ideal nuclear properties of Tc-99m, interest has been focused on the design of (+5) oxidation state Tc-99m dimercaptosuccinic acid (DMSA) as a tumor seeking agent. This Tc(V)-99m DMSA holding a TcO/sup 3-//sub 4/ core, alike PO/sup 3-//sub 4/, with competent characteristics for tumor uptake, had a different distribution behavior from the well-known renal scanning agent; Tc(III)-99m DMSA. Basic studies, carried out in vitro and in vivo with Ehrlich tumor cells or bearing mice, clearly substantiated its great potentiality for clinical use. Therefore, 193 untreated patients with histologically proven diagnosis (132 malignant and 61 benign tumors) were evaluated. In 53 primary head and neck tumor (mainly squamous cell carcinomas and plemorphic adenomas or abscess), its sensitivity and specificity was 78% and 87%, as opposed to Ga-67 citrate of 85% and 51% respectively. In 18 malignant soft tissue tumors, all but one (94%) showed significant uptake of Tc(V)-99m DMSA, while Ga-67 was positive in only 60% of these cases. The specificity of both agents was 74% and 86%, respectively. However in lung and abdominal tumors, lymphomas, melanomas and inflammatory lesions, the sensitivity was poor of less than 40%. Also negative were scans in most thyroid cancers, however, 5 patients with medullary thyroid cancers, were all positive with Tc(V)-99m DMSA and was useful follow patients after surgery. Thus, a different uptake mechanism for this agent could be visualized. The authors conclude that Tc(V)-99m DMSA provided a good basis for its clinical application as a tumor imaging agent, mainly in head and neck squamous cell carcinomas, medullary thyroid cancers and soft tissue tumors.

  20. Design and Evaluation of a Novel Trifluorinated Imaging Agent for Assessment of Bile Acid Transport Using Fluorine Magnetic Resonance Imaging

    PubMed Central

    Vivian, Diana; Cheng, Kunrong; Khurana, Sandeep; Xu, Su; Dawson, Paul A.; Raufman, Jean-Pierre; Polli, James E.

    2014-01-01

    Previously, we developed a trifluorinated bile acid, CA-lys-TFA, with the objective of noninvasively assessing bile acid transport in vivo using 19F magnetic resonance imaging (MRI). CA-lys-TFA was successfully imaged in the mouse gallbladder, but was susceptible to deconjugation in vitro by choloylglycine hydrolase (CGH), a bacterial bile acid deconjugating enzyme found in the terminal ileum and colon. The objective of the present study was to develop a novel trifluorinated bile acid resistant to deconjugation by CGH. CA-sar-TFMA was designed, synthesized, and tested for in vitro transport properties, stability, imaging properties, and its ability to differentially accumulate in the gallbladders of normal mice, compared with mice with known impaired bile acid transport (deficient in the apical sodium-dependent bile acid transporter, ASBT). CA-sar-TFMA was a potent inhibitor and substrate of ASBT and the Na+/taurocholate cotransporting polypeptide. Stability was favorable in all conditions tested, including the presence of CGH. CA-sar-TFMA was successfully imaged and accumulated at 16.1-fold higher concentrations in gallbladders from wild-type mice compared with those from Asbt-deficient mice. Our results support the potential of using MRI with CA-sar-TFMA as a noninvasive method to assess bile acid transport in vivo. PMID:25196788

  1. Anti-AIDS agents, 1. Isolation and characterization of four new tetragalloylquinic acids as a new class of HIV reverse transcriptase inhibitors from tannic acid.

    PubMed

    Nishizawa, M; Yamagishi, T; Dutschman, G E; Parker, W B; Bodner, A J; Kilkuskie, R E; Cheng, Y C; Lee, K H

    1989-01-01

    Four new tetragalloylquinic acids, 3,5-di-O-galloyl-4-O-digalloylquinic acid, 3,4-di-O-galloyl-5-O-digalloylquinic acid, 3-O-digalloyl-4,5-di-O-galloylquinic acid, and 1,3,4,5-tetra-O-galloylquinic acid, were isolated and characterized from a commercial tannic acid as a new class of human immunodeficiency virus (HIV) reverse transcriptase (RT) inhibitor. Compounds 2, 3, and 4 inhibit HIV RT activity 90, 89, and 84% at 100 microM and 73, 70, and 63% at 30 microM, respectively. Compounds 2-5 also inhibit the HIV growth in cells in the range of 61-70% with low cytotoxicity at 25 microM. The HIV cell growth inhibitory effects of these compounds at 25 microM and 6.25 microM (44-57%) are comparable to their effects against the HIV RT at 30 microM and 10 microM, respectively. The inhibitory effect of 3 against DNA polymerases indicates that the selective antiviral action of 3 is determined by more than its action with HIV RT.

  2. Light-controlled cellular internalization and cytotoxicity of nucleic acid-binding agents. Studies in vitro and in zebrafish embryos

    PubMed Central

    Penas, Cristina; Sánchez, Mateo I.; Guerra-Varela, Jorge; Sanchez-Piñón, Laura; Vázquez, M. Eugenio; Mascareñas, José L.

    2016-01-01

    We have synthesized oligoarginine conjugates of selected DNA-binding agents (a bisbenzamidine, acridine and thiazole orange) and demonstrated that the DNA binding and cell internalization properties of such conjugates can be inhibited by appending a negatively charged oligoglutamic tail through a photolabile linker. Irradiation with UV light releases the parent octaarginine conjugates, thus restoring their cell internalization and biological activity. Preliminary assays using zebrafish embryos demonstrates the potential of this prodrug strategy for controlling in vivo cytotoxicity. PMID:26534774

  3. Intensive lifestyle intervention provides rapid reduction of serum fatty acid levels in women with severe obesity without lowering omega-3 to unhealthy levels.

    PubMed

    Lin, C; Andersen, J R; Våge, V; Rajalahti, T; Mjøs, S A; Kvalheim, O M

    2016-08-01

    Serum fatty acid (FA) levels were monitored in women with severe obesity during intensive lifestyle intervention. At baseline, total FA levels and most individual FAs were elevated compared to a matching cohort of normal and overweight women (healthy controls). After 3 weeks of intensive lifestyle intervention, total level was only 11-12% higher than in the healthy controls and with almost all FAs being significantly lower than at baseline, but with levels of omega-3 being similar to the healthy controls. This is contrary to observations for patients subjected to bariatric surgery where omega-3 levels dropped to levels significantly lower than in the lifestyle patients and healthy controls. During the next 3 weeks of treatment, the FA levels in lifestyle patients were unchanged, while the weight loss continued at almost the same rate as in the first 3 weeks. Multivariate analysis revealed that weight loss and change of serum FA patterns were unrelated outcomes of the intervention for lifestyle patients. For bariatric patients, these processes were associated probably due to reduced dietary input and increased input from the patients' own fat deposits, causing a higher rate of weight loss and simultaneous reduction of the ratio of serum eicosapentaenoic to arachidonic acid.

  4. Omega-3 Fatty Acids from Fish Oil Lower Anxiety, Improve Cognitive Functions and Reduce Spontaneous Locomotor Activity in a Non-Human Primate

    PubMed Central

    Vinot, Nina; Jouin, Mélanie; Lhomme-Duchadeuil, Adrien; Guesnet, Philippe; Alessandri, Jean-Marc; Aujard, Fabienne; Pifferi, Fabien

    2011-01-01

    Omega-3 (ω3) polyunsaturated fatty acids (PUFA) are major components of brain cells membranes. ω3 PUFA-deficient rodents exhibit severe cognitive impairments (learning, memory) that have been linked to alteration of brain glucose utilization or to changes in neurotransmission processes. ω3 PUFA supplementation has been shown to lower anxiety and to improve several cognitive parameters in rodents, while very few data are available in primates. In humans, little is known about the association between anxiety and ω3 fatty acids supplementation and data are divergent about their impact on cognitive functions. Therefore, the development of nutritional studies in non-human primates is needed to disclose whether a long-term supplementation with long-chain ω3 PUFA has an impact on behavioural and cognitive parameters, differently or not from rodents. We address the hypothesis that ω3 PUFA supplementation could lower anxiety and improve cognitive performances of the Grey Mouse Lemur (Microcebus murinus), a nocturnal Malagasy prosimian primate. Adult male mouse lemurs were fed for 5 months on a control diet or on a diet supplemented with long-chain ω3 PUFA (n = 6 per group). Behavioural, cognitive and motor performances were measured using an open field test to evaluate anxiety, a circular platform test to evaluate reference spatial memory, a spontaneous locomotor activity monitoring and a sensory-motor test. ω3-supplemented animals exhibited lower anxiety level compared to control animals, what was accompanied by better performances in a reference spatial memory task (80% of successful trials vs 35% in controls, p<0.05), while the spontaneous locomotor activity was reduced by 31% in ω3-supplemented animals (p<0.001), a parameter that can be linked with lowered anxiety. The long-term dietary ω3 PUFA supplementation positively impacts on anxiety and cognitive performances in the adult mouse lemur. The supplementation of human food with ω3 fatty acids may

  5. Viscosity-Lowering Effect of Amino Acids and Salts on Highly Concentrated Solutions of Two IgG1 Monoclonal Antibodies.

    PubMed

    Wang, Shujing; Zhang, Ning; Hu, Tao; Dai, Weiguo; Feng, Xiuying; Zhang, Xinyi; Qian, Feng

    2015-12-01

    Monoclonal antibodies display complicated solution properties in highly concentrated (>100 mg/mL) formulations, such as high viscosity, high aggregation propensity, and low stability, among others, originating from protein-protein interactions within the colloidal protein solution. These properties severely hinder the successful development of high-concentration mAb solution for subcutaneous injection. We hereby investigated the effects of several small-molecule excipients with diverse biophysical-chemical properties on the viscosity, aggregation propensity, and stability on two model IgG1 (JM1 and JM2) mAb formulations. These excipients include nine amino acids or their salt forms (Ala, Pro, Val, Gly, Ser, HisHCl, LysHCl, ArgHCl, and NaGlu), four representative salts (NaCl, NaAc, Na2SO4, and NH4Cl), and two chaotropic reagents (urea and GdnHCl). With only salts or amino acids in their salt-forms, significant decrease in viscosity was observed for JM1 (by up to 30-40%) and JM2 (by up to 50-80%) formulations, suggesting charge-charge interaction between the mAbs dictates the high viscosity of these mAbs formulations. Most of these viscosity-lowering excipients did not induce substantial protein aggregation or changes in the secondary structure of the mAbs, as evidenced by HPLC-SEC, DSC, and FT-IR analysis, even in the absence of common protein stabilizers such as sugars and surfactants. Therefore, amino acids in their salt-forms and several common salts, such as ArgHCl, HisHCl, LysHCl, NaCl, Na2SO4, and NaAc, could potentially serve as viscosity-lowering excipients during high-concentration mAb formulation development.

  6. Evaluation of diethylenetriaminepentaacetic acid-manganese(II) complexes modified by narrow molecular weight distribution of chitosan oligosaccharides as potential magnetic resonance imaging contrast agents.

    PubMed

    Huang, Yan; Zhang, Xiaoyan; Zhang, Qi; Dai, Xueqin; Wu, Jingbo

    2011-05-01

    Novel conjugates of narrow molecular weight distribution of chitosan oligosaccharides (CSn; n=6, 8, 11) with manganese-diethylenetriaminepentaacetic acid (Mn-DTPA) as potential magnetic resonance imaging (MRI) contrast agents were synthesized. The structures were characterized by means of Fourier transform infrared spectra, (13)C nuclear magnetic resonance, size exclusion chromatography and inductively coupled plasma atomic emission spectrometry. The characterization results showed that Mn-DTPA was successfully linked to aminated CSn by an amide function. The magnetic properties were characterized by in vitro and T(1)-weighted FLASH image experiments. Relaxivities studies indicated that Mn-DTPA-CSn (n=8, 11) provided higher relaxivity, either in aqueous or bovine serum albumin solution (0.725 mM), than commercial contrast agent Gd-DTPA. The stability results showed that Mn-DTPA-CSn in aqueous were stable enough to prevent Mn(II) ions from releasing. The preliminary in vitro and T(1)-weighted FLASH image studies suggested that Mn-DTPA-CSn had the advantage of becoming promising MRI contrast agents.

  7. Folic acid-conjugated MnO nanoparticles as a T1 contrast agent for magnetic resonance imaging of tiny brain gliomas.

    PubMed

    Chen, Ning; Shao, Chen; Qu, Yanming; Li, Shuai; Gu, Wei; Zheng, Tingting; Ye, Ling; Yu, Chunjiang

    2014-11-26

    Detection of brain gliomas at the earliest stage is of great importance to improve outcomes, but it remains a most challenging task. In this study, oleic acid capped manganese oxide (MnO) nanoparticles (NPs) were prepared by the thermal decomposition of manganese oleate precursors and then transformed to water-dispersible MnO NPs by replacing oleic acid with N-(trimethoxysilylpropyl) ethylene diamine triacetic acid (TETT) silane. The covalently bonded TETT silane offers MnO NPs colloidal stability and abundant carboxylic functional groups allowing the further conjugation of the glioma-specific moiety, folic acid (FA). Moreover, the thin layer of TETT silane ensures a short distance between external Mn ion and water proton, which endows the FA-conjugated, TETT modified MnO (MnO-TETT-FA) NPs a longitudinal relaxivity as high as 4.83 mM(-1) s(-1). Accordingly, the in vivo magnetic resonance (MR) images demonstrated that MnO-TETT-FA NPs could efficiently enhance the MRI contrast for tiny brain gliomas. More importantly, due to the specificity of FA, MnO-TETT-FA NPs led to a clearer margin of the tiny glioma. This together with the good biocompatibility discloses the great potential of MnO-TETT-FA NPs as effective MRI contrast agents for the early diagnosis of brain gliomas.

  8. Design, synthesis, 3D pharmacophore, QSAR, and docking studies of carboxylic acid derivatives as Histone Deacetylase inhibitors and cytotoxic agents.

    PubMed

    Abdel-Atty, Mona M; Farag, Nahla A; Kassab, Shaymaa E; Serya, Rabah A T; Abouzid, Khaled A M

    2014-12-01

    In this study, five series of (E)-6-(4-substituted phenyl)-4-oxohex-5-enoic acids IIb-f (E), (E)-3-(4-(substituted)-phenyl)acrylic acids IIIa-g (E), 4-(4-(substituted)phenylamino)-4-oxobutanoic acids VIa,b,e, 5-(4-(substituted)phenylamino)-5-oxopentanoic acids VIIa,f and 2-[(4-(substituted)phenyl) carbamoyl]benzoic acids VIIIa,e were designed and synthesized. Selected compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumor cell lines. Compound IIf (E) displayed significant inhibitory activity against NCI Non-Small Cell Lung A549/ATCC Cancer cell line (68% inhibition) and NCI-H460 Cancer cell line (66% inhibition). Moreover, the final compounds were evaluated in vitro for their cytotoxic activity on HepG2 Cancer cell line in which histone deacetylase (HDAC) is overexpressed. Compounds IIc (E), IIf (E), IIIb (E), and IIIg (E) exhibited the highest cytotoxic activity against HepG2 human cancer cell lines with IC50 ranging from 2.27 to 10.71μM. In addition, selected compounds were tested on histone deacetylase isoforms (HDAC1-11). Molecular docking simulation was also carried out for HDLP enzyme to investigate their HDAC binding affinity. In addition, generation of 3D-pharmacophore model and quantitative structure activity relationship (QSAR) models were combined to explore the structural requirements controlling the observed cytotoxic properties.

  9. Effective uptake of decontaminating agent (citric acid) from aqueous solution by mesoporous and microporous materials: an adsorption process.

    PubMed

    Gokulakrishnan, Narasimhan; Pandurangan, Arumugam; Sinha, Pradeep Kumar

    2006-04-01

    The presence of citric acid in decontamination waste can cause complexation of the radioactive cations resulting in interferences in their removal by various treatment processes such as chemical precipitation, ion-exchange, etc., which are employed for the removal of radioactivity and may cause potential danger to the environment. Mesoporous Al-MCM-41 (Si/Al=30, 51, 72 and 97) and Si-MCM-41 molecular sieves were synthesized hydrothermally and characterized by XRD, BET (surface area) and FT-IR to evaluate the removal of citric acid through an adsorption process. Adsorption of citric acid over Al-MCM-41 shows the applicability of Freundlich and Langmuir isotherm and follows first order kinetics. The effects of contact time, concentration of citric acid, adsorbents (various Si/Al ratios of Al-MCM-41, Si-MCM-41, Hbeta zeolite and commercial carbon) and pH have been investigated. It has been found that the amount of citric acid adsorbed per unit gram of catalyst followed the order Al-MCM-41 (Si/Al=30)>Al-MCM-41 (Si/Al=51)>activated charcoal>Al-MCM-41 (Si/Al=72)>Al-MCM-41 (Si/Al=97)>Si-MCM-41>Hbeta zeolite.

  10. High-performance liquid chromatography of selenium compounds utilizing perfluorinated carboxylic acid ion-pairing agents and inductively coupled plasma and electrospray ionization mass spectrometric detection.

    PubMed

    Kotrebai, M; Tyson, J F; Block, E; Uden, P C

    2000-01-01

    Increasing speciation demands in clinical chemistry, toxicology and nutrition have made the determination of the total elements in a sample inadequate; the amount of an element and the chemical forms in which it is present need to be known. Inductively coupled plasma mass spectrometry (ICP-MS) was used after high-performance liquid chromatographic (HPLC) separation, as was electrospray ionization mass spectrometry (ESI-MS). The effect of variation of the number of carbon atoms in perfluorinated carboxylic acids used as ion-pairing agents for the separation of selenium compounds was examined. Trifluoroacetic acid (0.1%), pentafluoropropanoic acid (0.1%) or heptafluorobutanoic acid (0.1%; HFBA) were alternatively used as additives to methanol-water (1:99, v/v) solutions as mobile phases. Reversed-phase HPLC-ICP-MS with 0.1% HFBA in the mobile phase allowed more than 20 selenium compounds to be separated in 70 min in an isocratic elution mode; the separation of natural selenium-enriched sample extracts was examined and explained. The pH of the 0.1% HFBA solution was modified with hydrochloric acid or ammonia and the pH of the sample extracts before injection was modified in order to overcome unwanted double peak formation in the chromatograms of sample extracts. Oxidations of standard gamma-glutamyl-Se-methylselenocysteine and Se-methylselenocysteine were carried out using 30% H2O2 solution and identifications of selenium-containing oxidation products were made using HPLC-ICP-MS and HPLC-ESI-MS. The principal organic oxidation product in both cases was methaneseleninic acid (MeSeO2H).

  11. [Identification of causative agent of Brassica rapa bacterial diseases based on fatty acid composition of cellular lipids].

    PubMed

    Dankevych, L A; Votselko, S K; Zakharova, O M; Mel'nychuk, M D; Patina, V P

    2013-01-01

    The fatty acid composition of cell lipids of 15 strains isolated from the affected plants of rape and five collection strains has been studied. According to the results of chemotaxonomic analysis it has been found that 9 isolated strains are similar to representatives of species Pseudomonas marginalis and Pseudomonas fluorescens, and 6 - to those of Xanthomonas campestris pv. campestris. The authors have established the efficiency of certain methods for the extraction of fatty acids used for the identification of bacteria pathogenic for rape which belong to the genera Pseudomonas and Xanthomonas.

  12. [Influence of exogenous salicylic acid on the level of phytohormones in tissues of Phlox paniculata and Phlox setacea leaves with special reference to resistance against the powdery mildew causative agent Erysiphe cichoracearum D.C. f. phlogis Jacz].

    PubMed

    Talieva, M N; Kondrat'eva, V V

    2002-01-01

    We studied the effects of exogenous salicylic acid on the level of endogenous cytokinins and abscisic and salicylic acids in the tissues of leaves of phloxes contrasting in resistance against the powdery mildew causative agent: susceptible Phlox paniculata L. and resistant Ph. setacea L. Studies were carried out under the conditions of biotic stress. The initial level of salicylic and abscisic acids and cytokinins is the highest in the resistant phlox species. After treatment with salicylic species, the total level of cytokinins and endogenous salicylic acid increased in both species. When the treated phlox species were infected by the powdery mildew causative agent, the level of abscisic and salicylic acids increased in the susceptible Ph. paniculata, while that of cytokinins increased in the resistant Ph. setacea. The role of salicylic acid in the induction of plant defense reactions against phytopathogens is discussed.

  13. Counteracting foaming caused by lipids or proteins in biogas reactors using rapeseed oil or oleic acid as antifoaming agents.

    PubMed

    Kougias, P G; Boe, K; Einarsdottir, E S; Angelidaki, I

    2015-08-01

    Foaming is one of the major operational problems in biogas plants, and dealing with foaming incidents is still based on empirical practices. Various types of antifoams are used arbitrarily to combat foaming in biogas plants, but without any scientific support this action can lead to serious deterioration of the methanogenic process. Many commercial antifoams are derivatives of fatty acids or oils. However, it is well known that lipids can induce foaming in manure based biogas plants. This study aimed to elucidate the effect of rapeseed oil and oleic acid on foam reduction and process performance in biogas reactors fed with protein or lipid rich substrates. The results showed that both antifoams efficiently suppressed foaming. Moreover rapeseed oil resulted in stimulation of the biogas production. Finally, it was reckoned that the chemical structure of lipids, and more specifically their carboxylic ends, is responsible for their foam promoting or foam counteracting behaviour. Thus, it was concluded that the fatty acids and oils could suppress foaming, while salt of fatty acids could generate foam.

  14. Dual functionality of phosphonic-acid-appended phthalocyanines: inhibitors of urokinase plasminogen activator and anticancer photodynamic agents.

    PubMed

    Venkatramaiah, N; Pereira, Patrícia M R; Almeida Paz, Filipe A; Ribeiro, Carlos A F; Fernandes, Rosa; Tomé, João P C

    2015-11-01

    Phthalocyanines (Pcs) bearing phosphonic acid groups at the periphery exhibit a potential photodynamic effect to induce phototoxicity on human bladder cancer epithelial cells (UM-UC-3). In vitro photophysical and biological studies show high intrinsic ability to inhibit the activity of urokinase plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9).

  15. Radioactive diagnostic agent

    SciTech Connect

    Shigematsu, A.; Aihara, M.; Matsuda, M.; Suzuki, A.; Tsuya, A.

    1984-02-07

    A radioactive diagnostic agent for renal cortex, adrenal cortex, myocardium, brain stem, spinal nerve, etc., which comprises as an essential component monoiodoacetic acid wherein the iodine atom is radioactive.

  16. The role of spices and lactic acid bacteria as antimicrobial agent to extend the shelf life of metata ayib (traditional Ethiopian spiced fermented cottage cheese).

    PubMed

    Geremew, Tsehayneh; Kebede, Ameha; Andualem, Berhanu

    2015-09-01

    Spices and lactic acid bacteria have natural antimicrobial substances and organic compounds having antagonistic activity against microorganisms. The objective of this study was to investigate the role of spices and lactic acid bacteria as antimicrobial agent to extend the shelf life of metata ayib. Antimicrobial activities of spices and lactic acid bacteria (LAB) filtrates were determined by agar well diffusion method against E. coli, S. aureus, S. flexneri and S. peumoniae. Aantimicrobial activity of garlic was found to be the most effective against all the tested pathogens. Inhibition zones of garlic extract against all pathogens was significantly (P ≤ 0.05) greater than the remaining spice extracts. Inhibition zones (12.50 ± 1.00 to 15.50 ± 1.00 mm) of ginger and R. graveolens ethanol extracts against all tested pathogens were significantly (P ≤ 0.05) greater than the remaining solvent extracts. Inhibition zone of O. basilicum ethanol extract against all pathogenic bacteria was significantly (p ≤ 0.05) greater than hexane and acetone extracts. Lactobacillus isolates were shown the highest antimicrobial activity than the other LAB isolates against all pathogens. The synergistic effect of spices together with LAB might be contributed a lot to preserve and extend shelf life of metata ayib. Their antimicrobial activity can reduce the risk of spoilage and pathogenesis. The possible reason of LAB isolates was may be due to production of lactic acid, acetic acid and secondary metabolites like bacteriocins. Aseptic processing of traditional cottage cheese (ayib) is by far needed to minimize risks associated during consumption of metata ayib. PMID:26344979

  17. The role of spices and lactic acid bacteria as antimicrobial agent to extend the shelf life of metata ayib (traditional Ethiopian spiced fermented cottage cheese).

    PubMed

    Geremew, Tsehayneh; Kebede, Ameha; Andualem, Berhanu

    2015-09-01

    Spices and lactic acid bacteria have natural antimicrobial substances and organic compounds having antagonistic activity against microorganisms. The objective of this study was to investigate the role of spices and lactic acid bacteria as antimicrobial agent to extend the shelf life of metata ayib. Antimicrobial activities of spices and lactic acid bacteria (LAB) filtrates were determined by agar well diffusion method against E. coli, S. aureus, S. flexneri and S. peumoniae. Aantimicrobial activity of garlic was found to be the most effective against all the tested pathogens. Inhibition zones of garlic extract against all pathogens was significantly (P ≤ 0.05) greater than the remaining spice extracts. Inhibition zones (12.50 ± 1.00 to 15.50 ± 1.00 mm) of ginger and R. graveolens ethanol extracts against all tested pathogens were significantly (P ≤ 0.05) greater than the remaining solvent extracts. Inhibition zone of O. basilicum ethanol extract against all pathogenic bacteria was significantly (p ≤ 0.05) greater than hexane and acetone extracts. Lactobacillus isolates were shown the highest antimicrobial activity than the other LAB isolates against all pathogens. The synergistic effect of spices together with LAB might be contributed a lot to preserve and extend shelf life of metata ayib. Their antimicrobial activity can reduce the risk of spoilage and pathogenesis. The possible reason of LAB isolates was may be due to production of lactic acid, acetic acid and secondary metabolites like bacteriocins. Aseptic processing of traditional cottage cheese (ayib) is by far needed to minimize risks associated during consumption of metata ayib.

  18. A Lanthanum-Tagged Chemotherapeutic Agent HA-Pt to Track the In Vivo Distribution of Hyaluronic Acid Complexes

    PubMed Central

    Forrest, W.C.; Cai, Shuang; Aires, Daniel; Forrest, M. Laird

    2015-01-01

    Hyaluronic acid drug conjugates can target anti-cancer drugs directly to tumor tissue for loco-regional treatment with enhanced bioavailability, local efficacy and reduced toxicity. In this study, the distribution and pharmacokinetics of hyaluronic acid carrier and a conjugated cisplatin anti-cancer drug were tracked by lanthanum (III) [La(III)] affinity tagging of the nanocarrier. The strong binding affinity of La(III) to HA enabled the simple preparation of a physiologically stable complex HA-Pt-La and straightforward simultaneous detection of HA-La and Pt in biological matrices using inductively coupled plasma-mass spectrometry (ICP-MS). Consequently, after subcutaneous injection of HA-Pt-La nanoparticles in human head and neck squamous cell carcinoma (HNSCC) tumor-bearing mice, the HA and Pt content were detected and quantified simultaneously in the plasma, primary tumor, liver and spleen. PMID:26756040

  19. Synthetic thioamide, benzimidazole, quinolone and derivatives with carboxylic acid and ester moieties: a strategy in the design of antituberculosis agents.

    PubMed

    Ashfaq, M; Shah, S S A; Najam, T; Ahmad, M M; Tabassum, R; Rivera, G

    2014-03-01

    Synthetic heterocyclic compounds have remarkable potential activity against diseases; thioamides, benzimidazoles, quinolones and derivatives with carboxylic acid and esters moieties have shown excellent activity against Mycobacterium tuberculosis. We reviewed antituberculosis activities of above compounds with reference to half maximal inhibitory concentration, minimum inhibitory concentration and structural-activity relationship which clearly indicate that electron-withdrawing groups are the main inducers of antimycobacterium activity. Comparison between clinically used drugs and new synthetic derivatives showed recent advances made in the last decade.

  20. Effect of clavulanic acid on the activities of ten beta-lactam agents against members of the Bacteroides fragilis group.

    PubMed Central

    Lamothe, F; Auger, F; Lacroix, J M

    1984-01-01

    Clavulanic acid reduced the MICs of amoxicillin, carbencillin , cefamandole, cefotaxime, ceftazidime, ceftizoxime, cephalothin, and penicillin G, but not of cefoxitin or moxalactam, against 77 isolates of the Bacteroides fragilis group, all rapidly beta-lactamase positive by the nitrocefin slide test. It had no effect on the susceptibilities of eight Bacteroides distasonis strains that were slowly beta-lactamase positive (18 h of incubation). PMID:6732233

  1. Synthesis of the catechols of natural and synthetic estrogens by using 2-iodoxybenzoic acid (IBX) as the oxidizing agent.

    PubMed

    Saeed, Muhammad; Zahid, Muhammad; Rogan, Eleanor; Cavalieri, Ercole

    2005-03-01

    A method for the synthesis of 2-hydroxyestrone/estradiol, 4-hydroxyestrone/estradiol, 3'-hydroxydiethylstilbestrol, 3'-hydroxyhexestrol, and 3'-hydroxydienestrol is reported, in which 2-iodoxybenzoic acid (IBX) and the corresponding phenolic estrogen are reacted. Treatment of the natural estrogens, estrone/estradiol, with stoichiometric amounts of IBX in dimethylformamide initially yielded a mixture of estrone/estradiol-2,3- and -3,4-quinones, which were reduced in situ to the corresponding catechols by treatment with a 1 M aqueous solution of ascorbic acid. Chromatographic separation of the reaction products afforded 2- and 4-hydroxyestrone/estradiol in good overall yields (79%). In the case of the synthetic estrogens containing two identical phenolic rings, protection of one ring is a prerequisite for the synthesis of the monocatechol. Thus, diethylstilbestrol and dienestrol were protected at one phenol ring as their methyl ethers. The resulting monophenols were treated with stoichiometric amounts of IBX for 1 h, followed by treatment with 1 M aqueous ascorbic acid to obtain the corresponding catechols in more than 70% yield. Furthermore, the catechol of diethylstilbestrol, protected at one ring, was reduced by catalytic hydrogenation at the C3-C4 double bond to obtain 3'-hydroxyhexestrol in 90% yield. Removal of the protected methoxy groups of the synthetic estrogen catechols was carried out by treatment with a 1 M solution of boron tribromide in dichloromethane. This method is highly efficient for the preparative scale synthesis of catechols of both natural and synthetic estrogens.

  2. Homocysteine-Lowering and Cardiovascular Disease Outcomes in Kidney Transplant Recipients: Primary Results from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial

    PubMed Central

    Bostom, Andrew G.; Carpenter, Myra A.; Kusek, John W.; Levey, Andrew S.; Hunsicker, Lawrence; Pfeffer, Marc A.; Selhub, Jacob; Jacques, Paul F.; Cole, Edward; Gravens-Mueller, Lisa; House, Andrew A.; Kew, Clifton; McKenney, Joyce L.; Pacheco-Silva, Alvaro; Pesavento, Todd; Pirsch, John; Smith, Stephen; Solomon, Scott; Weir, Matthew

    2015-01-01

    Background Kidney transplant recipients, like other patients with chronic kidney disease (CKD), experience excess risk of cardiovascular disease (CVD) and elevated total homocysteine (tHcy) concentrations. Observational studies of patients with CKD suggest increased homocysteine is a risk factor for CVD. The impact of lowering total homocysteine (tHcy) levels in kidney transplant recipients is unknown. Methods and Results In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing tHcy concentrations reduced the rate of the primary composite arteriosclerotic CVD outcome (myocardial infarction, stroke, CVD death, resuscitated sudden death, coronary artery or renal artery revascularization, lower extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n= 547 total events; hazards ratio [95% confidence interval] = 0.99 [0.84–1.17]), or secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86–1.26]) or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93–1.43]) compared to the low dose multivitamin. Conclusions Treatment with a high dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level. PMID:21482964

  3. Bio-functionalization of magnetite nanoparticles using an aminophosphonic acid coupling agent: new, ultradispersed, iron-oxide folate nanoconjugates for cancer-specific targeting

    NASA Astrophysics Data System (ADS)

    Das, Manasmita; Mishra, Debasish; Maiti, T. K.; Basak, A.; Pramanik, P.

    2008-10-01

    The present study describes a systematic approach towards the design and development of novel, bio-functionalized, magneto-fluorescent nanoparticles for cancer-specific targeting. Biocompatible, hydrophilic, magneto-fluorescent nanoparticles with surface-pendant amine, carboxyl or aldehyde groups, to be later used for bio-conjugation, were designed using an aminophosphonic acid coupling agent. These magneto-fluorescent nanoparticles were further functionalized with folic acid, using diverse conjugation strategies. A series of new iron-oxide folate nanoconjugates with excellent aqueous dispersion stability and reasonably good hydrodynamic sizes under a wide range of physiological conditions were developed. These ultradispersed nanosystems were analyzed for their physicochemical properties and cancer-cell targeting ability, facilitated by surface modification with folic acid. The nanoparticle size, charge, surface chemistry, magnetic properties and colloidal stability were extensively studied using a variety of complementary techniques. Confocal microscopy, performed with folate receptor positive human cervical HeLa cancer cells, established that these non-cytotoxic iron-oxide folate nanoconjugates were effectively internalized by the target cells through receptor-mediated endocytosis. Cell-uptake behaviors of nanoparticles, studied using magnetically activated cell sorting (MACS), clearly demonstrated that cells over-expressing the human folate receptor internalized a higher level of these nanoparticle-folate conjugates than negative control cells.

  4. Succinic acid monoethyl ester, a novel insulinotropic agent: effect on lipid composition and lipid peroxidation in streptozotocin-nicotin-amide induced type 2 diabetic rats.

    PubMed

    Saravanan, Ramalingam; Pari, Leelavinothan

    2007-02-01

    Succinic acid monoethyl ester (EMS) is recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. Oxidative stress has been suggested to be a contributory factor in the development and complications of diabetes. In the present study the effect of EMS and Metformin on plasma glucose, insulin, serum and tissue lipid profile, lipoproteins and lipid peroxidation in streptozotocin-nicotinamide induced type 2 diabetic model was investigated. The carboxylic nutrient EMS was administered intraperitonially (8 micromol/g body weight) to streptozotocin diabetic rats for 30 days. The levels of thiobarbituric acid reactive substances (TBARS) and hydroperoxides in liver and kidney and serum and tissue lipids [cholesterol, triglycerides, phospholipids and free fatty acids] and very low density lipoprotein-cholesterol (VLDL-C) and low density lipoprotein-cholesterol (LDL-C), were significantly increased in diabetic rats, whereas the levels of high-density lipoprotein-cholesterol (HDL-C) and antiatherogenic index (AAI) (ratio of HDL to total cholesterol) were significantly decreased. The effect of EMS was compared with metformin, a reference drug. Treatment with EMS and metformin resulted in a significant reduction of plasma glucose with increase plasma insulin in diabetic rats. EMS also resulted in a significant decrease in serum and tissue lipids and lipid peroxidation products. These biochemical observations were supplemented by histopathological examination of liver and kidney section. Our results suggest the possible antihyperlipidemic and antiperoxidative effect of EMS apart from its antidiabetic effect. PMID:17006620

  5. Binding to plasma lipoproteins of chlorophenoxyisobutyric, tibric and nicotinic acids and their esters: its significance for the mechanism of lipid lowering by clofibrate and related drugs.

    PubMed

    Beaumont, J L; Dachet, C

    1976-01-01

    The binding of chlorophenoxyisobutyric (CPIB), tibric (TA) and nicotinic (NA) acids and CPIB ethyl ester (Clofibrate), TA and NA isopropyl esters (TAPE and NAPE) to human lipoproteins of low density of different classes (LDL2, LDL1 and VLDL) and high density (HDL) were studied by equilibrium dialysis and Sephadex gel filtration. Clofibrate and TAPE bound strongly to lipoproteins, but their acids, CPIB and TA and also NA and NAPE, did not bind. In the same experimental conditions, Clofibrate and TAPE bound only weakly to human serum albumin (HSA) and CPIB bound to HSA with a Ka of 3.3 X 10(5) M(-1) for 1 site of high affinity. The Clofibrate and TAPE bound to lipoproteins did not dissociate either during dialysis or during filtration on Sephadex G 25. The binding percentage remained constant for all drug concentrations studied, and the molar ratio of bound drug rose linearly with increasing concentrations. This suggests that the interaction may be irreversible, and there is some evidence that binding may induce irreversible changes in the lipoprotein molecules. These results, and those already found in experiments made with three other drugs related to Clofibrate, lead to the proposal that in their interaction with lipoproteins, the phenyl groups are necessary and the esterification is contributory. The possible role of this interaction in the lipid-lowering effect of the drugs is discussed with special reference to their possible implication in lipoprotein synthesis within the intestinal and hepatic cells.

  6. Silver(I) compounds of the anti-inflammatory agents salicylic acid and p-hydroxyl-benzoic acid which modulate cell function.

    PubMed

    Banti, C N; Giannoulis, A D; Kourkoumelis, N; Owczarzak, A M; Kubicki, M; Hadjikakou, S K

    2015-01-01

    Silver nitrate reacts with salicylic acid (salH2) or p-hydroxy-benzoic acid (p-HbzaH2) and equimolar amount of NaOH to yield a white precipitations which are then treated with tri(p-tolyl)phosphine (tptp) or tri(m-tolyl)phosphine (tmtp) to yield the complexes [Ag(tptp)2(salH)] (1), [Ag(tptp)2(p-Hbza)] (2) and [Ag(tmtp)2(salH)] (3). Complexes 1 and 3 are also obtained when aspirin (aspH) is used. The acetic ester of salicylic acid is hydrolyzed to form the complexes 1 and 3. However, when aspirin and tptp are used, a mixture of products was obtained which contains both 1 and an ionic complex of formula {[Ag(tptp)4](+)[(salH)(-)]∙[(CH3)2NCHO)]∙(H2O)} (1a). The complexes were characterized by m.p., e.a., mid-FT-IR, (1)H-,(31)P-NMR, HRMS, UV-vis spectroscopic techniques and X-ray crystallography. Two phosphorus and one carboxylic oxygen atoms form a trigonal planar geometry around Ag(I) ions in complexes 1-3. Complex 1a consists of a [Ag(tptp)4](+) cation and a deprotonated salH(-) counter anion. The influence of 1-3 on the viability of MCF-7 (breast) and HeLa (cervix) adenocarcinoma cells, is evaluated. DNA binding tests indicate the ability of 1-3 to modify the activity of cells. The binding constants of 1-3 towards calf-thymus DNA, reveal stronger interaction of 2. Changes in fluorescent emission light of ethidium bromide (EB) in the presence of DNA suggest intercalation or electrostatic interactions into DNA for 1 and 3. Docking studies on DNA-complex interactions confirm the binding of 1-3 in the minor groove of B-DNA. Moreover, the influence of 1-3 on the peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied.

  7. [High aluminum concentrations in well water of southern Lower Saxony sandy soil areas caused by acid precipitation--evaluation from the public health and ecologic viewpoint].

    PubMed

    Mühlenberg, W

    1990-01-01

    Decades of acid precipitation have caused soil acidification in regions with low neutralizing capacity of industrial countries, thus mobilizing aluminium from clay minerals into soil solution and ground water. In the southern sandy heath-land of Lower Saxony all the wells with pH values lower than 4.5 showed aluminium contents higher than 2.0 mg/l. 66.7% of the specimens within the pH-range 4.5 to 5.0 and 20% of the specimens within the pH-range 5.0 to 5.5 had aluminium levels of more than 0.2 mg/l, that is the maximum permissible limit value of the drinking water regulation. High contents of aluminium in drinking water are objectionable from the hygienic point of view, as they may cause intoxications in infants and patients with impaired renal function. In addition to this, the involvement of aluminium in the pathogenesis of severe degenerative disorders of the central nervous system cannot be excluded, such as Alzheimers disease, amyotrophic lateral sclerosis and Parkinsons dementia.

  8. Down-regulation of glutaminase C in human hepatocarcinoma cell by diphenylarsinic acid, a degradation product of chemical warfare agents.

    PubMed

    Kita, Kayoko; Suzuki, Toshihide; Ochi, Takafumi

    2007-05-01

    In a poisonous incident in Kamisu, Japan, it is understood that diphenylarsinic acid (DPAA) was a critical contaminant of ground water. Most patients showed dysfunction of the central nervous system. To understand the overall mechanism of DPAA toxicity and to gain some insight into the application of a remedy specific for intoxication, the molecular target must be clarified. As an approach, a high throughput analysis of cell proteins in cultured human hepatocarcinoma HpG2 exposed to DPAA was performed by two-dimensional electrophoresis (2-DE). Four proteins, which were up- and down-regulated by exposure of cultured HepG2 cells to DPAA, were identified. They were chaperonin containing TCP-1 (CCT) beta subunit, aldehyde dehydrogenase 1 (ALDH1), ribosomal protein P0 and glutaminase C (GAC). Of these, GAC was the only protein that was down-regulated by DPAA exposure, and cellular expression levels were reduced by DPAA in a concentration- and time-dependent manner. Decrease in cellular GAC levels was accompanied by decreased activity of the enzyme, phosphate-activated glutaminase (PAG). Decreased expression of GAC by DPAA was also observed in human cervical carcinoma HeLa and neuroblastoma SH-SY5Y cells. By contrast, no significant changes in GAC protein expression were observed when cells were incubated with arsenite [iAs (III)] and trivalent dimethylarsinous acid [DMA (III)]. In the central nervous system, GAC plays a role in the production of the neurotransmitter glutamic acid. Selective inhibition of GAC expression by DPAA may be a cause of dysfunction of glutamatergic neuronal transmission and the resultant neurological impairments. PMID:17321558

  9. Down-regulation of glutaminase C in human hepatocarcinoma cell by diphenylarsinic acid, a degradation product of chemical warfare agents

    SciTech Connect

    Kita, Kayoko . E-mail: kkayoko@pharm.teikyo-u.ac.jp; Suzuki, Toshihide; Ochi, Takafumi

    2007-05-01

    In a poisonous incident in Kamisu, Japan, it is understood that diphenylarsinic acid (DPAA) was a critical contaminant of ground water. Most patients showed dysfunction of the central nervous system. To understand the overall mechanism of DPAA toxicity and to gain some insight into the application of a remedy specific for intoxication, the molecular target must be clarified. As an approach, a high throughput analysis of cell proteins in cultured human hepatocarcinoma HpG2 exposed to DPAA was performed by two-dimensional electrophoresis (2-DE). Four proteins, which were up- and down-regulated by exposure of cultured HepG2 cells to DPAA, were identified. They were chaperonin containing TCP-1 (CCT) beta subunit, aldehyde dehydrogenase 1 (ALDH1), ribosomal protein P0 and glutaminase C (GAC). Of these, GAC was the only protein that was down-regulated by DPAA exposure, and cellular expression levels were reduced by DPAA in a concentration- and time-dependent manner. Decrease in cellular GAC levels was accompanied by decreased activity of the enzyme, phosphate-activated glutaminase (PAG). Decreased expression of GAC by DPAA was also observed in human cervical carcinoma HeLa and neuroblastoma SH-SY5Y cells. By contrast, no significant changes in GAC protein expression were observed when cells were incubated with arsenite [iAs (III)] and trivalent dimethylarsinous acid [DMA (III)]. In the central nervous system, GAC plays a role in the production of the neurotransmitter glutamic acid. Selective inhibition of GAC expression by DPAA may be a cause of dysfunction of glutamatergic neuronal transmission and the resultant neurological impairments.

  10. Nucleic Acid Ligands With Protein-like Side Chains: Modified Aptamers and Their Use as Diagnostic and Therapeutic Agents

    PubMed Central

    Rohloff, John C; Gelinas, Amy D; Jarvis, Thale C; Ochsner, Urs A; Schneider, Daniel J; Gold, Larry; Janjic, Nebojsa

    2014-01-01

    Limited chemical diversity of nucleic acid libraries has long been suspected to be a major constraining factor in the overall success of SELEX (Systematic Evolution of Ligands by EXponential enrichment). Despite this constraint, SELEX has enjoyed considerable success over the past quarter of a century as a result of the enormous size of starting libraries and conformational richness of nucleic acids. With judicious introduction of functional groups absent in natural nucleic acids, the “diversity gap” between nucleic acid–based ligands and protein-based ligands can be substantially bridged, to generate a new class of ligands that represent the best of both worlds. We have explored the effect of various functional groups at the 5-position of uracil and found that hydrophobic aromatic side chains have the most profound influence on the success rate of SELEX and allow the identification of ligands with very low dissociation rate constants (named Slow Off-rate Modified Aptamers or SOMAmers). Such modified nucleotides create unique intramolecular motifs and make direct contacts with proteins. Importantly, SOMAmers engage their protein targets with surfaces that have significantly more hydrophobic character compared with conventional aptamers, thereby increasing the range of epitopes that are available for binding. These improvements have enabled us to build a collection of SOMAmers to over 3,000 human proteins encompassing major families such as growth factors, cytokines, enzymes, hormones, and receptors, with additional SOMAmers aimed at pathogen and rodent proteins. Such a large and growing collection of exquisite affinity reagents expands the scope of possible applications in diagnostics and therapeutics. PMID:25291143

  11. Synthesis and biological activity of ester derivatives of mycophenolic acid and acridines/acridones as potential immunosuppressive agents.

    PubMed

    Cholewinski, Grzegorz; Iwaszkiewicz-Grzes, Dorota; Trzonkowski, Piotr; Dzierzbicka, Krystyna

    2016-12-01

    Improved derivatives of mycophenolic acid (MPA) are necessary to reduce the frequency of adverse effects, this drug exerts in treated patients. In this study, MPA was coupled with N-(ω-hydroxyalkyl)-9-acridone-4-carboxamides or N-(ω-hydroxyalkyl)acridine-4-carboxamides to give respective ester conjugates upon Yamaguchi protocol. This esterification required protection of phenol group in MPA. Designed conjugates revealed higher potency in vitro than parent MPA. Acridine derivatives were more active than acridone analogs and length of the alkyl linker between MPA and heterocyclic units influenced the observed cytotoxicity. Derivatives 2b, 2d, 3a, 3b displayed the most promising immunosuppressive activity.

  12. Synthesis of new chalcone derivatives bearing 2,4-thiazolidinedione and benzoic acid moieties as potential anti-bacterial agents.

    PubMed

    Liu, Xiao-Fang; Zheng, Chang-Ji; Sun, Liang-Peng; Liu, Xue-Kun; Piao, Hu-Ri

    2011-08-01

    A series of chalcone derivatives bearing the 2,4-thiazolidinedione and benzoic acid moieties (8a-s) were synthesized, characterized, and evaluated for their anti-bacterial activity. Among the tested compounds, the most effective were 8a, 8h, 8k, 8n and 8q with MIC value in the range of 0.5-4 μg/mL against six Gram-positive bacteria (including multidrug-resistant clinical isolates). None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 and E. coli 1682 at 64 μg/mL.

  13. Apple flavonols and n-3 polyunsaturated fatty acid-rich fish oil lowers blood C-reactive protein in rats with hypercholesterolemia and acute inflammation.

    PubMed

    Sekhon-Loodu, Satvir; Catalli, Adriana; Kulka, Marianna; Wang, Yanwen; Shahidi, Fereidoon; Rupasinghe, H P Vasantha

    2014-06-01

    Both quercetin glycosides and omega-3 polyunsaturated fatty acids (n-3 PUFA) are well established for their individual health benefits in ameliorating metabolic disease. However, their combined effects are not well documented. It was hypothesized that the beneficial properties of quercetin glycosides can be enhanced when provided in combination with n-3 PUFA. Therefore, the aim of the present study was to investigate the effects of apple flavonols (AF) and fish oil (FO), alone and in combination, on proinflammatory biomarkers and lipid profiles in rats fed a high-fat diet. Sixty male Wistar rats were randomly divided into 5 groups (n = 12) and fed a high-fat diet for 4 weeks. One of the 5 groups of rats was used as the high-fat control. The other 4 groups of rats were injected with lipopolysaccharide (LPS) (5 mg/kg body weight) intraperitoneally, 5 hours before euthanization. One of these 4 groups was used as the hypercholerolemic and inflammatory control (high-fat with lipopolysaccharide [HFL]), and the other 3 received AF (HFL + 25 mg/kg per day AF), FO (HFL + 1 g/kg per day FO), or the combination (HFL + AF + FO). Compared to the HFL group, the AF, FO, and AF + FO groups showed lower serum concentrations of interleukin-6 and C-reactive protein (CRP) levels. The AF, FO, and AF + FO also had lowered serum triacylglycerol and non-high-density lipoprotein cholesterol (HDL-C) concentrations, but higher HDL-C levels relative to the HFL group. An additive effect was observed on serum CRP in the AF + FO group as compared with the AF or FO groups. The results demonstrated that AF and FO inhibited the production of proinflammatory mediators and showed an improved efficacy to lower serum CRP when administered in combination, and they significantly improved blood lipid profiles in rats with diet-induced hyperlipidemia and LPS-induced acute inflammation.

  14. Apple flavonols and n-3 polyunsaturated fatty acid-rich fish oil lowers blood C-reactive protein in rats with hypercholesterolemia and acute inflammation.

    PubMed

    Sekhon-Loodu, Satvir; Catalli, Adriana; Kulka, Marianna; Wang, Yanwen; Shahidi, Fereidoon; Rupasinghe, H P Vasantha

    2014-06-01

    Both quercetin glycosides and omega-3 polyunsaturated fatty acids (n-3 PUFA) are well established for their individual health benefits in ameliorating metabolic disease. However, their combined effects are not well documented. It was hypothesized that the beneficial properties of quercetin glycosides can be enhanced when provided in combination with n-3 PUFA. Therefore, the aim of the present study was to investigate the effects of apple flavonols (AF) and fish oil (FO), alone and in combination, on proinflammatory biomarkers and lipid profiles in rats fed a high-fat diet. Sixty male Wistar rats were randomly divided into 5 groups (n = 12) and fed a high-fat diet for 4 weeks. One of the 5 groups of rats was used as the high-fat control. The other 4 groups of rats were injected with lipopolysaccharide (LPS) (5 mg/kg body weight) intraperitoneally, 5 hours before euthanization. One of these 4 groups was used as the hypercholerolemic and inflammatory control (high-fat with lipopolysaccharide [HFL]), and the other 3 received AF (HFL + 25 mg/kg per day AF), FO (HFL + 1 g/kg per day FO), or the combination (HFL + AF + FO). Compared to the HFL group, the AF, FO, and AF + FO groups showed lower serum concentrations of interleukin-6 and C-reactive protein (CRP) levels. The AF, FO, and AF + FO also had lowered serum triacylglycerol and non-high-density lipoprotein cholesterol (HDL-C) concentrations, but higher HDL-C levels relative to the HFL group. An additive effect was observed on serum CRP in the AF + FO group as compared with the AF or FO groups. The results demonstrated that AF and FO inhibited the production of proinflammatory mediators and showed an improved efficacy to lower serum CRP when administered in combination, and they significantly improved blood lipid profiles in rats with diet-induced hyperlipidemia and LPS-induced acute inflammation. PMID:25026921

  15. Improvement of the CuZn-superoxide dismutase enzyme activity and stability as a therapeutic agent by modification with polysialic acids.

    PubMed

    Wu, Jian Rong; Lin, Yi; Zheng, Zhi Yong; Lin, Chi Chung; Zhan, Xiao Bei; Shen, Ying Qiang

    2010-12-01

    The optimal process for the polysialylation reaction was as follows: polysialicacid (PSA) was activated by periodate oxidation, then coupled to CuZn superoxide dismutase (SOD) with a PSA:SOD molar ratio of 40:1 for 24 h. The resulting polysialylated protein contained 3.9 ± 0.3 mol PSA per mol SOD. SDS-PAGE and atomic force microscopy revealed that the molecular weight of polysialylated SOD was about 90-100 kDa. The average size was 10-15 nm, about four-fold of the native enzyme. Compared to the native enzyme, the activity and stability of the polysialylated SOD, as well as resistance to heat, acid, alkali and proteases present in human digestive system such as pepsin and trypsin, were improved significantly as therapeutic agent.

  16. An industry perspective on the use of “atoxigenic” strains of Aspergillus flavus as biological control agents and the significance of cyclopiazonic acid

    PubMed Central

    King, Eileen D; (Bobby) Bassi, Albeit B; Ross, David C; Druebbisch, Bernd

    2011-01-01

    Several nonaflatoxigenic strains of Aspergillus flavus have been registered in the United States to reduce aflatoxin accumulation in maize and other crops, but there may be unintended negative consequences if these strains produce cyclopiazonic acid (CPA). AF36, a nonaflatoxigenic, CPA-producing strain has been shown to produce CPA in treated maize and peanuts. Alternative strains, including Afla-Guard® brand biocontrol agent and K49, do not produce CPA and can reduce both aflatoxin and CPA in treated crops. Chronic toxicity of CPA has not been studied, and recent animal studies show significant harmful effects from short-term exposure to CPA at low doses. Grower and industry confidence in this approach must be preserved through transparency. PMID:22844262

  17. The outcomes of two different bulking agents (dextranomer hyaluronic acid copolymer and polyacrylate-polyalcohol copolymer) in the treatment of primary vesico-ureteral reflux

    PubMed Central

    Taşkinlar, Hakan; Avlan, Dincer; Bahadir, Gokhan Berktug; Delibaş, Ali; Nayci, Ali

    2016-01-01

    ABSTRACT Purpose Subureteral injection of bulking agents in the endoscopic treatment of vesicoureteral reflux is widely accepted therapy with high success rates. Although the grade of vesicoureteric reflux and experience of surgeon is the mainstay of this success, the characteristics of augmenting substances may have an effect particularly in the long term. In this retrospective study, we aimed to evaluate the clinical outcomes of the endoscopic treatment of vesicoureteric reflux (VUR) with two different bulking agents: Dextranomer/hyaluronic acid copolymer (Dx/HA) and Polyacrylate polyalcohol copolymer (PPC). Materials and Methods A total 80 patients (49 girls and 31 boys) aged 1-12 years (mean age 5.3 years) underwent endoscopic subureteral injection for correction of VUR last six years. The patients were assigned to two groups: subureteral injections of Dx/HA (45 patients and 57 ureters) and PPC (35 patients and 45 ureters). VUR was grade II in 27 ureters, grade III in 35, grade IV in 22 and grade V in 18 ureters. Results VUR was resolved in 38 (66.6%) of 57 ureters and this equates to VUR correction in 33 (73.3%) of the 45 patients in Dx/HA group. In PPC group, overall success rate was 88.8% (of 40 in 45 ureters). Thus, Thus, this equates to VUR correction in 31 (88.5%) of the 35 patients. Conclusions Our short term data show that two different bulking agent injections provide a high level of reflux resolution and this study revealed that success rate of PPC was significantly higher than Dx/HA with less material. PMID:27286115

  18. Agent Orange

    MedlinePlus

    ... Index Agent Orange Agent Orange Home Facts about Herbicides Veterans' Diseases Birth Defects Benefits Exposure Locations Provider ... millions of gallons of Agent Orange and other herbicides on trees and vegetation during the Vietnam War. ...

  19. Synthesis and biological activities of transition metal complexes based on acetylsalicylic acid as neo-anticancer agents.

    PubMed

    Rubner, Gerhard; Bensdorf, Kerstin; Wellner, Anja; Kircher, Brigitte; Bergemann, Silke; Ott, Ingo; Gust, Ronald

    2010-10-14

    [(μ(4)-η(2))-(Prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS), a derivative of aspirin (ASS), demonstrated high growth-inhibitory potential against various tumor cells with interference in the arachidonic acid cascade as probable mode of action. The significance of the kind of metal and cluster was verified in this structure-activity study: Co(2)(CO)(6) was respectively exchanged by a tetrameric cobalt-, trimeric ruthenium-, or trimeric ironcarbonyl cluster. Furthermore, the metal binding motif was changed from alkyne to 1,3-butadiene. Compounds were evaluated for growth inhibition, antiproliferative effects, and apoptosis induction in breast (MCF-7, MDA-MB 231) and colon cancer (HT-29) cell lines and for COX-1/2 inhibitory effects at isolated isoenzymes. Additionally, the major COX metabolite prostaglandin E2 (PGE(2)) was quantified in arachidonic acid-stimulated MDA-MB 231 breast tumor cells. It was demonstrated that the metal cluster was of minor importance for effects on cellular activity if an alkyne was used as ligand. Generally, no correlation existed between growth inhibition and COX activity. Cellular growth inhibition and antiproliferative activity at higher concentrations of the most active compounds Prop-ASS-Co(4) and Prop-ASS-Ru(3) correlated well with apoptosis induction.

  20. Gallic acid as a selective anticancer agent that induces apoptosis in SMMC-7721 human hepatocellular carcinoma cells

    PubMed Central

    SUN, GUOJUN; ZHANG, SHUQIN; XIE, YANRU; ZHANG, ZIYU; ZHAO, WENJING

    2016-01-01

    Gallic acid (3,4,5-trihydroxybenzoic acid; GA) is a naturally occurring plant polyphenol, isolated from water caltrop, which has been reported to exert anticancer effects. The present study investigated the antiproliferative effects of GA on the HepG2 and SMMC-7721 human hepatocellular carcinoma (HCC) cell lines using MTT and colony formation assays. In particular, the underlying mechanism of GA-induced apoptosis in SMMC-7721 cells was studied in vitro by flow cytometry and western blotting. The results of the present study indicated that GA was capable of inhibiting the proliferation of HepG2 and SMMC-7721 cells in a time- and dose-dependent manner, as well as inducing the apoptosis of SMMC-7721 cells. GA induced caspase-3, caspase-9 and reactive oxygen species activity, elevated the expression of apoptosis regulator Bcl-2-like protein 4 and reduced the mitochondrial membrane potential in SMMC-7721 cells. When compared with HL-7702 normal human hepatocytes, GA demonstrated selective toxicity for HCC cells. In conclusion, GA is able to induce apoptosis in SMMC-7721 cells in vitro via mitochondrial-mediated pathways, and may possess the potential to be a novel therapeutic compound for use in the treatment of HCC. PMID:26870182

  1. The disulfide compound α-lipoic acid and its derivatives: A novel class of anticancer agents targeting mitochondria.

    PubMed

    Dörsam, Bastian; Fahrer, Jörg

    2016-02-01

    The endogenous disulfide α-lipoic acid (LA) is an essential mitochondrial co-factor. In addition, LA and its reduced counterpart dihydro lipoic acid form a potent redox couple with antioxidative functions, for which it is used as dietary supplement and therapeutic. Recently, it has gained attention due to its cytotoxic effects in cancer cells, which is the key aspect of this review. We initially recapitulate the dietary occurrence, gastrointestinal absorption and pharmacokinetics of LA, illustrating its diverse antioxidative mechanisms. We then focus on its mode of action in cancer cells, in which it triggers primarily the mitochondrial pathway of apoptosis, whereas non-transformed primary cells are hardly affected. Furthermore, LA impairs oncogenic signaling and displays anti-metastatic potential. Novel LA derivatives such as CPI-613, which target mitochondrial energy metabolism, are described and recent pre-clinical studies are presented, which demonstrate that LA and its derivatives exert antitumor activity in vivo. Finally, we highlight clinical studies currently performed with the LA analog CPI-613. In summary, LA and its derivatives are promising candidates to complement the arsenal of established anticancer drugs due to their mitochondria-targeted mode of action and non-genotoxic properties.

  2. Synthesis and biological evaluation of boswellic acid-NSAID hybrid molecules as anti-inflammatory and anti-arthritic agents.

    PubMed

    Shenvi, Suvarna; Kiran, K R; Kumar, Krishna; Diwakar, Latha; Reddy, G Chandrasekara

    2015-06-15

    Methyl esters of the β-boswellic acid (BA) and 11-keto-β-boswellic acid (KBA) obtained from Boswellia serrata resin were subjected to Steglich esterification with the different non-steroidal anti-inflammatory drugs (NSAID) viz., ibuprofen, naproxen, diclophenac and indomethacin. The novel hybrids of methyl boswellate (5-8) and that of methyl 11-keto boswellate (9-12) were evaluated for anti-inflammatory activity by carrageenan-induced rat hind paw edema model and anti-arthritic activity by Complete Freund's Adjuvant (CFA) induced arthritis in Wister albino rat. Significant inhibition on carrageenan-induced paw edema has been observed with 5, 6 and 10 where as in CFA induced rats, hybrids 5, 8, 9 and 12 exhibited pronounced antiarthritic activity. Hybrid molecules 5 and 9 have been found to be more effective in inhibiting in-vivo COX-2 than ibuprofen by itself, thus showing the synergistic effect. Hybrid 5 and 9 tested for in-vitro lipoxygenase and cyclooxygenase-2 (LOX/COX-2) inhibitory activity. The studies revealed that both 5 and 9 inhibited COX-2 relatively better than LOX enzyme. PMID:26010018

  3. Magnetically directed poly(lactic acid) [sup 90]Y-microspheres: Novel agents for targeted intracavitary radiotherapy

    SciTech Connect

    Haefeli, U.O.; Sweeney, S.M.; Beresford, B.A.; Sim, E.H.; Macklis, R.M. . Joint Center for Radiation Therapy)

    1994-08-01

    High energy [beta]-emitting radioisotopes like Yttrium-90 have a radiotoxic range of about one centimeter. For cancer treatment they must be brought near the tumor cells and kept there for as long as they are radioactive. The authors developed as carriers for the ionic form of [sup 90]Y a matrix-type polymeric drug delivery system, poly(lactic acid) (PLA) microspheres. This radiopharmaceutical could be selectively delivered to the target site after incorporating 10% Fe[sub 3]O[sub 4] which made the magnetic microspheres (MMS) responsive to an external magnetic field. Furthermore, MMS are biodegradable and slowly hydrolyze into physiologic lactic acid after the radioactivity is completely decayed. Previously prepared 10--40 [mu]m MMS were radiochemically loaded to high specific activity with [sup 90]Y at a pH of 5.7. Stability studies showed that approximately 95% of added [sup 90]Y is retained within the PLA matrix after 28 days (> 10 half-lives) at 37 C in serum, and electron microscopy showed that the microspheres retained their characteristic morphologic appearance for the same time period. Cytotoxicity studies with SK-N-SH neuroblastoma cells growing in monolayer showed that the radiocytotoxicity of the microspheres could be directed magnetically to either kill or spare specific cell populations, thus making them of great interest for targeted intracavitary tumor therapy. The authors are currently optimizing this system for use in the treatment of neoplastic meningitis.

  4. Gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugate of arabinogalactan as a potential liver-targeting magnetic resonance imaging contrast agent.

    PubMed

    Xiao, Yan; Xue, Rong; You, Tianyan; Li, Xiaojing; Pei, Fengkui; Wang, Xuxia; Lei, Hao

    2014-08-18

    A novel biocompatible macromolecule (AG-CM-EDA-DOTA-Gd) was synthesized as a liver magnetic resonance imaging (MRI) contrast agent. AG-CM-EDA-DOTA-Gd consisted of a carboxymethyl-arabinogalactan unit conjugated with gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd-DOTA) via ethylenediamine, and was specifically designed to bind to hepatocyte asialoglycoprotein in vivo, in an effort to develop a potential new tool for the diagnosis of liver diseases. The T1-relaxivity (8.87mmol(-1)Ls(-1)) of AG-CM-EDA-DOTA-Gd was 1.86 times than that of Gd-DOTA (4.76mmol(-1)Ls(-1)) in D2O at 9.4 T and 25°C. MRI experiments showed significant enhancement in rat liver following the intravenous administration of AG-CM-EDA-DOTA-Gd (0.094mmol Gd(3+)/kg body weight), which persisted for longer than Gd-DOTA (0.098mmol Gd(3+)/kg body weight). The mean percentage enhancements in the liver parenchyma were 85.2±6.5% and 19.3±3.3% for AG-CM-EDA-DOTA-Gd and Gd-DOTA, respectively. The results of this study therefore indicate that AG-CM-EDA-DOTA-Gd could be used as a potential liver-targeting contrast agent for MRI.

  5. Single wall carbon nanotube/bis carboxylic acid-ICG as a sensitive contrast agent for in vivo tumor imaging in photoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Zanganeh, Saeid; Li, Hai; Kumavor, Patrick; Alqasemi, Umar; Aguirre, Andres; Mohammad, Innus; Stanford, Courtney; Smith, Michael B.; Zhu, Quing

    2013-03-01

    In this study, we present a novel photoacoustic contrast agent which is based on bis-carboxylic acid derivative of Indocyanine green (ICG) covalently conjugated to single-wall carbon nanotubes (ICG/SWCNT). Covalently attaching ICG to the functionalized SWCNT provides a more robust system that delivers much more ICG to the tumor site. The detection sensitivity of the new contrast agent in mouse tumor model is demonstrated in vivo by our custom built photoacoustic imaging system. PAT summation signal is defined to show the long-term light absorption of tumor areas in ICG injected mice and ICG/SWCNT injected mice. It is shown that ICG is able to provide 33% enhancement at approximately 20 minutes peak response time referred to pre-injection PAT summation level, while ICG/SWCNT provides 128% enhancement at 80 minutes and even higher enhancement of 196% at the end point of experiments (120 minutes on average). Additionally, the ICG/SWCNT enhancement was mainly observed at the tumor periphery as confirmed by fluorescence images of the tumor samples. This feature is highly valuable in guiding surgeons to assess tumor boundaries and dimensions in vivo and improve surgical resection of tumors for achieving clean tumor margins.

  6. Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates.

    PubMed

    Ferraz-Carvalho, Rafaela S; Pereira, Marcela A; Linhares, Leonardo A; Lira-Nogueira, Mariane Cb; Cavalcanti, Isabella Mf; Santos-Magalhães, Nereide S; Montenegro, Lílian Ml

    2016-05-01

    Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 µg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb.

  7. Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates

    PubMed Central

    Ferraz-Carvalho, Rafaela S; Pereira, Marcela A; Linhares, Leonardo A; Lira-Nogueira, Mariane CB; Cavalcanti, Isabella MF; Santos-Magalhães, Nereide S; Montenegro, Lílian ML

    2016-01-01

    Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 µg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb. PMID:27143488

  8. Facile and controllable preparation of mesoporous TiO2 using poly(ethylene glycol) as structure-directing agent and peroxotitanic acid as precursor

    NASA Astrophysics Data System (ADS)

    Nguyen, Dongthanh; Wang, Wei; Long, Haibo; Ru, Hongqiang

    2016-09-01

    This work demonstrated that mesoporous TiO2 (meso-TiO2) with controllable mesoporous and crystalline structures can be facilely prepared by using poly (ethylene glycol) (PEG) as structure-directing (SD) agent and peroxotitanic acid (PTA) as precursor. Meso-TiO2 with high specific surface area (157 m2•g-1), pore volume (0.45 cm3•g-1) and large mesopore size of 13.9 nm can be obtained after calcination at 450°C. Such meso-TiO2 also shows relatively high thermal stability. BET surface area still reaches 114 m2•g-1 after calcination at 550°C. In the synthesis and calcination process, PEG that plays multiple and important roles in delivering thermally stable and tunable mesoporous and crystalline structures shows to be a suitable low-cost SD agent for the controllable preparation of nanocrystalline meso-TiO2. The photocatalytic activity tests show that both high surface area and bi-crystallinity of obtained meso-TiO2 are important in enhancing the performance in photo-decomposing Rhodamine B in water.

  9. Caffeic acid phenethyl ester as a remedial agent for reproductive functions and oxidative stress-based pathologies of gonads.

    PubMed

    Akyol, Sumeyya; Akbas, Ali; Butun, Ilknur; Toktas, Muhsin; Ozyurt, Huseyin; Sahin, Semsettin; Akyol, Omer

    2015-01-01

    In recent years, the studies on the roles of caffeic acid phenethyl ester (CAPE) in several disease models and cell cultures are tremendously growing. It is such a great molecule that was used by ancient times to ameliorate some diseases and nowadays, it is used by modern medicine to test the effectiveness. In this mini-review article, the protection capability of CAPE, as a liposoluble antioxidant and a potent nuclear factor kappa B inhibitor, on oxidative and non-oxidative ovary, and testis damages has been summarized. In view of our laboratory findings/experience and those reported in the hitherto literature, we suggest that CAPE possesses protective effects for pathologies of the reproductive organs induced by untoward effects of harmful molecules such as free oxygen radicals, pesticides, methotrexate, and MK-801 (dizocilpine). PMID:26401405

  10. Effect of silanecoupling agent on properties of biocomposites based on poly(lactic acid)and durian rind cellulose

    NASA Astrophysics Data System (ADS)

    Penjumras, P.; AbdulRahman, R.; Talib, R. A.; Abdan, K.

    2016-07-01

    Durian rind cellulose reinforced poly(lactic acid) (PLA) biocomposites were prepared using Brabender internal mixer followed by hot compression molding technique. Cellulose was previously treated by 3-aminopropyltriethoxysilane for improving the compatibility with PLA matrix. The silane-grafting of cellulose was confirmed via Fourier transform infrared spectroscopy (FTIR) with the presence of Si-O-Si, Si-C, and Si-O-C bonds. The silane-treated cellulose was subsequently introduced into PLA matrix, and the effects of cellulose surface modification on mechanical, thermal and morphological properties, and water absorption of biocomposites were studied. It was found that silane-treated cellulose reinforced biocompositeshave superior mechanical properties compared with untreated cellulose reinforced biocomposites. The lowest crystallization temperature of silane-treated biocomposites was confirmed via Differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) investigation also showed that adhesion of cellulose and PLA matrix was improved by modification of cellulosesurfaceusing3-aminopropyltriethoxysilanewhich can result in less water absorption into biocomposites.

  11. Design, synthesis, and molecular hybrids of caudatin and cinnamic acids as novel anti-hepatitis B virus agents.

    PubMed

    Wang, Li-Jun; Geng, Chang-An; Ma, Yun-Bao; Luo, Jie; Huang, Xiao-Yan; Chen, Hao; Zhou, Ning-Jia; Zhang, Xue-Mei; Chen, Ji-Jun

    2012-08-01

    Forty-six conjugated derivatives of caudatin with substituted cinnamic acids were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the derivatives exhibited potent anti-HBV activity, especially inhibiting the HBV DNA replication with the IC(50) values from 2.44 to 22.89 μΜ. Compound 18 showed significant activity against the secretion of HBsAg, HBeAg, and HBV DNA replication with IC(50) values of 5.52, 5.52, 2.44 μΜ, respectively, and had good safety (LD(50) > 1250 mg/kg) according to the acute toxicity study. Preliminary mechanism investigation suggested that compound 18 exerted antivirus effects via interfering HBV X promoter and enhancer I to influence HBV transcriptions.

  12. 18β-Glycyrrhetinic Acid Derivatives Possessing a Trihydroxylated A Ring Are Potent Gram-Positive Antibacterial Agents.

    PubMed

    Huang, Li-Rong; Hao, Xiao-Jiang; Li, Qi-Ji; Wang, Dao-Ping; Zhang, Jian-Xin; Luo, Heng; Yang, Xiao-Sheng

    2016-04-22

    The oleanane-type triterpene 18β-glycyrrhetinic acid (1) was modified chemically through the introduction of a trihydroxylated A ring and an ester moiety at C-20 to enhance its antibacterial activity. Compounds 22, 23, 25, 28, 29, 31, and 32 showed more potent inhibitory activity against Streptomyces scabies than the positive control, streptomycin. Additionally, the inhibitory activity of the most potent compound, 29, against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was greater than that of the positive controls. The antibacterial mode of action of the active derivatives involved the regulation of the expression of genes associated with peptidoglycans, the respiratory metabolism, and the inherent virulence factors found in bacteria, as determined through a quantitative real-time reverse transcriptase PCR assay.

  13. Elucidation on enhanced application of synthesised kojic acid immobilised magnetic and chitosan tri-polyphosphate nanoparticles as antibacterial agents.

    PubMed

    Chaudhary, Jignesh; Lakhawat, Sudarshan; Pathak, Amrendra Nath

    2015-12-01

    Kojic acid (KA) is a secondary metabolite which is secreted by several aspergillus species. It is a multi-functional skeleton from which many derivatives can be synthesised and applied in various areas of biotechnology. KA grafting on synthesised magnetic nanoparticles (MNPs) and chitosan tri-polyphosphate (chitosan-TPP) nanoparticles was successfully done and characterised by Fourier transformation infrared spectroscopy. It was observed that amino propyl triethoxy silane-coated MNPs and chitosan-TPP nanoparticles enhanced the antibacterial activity of KA against both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa). The organic constitution and significant antibacterial activity of KA-chitosan-TPP nanoparticles can be applicable in the field of medical biotechnology.

  14. Caffeic Acid Phenethyl Ester as a Protective Agent against Nephrotoxicity and/or Oxidative Kidney Damage: A Detailed Systematic Review

    PubMed Central

    Akyol, Sumeyya; Ugurcu, Veli; Altuntas, Aynur; Hasgul, Rukiye; Cakmak, Ozlem

    2014-01-01

    Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been attracting the attention of different medical and pharmaceutical disciplines in recent years because of its antioxidant, anti-inflammatory, antiproliferative, cytotoxic, antiviral, antifungal, and antineoplastic properties. One of the most studied organs for the effects of CAPE is the kidney, particularly in the capacity of this ester to decrease the nephrotoxicity induced by several drugs and the oxidative injury after ischemia/reperfusion (I/R). In this review, we summarized and critically evaluated the current knowledge regarding the protective effect of CAPE in nephrotoxicity induced by several special medicines such as cisplatin, doxorubicin, cyclosporine, gentamycin, methotrexate, and other causes leading to oxidative renal injury, namely, I/R models and senility. PMID:25003138

  15. Lactic acid and thermal treatments trigger the hydrolysis of myo-inositol hexakisphosphate and modify the abundance of lower myo-inositol phosphates in barley (Hordeum vulgare L.).

    PubMed

    Metzler-Zebeli, Barbara U; Deckardt, Kathrin; Schollenberger, Margit; Rodehutscord, Markus; Zebeli, Qendrim

    2014-01-01

    Barley is an important source of dietary minerals, but it also contains myo-inositol hexakisphosphate (InsP6) that lowers their absorption. This study evaluated the effects of increasing concentrations (0.5, 1, and 5%, vol/vol) of lactic acid (LA), without or with an additional thermal treatment at 55°C (LA-H), on InsP6 hydrolysis, formation of lower phosphorylated myo-inositol phosphates, and changes in chemical composition of barley grain. Increasing LA concentrations and thermal treatment linearly reduced (P<0.001) InsP6-phosphate (InsP6-P) by 0.5 to 1 g compared to the native barley. In particular, treating barley with 5% LA-H was the most efficient treatment to reduce the concentrations of InsP6-P, and stimulate the formation of lower phosphorylated myo-inositol phosphates such as myo-inositol tetraphosphate (InsP4) and myo-inositol pentaphosphates (InsP5). Also, LA and thermal treatment changed the abundance of InsP4 and InsP5 isomers with Ins(1,2,5,6)P4 and Ins(1,2,3,4,5)P5 as the dominating isomers with 5% LA, 1% LA-H and 5% LA-H treatment of barley, resembling to profiles found when microbial 6-phytase is applied. Treating barley with LA at room temperature (22°C) increased the concentration of resistant starch and dietary fiber but lowered those of total starch and crude ash. Interestingly, total phosphorus (P) was only reduced (P<0.05) in barley treated with LA-H but not after processing of barley with LA at room temperature. In conclusion, LA and LA-H treatment may be effective processing techniques to reduce InsP6 in cereals used in animal feeding with the highest degradation of InsP6 at 5% LA-H. Further in vivo studies are warranted to determine the actual intestinal P availability and to assess the impact of changes in nutrient composition of LA treated barley on animal performance.

  16. Lactic Acid and Thermal Treatments Trigger the Hydrolysis of Myo-Inositol Hexakisphosphate and Modify the Abundance of Lower Myo-Inositol Phosphates in Barley (Hordeum vulgare L.)

    PubMed Central

    Metzler-Zebeli, Barbara U.; Deckardt, Kathrin; Schollenberger, Margit; Rodehutscord, Markus; Zebeli, Qendrim

    2014-01-01

    Barley is an important source of dietary minerals, but it also contains myo-inositol hexakisphosphate (InsP6) that lowers their absorption. This study evaluated the effects of increasing concentrations (0.5, 1, and 5%, vol/vol) of lactic acid (LA), without or with an additional thermal treatment at 55°C (LA-H), on InsP6 hydrolysis, formation of lower phosphorylated myo-inositol phosphates, and changes in chemical composition of barley grain. Increasing LA concentrations and thermal treatment linearly reduced (P<0.001) InsP6-phosphate (InsP6-P) by 0.5 to 1 g compared to the native barley. In particular, treating barley with 5% LA-H was the most efficient treatment to reduce the concentrations of InsP6-P, and stimulate the formation of lower phosphorylated myo-inositol phosphates such as myo-inositol tetraphosphate (InsP4) and myo-inositol pentaphosphates (InsP5). Also, LA and thermal treatment changed the abundance of InsP4 and InsP5 isomers with Ins(1,2,5,6)P4 and Ins(1,2,3,4,5)P5 as the dominating isomers with 5% LA, 1% LA-H and 5% LA-H treatment of barley, resembling to profiles found when microbial 6-phytase is applied. Treating barley with LA at room temperature (22°C) increased the concentration of resistant starch and dietary fiber but lowered those of total starch and crude ash. Interestingly, total phosphorus (P) was only reduced (P<0.05) in barley treated with LA-H but not after processing of barley with LA at room temperature. In conclusion, LA and LA-H treatment may be effective processing techniques to reduce InsP6 in cereals used in animal feeding with the highest degradation of InsP6 at 5% LA-H. Further in vivo studies are warranted to determine the actual intestinal P availability and to assess the impact of changes in nutrient composition of LA treated barley on animal performance. PMID:24967651

  17. Comparison of the concentration-effect relationship of a local antiinflammatory agent and oral acetylsalicylic acid: the value of local application.

    PubMed

    Poisson, M; Ralambosoa, C; Blehaut, H; Astoin, J

    1985-01-01

    Using a pharmacological model, the comparison between acetylsalicylic acid (ASA), administered orally, and a solution combining two salicylate derivatives (ethyl 5-methoxy-salicylate and 3-phenyl-propyl-salicylate), applied locally, demonstrated the value of the local application. Indeed, the pharmacological activity was highly significant and directly related to the tissue concentration of salicyl ions, which was higher after local application of the solution than after oral administration of ASA. The local solution also resulted in a lower plasma concentration of salicylate ions, allowing high plasma salicylate concentrations to be avoided. PMID:4074414

  18. Non-surgical treatment of deep wounds triggered by harmful physical and chemical agents: a successful combined use of collagenase and hyaluronic acid.

    PubMed

    Onesti, Maria G; Fino, Pasquale; Ponzo, Ida; Ruggieri, Martina; Scuderi, Nicolò

    2016-02-01

    Some chronic ulcers often occur with slough, not progressing through the normal stages of wound healing. Treatment is long and other therapies need to be performed in addition to surgery. Patients not eligible for surgery because of ASA class (American Society of Anesthesiologists class) appear to benefit from chemical therapy with collagenase or hydrocolloids in order to prepare the wound bed, promoting the healing process. We describe four cases of traumatic, upper limb deep wounds caused by different physical and chemical agents, emphasising the effectiveness of treatment based on topical application of collagenase and hyaluronic acid (HA) before standardised surgical procedures. We performed careful disinfection of lesions combined with application of topical cream containing hyaluronic acid, bacterial fermented sodium hyaluronate (0·2%w/w) salt, and bacterial collagenase obtained from non-pathogenic Vibrio alginolyticus (>2·0 nkat1/g). In one patient a dermo-epidermal graft was used to cover the wide loss of substance. In two patients application of a HA-based dermal substitute was done. We obtained successful results in terms of wound healing, with satisfactory aesthetic result and optimal recovery of the affected limb functionality. Topical application of collagenase and HA, alone or before standardised surgical procedures allows faster wound healing. PMID:24698215

  19. A Drug-Repositioning Screening Identifies Pentetic Acid as a Potential Therapeutic Agent for Suppressing the Elastase-Mediated Virulence of Pseudomonas aeruginosa

    PubMed Central

    Gi, Mia; Jeong, Junhui; Lee, Keehoon; Lee, Kang-Mu; Toyofuku, Masanori; Yong, Dong Eun

    2014-01-01

    Pseudomonas aeruginosa, a Gram-negative bacterium of clinical significance, produces elastase as a predominant exoprotease. Here, we screened a library of chemical compounds currently used for human medication and identified diethylene triamine penta-acetic acid (DTPA, pentetic acid) as an agent that suppresses the production of elastase. Elastase activity found in the prototype P. aeruginosa strain PAO1 was significantly decreased when grown with a concentration as low as 20 μM DTPA. Supplementation with Zn2+ or Mn2+ ions restored the suppressive effect of DTPA, suggesting that the DTPA-mediated decrease in elastase activity is associated with ion-chelating activity. In DTPA-treated PAO1 cells, transcription of the elastase-encoding lasB gene and levels of the Pseudomonas quinolone signal (PQS), a molecule that mediates P. aeruginosa quorum sensing (QS), were significantly downregulated, reflecting the potential involvement of the PQS QS system in DTPA-mediated elastase suppression. Biofilm formation was also decreased by DTPA treatment. When A549 alveolar type II-like adenocarcinoma cells were infected with PAO1 cells in the presence of DTPA, A549 cell viability was substantially increased. Furthermore, the intranasal delivery of DTPA to PAO1-infected mice alleviated the pathogenic effects of PAO1 cells in the animals. Together, our results revealed a novel function for a known molecule that may help treat P. aeruginosa airway infection. PMID:25246397

  20. Interaction of thalidomide, phthalimide analogues of thalidomide and pentoxifylline with the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid: concomitant reduction of serum tumour necrosis factor-alpha and enhancement of anti-tumour activity.

    PubMed Central

    Ching, L. M.; Browne, W. L.; Tchernegovski, R.; Gregory, T.; Baguley, B. C.; Palmer, B. D.

    1998-01-01

    DMXAA (5,6-dimethylxanthenone-4-acetic acid), a novel anti-tumour agent currently undergoing clinical evaluation, appears to mediate its anti-tumour effects through immune modulation and the production of the cytokine tumour necrosis factor-alpha (TNF). Our previous studies have shown that thalidomide, a potent inhibitor of TNF biosynthesis that has numerous biological effects, including inhibition of tumour angiogenesis, unexpectedly augments the anti-tumour response in mice to DMXAA. We show here that thalidomide (100 mg kg(-1)) has no effect when administered with inactive doses of DMXAA, and that it must be given simultaneously with an active dose of DMXAA to have its maximum potentiating effect on the growth of the murine Colon 38 adenocarcinoma. To address the issue of whether inhibition of serum TNF production is important for potentiation of anti-tumour activity, we have tested three potent analogues of thalidomide. All three analogues, when co-administered with DMXAA to mice at doses lower than those used with thalidomide, inhibited TNF production and were effective in potentiating the anti-tumour activity of DMXAA against transplanted Colon 38 tumours. One of the analogues, N-phenethyltetrafluorophthalimide, was 1000-fold more potent than thalidomide and at a dose of 0.1 mg kg(-1) in combination with DMXAA (30 mg kg(-1)) cured 100% of mice, compared with 67% for the group treated with DMXAA alone. We also tested pentoxifylline and found it to suppress TNF production in response to DMXAA and to potentiate the anti-tumour effect of DMXAA. The results are compatible with the hypothesis that pharmacological reduction of serum TNF levels might benefit the anti-tumour effects of DMXAA and suggest new strategies for therapy using this agent. PMID:9703279

  1. An special epithelial staining agents: folic acid receptor-mediated diagnosis (FRD) effectively and conveniently screen patients with cervical cancer.

    PubMed

    Lu, Meng-Han; Hu, Ling-Yun; Du, Xin-Xin; Yang, Min; Zhang, Wei-Yi; Huang, Ke; Li, Li-An; Jiang, Shu-Fang; Li, Ya-Li

    2015-01-01

    High-quality screening with cytology has markedly reduced mortality from cervical cancer. However, it needs experienced pathologists to review and make the final decisions. We have developed folic acid receptor-mediated diagnosis (FRD) kits to effectively and conveniently screen patients with cervical cancer. We conduct present study aim to assess clinical significances of FRD in screening cervical cancer. A total of 169 patients were enrolled at Chinese People's liberation Army (PLA) general hospital. We compared diagnostic significances of FRD with thinprep cytology test (TCT). Meanwhile, colposcopy was also performed to confirm any lesion suspicious for cervical cancer. The sensitivity and specificity of FRD were 71.93% and 66.07% in diagnosis cervical cancer, respectively. Meanwhile, the positive predictive values (PPV), negative predictive values (NPV), Youden index were 51.90%, 82.22%, 0.38, respectively. On the other hand, the sensitivity and specificity of TCT in diagnosis cervical cancer were 73.68% and 61.61% respectively. PPV, NPV and Youden index for TCT were 49.41%, 82.14% and 0.35 respectively. Overall, FRD have high values of sensitivity, specificity and Youden index. However, this difference failed to statistical significance. FRD have comparable diagnostic significance with TCT. Therefore, FRD might serve as one effective method to screen cervical cancer. Especially for those patients living in remote regions of China, where cytology was unavailable.

  2. Injectable poly-L: -lactic acid: a novel sculpting agent for the treatment of dermal fat atrophy after severe acne.

    PubMed

    Sadove, Richard

    2009-01-01

    Acne vulgaris affects up to 80% of people 11 to 30 years of age, and scarring can occur for up to 95% of these patients. Scarring may be pitted or hypertrophic in nature, although in most cases it is atrophic. Atrophic acne scarring follows dermal collagen and fat loss after moderate to severe acne infection. Injectable poly-L-acid (PLLA) is a biocompatible, biodegradable, synthetic polymer device that is hypothesized to enhance dermal volume via the endogenous production of fibroblasts and, subsequently, collagen. The gradual improvements in cutaneous volume observed after treatment with injectable PLLA have been noted to last up to 2 years. The case studies presented describe the use of injectable PLLA to correct dermal fat loss in macular atrophic acne scarring of the cheeks. Two female patients underwent three treatment sessions with injectable PLLA over a 12-week period. At each treatment session, the reconstituted product was injected into the deep dermis under the depressed portion of the scar. Both patients were extremely pleased with their results at, respectively, 1- and 4-year follow-up evaluations. Patients experienced minimal swelling and redness after injection and no product-related adverse events such as papule and/or nodule formation. The author believes these data suggest that injectable PLLA is a good treatment option for the correction of macular atropic scarring with thin dermis (off-label use), particularly compared with other injectable fillers currently used for this indication that have shorter durations of effect. PMID:18923863

  3. Grape seeds proanthocyanidin extract as a hepatic-reno-protective agent against gibberellic acid induced oxidative stress and cellular alterations.

    PubMed

    Hassan, Hanaa A; Al-Rawi, Maisaa M

    2013-08-01

    The present study aims to investigate the heptonephro-protective effect of grape seeds proanthocyanidin extract (GSPE) against the risks induced by gibberellic acid (GA3) in male rats. The results recorded that GA3 caused a significant increase in total lipids, total cholesterol, triglycerides and LDL-C levels in serum, concomitant with a significant decrease in serum HDL-C. A significant increase in serum AST, ALT, urea and creatinine, while, a significant decrease in total protein content in serum was observed in rats given GA3. Hepatic and renal lipid peroxidation product (MDA) was significantly increased, meanwhile, total antioxidant capacity (TAC), glutathione, and catalase levels were significantly decreased. In addition, there was a negative change in liver structure including dilatation in the central veins with degeneration of endothelium cells and cellular injury around the veins as well as in the kidney structure such as lesion in both glomeruli and tubules, detachment of the Malpighian corpuscles from the Bowman's capsule's epithelium, shrinkage in the glomerular capillary network. However, almost all of these adverse effects seemed to be ameliorated by oral administration of GSPE with GA3 to rats for 2 month indicating the protective effect of grape seeds GSPE on GA3 induced oxidative stress in rats. PMID:23135702

  4. 5,6-Dimethylxanthenone-4-acetic acid in the treatment of refractory tumors: a phase I safety study of a vascular disrupting agent.

    PubMed

    McKeage, Mark J; Fong, Peter; Jeffery, Mark; Baguley, Bruce C; Kestell, Phil; Ravic, Miroslav; Jameson, Michael B

    2006-03-15

    This phase I safety study aimed to identify the optimal dose of the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) for combination studies. Using a crossover design, 15 patients with refractory tumors were allocated randomly to receive six sequential doses of DMXAA (300, 600, 1,200, 1,800, 2,400, and 3,000 mg m(-2)), each given once-weekly as a 20-minute i.v. infusion. The drug was generally well tolerated. Transient, moderate increases in the heart rate-corrected cardiac QT interval occurred at the two highest doses. DMXAA produced transient dose-dependent increases in blood pressure. Transient, dose-related visual disturbances occurred at the two highest doses. No significant changes in K(trans) and k(ep) were observed but V(e), a secondary dynamic contrast-enhanced magnetic resonance imaging variable, increased significantly after giving DMXAA. At 1,200 mg m(-2), the Cmax and the area under the concentration-time curve over 24 hours for total and free DMXAA plasma concentrations were 315 +/- 25.8 microg/mL, 29 +/- 6.4 microg/mL x d, 8.0 +/- 1.77 microg/mL, and 0.43 +/- 0.07 microg/mL x d, respectively. Plasma levels of the vascular damage biomarker 5-hydroxyindoleacetic acid increased in the 4 hours after treatment in a dose-dependent fashion up to 1,200 mg m(-2), with a plateau thereafter. Doses in the range of 1,200 mg m(-2) have been selected for further studies (phase II combination studies with taxanes and platins are under way) because this dose produced no significant effect on heart rate-corrected cardiac QT interval, produced near maximum levels of 5-hydroxyindoleacetic acid, achieved DMXAA plasma concentrations within the preclinical therapeutic range, and was well tolerated. PMID:16551862

  5. Lower cytotoxicity, high stability, and long-term antibacterial activity of a poly(methacrylic acid)/isoniazid/rifampin nanogel against multidrug-resistant intestinal Mycobacterium tuberculosis.

    PubMed

    Chen, Tao; Li, Qiang; Guo, Lina; Yu, Li; Li, Zhenyan; Guo, Huixin; Li, Haicheng; Zhao, Meigui; Chen, Liang; Chen, Xunxun; Zhong, Qiu; Zhou, Lin; Wu, Ting

    2016-01-01

    To overcome the undesirable side effects and reduce the cytotoxicity of isoniazid (INH) and rifampin (RMP) in the digestive tract, a poly(methacrylic acid) (PMAA) nanogel was developed as a carrier of INH and RMP. This PMAA/INH/RMP nanogel was prepared as a treatment for intestinal tuberculosis caused by multidrug-resistant Mycobacterium tuberculosis (MTB). The morphology, size, and in vitro release properties were evaluated in a simulated gastrointestinal medium, and long-term antibacterial performance, cytotoxicity, stability, and activity of this novel PMAA/INH/RMP nanogel against multidrug-resistant MTB in the intestine were investigated. Our results indicate that the PMAA/INH/RMP nanogel exhibited extended antibacterial activity by virtue of its long-term release of INH and RMP in the simulated gastrointestinal medium. Further, this PMAA/INH/RMP nanogel exhibited lower cytotoxicity than did INH or RMP alone, suggesting that this PMAA/INH/RMP nanogel could be a more useful dosage form than separate doses of INH and RMP for intestinal MTB. The novel aspects of this study include the cytotoxicity study and the three-phase release profile study, which might be useful for other researchers in this field.

  6. Retinoic acid-inducible gene-I-like receptor (RLR)-mediated antiviral innate immune responses in the lower respiratory tract: Roles of TRAF3 and TRAF5.

    PubMed

    Chiba, Yuki; Matsumiya, Tomoh; Satoh, Tsugumi; Hayakari, Ryo; Furudate, Ken; Xing, Fei; Yoshida, Hidemi; Tanji, Kunikazu; Mizukami, Hiroki; Imaizumi, Tadaatsu; Ito, Etsuro

    2015-11-13

    Upon viral infection, the cytoplasmic viral sensor retinoic acid-inducible gene-I (RIG-I) recognizes viral RNA to activate antiviral signaling to induce type I interferon (IFN). RIG-I-like receptors (RLRs) activate antiviral signaling in a tissue-specific manner. The molecular mechanism underlying antiviral signaling in the respiratory system remains unclear. We studied antiviral signaling in the lower respiratory tract (LRT), which is the site of many harmful viral infections. Epithelial cells of the LRT can be roughly divided into two groups: bronchial epithelial cells (BECs) and pulmonary alveolar epithelial cells (AECs). These two cell types exhibit different phenotypes; therefore, we hypothesized that these cells may play different roles in antiviral innate immunity. We found that BECs exhibited higher antiviral activity than AECs. TNF receptor-associated factor 3 (TRAF3) has been shown to be a crucial molecule in RLR signaling. The expression levels of TRAF3 and TRAF5, which have conserved domains that are nearly identical, in the LRT were examined. We found that the bronchus exhibited the highest expression levels of TRAF3 and TRAF5 in the LRT. These findings suggest the importance of the bronchus in antiviral innate immunity in the LRT and indicate that TRAF3 and TRAF5 may contribute to RLR signaling. PMID:26454171

  7. Delayed gastric emptying rate as a potential mechanism for lowered glycemia after eating sourdough bread: studies in humans and rats using test products with added organic acids or an organic salt.

    PubMed

    Liljeberg, H G; Björck, I M

    1996-12-01

    The possible effects of organic acids or an organic salt on the rate of gastric emptying was studied to identify the cause for reduced postmeal responses of blood glucose and insulin to foods containing such components, eg, sourdough bread. Paracetamol was included in bread products with added lactic acid or sodium propionate and used as a marker for the rate of gastric emptying in healthy subjects. In parallel, postprandial glycemia, insulinemia, and satiety were evaluated. The influence of lactic acid, propionic acid, and sodium propionate was also studied in rats after they were tube-fed with glucose solutions. The bread products with lactic acid or sodium propionate both lowered blood glucose and insulin responses. The bread with sodium propionate also prolonged satiety. The reason for the lowered metabolic responses with sodium propionate was probably a lowered gastric emptying rate, as judged from reduced blood paracetamol concentrations; there was no such effect observed with bread with added lactic acid. A similar amount of lactic acid in solution tube-fed to rats did not affect the disappearance of glucose from the stomach. In contrast with the finding in humans, sodium propionate had no effect on the rate of gastric emptying in rats whereas an equimolar solution of propionic acid reduced gastric emptying rate in rats. Possibly, less of this acid was produced in the gastric contents after a bolus load of a sodium propionate solution (in rats) than in an eating situation. Also, the pH and/or the osmolarity may be important, and when provided in excessive amounts, lactic acid reduced the gastric emptying rate in rats. A hydrochloric acid solution of similar pH was much less effective in this respect.

  8. Targeting cancer stem cells in glioblastoma multiforme using mTOR inhibitors and the differentiating agent all-trans retinoic acid.

    PubMed

    Friedman, Marissa D; Jeevan, Dhruve S; Tobias, Michael; Murali, Raj; Jhanwar-Uniyal, Meena

    2013-10-01

    Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, portends a poor prognosis despite current treatment modalities. Recurrence of tumor growth is attributed to the presence of treatment-resistant cancer stem cells (CSCs). The targeting of these CSCs is therefore essential in the treatment of this disease. Mechanistic target of rapamycin (mTOR) forms two multiprotein complexes, mTORC1 and mTORC2, which regulate proliferation and migration, respectively. Aberrant function of mTOR has been shown to be present in GBM CSCs. All-trans retinoic acid (ATRA), a derivative of retinol, causes differentiation of CSCs as well as normal neural progenitor cells. The purpose of this investigation was to delineate the role of mTOR in CSC maintenance, and to establish the mechanism of targeting GBM CSCs using differentiating agents along with inhibitors of the mTOR pathways. The results demonstrated that ATRA caused differentiation of CSCs, as demonstrated by the loss of the stem cell marker Nestin. These observations were confirmed by western blotting, which demonstrated a time-dependent decrease in Nestin expression following ATRA treatment. This effect occurred despite combination with mTOR (rapamycin), PI3K (LY294002) and MEK1/2 (U0126) inhibitors. Expression of activated extracellular signal-regulated kinase 1/2 (pERK1/2) was enhanced following treatment with ATRA, independent of mTOR pathway inhibitors. Proliferation of CSCs, determined by neurosphere diameter, was decreased following treatment with ATRA alone and in combination with rapamycin. The motility of GBM cells was mitigated by treatment with ATRA, rapamycin and LY29002 alone. However, combination treatment augmented the inhibitory effect on migration suggesting synergism. These findings indicate that ATRA-induced differentiation is mediated via the ERK1/2 pathway, and underscores the significance of including differentiating agents along with inhibitors of mTOR pathways in the treatment of GBM.

  9. Potent and sustained cellular inhibition of miR-122 by lysine-derivatized peptide nucleic acids (PNA) and phosphorothioate locked nucleic acid (LNA)/2'-O-methyl (OMe) mixmer anti-miRs in the absence of transfection agents

    PubMed Central

    Torres, Adrian G.; Threlfall, Richard N.

    2011-01-01

    Efficient cell delivery of antisense oligonucleotides (ONs) is a key issue for their potential therapeutic use. It has been shown recently that some ONs can be delivered into cells without the use of transfection agents (gymnosis), but this generally requires cell incubation over several days and high amounts of ONs (micromolar concentrations). Here we have targeted microRNA 122 (miR-122), a small non-coding RNA involved in regulation of lipid metabolism and in the replication of hepatitis C virus, with ONs of different chemistries (anti-miRs) by gymnotic delivery in cell culture. Using a sensitive dual-luciferase reporter assay, anti-miRs were screened for their ability to enter liver cells gymnotically and inhibit miR-122 activity. Efficient miR-122 inhibition was obtained with cationic PNAs and 2'-O-methyl (OMe) and Locked Nucleic Acids (LNA)/OMe mixmers containing either phosphodiester (PO) or phosphorothioate (PS) linkages at sub-micromolar concentrations when incubated with cells for just 4 hours. Furthermore, PNA and PS-containing anti-miRs were able to sustain miR-122 inhibitory effects for at least 4 days. LNA/OMe PS anti-miRs were the most potent anti-miR chemistry tested in this study, an ON chemistry that has been little exploited so far as anti-miR agents towards therapeutics. PMID:22567190

  10. Gd(DOTAla): a single amino acid Gd-complex as a modular tool for high relaxivity MR contrast agent development.

    PubMed

    Boros, Eszter; Polasek, Miloslav; Zhang, Zhaoda; Caravan, Peter

    2012-12-01

    MR imaging at high magnetic fields benefits from an increased signal-to-noise ratio; however T(1)-based MR contrast agents show decreasing relaxivity (r(1)) at higher fields. High field, high relaxivity contrast agents can be designed by carefully controlling the rotational dynamics of the molecule. To this end, we investigated applications of the alanine analogue of Gd(DOTA), Gd(DOTAla). Fmoc-protected DOTAla suitable for solid phase peptide synthesis was synthesized and integrated into polypeptide structures. Gd(III) coordination results in very rigid attachment of the metal chelate to the peptide backbone through both the amino acid side chain and coordination of the amide carbonyl. Linear and cyclic monomers (GdL1, GdC1), dimers (Gd(2)L2, Gd(2)C2), and trimers (Gd(3)L3, Gd(3)C3) were prepared and relaxivities were determined at different field strengths ranging from 0.47 to 11.7 T. Amide carbonyl coordination was indirectly confirmed by determination of the hydration number q for the EuL1 integrated into a peptide backbone, q = 0.96 ± 0.09. The water residency time of GdL1 at 37 °C was optimal for relaxivity, τ(M) = 17 ± 2 ns. Increased molecular size leads to increased per Gd relaxivity (from r(1) = 7.5 for GdL1 to 12.9 mM(-1) s(-1) for Gd(3)L3 at 1.4 T, 37 °C). The cyclic, multimeric derivatives exhibited slightly higher relaxivities than the corresponding linearized multimers (Gd(2)C2: r(1) = 10.5 mM(-1) s(-1) versus Gd(2)C2-red r(1) = 9 mM(-1) s(-1) at 1.4 T, 37 °C). Overall, all six synthesized Gd complexes had higher relaxivities at low, intermediate, and high fields than the clinically used small molecule contrast agent [Gd(HP-DO3A)(H(2)O)].

  11. Gd(DOTAla) – A single amino acid Gd-complex as a modular tool for high relaxivity MR contrast agent development

    PubMed Central

    Boros, Eszter; Polasek, Miloslav; Zhang, Zhaoda; Caravan, Peter

    2012-01-01

    MR imaging at high magnetic fields benefits from an increased signal to noise ratio, however T1 based MR contrast agents show decreasing relaxivity (r1) at higher fields. High field, high relaxivity contrast agents can be designed by carefully controlling the rotational dynamics of the molecule. To this end, we investigated applications of the alanine analogue of Gd(DOTA), Gd(DOTAla). Fmoc protected DOTAla suitable for solid phase peptide synthesis was synthesized and integrated into polypeptide structures. Gd(III) coordination results in very rigid attachment of the metal chelate to the peptide backbone through both the amino acid sidechain and coordination of the amide carbonyl. Linear and cyclic monomers (GdL1, GdC1), dimers (Gd2L2, Gd2C2) and trimers (Gd3L3, Gd3C3) were prepared and relaxivities were determined at different field strengths ranging from 0.47T to 11.7T. Amide carbonyl coordination was indirectly confirmed by determination of the hydration number q for the EuL1 integrated into a peptide backbone, q = 0.96±0.09. The water residency time of GdL1 at 37 °C was optimal for relaxivity, τM=17±2 ns. Increased molecular size leads to increased per Gd relaxivity (from r1 = 7.5 for GdL1 to 12.9 mM−1s−1 for Gd3L3 at 1.4T, 37 °C). The cyclic, multimeric derivatives exhibited slightly higher relaxivities than the corresponding linearized multimers (Gd2C2: r1 = 10.5 mM−1 s−1 versus Gd2C2-red r1 = 9 mM−1s−1 at 1.4T, 37 °C). Overall, all six synthesized Gd complexes had higher relaxivities at low, intermediate and high fields than the clinically used small molecule contrast agent [Gd(HP-DO3A)(H2O)]. PMID:23157602

  12. Retinoic acid conjugates as potential antitumor agents: synthesis and biological activity of conjugates with Ara-A, Ara-C, 3(2H)-furanone, and aniline mustard moieties.

    PubMed

    Manfredini, S; Simoni, D; Ferroni, R; Bazzanini, R; Vertuani, S; Hatse, S; Balzarini, J; De Clercq, E

    1997-11-01

    In a dual targeting approach, to explore the ability of tretinoin (all-trans-retinoic acid) to behave as a covalent carrier for cytotoxic entities, conjugates of retinoic acid with a few representative molecules, being important examples of antitumor pharmacophores (i.e., nucleoside analogues and alkylating agents), have been synthesized and tested for their cytostatic and differentiating activity. All compounds were stable to in vitro hydrolysis in human plasma and more lipophilic than the parent compounds, thus consenting enhanced uptake into the cells. Among the nucleoside analogues the Ara-C derivatives 3 and 6 and the Ara-A derivative 7 proved the most cytostatic (IC50 < 0.32 microgram/mL) resulting from 25- to > 144-fold more active (Ara-A derivatives) or at least as equally active (Ara-C derivatives) as compared to the parent nucleosides. Compound 3, endowed with a highly lipophilic silyl moiety at the 3' and 5' positions, showed the highest differentiating activity (54% and 44% differentiated HL-60 cells at 0.2 and 0.05 microgram/mL respectively). With regard to the retinoic acid conjugates of alkylating agents, compound 10 was the most cytostatic agent (IC50 < 0.32 microgram/mL) and the most potent differentiating agent (33-34% at 0.32 and 0.08 microgram/mL). These structures may also be regarded as analogs of either retinoic acid or the cytotoxic compound.

  13. Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink.

    PubMed

    Wilson, Maxwell Z; Wang, Rurun; Gitai, Zemer; Seyedsayamdost, Mohammad R

    2016-02-01

    While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine bacteria that engage in dynamic symbioses with microscopic algae. TDA promotes algal health by killing unwanted marine pathogens; however, its mode of action (MoA) and significance for the survival of an algal-bacterial miniecosystem remains unknown. Using cytological profiling, we herein determine the MoA of TDA and surprisingly find that it acts by a mechanism similar to polyether antibiotics, which are structurally highly divergent. We show that like polyether drugs, TDA collapses the proton motive force by a proton antiport mechanism, in which extracellular protons are exchanged for cytoplasmic cations. The α-carboxy-tropone substructure is ideal for this purpose as the proton can be carried on the carboxyl group, whereas the basicity of the tropylium ion facilitates cation export. Based on similarities to polyether anticancer agents we have further examined TDA's cytotoxicity and find it to exhibit potent, broad-spectrum anticancer activities. These results highlight the power of MoA-profiling technologies in repurposing old drugs for new targets. In addition, we identify an operon that confers TDA resistance to the producing marine bacteria. Bioinformatic and biochemical analyses of these genes lead to a previously unknown metabolic link between TDA/acid resistance and the γ-glutamyl cycle. The implications of this resistance mechanism in the context of the algal-bacterial symbiosis are discussed. PMID:26802120

  14. Chromohalobacter is a Causing Agent for the Production of Organic Acids and Putrescine during Fermentation of Ganjang, a Korean Traditional Soy Sauce.

    PubMed

    Jung, Ji Young; Chun, Byung Hee; Jeon, Che Ok

    2015-12-01

    Ganjang, a Korean traditional fermented soy sauce, is prepared by soaking doenjang-meju (fermented soybeans) in approximately 20% (w/v) solar salt solution. The metabolites and bacterial communities during ganjang fermentation were simultaneously investigated to gain a better understanding of the roles of the microbial population. The bacterial community analysis based on denaturing gradient gel electrophoresis of 16S rRNA gene sequences showed that initially, the genus Cobetia was predominant (0 to 10 d), followed by Bacillus (5 to 74 d), and eventually, Chromohalobacter became predominant until the end of the fermentation process (74 to 374 d). Metabolite analysis using (1)H-NMR showed that carbon compounds, such as fructose, galactose, glucose, and glycerol, probably released from doenjang-meju, increased rapidly during the early fermentation period (0 to 42 d). After removal of doenjang-meju from the ganjang solution (42 d), the initial carbon compounds remained nearly constant without the increase of fermentation products. At this point, Bacillus species, which probably originated from doenjang-meju, were predominant, suggesting that Bacillus is not mainly responsible for ganjang fermentation. Fermentation products including acetate, lactate, α-aminobutyrate, γ-aminobutyrate, and putrescine increased quickly with the rapid decrease of the initial carbon compounds, while Chromohalobacter, probably derived from the solar salts, was predominant. Multivariate redundancy analysis indicated that the Chromohalobacter population was closely correlated with the production of the organic acids and putrescine during the ganjang fermentation. These results may suggest that Chromohalobacter is a causing agent responsible for the production of organic acids and putrescine during ganjang fermentation and that the solar salts, not doenjang-meju, is an important microbial source for ganjang fermentation.

  15. Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink

    PubMed Central

    Wilson, Maxwell Z.; Wang, Rurun; Gitai, Zemer; Seyedsayamdost, Mohammad R.

    2016-01-01

    While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine bacteria that engage in dynamic symbioses with microscopic algae. TDA promotes algal health by killing unwanted marine pathogens; however, its mode of action (MoA) and significance for the survival of an algal–bacterial miniecosystem remains unknown. Using cytological profiling, we herein determine the MoA of TDA and surprisingly find that it acts by a mechanism similar to polyether antibiotics, which are structurally highly divergent. We show that like polyether drugs, TDA collapses the proton motive force by a proton antiport mechanism, in which extracellular protons are exchanged for cytoplasmic cations. The α-carboxy-tropone substructure is ideal for this purpose as the proton can be carried on the carboxyl group, whereas the basicity of the tropylium ion facilitates cation export. Based on similarities to polyether anticancer agents we have further examined TDA’s cytotoxicity and find it to exhibit potent, broad-spectrum anticancer activities. These results highlight the power of MoA-profiling technologies in repurposing old drugs for new targets. In addition, we identify an operon that confers TDA resistance to the producing marine bacteria. Bioinformatic and biochemical analyses of these genes lead to a previously unknown metabolic link between TDA/acid resistance and the γ-glutamyl cycle. The implications of this resistance mechanism in the context of the algal-bacterial symbiosis are discussed. PMID:26802120

  16. Lewis acid-assisted isotopic 18F-19F exchange in BODIPY dyes: facile generation of positron emission tomography/fluorescence dual modality agents for tumor imaging.

    PubMed

    Liu, Shuanglong; Lin, Tzu-Pin; Li, Dan; Leamer, Lauren; Shan, Hong; Li, Zibo; Gabbaï, François P; Conti, Peter S

    2013-01-01

    Positron emission tomography (PET) is a powerful technique for imaging biological pathways in vivo, particularly those that are key targets in disease processes. In contrast, fluorescence imaging has demonstrated to be a superior method for image-guided surgery, such as tumor removal. Although the integration of PET and optical imaging could provide an attractive strategy for patient management, there is a significant shortage of established platforms/methods for PET/optical probe construction. In this study, various reaction conditions were explored to develop a simple and fast method allowing for the introduction of [(18)F]-fluoride into BODIPY dyes. Through a systematic optimization of the reaction conditions, we found that BODIPY dyes, including commercial amine-reactive BODIPY succinimidyl esters, may be converted into their radioactive analogues in the matter of minutes via a (18)F-(19)F isotopic exchange reaction promoted by a Lewis acid such as SnCl4. An integrin-targeting RGD peptide was also conjugated with [(18)F]BODIPY® R6G , derived from the commercially available BODIPY® R6G fluorescent tag, to provide a [(18)F]-RGD conjugate in 82% yield. In vivo evaluation of this imaging probe showed a discernible tumor uptake in the U87MG xenograft model. The dual modality imaging properties of the probe was confirmed by ex vivo fluorescence and microPET imaging experiments. In summary, in the matter of minutes, BODIPY dyes were converted into their "hot" radioactive analogues via a (18)F-(19)F isotopic exchange reaction promoted by a Lewis acid. This approach, which can be applied to commercial BODIPY dyes, provides easy access to positron emission tomography/fluorescence dual modality imaging agents. PMID:23471211

  17. Biological Agents

    MedlinePlus

    ... to Z Index Contact Us FAQs What's New Biological Agents This page requires that javascript be enabled ... and Health Topics A-Z Index What's New Biological agents include bacteria, viruses, fungi, other microorganisms and ...

  18. Lysophosphatidic acid and microtubule-destabilizing agents stimulate fibronectin matrix assembly through Rho-dependent actin stress fiber formation and cell contraction.

    PubMed Central

    Zhang, Q; Magnusson, M K; Mosher, D F

    1997-01-01

    Fibronectin (FN) matrix assembly is a cell-dependent process mediated by cell surface-binding sites for the 70-kDa amino-terminal region of FN. We have shown recently that lysophosphatidic acid (LPA) is a stimulator of FN matrix assembly. Disruption of microtubules has been shown to mimic some of the intracellular effects of LPA including the formation of actin stress fibers and myosin light chain phosphorylation. We compared the effects of microtubule disruption and LPA on FN binding and actin cytoskeleton organization. The disruption of microtubules by nocodazole or vinblastine increased FN binding to adherent cells. The modulation of binding sites was rapid, dynamic, and reversible. Enhanced binding was due to increases in both the number and affinity of binding sites. These effects are similar to the effects of LPA on FN binding. Binding induced by nocodazole was inhibited by the microtubule-stabilizing agent Taxol but not by pretreatment with a concentration of phospholipase B that totally abolished the stimulatory effect of LPA. Fluorescence microscopy revealed a close correlation among actin stress fiber formation, cell contraction, and FN binding. Blockage of the small GTP binding protein Rho or actin-myosin interactions inhibited the effects of both nocodazole and LPA on FN binding. These observations demonstrate that Rho-dependent actin stress fiber formation and cell contraction induce increased FN binding and represent a rapid labile way that cells can modulate FN matrix assembly. Images PMID:9285815

  19. First chemical feature-based pharmacophore modeling of potent retinoidal retinoic acid metabolism blocking agents (RAMBAs): identification of novel RAMBA scaffolds.

    PubMed

    Purushottamachar, Puranik; Patel, Jyoti B; Gediya, Lalji K; Clement, Omoshile O; Njar, Vincent C O

    2012-01-01

    The first three-dimensional (3D) pharmacophore model was developed for potent retinoidal retinoic acid metabolism blocking agents (RAMBAs) with IC(50) values ranging from 0.0009 to 5.84nM. The seven common chemical features in these RAMBAs as deduced by the Catalyst/HipHop program include five hydrophobic groups (hydrophobes), and two hydrogen bond acceptors. Using the pharmacophore model as a 3D search query against NCI and Maybridge conformational Catalyst formatted databases; we retrieved several compounds with different structures (scaffolds) as hits. Twenty-one retrieved hits were tested for RAMBA activity at 100nM concentration. The most potent of these compounds, NCI10308597 and HTS01914 showed inhibitory potencies less (54.7% and 53.2%, respectively, at 100nM) than those of our best previously reported RAMBAs VN/12-1 and VN/14-1 (90% and 86%, respectively, at 100nM). Docking studies using a CYP26A1 homology model revealed that our most potent RAMBAs showed similar binding to the one observed for a series of RAMBAs reported previously by others. Our data shows the potential of our pharmacophore model in identifying structurally diverse and potent RAMBAs. Further refinement of the model and searches of other robust databases is currently in progress with a view to identifying and optimizing new leads. PMID:22130607

  20. First chemical feature-based pharmacophore modeling of potent retinoidal retinoic acid metabolism blocking agents (RAMBAs): identification of novel RAMBA scaffolds.

    PubMed

    Purushottamachar, Puranik; Patel, Jyoti B; Gediya, Lalji K; Clement, Omoshile O; Njar, Vincent C O

    2012-01-01

    The first three-dimensional (3D) pharmacophore model was developed for potent retinoidal retinoic acid metabolism blocking agents (RAMBAs) with IC(50) values ranging from 0.0009 to 5.84nM. The seven common chemical features in these RAMBAs as deduced by the Catalyst/HipHop program include five hydrophobic groups (hydrophobes), and two hydrogen bond acceptors. Using the pharmacophore model as a 3D search query against NCI and Maybridge conformational Catalyst formatted databases; we retrieved several compounds with different structures (scaffolds) as hits. Twenty-one retrieved hits were tested for RAMBA activity at 100nM concentration. The most potent of these compounds, NCI10308597 and HTS01914 showed inhibitory potencies less (54.7% and 53.2%, respectively, at 100nM) than those of our best previously reported RAMBAs VN/12-1 and VN/14-1 (90% and 86%, respectively, at 100nM). Docking studies using a CYP26A1 homology model revealed that our most potent RAMBAs showed similar binding to the one observed for a series of RAMBAs reported previously by others. Our data shows the potential of our pharmacophore model in identifying structurally diverse and potent RAMBAs. Further refinement of the model and searches of other robust databases is currently in progress with a view to identifying and optimizing new leads.

  1. Oxyresveratrol and ascorbic acid O/W microemulsion: Preparation, characterization, anti-isomerization and potential application as antibrowning agent on fresh-cut lotus root slices.

    PubMed

    He, Jianfei; Zhu, Qin; Dong, Xue; Pan, Hongyang; Chen, Jie; Zheng, Zong-Ping

    2017-01-01

    The purpose of this study is to prepare an oxyresveratrol (Oxy) microemulsion (ME) with improved Oxy's solubility and stability and to investigate its antibrowning effects on fresh-cut lotus root slices. The formula of OxyME consisted of ethyl butyrate, Tween 80, PEG400, and water with w/w of 4%, 10.67%, 5.33%, and 80%, respectively. Encapsulating Oxy into OxyME greatly increased its solubility and stability compared with that of in water. Strong antibrowning effects were observed on fresh-cut lotus root slices treated with OxyME, even better than 4-hexylresorcinol. The addition of ascorbic acid (VC) into OxyME greatly improved the Oxy stability in long-term storage and antibrowning effects on fresh-cut lotus root slices. However, the simultaneous addition of calcium chloride and VC did not obviously improve the antibrowning effects compared with the addition of VC alone. These results indicated that Oxy+VCME may be suitable as an antibrowning agent for fresh-cut vegetables. PMID:27507475

  2. Red-Light Initiated Decomposition of α-Hydroxy Methylperoxy Radical in the Presence of Organic and Inorganic Acids: Implications for the HOx Formation in the Lower Stratosphere.

    PubMed

    Kumar, Manoj; Francisco, Joseph S

    2016-05-01

    Theoretical calculations have been carried out to investigate the gas-phase decomposition of α-hydroxy methylperoxy (HOCH2(OO)) radical in the absence and presence of formic acid, acetic acid, nitric acid, and sulfuric acid. The HOCH2(OO) radical decomposition represents a new source of the HOx radical in troposphere. The results suggest that sulfuric acid will be more effective than other acids in catalyzing the peroxy radical decomposition. However, the significant stability of prereaction and postreaction complexes in all the bimolecular reactions implies a new photomechanism for the acid-mediated decomposition of the HOCH2(OO) radical that involves the visible or near IR overtone excitation of the OH stretching modes or electronic excitation of the O-O peroxy moiety in the acid-bound radical. This new overtone or electronic excitation-based photomechanism for the peroxy radical decomposition may provide useful insight into the missing photolytic source of the HOx at high solar zenith angles corresponding to the dawn or dusk photochemistry. PMID:27070960

  3. Red-Light Initiated Decomposition of α-Hydroxy Methylperoxy Radical in the Presence of Organic and Inorganic Acids: Implications for the HOx Formation in the Lower Stratosphere.

    PubMed

    Kumar, Manoj; Francisco, Joseph S

    2016-05-01

    Theoretical calculations have been carried out to investigate the gas-phase decomposition of α-hydroxy methylperoxy (HOCH2(OO)) radical in the absence and presence of formic acid, acetic acid, nitric acid, and sulfuric acid. The HOCH2(OO) radical decomposition represents a new source of the HOx radical in troposphere. The results suggest that sulfuric acid will be more effective than other acids in catalyzing the peroxy radical decomposition. However, the significant stability of prereaction and postreaction complexes in all the bimolecular reactions implies a new photomechanism for the acid-mediated decomposition of the HOCH2(OO) radical that involves the visible or near IR overtone excitation of the OH stretching modes or electronic excitation of the O-O peroxy moiety in the acid-bound radical. This new overtone or electronic excitation-based photomechanism for the peroxy radical decomposition may provide useful insight into the missing photolytic source of the HOx at high solar zenith angles corresponding to the dawn or dusk photochemistry.

  4. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    2000-02-08

    Bicyclo[2.2.2]octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo[2.2.1]heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  5. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, M.P.; Mease, R.C.; Srivastava, S.C.

    1998-07-21

    Bicyclo[2.2.2] octane-2,3 diamine-N,N,N`,N`-tetraacetic acids (BODTA) and bicyclo[2.2.1] heptane-2,3 diamine-N,N,N`,N`-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  6. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    1998-07-21

    Bicyclo›2.2.2! octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo›2.2.1! heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  7. Topoisomerase I-mediated DNA cleavage as a guide to the development of antitumor agents derived from the marine alkaloid lamellarin D: triester derivatives incorporating amino acid residues.

    PubMed

    Tardy, Christelle; Facompré, Michaël; Laine, William; Baldeyrou, Brigitte; García-Gravalos, Dolores; Francesch, Andrés; Mateo, Cristina; Pastor, Alfredo; Jiménez, José A; Manzanares, Ignacio; Cuevas, Carmen; Bailly, Christian

    2004-04-01

    LoVo-Dox cells resistant to doxorubicin) cancer cells (but not with HT29 colon carcinoma cells), the most cytotoxic compounds correspond to the most potent topoisomerase I poisons. The observed correlation between cytotoxicity and topoisomerase I inhibition strongly suggests that topoisomerase I-mediated DNA cleavage assays can be used as a guide to the development of superior analogues in this series. LAM-D is the lead compound of a new promising family of antitumor