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Sample records for acid lowering agent

  1. Lipid Lowering Agents Aeromedical Concerns

    DTIC Science & Technology

    2001-06-01

    for those military concomitant measurement of triglyceride levels, aviators at high risk for CHD , in the second and Provided triglyceride levels are...The major classes of lipid lowering drugs are: protein levels are listed in Table 1. a. Bile acid sequestrants (cholestyramine, Risk Factors for...Level Level First CHD >200  >100  Second Without CHD , and with 2 or more risk >250  >130  factors, or genetically determined

  2. Overprescribing of lipid lowering agents.

    PubMed

    Smith, M A; Cox, E D; Bartell, J M

    2006-08-01

    Undertreatment of hyperlipidemia has received considerable attention. However, little is known about trends in overprescribing of lipid lowering agents. We examined these trends and their associations with physician, practice, and organisational factors. 2034 physicians were surveyed twice: baseline (1996-7) and follow up (1998-9). On each occasion they were asked: "For what percentage of 50 year old men without other cardiac risk factors would you recommend an oral agent for total cholesterol of 240, LDL 150, and HDL 50 after 6 months on a low cholesterol diet?" During the survey period the National Cholesterol Education Program guidelines did not recommend prescribing for these patients. Binomial and multinomial logistic regressions assessed baseline overprescribing and longitudinal changes in overprescribing, accounting for complex sampling. 39% of physicians recommended prescribing at baseline (round 1), increasing at follow up (round 2) to 51% (p < 0.001). Physicians who were more likely to overprescribe at baseline were less likely to be board certified (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.38 to 0.63; p < 0.001), were in solo or two-physician practices (OR 1.88, 95% CI 1.46 to 2.41; p < 0.001), had more revenue from Medicare (OR 1.10, 95% CI 1.03 to 1.17; p = 0.004) or Medicaid (OR 1.09, 95% CI 1.01 to 1.18; p = 0.03), or were family physicians (OR 1.87, 95% CI 1.35 to 2.58; p < 0.001). Physicians with large increases in overprescibing were more likely than those with small increases in overprescribing to be international medical graduates (OR 2.09, 95% CI 1.20 to 3.64; p = 0.011) and to spend more hours in patient care (OR 1.14, 95% CI 1.03 to 1.26; p = 0.016). Overprescribing of lipid lowering agents is commonplace and increased. At baseline and longitudinally, overprescribing was primarily associated with physician and practice characteristics and not with organisational factors.

  3. Overprescribing of lipid lowering agents

    PubMed Central

    Smith, M A; Cox, E D; Bartell, J M

    2006-01-01

    Background Undertreatment of hyperlipidemia has received considerable attention. However, little is known about trends in overprescribing of lipid lowering agents. We examined these trends and their associations with physician, practice, and organisational factors. Methods 2034 physicians were surveyed twice: baseline (1996–7) and follow up (1998–9). On each occasion they were asked: “For what percentage of 50 year old men without other cardiac risk factors would you recommend an oral agent for total cholesterol of 240, LDL 150, and HDL 50 after 6 months on a low cholesterol diet?” During the survey period the National Cholesterol Education Program guidelines did not recommend prescribing for these patients. Binomial and multinomial logistic regressions assessed baseline overprescribing and longitudinal changes in overprescribing, accounting for complex sampling. Results 39% of physicians recommended prescribing at baseline (round 1), increasing at follow up (round 2) to 51% (p<0.001). Physicians who were more likely to overprescribe at baseline were less likely to be board certified (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.38 to 0.63; p<0.001), were in solo or two‐physician practices (OR 1.88, 95% CI 1.46 to 2.41; p<0.001), had more revenue from Medicare (OR 1.10, 95% CI 1.03 to 1.17; p = 0.004) or Medicaid (OR 1.09, 95% CI 1.01 to 1.18; p = 0.03), or were family physicians (OR 1.87, 95% CI 1.35 to 2.58; p<0.001). Physicians with large increases in overprescibing were more likely than those with small increases in overprescribing to be international medical graduates (OR 2.09, 95% CI 1.20 to 3.64; p = 0.011) and to spend more hours in patient care (OR 1.14, 95% CI 1.03 to 1.26; p = 0.016). Conclusions Overprescribing of lipid lowering agents is commonplace and increased. At baseline and longitudinally, overprescribing was primarily associated with physician and practice characteristics and not with organisational factors

  4. Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Borgi, Lea; McMullan, Ciaran; Wohlhueter, Ann; Curhan, Gary C; Fisher, Naomi D; Forman, John P

    2017-02-01

    Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive, overweight, or obese individuals with higher serum uric acid (body mass index ≥25 kg/m(2) and serum uric acid ≥5.0 mg/dL), we assigned subjects to probenecid (500-1000 mg/d), allopurinol (300-600 mg/d), or matching placebo. The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49, and 53 participants had been allocated to receive probenecid, allopurinol, and placebo, respectively. Mean serum uric acid levels significantly decreased in the probenecid (from 6.1 to 3.5 mg/dL) and allopurinol groups (from 6.1 to 2.9 mg/dL) but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelium-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension. © 2016 American Heart Association, Inc.

  5. Coumarin and Derivates as Lipid Lowering Agents.

    PubMed

    Tejada, Silvia; Martorell, Miquel; Capo, Xavier; Tur, Josep A; Pons, Antoni; Sureda, Antoni

    2017-01-01

    Cardiovascular disease is the main cause of death in the developed countries. Dyslipidaemia is one of the risk factors associated to cardiovascular disease and it is characterised by abnormal amounts of lipids (i.e. cholesterol and fatty acids) and/or circulating lipoproteins in the blood. Oxidative stress has been implicated in the pathogenesis of various illnesses including cardiovascular disease. In this way, the potential therapeutic or preventive effects of antioxidant mediators have recently drawn much attention. Coumarin (1,2-benzopyrone) is a natural phenolic compound found in many plants such as citrus fruits, tomatoes, vegetables and green tea. Coumarin and derivates are proposed as lipid lowering agents due to its broad pharmacological activities, mainly the implicated in vasodilator and antioxidant effect. Several studies have evidenced a promising role of coumarin and several of its derivates as lipid lowering agents. In the current work, the available reports related to the promising function of these compounds are reviewed.

  6. Potential impact of policy regulation and generic competition on sales of cholesterol lowering medication, antidepressants and acid blocking agents in Belgium.

    PubMed

    Fraeyman, J; Van Hal, G; De Loof, H; Remmen, R; De Meyer, G R Y; Beutels, P

    2012-01-01

    Pharmaceutical expenditures are increasing as a proportion of health expenditures in most rich countries. Antidepressants, acid blocking agents and cholesterol lowering medication are major contributors to medicine sales around the globe. We aimed to document the possible impact of policy regulations and generic market penetration on the evolution of sales volume and average cost per unit (Defined Daily Doses and packages) of antidepressants, acid blocking agents and cholesterol lowering medication. We extracted data from the IMS health database regarding the public price and sales volume of the antidepressants (selective serotonin reuptake inhibitors (SSRI's), monoamine oxidase inhibitors (MAOl's) and tricyclic and remaining antidepressants (TCA's)), acid blocking agents (proton pump inhibitors (PPl's) and H2 receptor antagonists) and cholesterol lowering medication (statins and fibrates) in Belgium between 1995 and 2009. We describe these sales data in relation to various national policy measures which were systematically searched in official records. Our analysis suggests that particular policy regulations have had immediate impact on sales figures and expenditures on pharmaceuticals in Belgium: changes in reimbursement conditions, a public tender and entry of generic competitors in a reference pricing system. However, possible sustainable effects seem to be counteracted by other mechanisms such as marketing strategies, prescribing behaviour, brand loyalty and the entry of pseudogenerics. It is likely that demand-side measures have a more sustainable impact on expenditure. Compared with other European countries, generic penetration in Belgium remains low. Alternative policy regulations aimed at enlarging the generic market and influencing pharmaceutical expenditures deserve consideration. This should include policies aiming to influence physicians' prescribing and a shared responsibility of pharmacists, physicians and patients towards expenditures.

  7. Association between vitamin B12 deficiency and long-term use of acid-lowering agents: a systematic review and meta-analysis.

    PubMed

    Jung, S B; Nagaraja, V; Kapur, A; Eslick, G D

    2015-04-01

    Vitamin B12 (cobalamin) deficiency can result in irreversible structural brain changes if not treated appropriately. Long-term use of acid-lowering agents (ALA) has been linked to vitamin B12 deficiency, but results are inconsistent. To evaluate the association between prolonged ALA use and vitamin B12 deficiency by performing a meta-analysis. A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents, Cochrane Library, Google Scholar, Science Direct and Web of Science. Original data were abstracted from each study and used to calculate a pooled odds ratio and 95% confidence interval (95% CI). Of the articles reviewed, four case-control studies (4254 cases and 19,228 controls) and one observational study met full criteria for analysis. The long-term ALA use was significantly associated with development of vitamin B12 deficiency (hazard ratio 1.83, 95% CI: 1.36-2.46, P-value 0.00). Chronic use of ALA is a risk factor for developing vitamin B12 deficiency. Judicious prescribing of ALA and regular monitoring of vitamin B12 in patients who are inevitably on long-term ALA therapy are recommended. © 2015 Royal Australasian College of Physicians.

  8. Pyruvic acid as an etching agent.

    PubMed

    Retief, D H; Bischoff, J; van der Merwe, E H

    1976-07-01

    Phosphoric acid at different concentrations has been extensively used as an etching agent to improve bonding of dental materials to enamel surfaces. Recently attention has been drawn to the possible use of polyfunctional organic acids as conditioning agents. The object of this investigation was to determine the optimal concentration of pyruvic acid as an etching agent. A commercial composite resin with an intermediary bonding system supplied with 37% H3PO4 as an etching agent was used as the control system. In addition, a comparative study was carried out to evaluate 37% H3PO4, 20% lactic acid and the optimal concentration of pyruvic acid as conditioning solutions. Etching enamel surfaces with 10% pyruvic acid resulted in the optimal tensile bond strength of the resin to etched enamel surfaces. The use of 10% pyruvic acid did not adversely affect the bond strength of the resin system when compared to enamel surfaces etched with 37% H3PO4 for the same time period. Significantly lower tensile bond strengths were recorded on enamel surfaces etched with 20% lactic acid. The rate and depth of etching obtained with 37% H3PO4 can be considerably reduced by using 10% pyruvic acid as the conditioning agent.

  9. D-003 (Saccharum officinarum): The forgotten lipid-lowering agent.

    PubMed

    Awad, Kamal; Penson, Peter; Banach, Maciej

    2016-12-01

    Reduction of elevated cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C), is essential in primary and secondary prevention of cardiovascular disease (CVD). Therefore there is still a large need for new effective drugs, which would be able to essentially reduce LDL-C and in the consequence CV residual risk. D-003 is a mixture of high aliphatic primary acids purified from sugarcane (Saccharum officinarum) wax. It showed promising hypocholesterolemic effects in both animal and human studies; it significantly lowers both serum total cholesterol (TC) and LDL-C, and increases high-density lipoprotein cholesterol (HDL-C). In addition, it showed a favorable safety profile. In this review, we evaluated the profile of D-003 as a lipid-lowering agent based on data from available preclinical and clinical studies.

  10. Potential role of nonstatin cholesterol lowering agents.

    PubMed

    Trapani, Laura; Segatto, Marco; Ascenzi, Paolo; Pallottini, Valentina

    2011-11-01

    Although statins, 3β-hydroxy-3β-methylglutaryl coenzyme A reductase (HMGR) inhibitors, have revolutionized the management of cardiovascular diseases by lowering serum low density lipoproteins, many patients suffer from their side effects. Whether the statin side effects are related to their intrinsic toxicity or to the decrease of HMGR main isoprenoid end products, which are essential compounds for cell viability, is still debated. In addition to HMGR, the key and rate limiting step of cholesterol synthesis, many enzymes are involved in this multi-step pathway whose inhibition could be taken into account for a "nonstatin approach" in the management of hypercholesterolemia. In particular, due to their unique position downstream from HMGR, the inhibition of squalene synthase, farnesyl diphosphate farnesyltransferase (FDFT1), squalene epoxidase (SQLE), and oxidosqualene cyclase:lanosterol synthase (OSC) should decrease plasma levels of cholesterol without affecting ubiquinone, dolichol, and isoprenoid metabolism. Thus, although FDFT1, SQLE and OSC are little studied, they should be considered as perspective targets for the development of novel drugs against hypercholesterolemia. Here, structure-function relationships of FDFT1, SQLE, and OSC are reviewed highlighting the advantages that the downstream inhibition of HMGR could provide when compared to the statin-based therapy.

  11. Glutamic acid as anticancer agent: An overview

    PubMed Central

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    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. PMID:24227952

  12. 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.

  13. Uric acid lowering therapy in cardiovascular diseases.

    PubMed

    Volterrani, Maurizio; Iellamo, Ferdinando; Sposato, Barbara; Romeo, Franco

    2016-06-15

    Recent evidence would indicate that high serum uric acid (SUA) levels can be a significant and independent risk factor for hypertension and cardiovascular diseases, such as ischemic heart disease and heart failure. In the last few years an independent risk relationship between hyperuricemia, cardiovascular disease and mortality has also been reported. Hyperuricemia has been shown as an independent risk factor for acute myocardial infarction and an independent and conjoint association of either gout and SUA with total and cardiovascular mortality has been reported, with mortality impact in gout patients increasing with rising SUA concentrations, even for SUA levels in the normal to high range. These findings prompted a growing research interest on the possible benefits of uric acid lowering drugs in cardiovascular diseases. Indeed, clinical studies have reported on the beneficial effects of uric acid lowering drugs, in particular of xanthine oxidase inhibitors, in hypertension, ischemic heart disease and heart failure. Two main mechanisms have been claimed to explain the dangerous effects of hyperuricemia and, as a consequence, the benefits of uric acid lowering therapy: endothelial dysfunction and systemic inflammation. This brief review aims to summarize current evidence from human studies on the role of acid uric lowering therapy in cardiovascular diseases for practical and clinical purposes. The possible mechanisms underlying the benefits of acid uric lowering therapy are also addressed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Nucleic acids as therapeutic agents.

    PubMed

    Alvarez-Salas, Luis M

    2008-01-01

    Therapeutic nucleic acids (TNAs) and its precursors are applied to treat several pathologies and infections. TNA-based therapy has different rationales and mechanisms and can be classified into three main groups: 1) Therapeutic nucleotides and nucleosides; 2) Therapeutic oligonucleotides; and 3) Therapeutic polynucleotides. This review will focus in those TNAs that have reached clinical trials with anticancer and antiviral protocols, the two most common applications of TNAs. Although therapeutic nucleotides and nucleosides that interfere with nucleic acid metabolism and DNA polymerization have been successfully used as anticancer and antiviral drugs, they often produce toxic secondary effects related to dosage and continuous use. The use of oligonucleotides such as ribozyme and antisense oligodeoxynucleotides (AS-ODNs) showed promise as therapeutic moieties but faced several issues such as nuclease sensitivity, off-target effects and efficient delivery. Nevertheless, immunostimulatory oligodeoxynucleotides and AS-ODNs represent the most successful group of therapeutic oligonucleotides in the clinic. A newer group of therapeutic oligonucleotides, the aptamers, is rapidly advancing towards early detection and treatment alternatives the have reached the commercial interest. Despite the very high in vitro efficiency of small interfering RNAs (siRNAs) they present issues with intracellular target accessibility, specificity and delivery. DNA vaccines showed great promise, but they resulted in very poor responses in the clinic and further development is uncertain. Despite their many issues, the exquisite specificity and versatility of therapeutic oligonucleotides attracts a great deal of research and resources that will certainly convert them in the TNA of choice for treating cancer and viral diseases in the near future.

  15. 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

  16. Does nicotinic acid (niacin) lower blood pressure?

    PubMed Central

    Bays, H E; Rader, D J

    2009-01-01

    Nicotinic acid (niacin) is a well-established treatment for dyslipidaemia – an important cardiovascular disease (CVD) risk factor. However, niacin may also reduce blood pressure (BP), which is another important CVD risk factor. This review examines the limited publicly available data on niacin’s BP effects. Acute administration of immediate-release niacin may lower BP because of niacin’s acute vasodilatory effects. Although not always supported by clinical trial data, the package insert of a prescription, extended-release niacin describes niacin-induced acute hypotension. From a chronic standpoint, larger studies, such as the Coronary Drug Project, suggest that niacin may lower BP when administered over a longer period of time. Post hoc analyses of some of the more recent niacin clinical trials also support a more chronic, dose-dependent, BP-lowering effect of niacin. Because laropiprant [a prostaglandin D2 (PGD2) type 1 (DP1) receptor antagonist] does not attenuate niacin’s BP-lowering effects, it is unlikely that any chronic lowering of BP by niacin is due to dilation of dermal vessels through activation of the DP1 receptor by PGD2. Further research is warranted to evaluate the extent and mechanisms of niacin’s effects on BP. PMID:19054161

  17. Overcoming Platinum Drug Resistance with Copper-lowering Agents

    PubMed Central

    CHEN, HELEN H.W.; KUO, MACUS TIEN

    2014-01-01

    Platinum (Pt)-based antitumor agents have been the mainstay of cancer chemotherapy for the last three decades. While multiple mechanisms are responsible for treatment failure, deficiency in drug transport is an important contributor. The human high-affinity copper (Cu) transporter-1 (hCtr1) can also transport Pt-based drugs including cisplatin (cDDP) and carboplatin. Reduced hCtr1 expression frequently occurs in cDDP-resistant cell lines and in cancer in patients who failed chemotherapy with these drugs. We previously demonstrated that Cu chelation induces the expression of transcription factor Sp1 which binds the promoters of Sp1 and hCtr1, thereby, up-regulating their expression, whereas Cu overload shuts down hCtr1 and Sp1 expression by dissociating Sp1 from their promoter promoters. Thus, mammalian Cu homeostasis is transcriptionally regulated within a loop consisting of Sp1, hCtr1, and Cu in a three-way mutually regulated manner. These findings suggest that it is feasible to module cDDP transport capacity through intervention of mammalian Cu homeostasis. Indeed, we found that cDDP resistance can be overcome by Cu-lowering agents through enhanced hCtr1 expression by up-regulation of Sp1 in cultured cells. This discovery provided a mechanistic basis for the ongoing clinical study using Cu chelator to overcome cDDP resistance in ovarian cancer chemotherapy. Preliminary study using copper chelator (trientine) for enhancing the treatment efficacy of carboplatin in 5 ovarian cancer patients showed encouraging results. This short review describes the perspectives of using Cu-lowering agents in overcoming Pt resistance in cancer chemotherapy. PMID:24122978

  18. 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.

  19. Lower omega-3 polyunsaturated fatty acids and lower docosahexaenoic acid in men with pedophilia.

    PubMed

    Mincke, Elda; Cosyns, Paul; Christophe, Armand B; De Vriese, Stephanie; Maes, Michael

    2006-12-01

    Previous studies have suggested that abnormalities in plasma phospholipid fatty acids may play a role in aggressive behavior. Recently, it was suggested that a dysfunctional serotonergic turnover in the brain may be involved in the etiopathology of pedophilia. Depletion of n-3 polyunsaturated fatty acids (PUFA) may cause alterations in the serotonergic system that may be related to pedophilia and aggression. This study examines the serum phospholipid n-3 and n-6 PUFA fractions in pedophilia. Twenty-seven pedophilic men and eighteen healthy volunteers participated in this study. In pedophilia there was a significant depletion of the C22:6n-3 (docosahexaenoic acid, DHA), total n-3 fractions and an increase in the total n-6/n-3 and C20:4n-6/C20:5n-3 (arachidonic acid/eicosapentaenoic acid) ratios. Using the NEO Personality Inventory, lower DHA in pedophiles is related to more impulsiveness and lower agreeableness (trust, altruism, straightforwardness, compliance) and conscientiousness (self-discipline). The results of this study suggest that a depletion of the serum phospholipid n-3 higher unsaturated fatty acids (HUFAs) and, in particular, of DHA may take part in the pathophysiology of pedophilia. One hypothesis is that a depletion of n-3 HUFAs and DHA may cause alterations in the serotonergic turnover, which are related to impulse discontrol and aggression-hostility, behaviors which are associated with pedophilia.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. Long-acting contraceptive agents: levonorgestrel esters of unsaturated acids.

    PubMed

    Wan, A S; Ngiam, T L; Leung, S L; Go, M L; Francisco, C G; Freire, R; Hernandez, R; Salazar, J A; Suarez, E; García, G A

    1983-03-01

    Esters of levonorgestrel (13 beta-ethyl-17 beta-ethynyl-17 beta-hydroxygon-4-en-3-one) with a variety of unsaturated carboxylic acids have been synthesized for evaluation as potential long-acting, injectable contraceptive agents.

  7. Additive Intraocular Pressure-Lowering Effects of Ripasudil with Glaucoma Therapeutic Agents in Rabbits and Monkeys

    PubMed Central

    Ohta, Masayuki; Isobe, Tomoyuki; Nakamura, Yuto; Mizuno, Ken

    2017-01-01

    Ripasudil hydrochloride hydrate (K-115), a specific Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor, is developed for the treatment of glaucoma and ocular hypertension. Topical administration of ripasudil decreases intraocular pressure (IOP) by increasing conventional outflow through the trabeculae to Schlemm's canal, which is different from existing agents that suppress aqueous humor production or promote uveoscleral outflow. In this study, we demonstrated that ripasudil significantly lowered IOP in combined regimens with other glaucoma therapeutic agents in rabbits and monkeys. Ripasudil showed additional effects on maximum IOP lowering or prolonged the duration of IOP-lowering effects with combined administration of timolol, nipradilol, brimonidine, brinzolamide, latanoprost, latanoprost/timolol fixed combination, and dorzolamide/timolol fixed combination. These results indicate that facilitation of conventional outflow by ripasudil provides additive IOP-lowering effect with other classes of antiglaucoma agents. Ripasudil is expected to have substantial utility in combined regimens with existing agents for glaucoma treatment. PMID:28540083

  8. 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.

  9. Lipid-Lowering Therapy in HIV-Infected Patients: Relationship with Antiretroviral Agents and Impact of Substance-Related Disorders.

    PubMed

    Bednasz, Cindy; Luque, Amneris E; Zingman, Barry S; Fischl, Margaret A; Gripshover, Barbara M; Venuto, Charles S; Gu, Jie; Feng, Zekun; DiFrancesco, Robin; Morse, Gene D; Ma, Qing

    2016-01-01

    The use of combination antiretroviral therapy (cART) has significantly decreased the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. Lipid disorders, including lipodystrophy, hypertriglyceridemia, and hypercholesterolemia, remain the most commonly reported metabolic disorders among those treated with long-term cART. Mounting evidence suggests an association between drug abuse and poor glycemic control and diabetes complications. Substance related disorders (SRD) may increase the risk of metabolic syndrome. The aim of this retrospective cohort study was to examine the relationship between SRD, cART, and lipid-lowering agent use in an HIV infected population. Patients received efavirenz or protease inhibitor-based cART for at least 6 months. Prescription information was retrieved from the medical records. The primary outcome was the use of lipid-lowering agents including statins, fibrates and fish oil. The impact of SRD and cART was assessed on the lipid-lowering agent use. A total of 276 subjects with HIV infection were included, 90 (33%) received lipid-lowering agents, and 31 (34%) had SRD. Smoking was prevalent among subjects with SRD (84 vs 15%, p<0.001). Statins were the mainstay for the management of dyslipidemia (66%), followed by the fibrates (24%), omega-3 fatty acids (5%), nicotinic acid (3%) and the cholesterol absorption inhibitors (3%). Use of statins or fibrates was significantly higher among subjects without SRD than those with (40 vs 23%, p=0.005). The type of cART, including efavirenz and protease inhibitors, appeared to have no significant impact on the use pattern of lipid-lowering agents. Lopinavir/ritonavir (lopinavir/r) was mostly prescribed for subjects with SRD (25 vs 8%, p=0.02). Among HIV-infected patients, statins remain the mainstay for the management of dyslipidemia in routine clinical care, followed by fibrates. A significant high risk of metabolic disorders among patients with SRD is implicated by

  10. Lipid-lowering therapy in HIV-infected patients: relationship with antiretroviral agents and impact of substance-related disorders

    PubMed Central

    Bednasz, Cindy; Zingman, Barry S.; Luque, Amneris E.; Fischl, Margaret A.; Gripshover, Barbara M.; Venuto, Charles S.; Gu, Jie; Feng, Zekun; DiFrancesco, Robin; Morse, Gene D.; Ma, Qing

    2016-01-01

    BACKGROUND The use of combination antiretroviral therapy (cART) has significantly decreased the morbidity and mortality associated with HIV infection. Lipid disorders, including lipodystrophy, hypertriglyceridemia, hypercholesterolemia, and dyslipidemia, remain the most commonly reported metabolic disorders among those treated with long-term cART. Mounting evidence suggests an association between drug abuse and poor glycemic control and diabetes complications. Substance related disorders (SRD) may increase the risk of metabolic syndrome. MATERIALS AND METHODS The aim of this retrospective cohort study was to examine the relationship between SRD, cART, and lipid-lowering agent use in an HIV infected population. A total of 276 subjects with HIV infection were included, 90 (33%) received lipid-lowering agents, and 31 (34%) had SRD. Patients received efavirenz or protease inhibitor-based cART for at least 6 months. Prescription information was retrieved from the medical records. The primary outcome was the use of lipid-lowering agents including statins, fibrates and fish oil. The impact of SRD and cART was assessed on the lipid-lowering agent use. RESULTS Smoking was prevalent among subjects with SRD (84% vs. 15%, p<0.001). Statins were the mainstay for the management of dyslipidemia (66%), followed by the fibrates (24%), omega-3 fatty acids (5%), nicotinic acid (3%) and the cholesterol absorption inhibitors (3%). Use of statins or fibrates was significantly higher among subjects without SRD than those with (40% vs. 23%, p=0.005). The type of cART, including efavirenz and protease inhibitors, appeared to have no significant impact on the use pattern of lipid-lowering agents. Lopinavir/r was mostly prescribed for subjects with SRD (25% vs. 8%, p=0.02). CONCLUSIONS Among HIV-infected patients, statins remain the mainstay for the management of dyslipidemia in routine clinical care, followed by fibrates. A significant high risk of metabolic disorders among patients with

  11. 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.

  12. Long-acting contraceptive agents: norethisterone esters of polyunsaturated acids.

    PubMed

    Francisco, C G; Freire, R; Hernandez, R; Salazar, J A; Suarez, E; Vlahov, R; Tarpanov, V; Boshkova-Ljapova, M; Milenkov, B; Stoilova, V

    1983-03-01

    Some new derivatives of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) are described in which the 17 beta-hydroxyl group of the steroid is esterified with polyunsaturated aliphatic acids. The potential of these compounds as long-acting contraceptive agents has been evaluated.

  13. Enhancement of commercial antifungal agents by kojic acid

    USDA-ARS?s Scientific Manuscript database

    Kojic acid (KA), a natural by-product of fungal fermentation, is a commonly used food and cosmetic additive. We show that KA increases activity of amphotericin B and strobilurin, medical and agricultural antifungal agents, respectively, possibly targeting the fungal antioxidative system. KA shows pr...

  14. 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.

  15. 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

    2015-06-07

    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.

  16. The use of glycolic acid as a peeling agent.

    PubMed

    Murad, H; Shamban, A T; Premo, P S

    1995-04-01

    Glycolic acid is a member of the AHA family, which occurs naturally in foods and has been used for centuries as a cutaneous rejuvenation treatment. Recently it has proved to be a versatile peeling agent and it is now widely used to treat many defects of the epidermis and papillary dermis in a variety of strengths, ranging from 20% to 70%, depending on the condition being treated. People of almost any skin type and color are candidates, and almost any area of the body can be peeled. Several weeks prior to a peel the skin may be prepared with topical tretinoin or glycolic acid, and immediately prior to the peel the skin may be degreased with a variety of agents. Following the peel the skin is carefully observed for any complications such as hyperpigmentation and infection. Results are maintained with serial peels and at-home use of tretinoin or glycolic acid, as well as sun avoidance. The glycolic acid can be applied simultaneously with TCA and is another technique for a medium-depth peel. Comparison of 35% TCA-treated skin with 70% glycolic acid-treated skin examined histologically at different times reveals similar changes in papillary dermis connective tissue proteins, epidermal necrosis seen only with TCA, and reversion at 2 years postpeel to pretreatment appearance.

  17. Nucleic acid-binding polymers as anti-inflammatory agents

    PubMed Central

    Lee, Jaewoo; Sohn, Jang Wook; Zhang, Ying; Leong, Kam W.; Pisetsky, David; Sullenger, Bruce A.

    2011-01-01

    Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs can engender a variety of inflammatory and autoimmune diseases. The redundancy of the TLR family encouraged us to seek materials that can neutralize the proinflammatory effects of any nucleic acid regardless of its sequence, structure or chemistry. Herein we demonstrate that certain nucleic acid-binding polymers can inhibit activation of all nucleic acid-sensing TLRs irrespective of whether they recognize ssRNA, dsRNA or hypomethylated DNA. Furthermore, systemic administration of such polymers can prevent fatal liver injury engendered by proinflammatory nucleic acids in an acute toxic shock model in mice. Therefore these polymers represent a novel class of anti-inflammatory agent that can act as molecular scavengers to neutralize the proinflammatory effects of various nucleic acids. PMID:21844380

  18. Feasibility of using lower doses of chemopreventive agents in a combination regimen for cancer protection.

    PubMed

    Ip, C

    1988-04-01

    In experimental cancer chemoprevention studies, the doses of the agent used to produce an inhibitory response are generally very high, sometimes bordering on levels that will result in toxicity to the test animals. The present study was designed to test the hypothesis that low doses of two or more agents may be just as effective as high doses of a single agent. An earlier report from our laboratory showed that vitamin E, although ineffective by itself, potentiates the anti-carcinogenic potency of selenite. Our objective was to complete a comprehensive set of dose titration experiments in the quantitative analysis of the synergism between selenium (Se) and vitamin E. Results indicated that the minimal amount of vitamin E required was around 500 ppm, which when combined with as little as 1 ppm Se, produced a significant protective effect in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumor model. This level of Se is 5 times below the marginal toxicity level of 5 ppm observed in our previous experience. With a 3-agent combination protocol involving Se (1 ppm), vitamin E (500 ppm) and vitamin A (66 ppm), it was found that vitamin A at this particular dose did not contribute any further chemoprevention than that provided by the Se/vitamin E duo. Both Se and vitamin E were present at a concentration 10 times, while vitamin A was present at 30 times their respective nutritional requirement. Our findings thus suggest that the minimum effective dose has to be systematically established for each micronutrient, and that it is feasible to use lower doses of a combination of agents if the threshold level of each agent can be determined under a prescribed set of conditions.

  19. 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

  20. Cancer preventive agents 9. Betulinic acid derivatives as potent cancer chemopreventive agents.

    PubMed

    Nakagawa-Goto, Kyoko; Yamada, Koji; Taniguchi, Masahiko; Tokuda, Harukuni; Lee, Kuo-Hsiung

    2009-07-01

    C-3 esterifications of betulinic acid (BA, 1) and its A-ring homolog, ceanothic acid (CA, 2), were carried out to provide sixteen terpenoids, 4-19, including nine new compounds (4-12). All synthesized compounds were evaluated in an in vitro antitumor-promoting assay using the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Among them, compounds 4-6, 11-14, 16, and 17 displayed remarkable inhibitory effects of EBV-EA activation. BA analog 6, which contains a prenyl-like group, showed the most potent inhibitory effect (100%, 76%, 37%, and 11% inhibition of EBA activation at 1000, 500, 100, and 10mol ratio/TPA, respectively, with IC(50) value of 285mol ratio/32pmol TPA). Compound 6 merits further development as a cancer preventive agent.

  1. 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.

  2. Resistant starch is more effective than cholestyramine as a lipid-lowering agent in the rat.

    PubMed

    Younes, H; Levrat, M A; Demigné, C; Rémésy, C

    1995-09-01

    Amylase-resistant starch (RS) represents a substrate for the bacterial flora of the colon, and the question arises as whether RS shares with soluble fibers common mechanisms for their lipid-lowering effects. It is uncertain whether a cholesterol-lowering effect depends basically on an enhanced rate of steroid excretion or whether colonic fermentations also play a role in this effect. In the present study, the effect of RS (25% raw potato starch), of a steroid sequestrant (0.8% cholestyramine), or both were compared on bile acid excretion and lipid metabolism in rats fed semipurified diets. RS diets led to a marked rise in cecal size and the cecal pool of short-chain fatty acids (SCFA), as well as SCFA absorption; cholestyramine did not noticeably affect cecal fermentation. Whereas cholestyramine was particularly effective at enhancing bile acid excretion, RS was more effective in lowering plasma cholesterol (-32%) and triglycerides (-29%). The activity of 3-hydroxy-3-methylglutaryl-CoA reductase was increased fivefold by cholestyramine and twofold by RS. This induction in rats fed RS diets was concomittant to a depressed fatty acid synthase activity. In rats fed the RS diet, there was a lower concentration of cholesterol in all lipoprotein fractions, especially the (d = 1.040-1.080) fraction high-density lipoprotein (HDL1), while those fed cholestyramine had only a significant reduction of HDL1 cholesterol. In contrast to cholestyramine, RS also depressed the concentration of triglycerides in the triglyceride-rich lipoprotein fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Solution of Azelaic Acid (20%), Resorcinol (10%) and Phytic Acid (6%) Versus Glycolic Acid (50%) Peeling Agent in the Treatment of Female Patients with Facial Melasma.

    PubMed

    Faghihi, Gita; Taheri, Azam; Shahmoradi, Zabihollah; Nilforoushzadeh, Mohammad Ali

    2017-01-01

    Melasma, a common acquired disorder of hyperpigmentation, especially in women, is often resistant to therapy. This study was aimed to evaluate the efficacy and safety of azelaic acid, resorcinol and phytic acid solution in chemical peeling of melasma in comparison to 50% glycolic acid. This clinical trial was performed, on 42 female patients with bilateral melasma. Severity of melasma was assessed by melasma area and severity index (MASI). Combination of (20% azelaic acid + 10% resorcinol + 6% phytic acid) was used as a new peeling agent on the right side of the face and 50% glycolic acid on the left side every 2 weeks for 6 times. Follow-up was carried out for 3 months after the last session. Any decrease in MASI score and unwanted complications following peeling were evaluated and compared during the trial. Patients showed marked improvement as calculated with MASI score before and after treatment in both sides of the face. The efficacy of combination formula (azelaic acid, resorcinol and phytic acid) was similar to glycolic acid, but with fewer complications. There was no statistically difference in improvement between two groups (P > 0.05). However, the patient's discomfort following procedures was significantly lower with azelaic acid, resorcinol and phytic compared with the glycolic acid peels (P < 0.05) and there was the same duration in the beginning of the therapeutic response in both groups. Results showed that triple-combination was found to be an effective and safe peeling agent in the treatment of melasma and it was as effective as 50% glycolic acid peel.

  4. Solution of Azelaic Acid (20%), Resorcinol (10%) and Phytic Acid (6%) Versus Glycolic Acid (50%) Peeling Agent in the Treatment of Female Patients with Facial Melasma

    PubMed Central

    Faghihi, Gita; Taheri, Azam; Shahmoradi, Zabihollah; Nilforoushzadeh, Mohammad Ali

    2017-01-01

    Background: Melasma, a common acquired disorder of hyperpigmentation, especially in women, is often resistant to therapy. This study was aimed to evaluate the efficacy and safety of azelaic acid, resorcinol and phytic acid solution in chemical peeling of melasma in comparison to 50% glycolic acid. Materials and Methods: This clinical trial was performed, on 42 female patients with bilateral melasma. Severity of melasma was assessed by melasma area and severity index (MASI). Combination of (20% azelaic acid + 10% resorcinol + 6% phytic acid) was used as a new peeling agent on the right side of the face and 50% glycolic acid on the left side every 2 weeks for 6 times. Follow-up was carried out for 3 months after the last session. Any decrease in MASI score and unwanted complications following peeling were evaluated and compared during the trial. Results: Patients showed marked improvement as calculated with MASI score before and after treatment in both sides of the face. The efficacy of combination formula (azelaic acid, resorcinol and phytic acid) was similar to glycolic acid, but with fewer complications. There was no statistically difference in improvement between two groups (P > 0.05). However, the patient's discomfort following procedures was significantly lower with azelaic acid, resorcinol and phytic compared with the glycolic acid peels (P < 0.05) and there was the same duration in the beginning of the therapeutic response in both groups. Conclusion: Results showed that triple-combination was found to be an effective and safe peeling agent in the treatment of melasma and it was as effective as 50% glycolic acid peel. PMID:28299301

  5. 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.

  6. 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

  7. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Exploratory study of carboplatin plus the copper-lowering agent trientine in patients with advanced malignancies.

    PubMed

    Fu, Siqing; Hou, Ming-Mo; Wheler, Jennifer; Hong, David; Naing, Aung; Tsimberidou, Apostolia; Janku, Filip; Zinner, Ralph; Piha-Paul, Sarina; Falchook, Gerald; Kuo, Macus Tien; Kurzrock, Razelle

    2014-06-01

    Preclinical data showed that trientine, a copper-lowering agent, re-sensitized cancer cells to carboplatin through enhanced human copper transporter 1 (hCtr1) -mediated platinum uptake. We studied carboplatin and trientine in patients (n = 55; 45 who had failed platinum) with advanced malignancies (Phase I, modified 3 + 3 design). The most common cancers were head and neck (n = 13), non-small cell lung (n = 10) and epithelial ovarian (n = 8). The median number of prior regimens was four. No dose-limiting toxicity or treatment-related deaths were observed at doses up to carboplatin AUC 6 given with trientine. Eight patients achieved stable disease (SD) ≥ 6 months (six platinum failures) and one patient with platinum-resistant ovarian cancer, partial response (PR) (total SD ≥ 6 months/PR = 9, 16.4 %). The mean nadir serum copper level in the nine patients with SD ≥ 6 months/PR was 0.55 μg/mL (95 % CI, 0.34-0.75) versus 1.22 μg/mL (95 % CI, 1.02-1.42) (p < 0.001) in 38 tested patients with progression. In patients who maintained their ceruloplasmin (major copper-carrying protein) levels at 5-15 mg/dL (n = 9), the median progression-free and overall survivals were 9.2 and 15.2 months versus 1.9 (p = 0.001) and 5.7 months (p = 0.033) in patients who did not (n = 38), respectively. The combination of a copper-lowering agent with carboplatin was well tolerated and associated with antitumor activity, especially in patients in whom copper and/or ceruloplasmin levels were lowered. Further investigation of this strategy for reversing platinum resistance is warranted.

  9. Effects of lipid-lowering agents in the Dahl salt-sensitive rat.

    PubMed

    Wilson, T W; Alonso-Galicia, M; Roman, R J

    1998-01-01

    Inducing renal cytochrome P4504A (P4504A) activity with clofibrate prevents the development of hypertension in Dahl salt-sensitive (Dahl S) rats. To determine if this also occurs with other antilipidemic agents, we compared the effects of a related drug, fenofibrate, with those of an unrelated agent, pravastatin, on blood pressure, renal histology, and P4504A activity. Dahl S rats were pretreated with fenofibrate (95 mg/kg per day), pravastatin (70 mg/kg per day), or vehicle for 7 days before and after being switched from a low-salt (0.1% NaCl) to a high-salt (8.0% NaCl) diet. After 3 weeks on the high-salt diet, mean arterial pressures averaged 183+/-13 (n=9), 126+/-10 (n=9), and 148+/-11 mm Hg (n=8), respectively, in vehicle-, fenofibrate-, and pravastatin-treated animals. Both drugs reduced the degree of proteinuria and glomerular injury. P4504A protein levels and the synthesis of 20-hydroxyeicosa-5,8,11,14-tetraenoic acid (20-HETE) were increased in the liver and kidney of fenofibrate-treated, but not pravastatin-treated rats. We also administered these agents to Dahl S rats in which hypertension had previously been induced by a high-salt diet. Mean arterial pressures averaged 164+/-10, 113+/-23, and 160+/-15 mm Hg in rats treated with vehicle, fenofibrate, or pravastatin for 3 weeks. Fenofibrate-treated rats exhibited a natriuresis. Proteinuria and glomerular injury were reduced by pravastatin but not by fenofibrate. These results indicate that fenofibrate prevented the development of hypertension and reduced subsequent glomerular injury in Dahl S rats, probably secondary to increased renal production of 20-HETE. Although pravastatin did not induce renal P4504A activity in these animals, it reduced the severity of hypertension and renal damage through some other mechanism.

  10. Phytic acid: an alternative root canal chelating agent.

    PubMed

    Nassar, Mohannad; Hiraishi, Noriko; Tamura, Yukihiko; Otsuki, Masayuki; Aoki, Kazuhiro; Tagami, Junji

    2015-02-01

    The objectives of this study were to investigate the effect of phytic acid, inositol hexakisphosphate (IP6), as a final rinse on the surface of instrumented root canals and smear-layered flat dentin surfaces treated with sodium hypochlorite (NaOCl) and to evaluate its effect on the viability and alkaline phosphatase activity of osteoblast-like cells (MC3T3-E1). The universally accepted chelating agent EDTA was used as the control in all conducted experiments. Root canals of human canines were instrumented with rotary files and irrigated with 5% NaOCl, followed by a final rinse of 17% EDTA (1 minute), 1% IP6 (1 minute or 30 seconds), or distilled water. NaOCl-treated flat coronal dentin surfaces were also treated with 17% EDTA (1 minute), 1% IP6 (1 minute or 30 seconds), or distilled water. The presence or absence of smear layer was evaluated with scanning electron microscopy. Cell viability and alkaline phosphatase assays were performed to evaluate the effect of IP6 and EDTA on cultured MC3T3-E1 cells. The results demonstrated the ability of IP6 to remove the smear layer from instrumented root canals and flat coronal dentin surfaces. When compared with EDTA, IP6 was less cytotoxic and did not affect the differentiation of MC3T3-E1 cells. IP6 shows the potential to be an effective and biocompatible chelating agent. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  11. Medication persistence and the use of generic and brand-name blood pressure-lowering agents.

    PubMed

    Corrao, Giovanni; Soranna, Davide; La Vecchia, Carlo; Catapano, Alberico; Agabiti-Rosei, Enrico; Gensini, Gianfranco; Merlino, Luca; Mancia, Giuseppe

    2014-05-01

    Because of their lower cost, healthcare systems recommend physicians to prefer generic products, rather than brand-name medicaments. There is then considerable interest and debate concerning safety and effectiveness of generic products. Few studies have compared patients treated with brand-name and generic drugs for adherence to treatment, with somewhat inconsistent results. The primary objective of this study was to compare the risk of discontinuing antihypertensive drug therapy in patients treated with generic or brand-name agents. The 101,618 beneficiaries of the Healthcare system of Lombardy, Italy, aged 18 years or older who were newly treated on monotherapy with antihypertensive generic or brand-name drugs during 2008, were followed until the earliest date among those of the occurrence of treatment discontinuation to whatever antihypertensive drug therapy (outcome), or censoring (death, emigration, 12 months after treatment initiation). Hazard ratios of discontinuation associated with starting on generic or brand-name products (intention-to-treat analysis), and incidence rate ratio of discontinuation during periods on generic and brand-name products (as-treated analysis) were respectively estimated from a cohort and self-controlled case series analyses. Patients who started on generics did not experience a different risk of discontinuation compared with those starting on brand-name agents (hazard ratio: 1.00; 95% confidence interval 0.98-1.02). Discontinuation did not occur with different rates during periods covered by generics or brand-name agents (incidence rate ratio: 1.01; 95% confidence interval 0.96-1.11) within the same individuals. A number of sensitivity and subgroup analyses confirmed the robustness of these findings. Generic products are not responsible for the high rate of discontinuation from antihypertensive drug therapy. Assuming therapeutic equivalence, clinical implication is of prescribing generic drug therapies.

  12. Role of lipid-lowering agents in the management of diabetic retinopathy

    PubMed Central

    Ioannidou, Estelle; Tseriotis, Vasilis-Spyridon; Tziomalos, Konstantinos

    2017-01-01

    Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus (DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined in the last decades, its prevalence increased and is expected to rise further as a result of the increasing incidence of type 2 DM (T2DM) and the longer life expectancy of patients with DM. The pathogenesis of diabetic retinopathy is multifactorial. Some observational studies suggested an association between dyslipidemia and the development and progression of retinopathy in patients with DM but others did not confirm this association. Regarding lipid-lowering agents, studies that evaluated the role of statins in the management of these patients are mostly small and yielded discrepant results. Large randomized studies with statins in patients with T2DM showed no benefit of these agents on diabetic retinopathy but were not designed to address this effect. In contrast, both preclinical data and two large randomized controlled studies, the FIELD and the ACCORD trial, showed that fenofibrate delays the progression of diabetic retinopathy. Even though the mechanisms underpinning this favorable effect are not entirely clear, these findings suggest that fenofibrate might represent a useful tool for the management of diabetic retinopathy. PMID:28138358

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

    USDA-ARS?s Scientific Manuscript database

    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...

  14. Gender effects of tall oil versus soybean phytosterols as cholesterol-lowering agents in hamsters.

    PubMed

    Ntanios, F Y; MacDougall, D E; Jones, P J

    1998-01-01

    To examine the effect of gender on the mechanisms of action of phytosterols extracted from tall oil (TO) and soybean (SB) on cholesterol and phytosterol metabolism, male and female hamsters were fed cholesterol-enriched diets containing 0.5 or 1% (w/w) TO or SB phytosterols for 90 days. Plasma lipoprotein cholesterol profile and tissue phytosterol and cholesterol biosynthesis levels were determined. Mean plasma total-cholesterol level in females fed 1% (w/w) SB was reduced (p<0.05) by 44%, while in males it was lowered (p<0.05) by 25% compared with their respective controls. Moreover, mean plasma total-cholesterol level was reduced (p<0.05) in male hamsters by -31% and female hamsters by -32% when fed 1% (w/w) TO. Cholesterol biosynthesis was higher (p<0.05) by twofold in groups fed TO at 0.5 and 1% (w/w) concentrations, compared with SB. Hamsters fed TO at 0.5 and 1% (w/w) levels also had higher (p<0.05) hepatic and enterocytic campesterol contents than SB-fed animals. These findings demonstrate gender differences in cholesterol metabolism in TO- and SB-fed hamsters. The results suggest that TO, conversely to SB phytosterol, is a more effective cholesterol-lowering agent in male, but not as much in female, hamsters, over a feeding period of 90 days.

  15. 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

  16. Statins more than cholesterol lowering agents in Alzheimer disease: their pleiotropic functions as potential therapeutic targets.

    PubMed

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

    2014-04-15

    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 and 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. [Effects of tooth whitening agents and acidic drinks on the surface properties of dental enamel].

    PubMed

    Chen, Xiaoling; Chen, Zhiqun; Lin, Yao; Shao, Jinquan; Yin, Lu

    2013-10-01

    Using tooth whitening agents (bleaching clip) in vitro and acidic drinks, we conducted a comparative study of the changes in enamel surface morphology, Ca/P content, and hardness. Tooth whitening glue pieces, cola, and orange juice were used to soak teeth in artificial saliva in vitro. Physiological saline was used as a control treatment. The morphology of the four groups was observed under a scanning electron microscope (SEM) immediately after the teeth were soaked for 7 and 14 d. The changes in Ca/P content and microhardness were analyzed. The enamel surfaces of the teeth in the three test groups were demineralized. The Ca/P ratio and the average microhardness were significantly lower than those of the control group immediately after the teeth were soaked (P < 0.05). The Ca/P ratio and microhardness gradually increased after 7 d. No significant difference was observed between the control group and the test groups after 14 d (P > 0.05). Bleaching agents caused transient demineralization of human enamel, but these agents could induce re-mineralization and repair of enamel over time. Demineralization caused by bleaching covered a relatively normal range compared with acidic drinks and daily drinking.

  18. 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.; hide

    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.

  19. 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.

  20. A Potent, Versatile Disulfide-Reducing Agent from Aspartic Acid

    PubMed Central

    2013-01-01

    Dithiothreitol (DTT) is the standard reagent for reducing disulfide bonds between and within biological molecules. At neutral pH, however, >99% of DTT thiol groups are protonated and thus unreactive. Herein, we report on (2S)-2-amino-1,4-dimercaptobutane (dithiobutylamine or DTBA), a dithiol that can be synthesized from l-aspartic acid in a few high-yielding steps that are amenable to a large-scale process. DTBA has thiol pKa values that are ∼1 unit lower than those of DTT and forms a disulfide with a similar E°′ value. DTBA reduces disulfide bonds in both small molecules and proteins faster than does DTT. The amino group of DTBA enables its isolation by cation-exchange and facilitates its conjugation. These attributes indicate that DTBA is a superior reagent for reducing disulfide bonds in aqueous solution. PMID:22353145

  1. The use of immunosuppressive agents in the management of recalcitrant lower limb ulcers.

    PubMed

    Millen, A; Coulston, J; Brennan, J; Kennedy, T

    2014-08-01

    Lower limb ulcers that are resistant to standard forms of treatment place a significant burden on both patients and health services. There is no widely agreed definition of a recalcitrant ulcer but failure to heal following 6-12 months of focused treatment would identify a small group of patients with highly resistant ulceration. We describe a series of patients with recalcitrant ulceration for which immunosuppressive agents have been used. This is a case series of 13 patients who underwent immunomodulation therapy for lower limb ulcers at a tertiary referral university hospital. Regimens of immunomodulation used mainly ciclosporin and/or cyclophosphamide, with concurrent antibiotic therapy. Case notes and computer systems were analysed by two reviewers. A patient was deemed to have a success if their ulcer fully healed while on immunomodulation therapy. Over a period of eight years, from 2004-2012, 13 patients underwent immunomodulation therapy. Among these patients there were 18 ulcerated limbs. Ulcer healing occurred in 10 limbs out of 18 (55.6%) and full healing occurred in six patients (46.2%). Ulcers were present for a median of five years (range 2-40 years), with a median diameter of 7.5 cm (range 4-18 cm) before treatment. Treatment of truly recalcitrant ulceration can be very frustrating for both the patient and physician, with poor success from more standard forms of treatment. We report experience with immunomodulation therapy that suggests there may be benefit from using this treatment in a subset of patients with this debilitating disease.

  2. Cardiovascular disease and oral agent glucose-lowering therapies in the management of type 2 diabetes.

    PubMed

    Home, Philip

    2012-06-01

    Although glucose-lowering oral agents have been available for clinical use for over 60 years, the formal evidence base supporting their advantage and safety in regard of cardiovascular (CV) outcomes remains less than optimal. However, a synthesis of the evidence results in a high probability of benefit. For metformin, the United Kingdom Prospective Diabetes Study (UKPDS) substudy is convincing for a definite effect in reducing myocardial infarction (MI), but the quantitative extent of that is uncertain. For sulfonylureas, support for reduction in MI comes from the UKPDS extension study, where the central estimate for risk reduction remains the same as in the original planned end to the study, but the greater number of events was statistically significant for the sulfonylurea/insulin arm. Other studies do not support the view that metformin and sulfonylureas differ with respect to MI or indeed CV outcomes more generally. The data available for acarbose, an α-glucosidase inhibitor, are weak but not of concern, although some positive substudy data are available for people with impaired glucose tolerance. For peroxisome proliferator-activated receptor-γ agonists the CV data are more controversial, but the purpose-designed randomized controlled trials are clear that pioglitazone is advantageous to placebo (except for heart failure [HF]), whereas rosiglitazone is indistinguishable from metformin/sulfonylureas (even when including HF data). Lower-quality data do, however, lead to significant concerns for MI with rosiglitazone. Early and somewhat low-quality data for the dipeptidyl peptidase inhibitors show they are safe and hold promise for cardiovascular advantage, with major randomized controlled trials being underway. Preliminary CV data are available for one sodium/glucose cotransporter 2 inhibitor and look reassuring.

  3. 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. ©2012 AACR

  4. Overcoming Platinum Resistance through the Use of a Copper-Lowering Agent

    PubMed Central

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

    2013-01-01

    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. PMID:22491798

  5. Three amino acid derivatives of valproic acid: design, synthesis, theoretical and experimental evaluation as anticancer agents.

    PubMed

    Luna-Palencia, Gabriela R; Martinez-Ramos, Federico; Vasquez-Moctezuma, Ismael; Fragoso-Vazquez, Manuel Jonathan; Mendieta-Wejebe, Jessica Elena; Padilla-Martínez, Itzia I; Sixto-Lopez, Yudibeth; Mendez-Luna, David; Trujillo-Ferrara, Jose; Meraz-Rios, Marco A; Fonseca-Sabater, Yadira; Correa-Basurto, Jose

    2014-01-01

    Valproic acid (VPA) is extensively used as an anticonvulsive agent and as a treatment for other neurological disorders. It has been shown that VPA exerts an anti-proliferative effect on several types of cancer cells by inhibiting the activity of histone deacetylases (HDACs), which are involved in replication and differentiation processes. However, VPA has some disadvantages, among which are poor water solubility and hepatotoxicity. Therefore, the aim of the present study was to design and synthesize three derivatives of VPA to improve its physicochemical properties and anti-proliferative effects. For this purpose, the amino acids aspartic acid, glutamic acid and proline were added to the molecular structure of VPA. Docking and molecular dynamics simulations were used to determine the mode of recognition of these three derivatives by different conformations of HDAC8. This receptor was used as the specific target because of its high affinity for this type of substrate. The results demonstrate that, compared to VPA, the test compounds bind to different sites on the enzyme and that hydrogen bonds and hydrophobic interactions play key roles in this difference. The IC50 values of the VPA derivatives, experimentally determined using HeLa cells, were in the mM range. This result indicates that the derivatives have greater antiproliferative effects than the parent compound. Hence, these results suggest that these amino acid derivatives may represent a good alternative for anticancer treatment.

  6. Lower mortality among patients with community-acquired pneumonia treated with a macrolide plus a beta-lactam agent versus a beta-lactam agent alone.

    PubMed

    García Vázquez, E; Mensa, J; Martínez, J A; Marcos, M A; Puig, J; Ortega, M; Torres, A

    2005-03-01

    A cohort of 1,391 patients with community-acquired pneumonia of unknown etiology, atypical pneumonia, Legionella pneumophila pneumonia, viral pneumonia, or pneumococcal pneumonia was studied according to a standard protocol to analyse whether the addition of a macrolide to beta-lactam empirical treatment decreases mortality rates. Patients admitted to the intensive care unit were excluded. Severity was assessed using the PORT score. An etiological diagnosis was achieved in 498 (35.8%) patients (292 infections due to Streptococcus pneumoniae). Treatment was chosen by the attending physician according to his/her own criteria: beta-lactam agent in 270 and beta-lactam agent plus a macrolide in 918 cases. The mortality rate was 13.3% in the group treated with a beta-lactam agent alone and 6.9% in the group treated with a beta-lactam agent plus a macrolide (p=0.001). The percentage of PORT-group V patients was 32.6% in the group treated with a beta-lactam agent alone compared to 25.7% in the group who received a beta-lactam agent plus a macrolide (p=0.02). After controlling for PORT score, the odds of fatal outcome was two times higher in patients treated with a beta-lactam agent alone than in those treated with a beta-lactam agent plus a macrolide (adjusted OR = 2, 95%CI 1.24-3.23). The results suggest that the addition of a macrolide to an initial beta-lactam-based antibiotic regimen is associated with lower mortality in patients with community-acquired pneumonia, independent of severity of infection, thus supporting the recommendation of a beta-lactam-agent plus a macrolide as empirical therapy.

  7. Plant sterols/stanols as cholesterol lowering agents: A meta-analysis of randomized controlled trials

    PubMed Central

    AbuMweis, Suhad S.; Barake, Roula; Jones, Peter J.H.

    2008-01-01

    Background Consumption of plant sterols has been reported to reduce low density lipoprotein (LDL) cholesterol concentrations by 5–15%. Factors that affect plant sterol efficacy are still to be determined. Objectives To more precisely quantify the effect of plant sterol enriched products on LDL cholesterol concentrations than what is reported previously, and to identify and quantify the effects of subjects’ characteristics, food carrier, frequency and time of intake on efficacy of plant sterols as cholesterol lowering agents. Design Fifty-nine eligible randomized clinical trials published from 1992 to 2006 were identified from five databases. Weighted mean effect sizes were calculated for net differences in LDL levels using a random effect model. Results Plant sterol containing products decreased LDL levels by 0.31 mmol/L (95% CI, –0.35 to –0.27, P= < 0.0001) compared with placebo. Between trial heterogeneity was evident (Chi-square test, P = <0.0001) indicating that the observed differences between trial results were unlikely to have been caused by chance. Reductions in LDL levels were greater in individuals with high baseline LDL levels compared with those with normal to borderline baseline LDL levels. Reductions in LDL were greater when plant sterols were incorporated into fat spreads, mayonnaise and salad dressing, milk and yoghurt comparing with other food products such as croissants and muffins, orange juice, non-fat beverages, cereal bars, and chocolate. Plant sterols consumed as a single morning dose did not have a significant effect on LDL cholesterol levels. Conclusion Plant sterol containing products reduced LDL concentrations but the reduction was related to individuals’ baseline LDL levels, food carrier, and frequency and time of intake. PMID:19109655

  8. Synthesis of amino Derivatives of Dithio Acids as Potential Radiation Protective Agents

    DTIC Science & Technology

    1984-08-01

    ation Management S SI ____ K> AD Synthesis of Amino Derivatives of Dithio Acids as Potential Radiation Protective Agents * 0 Annual Report "TIi: o DTIC...Sftcuntiy Clatuftcatio") Synthesis of Amino Derivatives of Dithio Acids as PotentitI- Radiation Protective Agents 12l PERISONAL. Ak.TI4OR(S) * William...methyl- picoline derivatives was accomplished. Use of N-mthyl-2,6-dimethylpyridine also allowed the synthesis of a bis(dithioacetic acid) function not

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

    USDA-ARS?s Scientific Manuscript database

    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...

  10. Hyaluronic acid as an internal wetting agent in model DMAA/TRIS contact lenses.

    PubMed

    Weeks, Andrea; Luensmann, Doerte; Boone, Adrienne; Jones, Lyndon; Sheardown, Heather

    2012-11-01

    Model silicone hydrogel contact lenses, comprised of N,N-dimethylacrylamide and methacryloxypropyltris (trimethylsiloxy) silane, were fabricated and hyaluronic acid (HA) was incorporated as an internal wetting agent using a dendrimer-based method. HA and dendrimers were loaded into the silicone hydrogels and cross-linked using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry. The presence and location of HA in the hydrogels was confirmed using X-ray photoelectron spectroscopy and confocal laser scanning microscopy, respectively. The effects of the presence of HA on the silicone hydrogels on hydrophilicity, swelling behavior, transparency, and lysozyme sorption and denaturation were evaluated. The results showed that HA increased the hydrophilicity and the equilibrium water content of the hydrogels without affecting transparency. HA also significantly decreased the amount of lysozyme sorption (p < 0.002). HA had no effect on lysozyme denaturation in hydrogels containing 0% and 1.7% methacrylic acid (MAA) (by weight) but when the amount of MAA was increased to 5%, the level of lysozyme denaturation was significantly lower compared to control materials. These results suggest that HA has great potential to be used as a wetting agent in silicone hydrogel contact lenses to improve wettability and to decrease lysozyme sorption and denaturation.

  11. 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%.

  12. 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%.

  13. Bioconverted Products of Essential Fatty Acids as Potential Antimicrobial Agents

    USDA-ARS?s Scientific Manuscript database

    This review deals with the recent findings on the microbial conversion of essential fatty acids (EFAs) through Pseudomonas aeruginosa PR3 NRRL-B-18602, and the antimicrobial properties of bioconverted essential fatty acids, with particular emphasis on n-3 or n-6 fatty acids. The first section deals...

  14. [The action of week inorganic acids and lower carboxylic acids on the conductivity of bilayer lipid membranes].

    PubMed

    Kilivnik, K E; Khmarskaia, L A; Ksenzhek, O S

    2009-01-01

    The ability of weak inorganic acids (H2S, HCN) and lower carboxylic acids to interact with bilayer lipid membranes, change their conductivity, and act as protonophores has been investigated. The mechanism of changes in BLM conductivity was studied. Factors influencing the interaction of acids with model lipid membranes were determined. Maximum changes in conductivity were observed at pH values equal to the dissociation constants of weak acids and depend on the coefficients of distribution "octanol-water".

  15. 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

  16. Combination of amino acid/dipeptide with ligustrazine-betulinic acid as antitumor agents.

    PubMed

    Xu, Bing; Yan, Wen-Qiang; Xu, Xin; Wu, Gao-Rong; Zhang, Chen-Ze; Han, Yao-Tian; Chu, Fu-Hao; Zhao, Rui; Wang, Peng-Long; Lei, Hai-Min

    2017-04-21

    The lead compound TBA, 3β-Hydroxy-lup-20(29)-ene-28-oic acid-3, 5, 6-trimethylpyrazin-2-methyl ester, which exhibited promising antitumor activity and induced tumor cell apoptosis in various cancer cell lines, had previously been reported. Moreover, reports have revealed that the introduction of amino acid to betulinic acid could improve selective cytotoxicity as well as water solubility. Thus, a series of novel TBA amino acid and dipeptide derivatives were designed, synthesized and screened for selective cytotoxic activity against five cancer cell lines (HepG2, HT-29, Hela, BCG-823 and A549) and the not malignant cell line MDCK by standard MTT assay. Most of the tested TBA-amino acid and dipeptide analogues showed stronger anti-proliferative activity against all tested tumor cell lines than TBA. Among them, BA-25 exhibited the greatest cytotoxic activity on tumor cell lines (mean IC50 = 2.31 ± 0.78 μM), that was twofold than the positive drug cisplatin (DDP), while it showed lower cytotoxicity on MDCK cell line than DDP. Further cell apoptosis analyses indicated BA-25-induced apoptosis was associated with loss of mitochondrial membrane potential and increase of intracellular free Ca(2+) concentration.

  17. Amino acid derivatives of ligustrazine-oleanolic acid as new cytotoxic agents.

    PubMed

    Chu, Fuhao; Xu, Xin; Li, Guoliang; Gu, Shun; Xu, Kuo; Gong, Yan; Xu, Bing; Wang, Mina; Zhang, Huazheng; Zhang, Yuzhong; Wang, Penglong; Lei, Haimin

    2014-11-07

    A series of novel ligustrazine-oleanolic acid (TOA) derivatives were designed, and synthesized by conjugating amino acids to the 3-hydroxy group of TOA by ester bonds. Their cytotoxicity was evaluated on four cancer cell lines (HepG2, HT-29, Hela and BGC-823) by standard MTT assays. The ClogP values were calculated by means of computer simulation, and logP values of both 3β-glycine ester olean-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester (6a) and TOA were determined using a shake flask-ultraviolet spectrophotometry method. It was found that 6a and the 3β-L-lysine ester-6g not only displayed good cytotoxicity (IC50<3.5 μM) but also possessed better hydrophilicity than TOA. Moreover, 6a (IC50=4.884 μM) had lower nephrotoxicity than both 6g (IC50=2.310 μM) and cisplatin (CDDP, IC50=3.691 μM) on MDCK cells. Combining Giemsa and DAPI staining, it was further verified that 6a could induce HepG2 apoptosis via nuclei fragmentation and had lower nephrotoxicity. In addition, the structure-activity relationships of these derivatives are briefly discussed.

  18. Pharmacoeconomics of lipid-lowering agents for primary and secondary prevention of coronary artery disease.

    PubMed

    Hay, J W; Yu, W M; Ashraf, T

    1999-01-01

    Cardiovascular disease is the leading cause of death and the leading source of healthcare expenditure in the US and most other industrialised countries. Cholesterol lowering by pharmacological means prevents atherosclerotic plaque progression and has been shown to reduce both fatal and nonfatal coronary events in patients with or without coronary artery disease (CAD). Because of their excellent efficacy and safety profiles, the introduction of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (also known an 'statins') in 1987 raised hopes for demonstrating the survival benefit of cholesterol reduction. In the past decade, several large-scale placebo-controlled trials with statin therapy have revisited the relationship between cholesterol reduction, cardiovascular disease and mortality. The West of Scotland Coronary Prevention Study (WOSCOPS) [pravastatin] and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) [lovastatin] have shown significant cardiovascular disease reduction in primary prevention trials of patients with elevated and normal cholesterol levels, respectively. The Scandinavian Simvastatin Survival Study (4S), the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study and the Cholesterol and Recurrent Events (CARE) trial [pravastatin] have shown significant cardiovascular disease reduction in patients with a previous history of CAD with high, moderate and normal cholesterol levels, respectively. Three of these studies (4S, WOSCOPS and LIPID) have shown significant reduction in all-cause mortality, while all the statin secondary prevention trials (4S, CARE and LIPID) have demonstrated significant reduction in cerebrovascular disease/ Earlier cholesterol reduction cost-effectiveness studies with nonstatin treatments (bile acid resins, fibrates, niacin and diet) suggested that only patients at extremely high risk could be treated with lipid therapy in a cost-effective manner. More

  19. Long-acting contraceptive agents: testosterone esters of unsaturated acids.

    PubMed

    Francisco, C G; Freire, R; Gawronski, J; Hernández, R; Kielczewski, M; Salazar, J A; Savabi, F; Shafiee, A; Strekowski, L; Suárez, E

    1990-01-01

    The synthesis of 13 new esters of testosterone is described, with the esterifying acids bearing acetylenic, olefinic, or polyunsaturated functions in the chain, for evaluation as long-acting androgens.

  20. Mitigating the antimicrobial activities of selected organic acids and commercial sanitizers with various neutralizing agents.

    PubMed

    Park, Yoen Ju; Chen, Jinru

    2011-05-01

    This study was conducted to evaluate the abilities of five neutralizing agents, Dey-Engley (DE) neutralizing broth (single or double strength), morpholinepropanesulfonic acid (MOPS) buffer, phosphate-buffered saline (PBS), and sodium thiosulfate buffer, in mitigating the activities of acetic or lactic acid (2%) and an alkaline or acidic sanitizer (a manufacturer-recommended concentration) againt the cells of Shiga toxin-producing Escherichia coli (STEC; n = 9). To evaluate the possible toxicity of the neutralizing agents to the STEC cells, each STEC strain was exposed to each of the neutralizing agents at room temperature for 10 min. Neutralizing efficacy was evaluated by placing each STEC strain in a mixture of sanitizer and neutralizer under the same conditions. The neutralizing agents had no detectable toxic effect on the STEC strains. PBS was least effective for neutralizing the activity of selected organic acids and sanitizers. Single-strength DE and sodium thiosulfate neutralized the activity of both acetic and lactic acids. MOPS buffer neutralized the activity of acetic acid and lactic acid against six and five STEC strains, respectively. All neutralizing agents, except double-strength DE broth, had a limited neutralizing effect on the activity of the commercial sanitizers used in the study. The double-strength DE broth effectively neutralized the activity of the two commercial sanitizers with no detectable toxic effects on STEC cells.

  1. [Effects of peeling agents (resorcinol, crystalline sulfur, salicylic acid) on the epidermis of guinea pig (author's transl)].

    PubMed

    Windhager, K; Plewig, G

    1977-08-22

    The mode of action of "classical peeling agents" such as resorcinol, crystalline sulfur, and salicylic acid on the epidermis is almost unknown. There are only a few experimental data available. Therefore the effects of resorcinol, crystalline sulfur, and salicylic acid were studied. A 1% and 3% concentration of these chemicals in vaselinum flavum or Unguentum Cordes was applied to the ears and flanks of adult male guinea pigs up to 14 days. Prior to biopsies at various time intervals, 3H-thymidine was injected intradermally. Specimens were paraffin embedded and routinely processed for autoradiographical analysis. The following parameters were assessed: Labelling index (L.I. in %); number of labelled basal cells per unit length of basement membrane; papillomatosis-index; and acanthosis-factor (projection histoplanimetry). The data were statistically analysed. The peeling agents induced a concentration-dependent increase of the L.I., acanthosis, and papillomatosis. Crystalline sulfur caused the most pronounced effect, followed by resorcinol. In contrast salicylic acid caused only a minute acanthosis factor and a slight increase in labelling. The correlation coefficient r of epidermal thickness to the L.I. for all concentrations and peeling agents used reaches the high figure of 0.978 for the ear. The 1% and 3% salicylic acid has a lower acanthosis factor than vaselinum flavum by itself. Preliminary autoradiographical studies in humans with 1% and 10% salicylic acid confirm these data. Salicylic acid counteracts acanthosis. These experiments show that crystalline sulfur and resorcinol have a potent effect on cell proliferation and acanthosis. They peel via proliferation hyperkeratosis. The mode of peeling by salicylic acid must be different, as cell proliferation and acanthosis are barely enhanced. The clinically known "keratolytic" effect of salicylic acid may be due to a direct action on the intercellular cement substance of the horny cells.

  2. 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.

  3. 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.

  4. Morroniside cinnamic acid conjugate as an anti-inflammatory agent.

    PubMed

    Takeda, Yoshinori; Tanigawa, Naomi; Sunghwa, Fortunatus; Ninomiya, Masayuki; Hagiwara, Makoto; Matsushita, Kenji; Koketsu, Mamoru

    2010-08-15

    A morroniside cinnamic acid conjugate was prepared and evaluated on E-selectin mediated cell-cell adhesion as an important role in inflammatory processes. 7-O-Cinnamoylmorroniside exhibited excellent anti-inflammatory activity (IC(50)=49.3 microM) by inhibiting the expression of E-selectin; further, it was more active than another cinnamic-acid-conjugated iridoid glycoside (harpagoside; IC(50)=88.2 microM), 7-O-methylmorroniside, and morroniside itself. As a result, 7-O-cinnamoylmorroniside was observed to be a potent inhibitor of TNF-alpha-induced E-selectin expression.

  5. Antitumor Agents 255. Novel Glycyrrhetinic Acid-Dehydrozingerone Conjugates as Cytotoxic Agents

    PubMed Central

    Tatsuzaki, Jin; Taniguchi, Masahiko; Bastow, Kenneth F.; Nakagawa-Goto, Kyoko; Morris-Natschke, Susan L.; Itokawa, Hideji; Baba, Kimiye; Lee, Kuo-Hsiung

    2007-01-01

    Esterification of glycyrrhetinic acid (GA) with dehydrozingerone (DZ) resulted in a novel cytotoxic GA-DZ conjugate. Based on this exciting finding, we conjugated eleven different DZ analogs with GA or other triterpenoids, including oleanoic acid (OA) or ursolic acid (UA). In an in vitro anticancer assay using nine different human tumor cell lines, most of the GA-DZ conjugates showed significant potency. Particularly, compounds 5, 29, and 30 showed significant cytotoxic effects against LN-Cap, 1A9, and KB cells with ED50 values of 0.6, 0.8, and 0.9 μM, respectively. Similar conjugates between DZ and OA or UA were inactive suggesting that the GA component is critical for activity. Notably, although GA-DZ conjugates showed potent cytotoxic activity, the individual components (GA and DZ analogs) were inactive. Thus, GA-DZ conjugates are new chemical entities and represent interesting hits for anticancer drug discovery and development. PMID:17591444

  6. Synthesis of Nucleic Acid and Protein in L Cells Infected with the Agent of Meningopneumonitis

    PubMed Central

    Schechter, Esther M.

    1966-01-01

    Schechter, Esther M. (The University of Chicago, Chicago, Ill.). Synthesis of nucleic acid and protein in L cells infected with the agent of meningopneumonitis. J. Bacteriol. 91:2069–2080. 1966.—Synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein in uninfected L cells and in L cells infected with the meningopneumonitis agent was compared by measuring rates of incorporation of H3-cytidine and C14-lysine into nuclear, cytoplasmic, and agent fractions in successive 5-hr periods during the meningopneumonitis growth cycle. Synthesis of meningopneumonitis DNA, RNA, and protein was first clearly evident in the labeling period 15 to 20 hr after infection, soon after initiation of agent multiplication. The rates of synthesis of agent DNA, RNA, and protein increased logarithmically for a brief period and then declined. However, rates of isotope incorporation into all three meningopneumonitis macromolecules were sustained at near maximal values throughout the remainder of the meningopneumonitis growth cycle. These data are most readily interpreted in terms of multiplication of the meningopneumonitis agent by binary fission. The L cell response to infection was a decreased rate of DNA and RNA synthesis and an accelerated rate of cell death. Host protein synthesis was unaffected. The inhibition of nucleic acid synthesis in infected L cells probably involved competition between host and parasite for nucleic acid precursors. Different sublines of L cells varied greatly in the degree to which their nucleic acid-synthesizing mechanisms were damaged by infection. The cytoplasm of infected L cells contained newly synthesized DNA and RNA that could not be accounted for as intact meningopneumonitis cells. This nucleic acid probably arose from disintegration of the fragile intracellular forms of the meningopneumonitis agent. Images PMID:5937251

  7. 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.

  8. Anti-tumor agents 255: novel glycyrrhetinic acid-dehydrozingerone conjugates as cytotoxic agents.

    PubMed

    Tatsuzaki, Jin; Taniguchi, Masahiko; Bastow, Kenneth F; Nakagawa-Goto, Kyoko; Morris-Natschke, Susan L; Itokawa, Hideji; Baba, Kimiye; Lee, Kuo-Hsiung

    2007-09-15

    Esterification of glycyrrhetinic acid (GA) with dehydrozingerone (DZ) resulted in a novel cytotoxic GA-DZ conjugate. Based on this exciting finding, we conjugated eleven different DZ analogs with GA or other triterpenoids, including oleanoic acid (OA) or ursolic acid (UA). In an in vitro anti-cancer assay using nine different human tumor cell lines, most of the GA-DZ conjugates showed significant potency. Particularly, compounds 5, 29, and 30 showed significant cytotoxic effects against LN-Cap, 1A9, and KB cells with ED(50) values of 0.6, 0.8, and 0.9 microM, respectively. Similar conjugates between DZ and OA or UA were inactive suggesting that the GA component is critical for activity. Notably, although GA-DZ conjugates showed potent cytotoxic activity, the individual components (GA and DZ analogs) were inactive. Thus, GA-DZ conjugates are new chemical entities and represent interesting hits for anti-cancer drug discovery and development.

  9. Hyaluronic acid solution injection for upper and lower gastrointestinal bleeding after failed conventional endoscopic therapy.

    PubMed

    Lee, Jin Wook; Kim, Hyung Hun

    2014-03-01

    Hyaluronic acid solution injection can be an additional endoscopic modality for controlling bleeding in difficult cases when other techniques have failed. We evaluated 12 cases in which we used hyaluronic acid solution injection for stopping bleeding. Immediately following hyaluronic acid solution injection, bleeding was controlled in 11 out of 12 cases. There was no clinical evidence of renewed bleeding in 11 cases during follow up.Hyaluronic acid solution injection can be a simple and efficient additional method for controlling upper and lower gastrointestinal bleeding after failed endoscopic therapy.

  10. [Use of a domestic hydrogel as an occlusive agent of varicose veins of the lower limbs].

    PubMed

    Sannikov, A B; Nazarenko, P M

    1997-01-01

    The authors propose experimental grounds of the method of surgical correction of the pathological blood flow along varicose subcutaneous veins and the endovasal catheter obliteration of them. The method was used in operations on 70 patients with varicosities of the lower extremity veins at the I and II stages of the disease. No complications or recurrences were noted in the following 1-3 years of observation.

  11. 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.

  12. Heart Rate As a Biomarker in Heart Failure: Role of Heart Rate Lowering Agents.

    PubMed

    Shaaya, Ghazwan; Al-Khazaali, Ali; Arora, Rohit

    Heart failure (HF) is a common clinical condition affecting more than 5.8 million people in the United States, it remains the leading cause of death in the United States and worldwide. Ongoing challenges for biomarker identification include the need for objective assessment, measurement precision, and meaningful replication. Biomarkers not only serve as traditional predictors of prognosis, they can also help to identify high-risk patients who need closer monitoring and more aggressive therapy; therefore, we reviewed the use of heart rate (HR) as a biomarker in HF both of diagnostic and prognostic values, in addition, to being easily detected. HR is a determinant of myocardial oxygen demand, coronary blood flow, and myocardial performance and is central to the adaptation of cardiac output to metabolic needs. Increased HR is known to predict adverse outcome in the general population and in patients with chronic HF. Part of the ability of HR to predict risk is related to the forces driving it, namely, neurohormonal activation. We reviewed therapies, which slow the HR like β-blockers and ivabradine (a drug that is a pure HR-reducing agent), and all the clinical studies suggest the benefit of these drugs in the management of HF, and increasing evidence suggests HR as a biomarker of both diagnostic and prognostic values in HF.

  13. Monofunctionalization of Calix[4]arene Tetracarboxylic Acid at the Upper Rim with Isothiocyanate Group: First Bifunctional Chelating Agent for Alpha-Emitter Ac-225

    PubMed Central

    Chen, Xiaoyuan; Ji, Min; Fisher, Darrell R.

    2010-01-01

    A procedure is reported for synthesizing a novel, water-soluble bifunctional chelating agent derived from calix[4]arene. This chelate features tetracarboxylic acid groups at the lower rim as an actinium-225 ionophore, and an isothiocyanate functional group at the upper rim for labeling of the N-terminus of monoclonal antibodies through thiourea linkage. PMID:20651937

  14. Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools.

    PubMed

    Taha, Ameer Y; Cheon, Yewon; Faurot, Keturah F; Macintosh, Beth; Majchrzak-Hong, Sharon F; Mann, J Douglas; Hibbeln, Joseph R; Ringel, Amit; Ramsden, Christopher E

    2014-05-01

    Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6 polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations. To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering, with or without increased dietary n-3 PUFAs, alters unesterified and esterified plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. Secondary analysis of a randomized trial. Subjects with chronic headache were randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3, low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were quantified at baseline (0 weeks) and after 12 weeks on a diet. Compared to baseline, the L6 diet reduced esterified plasma LA and increased esterified n-3 PUFA concentrations (nmol/ml), but did not significantly change plasma arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA concentration was increased significantly among unesterified fatty acids. The H3-L6 diet decreased esterified LA and AA concentrations, and produced more marked increases in esterified and unesterified n-3 PUFA concentrations. Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3 PUFA concentrations in plasma, without altering plasma AA concentration. A concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA plasma concentrations and reduces AA. Published by Elsevier Ltd.

  15. 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.

  16. Nitrilotriacetic acid: a novel reducing agent for synthesizing colloidal gold.

    PubMed

    Njagi, John I; Goia, Dan V

    2014-05-01

    We report for the first time that nitrilotriacetic acid (NTA) is an effective reductant for the preparation of stable dispersions of uniform gold nanoparticles. The method described is capable of generating stable sols with a metal concentration as high as 1.5×10(-3)moldm(-3). The size of gold nanoparticles can be tuned from 10 to 160 nm by adjusting the stoichiometric excess of NTA. For a constant [Au]/[NTA] ratio the temperature affects the reduction kinetics but has little impact on the size of gold nanoparticles. The mechanisms of the reduction of Au(III) species and the formation and stabilization of gold nanoparticles are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Safety evaluation of a potential ablation agent-hydrochloric acid in the rabbits' model.

    PubMed

    Yao, Wang; Gu, Yang-Kui; Wang, Jian; Gao, Fei; Liu, Wan-Li; Huang, Jin-Hua

    2014-10-01

    To evaluate the safety of a potential ablation agent-hydrochloric acid (HCl), which may apply to treat hepatocellular carcinoma (HCC). Eighty adult New Zealand rabbits were divided into five groups of equal size (n=16), i.e., untreated group, normal saline (NS) control group, 10% HCl group, 20% HCl group and 30% HCl group. Each group was divided into two subgroups: ten rabbits for two-week toxicology study at the time points of hours 0, 0.25, 0.5, 1, 3, 6 and days 2, 7, 14 and six rabbits for imaging and histopathology study at the time points of days 2, 7 and 14. In toxicology study we evaluated the safety of HCl from arterial blood gas status, hematology and hepatic and renal functions. In imaging and histopathology study, we observed the relationship between the sizes of lesion and the concentration of HCl, as well as extension of necrosis and concentration of HCl. In this study we also observed the microcosmic and macroscopic lesion that caused by HCl. In general condition, food, water consumption and body weight decreased notablely during the beginning of the experiment. In toxicology study, alanine aminotransferase, aspartate aminotransferase and lactic acid contents were higher in the 30% hydrochloric acid group than in other groups (P<0.005), all test items returned to normal on day 14. Imaging and histopathology study showed that 30% HCl caused larger lesion area than other HCl concentration and the necrosis that caused by HCl was complete. There was also a close relationship between the size of minor damaged area and HCl concentration. The 30% HCl caused larger minor damaged area than other HCl concentration. Because the damaged area was surrounded by a layer of fiber tissue, the lesion area became larger at days 7 and 14 time points. This study also demonstrated that the adjacent organs had no obvious damage, and all the damaged areas were limited in the liver. HCl is a safe ablation agent for local injection in the liver. HCl at a lower concentration is

  18. Latest treatment for lower urinary tract dysfunction: therapeutic agents and mechanism of action.

    PubMed

    Yamaguchi, Osamu

    2013-01-01

    Recent studies suggest that antimuscarinics might suppress bladder afferent activity by blocking muscarinic receptors in the urothelium, myofibroblasts and detrusor, thereby improving overactive bladder symptoms. β(3)-Adrenoceptors are predominantly expressed in the human bladder and mediate relaxation of detrusor muscle. β(3)-Adrenoceptor agonists increase bladder capacity and prolong micturition interval. It is assumed that β(3)-adrenoceptor agonists could exert an inhibitory effect on bladder afferent through β(3)-adrenoceptors in the urothelium and detrusor, which eventually improve the symptom of urgency. Mirabegron is a potent and selective β(3)-adrenoceptor agonist. A Japanese phase 3 study showed that mirabegron has excellent efficacy and safety for treating overactive bladder. α(1)-Adrenoceptor antagonists (α(1)-blockers) have become a mainstay of male lower urinary tract symptoms treatment. The α(1)(A) subtype is known to mediate functional obstruction as a result of benign prostatic enlargement. Recent studies have suggested that α(1)(A)-adrenoceptors are additionally involved in the generation of storage symptoms. The α(1)(D) subtype is thought to play a role in the facilitation of voiding reflex; that is; storage symptoms. α(1)-Blockers often fail to alleviate overactive bladder symptoms. In this context, combination therapy with α(1)-blockers and antimuscarinics has been recommended. Treatment with 5α-reductase inhibitor for 1 year improves urinary symptoms and flow rate by reducing prostatic volume in men with benign prostatic enlargement. A pooled analysis showed that the long-term (2 or 4 years) treatment with 5α-reductase inhibitor reduced the rate of progression to acute urinary retention and surgery. Combination therapy with 5α-reductase inhibitor and α(1)-blocker was shown to provide a rapid improvement in lower urinary tract symptoms, and reduce the relative risk of acute urinary retention and benign prostatic hyperplasia

  19. 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.

  20. Selective Extraction of Zinc from Refractory Hemimorphite Using Iminodiacetic Acid as a Complexing Agent

    NASA Astrophysics Data System (ADS)

    Rao, Shuai; Zhang, Duchao; Yang, Tianzu; Liu, Weifeng; Chen, Lin; Ling, Hongbin; Zhang, Xinwang

    2017-10-01

    An environmentally friendly process for the selective extraction of zinc from refractory hemimorphite using iminodiacetic acid (H2Ida) as a complexing agent was investigated. Thermodynamic simulations demonstrated that the partially dissociated protons and amino carboxylate anions synergistically affect the dissolution of hemimorphite. The experimental results were consistent with the theoretical analyses. Under optimal conditions, the leaching extraction of zinc was above 88% and that of iron was below 4%. Furthermore, the complexing agent could be recovered from the leaching solution at the isoelectric point by adding dilute sulfuric acid.

  1. 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.

  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. Tranexamic Acid as Antifibrinolytic Agent in Non Traumatic Intracerebral Hemorrhages

    PubMed Central

    ARUMUGAM, Ananda; A RAHMAN, Noor Azman; THEOPHILUS, Sharon Casilda; SHARIFFUDIN, Ashraf; ABDULLAH, Jafri Malin

    2015-01-01

    Background: Mortality and morbidity associated with intracerebral hemorrhage is still high. Up to now, there are no evidence-based effective treatments for acute ICH. This study is to assess the effect of tranexamic acid (TXA) on hematoma growth of patients with spontaneous ICH compared to a placebo. Methods: We performed a single-blinded, randomised placebo-controlled trial of TXA (intravenous 1g bolus, followed by infusion TXA 1 g/hour for 8 hours) in acute (< 8 hours) primary ICH. Strict blood pressure control (target SBP 140-160 mmHg). A repeat Computed Tomography brain was done after 24 hours to reassess hematoma growth. The primary objective is to test the effect of TXA on hematoma growth. Other objective was to test the feasibility, tolerability, and adverse events of TXA in primary ICH. Results: Statistical analysis showed significant hematoma growth in control group after 24 hours compared to baseline (14.3300 vs 17.9940, P = 0.001) whereas the treatment group there is no significant hematoma size expansion between baseline and after 24 hours (P = 0.313). Conclusions: This study showed a significant hematoma volume expansion in the control group compared to the treatment group. PMID:27006639

  4. Remineralizing agents: effects on acid-softened enamel.

    PubMed

    Porcelli, H Bp; Maeda, F A; Silva, B R; Miranda, W G; Cardoso, P Ec

    2015-01-01

    This study sought to evaluate whether remineralizing toothpastes can protect acid-softened enamel against further erosive episodes. Fifty enamel slabs of bovine teeth with preformed erosion-like lesions were randomly assigned to 1 control and 4 experimental groups (n = 10): group 1, nanohydroxyapatite (nanoHAp) dentifrice; group 2, arginine and calcium carbonate (CaCO3) dentifrice; group 3, potassium nitrate (KNO3) and high-fluoride (F) availability dentifrice; group 4, ordinary fluoridated dentifrice (OFD); and group 5, control (deionized water). Initial hardness measurements were taken after the different treatments were applied. Statistically significant mineral gains of 8.0% and 10.0% were exhibited in groups 1 and 4, respectively. Groups 2 and 3 showed mineral gains of 4.5% and 2.1%, respectively; these were not statistically significant. Group 5 showed mineral loss (-11.8%). A 1-way analysis of variance showed no statistically significant differences in the mean microhardness values among groups. However, there are indications that the nanoHAp and OFD toothpastes may decrease erosive lesions after treatment, while the arginine + CaCO3 and KNO3 + F pastes may prevent the progression of erosive lesions.

  5. Gastric acid reduction leads to an alteration in lower intestinal microflora

    SciTech Connect

    Kanno, Takayuki; Matsuki, Takahiro; Oka, Masashi; Utsunomiya, Hirotoshi; Inada, Kenichi; Magari, Hirohito; Inoue, Izumi; Maekita, Takao; Ueda, Kazuki; Enomoto, Shotaro; Iguchi, Mikitaka; Yanaoka, Kimihiko; Tamai, Hideyuki; Akimoto, Shigeru; Nomoto, Koji; Tanaka, Ryuichiro; Ichinose, Masao

    2009-04-17

    To clarify the alterations in lower intestinal microflora induced by gastric acid reduction, the dynamics of 12 major genera or groups of bacteria comprising the microflora in feces and colonic contents were examined by quantitative real-time PCR in proton pump inhibitor-treated rats and in asymptomatic human subjects with hypochlorhydria. In both rat and human experiments, most genera or groups of intestinal microflora (facultative and obligate anaerobes) proliferated by gastric acid reduction, and marked and significant increases in the Lactobacilli group and Veillonella, oropharyngeal bacteria, were observed. In rats, potent gastric acid inhibition led to a marked and significant increase of intestinal bacteria, including the Bacteroidesfragilis group, while Bifidobacterium, a beneficial bacterial species, remained at a constant level. These results strongly indicate that the gastric acid barrier not only controls the colonization and growth of oropharyngeal bacteria, but also regulates the population and composition of lower intestinal microflora.

  6. Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters.

    PubMed

    Lin, Yuguang; Vermeer, Mario A; Trautwein, Elke A

    2011-01-01

    Hawthorn (Crataegus pinnatifida) is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT) activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA) and ursolic acid (UA)) contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE) were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w) cholesterol (control) or the same diet supplemented with (i) 0.37% hawthorn dichloromethane extract, (ii) 0.24% PSE, (iii) hawthorn dichloromethane extract (0.37%) plus PSE (0.24%) or (iv) OA/UA mixture (0.01%) for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL) cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA) enhanced the cholesterol lowering effect of plant sterols.

  7. Non-grazing and gophers lower bulk density and acidity in annual-plant soil

    Treesearch

    Raymond D. Ratliff; Stanley E. Westfall

    1971-01-01

    The effects of non-grazing on Ahwahnee coarse sandy loam were studied at the San Joaquin Experimental Range in central California. An exclosure, on which there had been no livestock grazing for 34 years, had a lower surface bulk density and lower acidity than an adjacent range that had been grazed. Bulk density averaged 1.08 gm./cc. on the ungrazed range, and 1.43 gm./...

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

    PubMed Central

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

    2011-01-01

    We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterwards 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 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 Trp exposure of 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 still displayed 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 the medical measures against the organophosphorus nerve agents. PMID:22019765

  9. Modulation of biomechanical properties of hyaluronic acid hydrogels by crosslinking agents.

    PubMed

    Choi, Sung Chul; Yoo, Mi Ae; Lee, Su Yeon; Lee, Hyun Ji; Son, Dong Hoon; Jung, Jessica; Noh, Insup; Kim, Chan-Wha

    2015-09-01

    Modulation of both mechanical properties and biocompatibilities of hyaluronic acid (HA) hydrogels is very importance for their applications in biomaterials. Pure HA solution was converted into a hydrogel by using butanediol diglycidyl ether (BDDE) as a crosslinking agent. Mechanical properties of the HA hydrogels have been evaluated by adding up different amount of BDDEs. While the mechanical properties of the obtained HA hydrogels were evaluated by measuring their crosslinking degrees, elastic modulus and viscosity, their in vitro biocompatibilities were done by measuring the degrees of anti-inflammatory reactions, cell viabilities and cytotoxicity. The degrees of anti-inflammatory reactions were determined by measuring the amount of nitric oxides (NOs) released from lipopolysaccharide(LPS)(+)-induced macrophages; cell viability was evaluated by observing differences in the behaviors of fibroblasts covered with the HA hydrogels, compared with those covered with the films of Teflon and Latex. Cytotoxicity of the HA hydrogels was also evaluated by measuring the degrees of viability of the cells exposed on the extracts of the HA hydrogels over those of Teflon, Latex and pure HA solutions by the assays of thiazoly blue tetrazolium bromide (MTT), neutral reds, and bromodeoxyuridine (BrdU). The results showed that employment of BDDEs beyond critical amounts showed lower biocompatibility of the crosslinked HA hydrogels but higher crosslinking degrees and mechanical properties, indicating the importance of controlling the HA concentrations, BDDE amounts and their reaction times for the synthesis of the crosslinked HA hydrogels for their clinical applications as biomaterials. © 2015 Wiley Periodicals, Inc.

  10. 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.

  11. Synthesis and biological activity of thiazolyl-acetic acid derivatives as possible antimicrobial agents.

    PubMed

    Shirai, Akihiro; Fumoto, Yasuko; Shouno, Tomoaki; Maseda, Hideaki; Omasa, Takeshi

    2013-01-01

    5a-h, a series of (5-substituted-2-methyl-1,3-thiazole-4-yl) acetic acids as heterocyclic acetic acid derivatives, was designed and synthesized from ethyl acetoacetate. The synthesized compounds were screened for their antimicrobial activities against bacterial and fungal strains, and their characteristics were investigated by assays under various temperature and pH conditions. Cytotoxicity was evaluated with the use of sheep erythrocytes and human neonate dermal fibroblasts. Similarly, agents such as lauric acid 6 and parabens 7a-b, which are used as preservative agents for commercial cosmetics and detergents, were assayed for comparison. Although the structure of 5a is simple, comprising a thiazole attached with an octyl group and acetic acid moiety, the compound showed stronger and broader antibacterial and antifungal activities among the 5 series against the tested microbes other than gram-negative bacteria. Interestingly, 5a overcame the weak antifungal activity of parabens 7a-b. Also, the cytotoxicity of 5a was less than that of parabens 7a-b, especially to human dermal fibroblasts. These results suggest that thiazolyl-acetic acid 5a is a potentially effective biocide, and that it could be used as a preservative agent in commercially sold cosmetics and detergents, facilitated by the hydrophilic and charge properties of its carboxylic acid moiety.

  12. 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.

  13. Long-acting contraceptive agents: norethisterone esters of monoalkenyl and monoalkynyl acids.

    PubMed

    Francisco, C G; Freire, R; Hernandez, R; Salazar, J A; Suarez, E; García de la Mora, G A; Noguez, J A; Acosta, A; Jimeno, O

    1983-03-01

    The synthesis of nine new esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) is described, with the esterifying acids bearing an acetylenic or olefinic function in a chain of eight or nine carbon atoms, for evaluation as long-acting contraceptive agents.

  14. Influence of polycarboxylic acid chelating agents on the kinetics of the dissolution of metal oxides

    SciTech Connect

    Dyatlova, N.M.; Gorichev, I.G.; Dukhanin, V.S.; Malov, L.V.

    1986-11-01

    The factors influencing the rate of dissolution of metal oxides in aqueous solutions of acids in the presence of polycarboxylic acid chelating agents and other complexing agents have been quantitatively compared in this review, and the decisive role of the gradient of protons and electrons in the realization of this process has been revealed. The main hypotheses of the proposed conceptions of the electron-proton theory for the dissolution of metal oxides have been stated: 1) The rate-limiting step is charge transfer (first hypothesis); 2) The rate limiting step is the desorption of the dissolution products (second hypothesis). The applicability of the proposed electron-proton theory to the theoretical substantiation of all the experimentally observed kinetic features of the influence of various factors has been demonstrated. Practical recommendations for the effective utilization of the chelating agents considered for removing iron oxide surface deposits have been given.

  15. Selection of a biocontrol agent based on a potential mechanism of action: degradation of nicotinic acid, a growth factor essential for Erwinia amylovora.

    PubMed

    Paternoster, Thomas; Défago, Geneviève; Duffy, Brion; Gessler, Cesare; Pertot, Ilaria

    2010-12-01

    This work describes a medium-based screening method for selecting microbial biocontrol agents against Erwinia amylovora based on the degradation of a specific growth factor. Erwinia amylovora, the causal agent of the devastating fire blight disease, requires nicotinic acid or nicotinamide as an essential growth factor. Potential biocontrol agents are either selected for antimicrobial production in plate or directly on immature pears or apple blossoms. In this work, we have attempted to streamline the selection of a new potential biocontrol agent with a lower risk of non-target effects by isolation based on the ability to degrade nicotinic acid in vitro, using therefore few plant materials. A total of 735 bacteria and 1237 yeast were isolated from apple blossoms and pre-screened for nicotinic acid-degradation. Pseudomonas rhizosphaerae strain JAN was able to degrade both nicotinic acid and nicotinamide. Mutants deficient in this ability were constructed. JAN, but not the mutants, controlled E. amylovora on pear slices. On detached apple blossoms, JAN colonized apple hypanthia and strongly suppressed E. amylovora growth. Under greenhouse conditions, JAN was more effective in controlling blossom blight than P. fluorescens A506, a commercial biocontrol agent of fire blight unable to degrade nicotinic acid and nicotinamide.

  16. 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.

  17. Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia.

    PubMed

    Takir, Mumtaz; Kostek, Osman; Ozkok, Abdullah; Elcioglu, Omer Celal; Bakan, Ali; Erek, Aybala; Mutlu, Hasan Huseyin; Telci, Ozge; Semerci, Aysun; Odabas, Ali Riza; Afsar, Baris; Smits, Gerard; ALanaspa, Miguel; Sharma, Shailendra; Johnson, Richard J; Kanbay, Mehmet

    2015-12-01

    Hyperuricemia is an independent predictor of impaired fasting glucose and type 2 diabetes, but whether it has a causal role in insulin resistance remains controversial. Here we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance. Subjects with asymptomatic hyperuricemia (n = 73) were prospectively placed on allopurinol (n = 40) or control (n = 33) for 3 months. An additional control group consisted of 48 normouricemic subjects. Serum uric acid, fasting glucose, fasting insulin, HOMA-IR (homeostatic model assessment of insulin resistance), and high-sensitivity C-reactive protein were measured at baseline and at 3 months. Allopurinol-treated subjects showed a reduction in serum uric acid in association with improvement in fasting blood glucose, fasting insulin, and HOMA-IR index, as well as a reduction in serum high-sensitivity C-reactive protein. The number of subjects with impaired fasting glucose significantly decreased in the allopurinol group at 3 months compared with baseline (n = 8 [20%] vs n = 30 [75%], 3 months vs baseline, P < 0.001). In the hyperuricemic control group, only glucose decreased significantly and, in the normouricemic control, no end point changed. Allopurinol lowers uric acid and improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia. Larger clinical trials are recommended to determine if lowering uric acid can help prevent type 2 diabetes.

  18. Outcome of Lower-Risk Patients With Myelodysplastic Syndromes Without 5q Deletion After Failure of Erythropoiesis-Stimulating Agents.

    PubMed

    Park, Sophie; Hamel, Jean-François; Toma, Andrea; Kelaidi, Charikleia; Thépot, Sylvain; Campelo, Maria Diez; Santini, Valeria; Sekeres, Mikkael A; Balleari, Enrico; Kaivers, Jennifer; Sapena, Rosa; Götze, Katharina; Müller-Thomas, Catharina; Beyne-Rauzy, Odile; Stamatoullas, Aspasia; Kotsianidis, Ioannis; Komrokji, Rami; Steensma, David P; Fensterl, Jaime; Roboz, Gail J; Bernal, Teresa; Ramos, Fernando; Calabuig, Marisa; Guerci-Bresler, Agnès; Bordessoule, Dominique; Cony-Makhoul, Pascale; Cheze, Stéphane; Wattel, Eric; Rose, Christian; Vey, Norbert; Gioia, Daniela; Ferrero, Dario; Gaidano, Gianluca; Cametti, Giovanni; Pane, Fabrizio; Sanna, Alessandro; Germing, Ulrich; Sanz, Guillermo F; Dreyfus, François; Fenaux, Pierre

    2017-03-28

    Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results Erythroid response to ESAs was 61.5%, and median response duration was 17 months. Of 1,147 patients experiencing ESA failure, 653 experienced primary failure and 494 experienced relapse after a response. Primary failure of ESAs was associated with a higher risk of acute myeloid leukemia (AML) progression, which did not translate into an OS difference. Of 450 patients (39%) who received second-line treatment, 194 received HMAs, 148 received LEN, and 108 received other treatments (MISC), whereas 697 received RBC transfusions only. Five-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for those receiving HMAs, LEN, and MISC, respectively ( P = .05). Five-year OS for patients receiving HMA, LEN, and MISC was 36.5%, 41.7%, and 51%, respectively ( P = .21). In a multivariable analysis adjusted for age, sex, revised International Prognostic Scoring System score, and progression at ESA failure, there was no significant OS difference among the three groups. Conclusion In this large, multicenter, retrospective cohort of patients with non-del(5q) lower-risk MDS treated with ESAs, none of the most commonly used second-line treatments (HMA and LEN) significantly improved OS. Early failure of ESAs was associated with a higher risk of AML progression.

  19. Augmenting the antifungal activity of an oxidizing agent with kojic Acid: control of penicillium strains infecting crops.

    PubMed

    Kim, Jong H; Chan, Kathleen L

    2014-11-12

    Oxidative treatment is one of the strategies for preventing Penicillium contamination in crops/foods. The antifungal efficacy of hydrogen peroxide (H2O2; oxidant) was investigated in Penicillium strains by using kojic acid (KA) as a chemosensitizing agent, which can enhance the susceptibility of pathogens to antifungal agents. Co-application of KA with H2O2 (chemosensitization) resulted in the enhancement of antifungal activity of either compound, when compared to the independent application of each agent alone. Of note, heat enhanced the activity of H2O2 to a greater extent during chemosensitization, whereby the minimum inhibitory or minimum fungicidal concentrations of H2O2 was decreased up to 4 or 13 fold, respectively, at 35-45 °C (heat), when compared to that at 28 °C (normal growth temperature). However, heat didn't increase the antifungal activity of KA, indicating specificity exists between heat and types of antifungals applied. The effect of chemosensitization was also strain-specific, where P. expansum (both parental and fludioxonil-resistant mutants) or P. italicum 983 exhibited relatively higher susceptibility to the chemosensitization, comparing to other Penicillium strains tested. Collectively, chemosensitization can serve as a potent antifungal strategy to lower effective dosages of toxic antifungal substances, such as H2O2. This can lead to coincidental lowering of environmental and health risks.

  20. New Advances in Fatty Acids as Antimalarial, Antimycobacterial and Antifungal Agents

    PubMed Central

    Carballeira, N.M.

    2008-01-01

    This review deals with the most recent findings on the antimalarial, antimycobacterial, and antifungal properties of fatty acids, with particular emphasis on novel marine fatty acids. The first section deals with the most recent and some background literature on what has been the latest developments with respect to fatty acids as antimalarial agents and the importance of enzyme inhibition, in particular the inhibition of the enoyl-ACP-reductase (Fab I) of P. falciparum, the principal agent responsible for malaria. This section of the review also emphasizes the latest antimalarial research with the very long-chain Δ5,9 fatty acids from sponges. The second section of the review deals with the recent literature on the antimycobacterial activity of fatty acids and the importance of enzyme inhibition, in particular the inhibition of the enoyl-ACP-reductase (InhA) of M. tuberculosis for antimycobacterial activity. The inhibitory activities of the Δ5,9 fatty acids against InhA as well as that of the α-methoxylated fatty acids are also discussed. The importance of Δ5,9 fatty acids as topoisomerase I inhibitors and its connection to cancer is also reviewed. The last part of the review, the antifungal section, also emphasizes the most recent research with antifungal fatty acids and the importance of enzyme inhibition, in particular N-myristoyltransferase (NMT) inhibition, for antifungal activity. This last section of the review emphasizes the latest research with the α-methoxylated fatty acids but the importance of acetylenic fatty acids is also considered. PMID:18023422

  1. 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.

  2. Agents.

    PubMed

    Chambers, David W

    2002-01-01

    Although health care is inherently an economic activity, it is inadequately described as a market process. An alternative, grounded in organizational economic theory, is to view professionals and many others as agents, contracted to advance the best interests of their principals (patients). This view untangles some of the ethical conflicts in dentistry. It also helps identify major controllable costs in dentistry and suggests that dentists can act as a group to increase or decrease agency costs, primarily by controlling the bad actors who damage the value of all dentists.

  3. 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.

  4. Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance.

    PubMed

    Liu, Chao; Zhen, Yuzhi; Zhao, Qingzhen; Zhai, Jian-Long; Liu, Kunshen; Zhang, Jian-Xin

    2016-07-01

    Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF.

  5. Artichoke extract lowered plasma cholesterol and increased fecal bile acids in Golden Syrian hamsters.

    PubMed

    Qiang, Zhiyi; Lee, Sun-Ok; Ye, Zhong; Wu, Xianai; Hendrich, Suzanne

    2012-07-01

    A study was conducted in hamsters to determine if artichoke leaf extract (ALE) could lower plasma total and non-HDL cholesterol by increasing fecal excretion of neutral bile acids and sterols. Sixty-four Golden Syrian hamsters (8 week old) were fed control diet or a similar diet containing ALE (4.5 g/kg diet) for 6 weeks. No significant changes for total cholesterol, HDL, non-HDL cholesterol triglycerides or fecal neutral sterols and bile acids were found after 21 days for ALE-fed animals compared with controls. But after 42 days, ALE-fed male hamsters had significantly lower total cholesterol (15%), non-HDL cholesterol (30%) and triglycerides (22%) and female hamsters fed ALE showed reductions of 15% for total cholesterol, 29% for non-HDL cholesterol and 29% for triglycerides compared with controls. Total neutral sterol and bile acids concentrations increased significantly by 50% and 53% in fecal samples of ALE fed males, and 82.4% and 25% in ALE fed females compared with controls. The ALE lowered hamster plasma cholesterol levels by a mechanism involving the greater excretion of fecal bile acids and neutral sterols after feeding for 42 days. Copyright © 2011 John Wiley & Sons, Ltd.

  6. In situ gelling properties of chitosan-thioglycolic acid conjugate in the presence of oxidizing agents.

    PubMed

    Sakloetsakun, Duangkamon; Hombach, Juliane M R; Bernkop-Schnürch, Andreas

    2009-10-01

    The rheological behaviour of chitosan-thioglycolic acid conjugate (chitosan-TGA) in the presence of four oxidizing agents was investigated. Chitosan-TGA was synthesized via amide bond formation between the primary amino group of chitosan and the carboxylic acid group of thioglycolic acid. The sol-gel phase transition of the polymer was determined by rheological measurements. Moreover, cytotoxicity of the gel in combination with each oxidizing agent was evaluated utilizing LDH and MTT assay. The modified chitosan displayed 1053+/-44 micromol/g thiol groups. Results of rheological studies showed that 1% (m/v) chitosan-TGA without any oxidizing agents became gel within 40 min. In contrast, when the oxidizing agents hydrogen peroxide, sodium periodate, ammonium persulfate and sodium hypochlorite were added, respectively, gelation took place within a few minutes. Within 20 min, hydrogen peroxide having been added in a final concentration of 25.2 nmol/L increased dynamic viscosity of 1% (m/v) chitosan-TGA up to 16,500-fold. This can be explained by the formation of inter- and/or intramolecular disulfide bonds which were indirectly verified via the decrease in thiol groups. Additionally, evidence of an increase in cross-linking of thiolated chitosan as a function of time was provided by frequency sweep measurements. Furthermore, viability of Caco-2 cells having been incubated with chitosan-TGA/oxidizing agent systems assessed by MTT assay was 70-85% and the percentage of LDH release was only in case of the chitosan-TGA/ammonium persulfate system significantly (p<0.05) raising compared to the negative control. According to these results, chitosan-TGA/oxidizing agent combinations might be a promising novel in situ gelling system for various pharmaceutical applications such as a controlled drug release carrier or for tissue engineering.

  7. Limb and lower-body duplications induced by retinoic acid in mice

    SciTech Connect

    Rutledge, J.C. ); Shourbaji, A.G.; Hughes, L.A.; Generoso, W.M. ); Polifka, J.E. ); Cruz, Y.P. ); Bishop, J.B. )

    1994-06-07

    The zygote and subsequent preimplantation stages of early mammalian development are susceptible to certain chemical perturbations that cause abnormal development of the conceptus. In certain cases, disruption in patterns of gene expression could be a primary event leading to abnormal development. To investigate this hypothesis, the authors treated pregnant mice with trans-retinoic acid, a known modulator of gene expression. Treatments were administered at various times during pregastrulation stages and the presumed onset of gastrulation. Trans-Retinoic acid induced a distinctive set of malformations, as manifested by supernumerary and ectopic limbs and duplication of portions of the lower body, but only when administered during the period of 4.5-5.5 days after mating (other malformations were induced at different stages). The limb and lower-body duplications suggest that exogenous trans-retinoic acid may influence not only the pattern for the hindlimbs but also that for the entire lower body. Since it appears likely that the embryos were affected in the late blastocyst and proamniotic-embryo stages, the provocative possibility arises that aspects of pattern formation of limbs and lower body actually occur prior to gastrulation.

  8. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Awareness and use of folic acid among women in the lower Mississippi Delta.

    PubMed

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

    2006-01-01

    National and state efforts to increase folic acid awareness and use may not be reaching large segments of the population. 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. A cross-sectional random digit dialing telephone survey was completed with a representative sample of 646 women aged 14-45 years in 36 counties of the lower Mississippi Delta. Folic acid awareness and supplement use were estimated by percentages weighted to reflect the 36-county population. Pregnancy intentions and the ability to become pregnant were used to predict awareness and use among a subsample of sexually active women. Compared to national samples, Delta women were less likely to have heard of folic acid (75% vs 64%) or to take a regular (5-7 days/wk) folic acid supplement (34% vs 22%). The proportion of women who took regular folic acid supplements was very low among some subgroups: African Americans (14%), those 14-19 years of age (12%), and those with low incomes (13%) and low educational levels (14%). Of the women who reported being sexually active, the ability to become pregnant more than doubled their likelihood of regular supplement use. The national folic acid campaign has not reached many women in the rural Mississippi Delta. A new mode of folic acid education is needed that is focused on low-income and young women and women not planning pregnancies. In the Delta and similar geographic regions, health care providers, black church leaders, and youth group leaders could be valuable advocates for folic acid.

  10. Effect of amino acids on lower esophageal sphincter characteristics and gastroesophageal reflux in humans.

    PubMed

    Gielkens, H A; Lamers, C B; Masclee, A A

    1998-04-01

    The effect of a commercially available mixed amino acids solution, when given either intravenously or intragastrically, on lower esophageal sphincter (LES) pressure, frequency of transient LES relaxations (TLESRs) and gastroesophageal reflux (GER) was investigated in six healthy volunteers. LES pressure and esophageal pH were simultaneously recorded on three separate occasions 1 hr before (basal) and 3 hr during intravenous or intragastric infusion of amino acids (250 mg protein/kg/hr) or saline (control). No significant changes in LES pressure were seen in the control experiment. Intravenous amino acids caused a rapid and sustained (P < 0.01) decrease in LES pressure whereas intragastric amino acids decreased LES pressure only gradually and temporarily (P < 0.01). In the three experiments no significant differences were observed in TLESR frequency, the number of GER episodes, the mechanism of reflux, or duration of acid exposure. In healthy subjects both intragastric and, especially, intravenous infusion of amino acids significantly decrease LES pressure but do not affect the frequency of TLESRs or GER episodes during a continuous liquid gastric load.

  11. [Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes].

    PubMed

    Scheen, A J

    2016-10-01

    Dapagliflozin, a specific inhibitor of sodium-glu¬cose cotransporters type 2 (SGLT2, inhibits glucose reabsorp¬tion in renal tubules and thus promotes glucosuria. This effect results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA1c), with a minor risk of hypoglycaemia, a weight reduction and a reduction in arterial blood pressure. The efficacy of empagliflozin on HbA1c reduction increases according to the level of hyper¬glycaemia but decreases in patients with renal insufficiency. Mycotic genital infections occur more frequently, especially in women, while a negligible increase in mild urinary tract infections may be observed. Dapagliflozin (Forxiga®), 10 mg once daily, is indicated for the treatment of T2DM and reim¬bursed in Belgium with conditions as add-on to a background glucose-lowering therapy (either metformin or sulfonylurea/ repaglinide or metformin plus sulfonylurea/repaglinide or basal insulin plus at least one of these oral glucose-lowering agents). Preliminary results suggest some cardiovascular and renal protection. These results should be confirmed in an ongoing large prospective controlled trial (DECLARE) in type 2 diabetic patients at high cardiovascular risk.

  12. 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

  13. Biological agent identification by nucleic acid base-pair analysis using surface-enhanced Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Farquharson, Stuart; Smith, Wayne W.; Elliott, Susan; Sperry, Jay F.

    1999-01-01

    Recently, a number of analytical methods have been successfully developed which use nucleic acid sequencing to identify biological warfare agents. However, the effectiveness of these methods, towards the safety and protection of US Armed Forces and their allies are limited by the period required to enumerate the nucleic acid through polymerase chain reactions or culture growth to produce sufficient quantities for analysis. To overcome this limitation, we have been investigating the ability of surface-enhanced Raman spectroscopy to detect nucleic acids with sufficient sensitivity and selectivity to eliminate the need for enumeration. The design of a small volume electrolytic sample cell will be presented along with analysis of the nucleic acid bases and preliminary analysis of model bacteria.

  14. 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.

  15. Synthesis of palm oil fatty acid as foaming agent for firefighting application

    NASA Astrophysics Data System (ADS)

    Rivai, M.; Hambali, E.; Suryani, A.; Fitria, R.; Firmansyah, S.; Pradesi, J.

    2017-05-01

    Many factors including natural factor, human carelessness, new land clearance or agricultural burning/act of vandalism and ground fire are suspected as the causes of forest fire. Foam, which cools the fire down, covers the burning material/fuel, and avoids contact between burning materials with oxygen, is an effective material used to fight large-scale fires. For this purpose, surfactant which can facilitate foam formation and inhibit the spread of smoke is required. This study was aimed at producing prototype product of foaming agent from palm oil and its formulation as a fire fighting material. Before the formulation stage, the foaming agent was resulted from saponification process of oleic, lauric, and palmitic acids by using NaOH and KOH alkaline. Foam stability was used as the main indicator of foaming agent. Results showed that potassium palmitate had the highest foam stability of 82% until the 3rd day. The best potassium palmitate concentration was 7%.

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

    SciTech Connect

    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

    2015-03-09

    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. In conclusion, 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.

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

    DOE PAGES

    Piotrowski, Jeff S.; Okada, Hiroki; Lu, Fachuang; ...

    2015-03-09

    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.more » 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. In conclusion, 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.« less

  18. Could valproic acid be an effective anticancer agent? The evidence so far.

    PubMed

    Brodie, Seth A; Brandes, Johann C

    2014-10-01

    Valproic acid is an inhibitor of class I histone deacetylases. Epigenetic therapies in cancer have been focus of a keen interest and histone deacetylase inhibitors, in particular, have been approved for certain types of hematologic malignancies. Valproic acid is an attractive candidate for cancer therapy due to its mechanism of action, its low cost and generally good clinical tolerability. In the following editorial, we will review its role as monotherapy for cancer, its place in combination epigenetic therapy, and its role as chemosensitizer, and cancer preventative agent.

  19. An amino acid mixture improves glucose tolerance and lowers insulin resistance in the obese Zucker rat.

    PubMed

    Bernard, Jeffrey R; Liao, Yi-Hung; Ding, Zhenping; Hara, Daisuke; Kleinert, Maximilian; Nelson, Jeffrey L; Ivy, John L

    2013-07-01

    The purpose of this investigation was to test an amino acid mixture on glucose tolerance in obese Zucker rats [experiment (Exp)-1] and determine whether differences in blood glucose were associated with alterations in muscle glucose uptake [experiment (Exp)-2]. Exp-1 rats were gavaged with either carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1), carbohydrate plus amino acid mixture with increased leucine concentration (OB-AA-2) or water (OB-PLA). The glucose response in OB-AA-1 and OB-AA-2 were similar, and both were lower compared to OB-CHO. This effect of the amino acid mixtures did not appear to be solely attributable to an increase in plasma insulin. Rats in Exp-2 were gavaged with carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1) or water (OB-PLA). Lean Zuckers were gavaged with carbohydrate (LN-CHO). Fifteen minutes after gavage, a radiolabeled glucose analog was infused through a catheter previously implanted in the right jugular vein. Blood glucose was significantly lower in OB-AA-1 compared to OB-CHO while the insulin responses were similar. Glucose uptake was greater in OB-AA-1 compared with OB-CHO, and similar to that in LN-CHO in red gastrocnemius muscle (5.15 ± 0.29, 3.8 ± 0.27, 5.18 ± 0.34 µmol/100 g/min, respectively). Western blot analysis showed that Akt substrate of 160 kDa (AS160) phosphorylation was enhanced for OB-AA-1 and LN-CHO compared to OB-CHO. These findings suggest that an amino acid mixture improves glucose tolerance in an insulin resistant model and that these improvements are associated with an increase in skeletal muscle glucose uptake possibly due to improved intracellular signaling.

  20. Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients.

    PubMed

    Lo, Clement; Jun, Min; Badve, Sunil V; Pilmore, Helen; White, Sarah L; Hawley, Carmel; Cass, Alan; Perkovic, Vlado; Zoungas, Sophia

    2017-02-27

    Kidney transplantation is the preferred form of kidney replacement therapy for patients with end-stage kidney disease (ESKD) and is often complicated by worsening or new-onset diabetes. Management of hyperglycaemia is important to reduce post-transplant and diabetes-related complications. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. To evaluate the efficacy and safety of pharmacological interventions for lowering glucose levels in patients who have undergone kidney transplantation and have diabetes. We searched the Cochrane Kidney and Transplant Specialised Register to 15 April 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion. Two authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). We included seven studies that involved a total of 399 kidney transplant recipients. All included studies had observed heterogeneity in the patient population, interventions and measured outcomes or missing data (which was unavailable despite correspondence with authors). Many

  1. Trivalent phosphorus acids amides as phosphorylating agents for alcohols and amines

    NASA Astrophysics Data System (ADS)

    Nifantiev, Edward E.; Grachev, M. K.

    1994-07-01

    The principal results of studies on trivalent phosphorus acid amides (TPAA) as phosphorylating agents for alcohols, phenols, and amines are summarised and discussed. Problems concerning the catalysis and mechanism of the phosphorylation of proton-donating nucleophiles by TPAA are considered and new possibilities for the development of investigations on these lines are analysed. The preparative advantages of TPAA and the specific prospects for their use in fine organic synthesis and macromolecular chemistry are demonstrated. The bibliography includes 560 references.

  2. Heritable and cancer risks of exposures to anticancer drugs: inter-species comparisons of covalent deoxyribonucleic acid-binding agents.

    PubMed

    Vogel, E W; Barbin, A; Nivard, M J; Stack, H F; Waters, M D; Lohman, P H

    1998-05-25

    In the past years, several methodologies were developed for potency ranking of genotoxic carcinogens and germ cell mutagens. In this paper, we analyzed six sub-classes of covalent deoxyribonucleic acid (DNA) binding antineoplastic drugs comprising a total of 37 chemicals and, in addition, four alkyl-epoxides, using four approaches for the ranking of genotoxic agents on a potency scale: the EPA/IARC genetic activity profile (GAP) database, the ICPEMC agent score system, and the analysis of qualitative and quantitative structure-activity and activity-activity relationships (SARs, AARs) between types of DNA modifications and genotoxic endpoints. Considerations of SARs and AARs focused entirely on in vivo data for mutagenicity in male germ cells (mouse, Drosophila), carcinogenicity (TD50s) and acute toxicity (LD50s) in rodents, whereas the former two approaches combined the entire database on in vivo and in vitro mutagenicity tests. The analysis shows that the understanding and prediction of rank positions of individual genotoxic agents requires information on their mechanism of action. Based on SARs and AARs, the covalent DNA binding antineoplastic drugs can be divided into three categories. Category 1 comprises mono-functional alkylating agents that primarily react with N7 and N3 moieties of purines in DNA. Efficient DNA repair is the major protective mechanism for their low and often not measurable genotoxic effects in repair-competent germ cells, and the need of high exposure doses for tumor induction in rodents. Due to cell type related differences in the efficiency of DNA repair, a strong target cell specificity in various species regarding the potency of these agents for adverse effects is found. Three of the four evaluation systems rank category 1 agents lower than those of the other two categories. Category 2 type mutagens produce O-alkyl adducts in DNA in addition to N-alkyl adducts. In general, certain O-alkyl DNA adducts appear to be slowly repaired, or

  3. Potential Novel Treatments for Bipolar Depression: Ketamine, Fatty Acids, Anti-inflammatory Agents, and Probiotics.

    PubMed

    Vázquez, G H; Camino, S; Tondo, L; Baldessarini, Ross J

    2017-07-28

    Treatments for depression in bipolar disorder (BD) are far less well developed than for unipolar major depressive disorder. Several innovative and experimental approaches have been emerging recently, including use of the dissociative anesthetic ketamine and other antagonists of central NMDA glutamate receptors, as well as unsaturated fatty acids, anti-inflammatory agents, and possibly probiotic methods. We reviewed relevant reports from the past decade. Ketamine, a phencyclidine-like NMDA-glutamate receptor antagonist, has emerged as a highly innovative, experimental treatment for treatment-resistant unipolar major depression, possibly in bipolar depression, and with brief antisuicidal effects. Its limitations include poor bioavailability, rapid but short-lived effects, and little information about long-term benefits and safety of repeated administration. Polyunsaturated fatty acids critical for the structure and functioning of neuronal and other cell membranes have some evidence of benefit as experimental treatments for depression including in BD. There also is evidence of altered expression of peptides associated with inflammation in mood disorder patients, encouraging experimental treatment with anti-inflammatory agents; of these, the COX-II inhibitor celecoxib has shown some evidence of benefit. The concept of altering intestinal flora with probiotic treatments to treat mood disorders remains speculative. Ketamine represents an innovative, rapidly acting, experimental treatment for bipolar depression with practical limitations. Unsaturated fatty acids and anti-inflammatory agents have inconsistent support; probiotic treatments lack evidence. These innovative approaches require much more clinical investigation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. [Enhanced phytoextraction of heavy metal contaminated soil by chelating agents and auxin indole-3-acetic acid].

    PubMed

    Zhou, Jian-min; Dang, Zhi; Chen, Neng-chang; Xu, Sheng-guang; Xie, Zhi-yi

    2007-09-01

    The environmental risk of chelating agents such as EDTA application to the heavy metals polluted soils and the stress on plant roots due to the abrupt increase metals concentration limit the wide commercial use of chelate-induced phytoextraction. Chelating agent ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid (NTA) and auxin indole-3-acetic acid (IAA) were used for enhancing heavy metals uptake from soils by Zea mays L. (corn) in pot experiments. The metals content in plant tissues was quantified using an inductively coupled plasma mass spectrometer (ICP-MS). The results showed that the combination of IAA and EDTA increased the biomass by about 40.0% and the contents of Cu, Zn, Cd and Pb in corn shoots by 27.0%, 26.8%, 27.5% and 32.8% respectively, as compared to those in EDTA treatment. While NTA&IAA treatment increased the biomass by about 29.9% and the contents of Cu, Zn, Cd and Pb in corn shoots by 31.8%, 27.6%, 17.0% and 26.9% respectively, as compared to those in NTA treatment. These results indicated that corn growth was promoted, and the biomass and the accumulation of heavy metals in plant shoots were increased significantly with the addition of IAA, which probably helps to change the cell membrane properties and the biomass distribution, resulting in the alleviation of the phytotoxicity of metals and the chelating agents.

  5. 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

  6. Synthesis of Ba 2YCu 3O 7 by the SCD method using amino acid salt reducing agents

    NASA Astrophysics Data System (ADS)

    Kourtakis, K.; Robbins, M.; Gallagher, P. K.

    1990-01-01

    The anionic oxidation-reduction or SCD method relies on an internal oxidation-reduction reaction which converts spray-dried precursors into intimately mixed and highly reactive metal oxide powders. Earlier studies focused on precursor mixtures containing oxidizing components such as NO -3 salts with reducing salts (RCOO -, where R is H, CH 3, or CH 2CH 3) which react to form Ba 2YCu 3O 7 powder. In this work, amino acid reducing agents are used. The impact of the functional group change, in the reducing agent of the {NO -3}/{amino acid} precursors, is shown by DSC to result in sharp (and therefore rapid) oxidation-reduction reactions which occur at lower temperatures. The trend in reaction temperature correlates inversely with the expected basicity of the amino group in the series (numbers in parentheses represent mole ratios): {CH 3CH(NH 2)COO -}/{NO -3} ( {4}/{9}) = 206° C > {NH 2CH 2COO -}/{NO -3} ( {4}/{9}) = 195° C > {NH 2CH 2CH 2COO -}/{NO -3} ( {4}/{9}) = 191° C. The mixed oxide product is highly reactive and can be converted to single-phase Ba 2YCu 3O x when fired at 900-910°C for 10 min in flowing oxygen.

  7. 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.

  8. 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.

  9. 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.

  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.

  11. Nucleic Acid-directed Self-assembly of Multifunctional Gold Nanoparticle Imaging Agents1

    PubMed Central

    Zhang, Ziyan; Liu, Yongjian; Jarreau, Chad; Welch, Michael J.; Taylor, John-Stephen A.

    2013-01-01

    Gold nanoparticles have attracted much interest as a platform for development of multifunctional imaging and therapeutic agents. Multifunctionalized gold nanoparticles are generally constructed by covalent assembly of a gold core with thiolated ligands. In this study, we have assembled multifunctionalized gold nanoparticles in one step by nucleic acid hybridization of ODN (oligodeoxynucleotide)-derivatized gold nanoparticles with a library of pre-functionalized complementary PNAs (peptide nucleic acids). The PNAs were functionalized by conjugation with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for chelating 64Cu for PET imaging, PEG (polyethylene glycol) for conferring stealth properties, and Cy5 for fluorescent imaging. The resulting nanoparticles showed good stability both in vitro and in vivo showing biodistribution behavior in a mouse that would be expected for a PEGylated gold nanoparticle rather than that for the radiolabelled PNA used in its assembly. PMID:24058728

  12. Lipid-Lowering Effects of Tetradecylthioacetic Acid in Antipsychotic-Exposed, Female Rats: Challenges with Long-Term Treatment

    PubMed Central

    Skrede, Silje; Fernø, Johan; Bjørndal, Bodil; Brede, Wenche Rødseth; Bohov, Pavol; Berge, Rolf Kristian; Steen, Vidar Martin

    2012-01-01

    Background Psychiatric patients often require chronic treatment with antipsychotic drugs, and while rats are frequently used to study antipsychotic-induced metabolic adverse effects, long-term exposure has only partially mimicked the appetite-stimulating and weight-inducing effects found in the clinical setting. Antipsychotic-induced effects on serum lipids are also inconsistent in rats, but in a recent study we demonstrated that subchronic treatment with the orexigenic antipsychotic olanzapine resulted in weight-independent increase in serum triglycerides and activation of lipogenic gene expression in female rats. In addition, a recent long-term study in male rats showed that chronic treatment with antipsychotic drugs induced dyslipidemic effects, despite the lack of weight gain. Aims In the current study, we sought to examine long-term effects of antipsychotic drugs on weight gain, lipid levels and lipid composition after twice-daily administration of antipsychotics to female rats, and to investigate potential beneficial effects of the lipid-lowering agent tetradecylthioacetic acid (TTA), a modified fatty acid. Methods Female rats were exposed to orexigenic antipsychotics (olanzapine or clozapine), metabolically neutral antipsychotics (aripiprazole or ziprasidone), or TTA for 8 weeks. Separate groups received a combination of clozapine and TTA or olanzapine and TTA. The effects of TTA and the combination of olanzapine and TTA after 2 weeks were also investigated. Results The antipsychotic-induced weight gain and serum triglyceride increase observed in the subchronic setting was not present after 8 weeks of treatment with antipsychotics, while lipid-lowering effect of TTA was much more pronounced in the chronic than in the subchronic setting, with concomitant upregulation of key oxidative enzymes in the liver. Unexpectedly, TTA potentiated weight gain in rats treated with antipsychotics. Conclusion TTA is a promising candidate for prophylactic treatment of

  13. Lipid-lowering effects of tetradecylthioacetic acid in antipsychotic-exposed, female rats: challenges with long-term treatment.

    PubMed

    Skrede, Silje; Fernø, Johan; Bjørndal, Bodil; Brede, Wenche Rødseth; Bohov, Pavol; Berge, Rolf Kristian; Steen, Vidar Martin

    2012-01-01

    Psychiatric patients often require chronic treatment with antipsychotic drugs, and while rats are frequently used to study antipsychotic-induced metabolic adverse effects, long-term exposure has only partially mimicked the appetite-stimulating and weight-inducing effects found in the clinical setting. Antipsychotic-induced effects on serum lipids are also inconsistent in rats, but in a recent study we demonstrated that subchronic treatment with the orexigenic antipsychotic olanzapine resulted in weight-independent increase in serum triglycerides and activation of lipogenic gene expression in female rats. In addition, a recent long-term study in male rats showed that chronic treatment with antipsychotic drugs induced dyslipidemic effects, despite the lack of weight gain. In the current study, we sought to examine long-term effects of antipsychotic drugs on weight gain, lipid levels and lipid composition after twice-daily administration of antipsychotics to female rats, and to investigate potential beneficial effects of the lipid-lowering agent tetradecylthioacetic acid (TTA), a modified fatty acid. Female rats were exposed to orexigenic antipsychotics (olanzapine or clozapine), metabolically neutral antipsychotics (aripiprazole or ziprasidone), or TTA for 8 weeks. Separate groups received a combination of clozapine and TTA or olanzapine and TTA. The effects of TTA and the combination of olanzapine and TTA after 2 weeks were also investigated. The antipsychotic-induced weight gain and serum triglyceride increase observed in the subchronic setting was not present after 8 weeks of treatment with antipsychotics, while lipid-lowering effect of TTA was much more pronounced in the chronic than in the subchronic setting, with concomitant upregulation of key oxidative enzymes in the liver. Unexpectedly, TTA potentiated weight gain in rats treated with antipsychotics. TTA is a promising candidate for prophylactic treatment of antipsychotic-induced dyslipidemic effects, but a

  14. Cholesterol-lowering effect of rice bran protein containing bile acid-binding proteins.

    PubMed

    Wang, Jilite; Shimada, Masaya; Kato, Yukina; Kusada, Mio; Nagaoka, Satoshi

    2015-01-01

    Dietary plant protein is well known to reduce serum cholesterol levels. Rice bran is a by-product of rice milling and is a good source of protein. The present study examined whether feeding rats a high-cholesterol diet containing 10% rice bran protein (RBP) for 10 d affected cholesterol metabolism. Rats fed dietary RBP had lower serum total cholesterol levels and increased excretion of fecal steroids, such as cholesterol and bile acids, than those fed dietary casein. In vitro assays showed that RBP strongly bound to taurocholate, and inhibited the micellar solubility of cholesterol, compared with casein. Moreover, the bile acid-binding proteins of the RBP were eluted by a chromatographic column conjugated with cholic acid, and one of them was identified as hypothetical protein OsJ_13801 (NCBI accession No. EAZ29742) using MALDI-TOF mass spectrometry analysis. These results suggest that the hypocholesterolemic action of the RBP may be caused by the bile acid-binding proteins.

  15. Bezafibrate lowers very long-chain fatty acids in X-linked adrenoleukodystrophy fibroblasts by inhibiting fatty acid elongation.

    PubMed

    Engelen, Marc; Schackmann, Martin J A; Ofman, Rob; Sanders, Robert-Jan; Dijkstra, Inge M E; Houten, Sander M; Fourcade, Stéphane; Pujol, Aurora; Poll-The, Bwee Tien; Wanders, Ronald J A; Kemp, Stephan

    2012-11-01

    X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene encoding ALDP, an ATP-binding-cassette (ABC) transporter located in the peroxisomal membrane. ALDP deficiency results in impaired peroxisomal β-oxidation and the subsequent accumulation of very long-chain fatty acids (VLCFA; > C22:0) in plasma and tissues. VLCFA are primarily derived from endogenous synthesis by ELOVL1. Therefore inhibiting this enzyme might constitute a feasible therapeutic approach. In this paper we demonstrate that bezafibrate, a PPAR pan agonist used for the treatment of patients with hyperlipidaemia reduces VLCFA levels in X-ALD fibroblasts. Surprisingly, the VLCFA-lowering effect was independent of PPAR activation and not caused by the increase in either mitochondrial or peroxisomal fatty acid β-oxidation capacity. In fact, our results show that bezafibrate reduces VLCFA synthesis by decreasing the synthesis of C26:0 through a direct inhibition of fatty acid elongation activity. Taken together, our data indicate bezafibrate as a potential pharmacotherapeutic treatment for X-ALD. A clinical trial is currently ongoing to evaluate the effect in patients with X-ALD.

  16. [The uric acid-lowering action of benzbromarone effervescent granules and allopurinol. Comparative studies (author's transl)].

    PubMed

    Mertz, D P

    1978-10-20

    The daily administration of 25 mg effervescent granules is about equipotent with a daily dose of 200 mg allopurinol, giving due attention to the caution necessary for uricosuric therapy. The daily administration of 50 mg benzbromarone effervescent granules has a slight but significantly greater uric acid-lowering effect than treatment with 300 mg allopurinol per day. The tolerance of benzbromarone in the active form named was good in all cases. Side effects were not observed. Since benzbromarone as effervescent granules is taken with plenty of fluid this takes care of an increased fluid intake and introduces a motivation for doing so.

  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. MULTIFUNCTIONAL SYNTHETIC POLY(L-GLUTAMIC ACID)-BASED CANCER THERAPEUTIC AND IMAGING AGENTS

    PubMed Central

    Melancon, Marites P.

    2012-01-01

    Modern polymer chemistry has led to the generation of a number of biocompatible synthetic polymers have been increasingly studied as efficient carriers for drugs and imaging agents. Synthetic biocompatible polymers have been used to improve the efficacy of both small-molecular-weight therapeutics and imaging agents. Furthermore, multiple targeted anticancer agents and/or imaging reporters can be attached to a single polymer chain, allowing multifunctional and/or multimodality therapy and molecular imaging. Having both an anticancer drug and an imaging reporter in a single polymer chain allows noninvasive real-time visualization of the pharmacokinetics of polymeric drug delivery systems, which can uncover and explain the complicated mechanisms of in vivo drug delivery and their correlation to pharmacodynamics. This review examines use of the synthetic biocompatible polymer poly(L-glutamic acid) (PG) as an efficient carrier of cancer therapeutics and imaging agents. This review will summarize and update our recent research on use of PG as a platform for drug delivery and molecular imaging, including recent clinical findings with respect to PG-paclitaxel (PG-TXL); the combination of PG-TXL with radiotherapy; mechanisms of action of PG-TXL; and noninvasive visualization of in vivo delivery of polymeric conjugates with contrast-enhanced magnetic resonance imaging (MRI), optical imaging, and multimodality imaging. PMID:21303613

  19. Radioiodinated 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid: a useful new agent to evaluate myocardial fatty acid uptake

    SciTech Connect

    Knapp, F.F. Jr.; Goodman, M.M.; Callahan, A.P.; Kirsch, G.

    1986-04-01

    Radioiodinated 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) has been prepared as a new terminal iodophenyl-substituted fatty acid containing dimethyl-branching at the beta position. For the synthesis of this new agent, chain homologation was accomplished by fabrication of a 2,5-disubstituted thiophene by successive Friedel-Crafts acylation and Wolff-Kishner reduction reactions, followed by thiophene ring opening. The dimethyl-branching was introduced using the monomethyl ester of dimethylglutaryl chloride. Radioiodination of the 15-phenyl-3,3-dimethylpentadecanoic acid substrate in the para position then gave DMIPP. Iodine-125-labeled DMIPP showed rapid, high myocardial uptake (min, mean % injected dose/g) in fasted rats (5, 4.67; 30, 5.06; 60, 4.79; 120, 4.37), and also exhibited good heart:blood ratios (min, heart:blood: 5, 3:1; 30, 12:1; 60, 12:1; 120, 13:1). To further evaluate the effects of dimethyl-branching, the biodistribution properties of DMIPP were compared with the 3-monomethyl-branched (15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid; BMIPP) and the unbranched (15-(p-iodophenyl)pentadecanoic acid; IPP) analogs. A triple-labeled (/sup 123/I)DMIPP/(/sup 131/I)BMIPP/(/sup 125/I)IPP mixture was administered to groups of fasted rats. These results confirmed the greater myocardial retention and higher heart:blood ratios observed with DMIPP in comparison with both the 3-monomethyl-(BMIPP) and unbranched (IPP) analogs. These data suggest that (/sup 123/3I)DMIPP is an excellent candidate for clinical evaluation of regional energy substrates (fatty acid) uptake.

  20. Effect of crilvastatin, a new cholesterol lowering agent, on unesterified LDL-cholesterol metabolism into bile salts by rat isolated hepatocytes.

    PubMed Central

    Clerc, T; Sbarra, V; Diaconescu, N; Lafont, H; Jadot, G; Laruelle, C; Chanussot, F

    1995-01-01

    1. The aim of these experiments was to determine the effect of crilvastatin, a new cholesterol lowering agent, on the metabolism of unesterified low density lipoprotein (LDL)-cholesterol by rat freshly isolated hepatocytes. This preclinical model was developed as an alternative to in vivo experiments, to mimic the metabolic effects of a molecule on its target cells and to define optimal conditions for future experimentation on human hepatocytes. 2. Cells were obtained from normolipidaemic or hypercholesterolaemic rats, hypercholesterolaemia was nutritionally induced. Incubations were performed in a medium containing 600 microM taurocholate and 50 microM or 300 microM crilvastatin. 3. This molecule was shown in vitro to be carried by physiological transporters, i.e., albumin-bile salt micellar associations and LDL. Crilvastatin induced a significance increase in the synthesis and secretion by hepatocytes of bile salts resulting from the metabolism of unesterified LDL-cholesterol in both normolipidaemic and hypercholesterolaemic rats. Stimulation involved non-conjugated as well as tauro- and glyco-conjugated bile salts. These findings corroborate preliminary studies showing in vivo that crilvastatin enhances the secretion of bile acids by stimulating the uptake and incorporation of LDL-cholesterol by the liver. PMID:7735689

  1. Acidic herbicides in surface waters of Lower Fraser Valley, British Columbia, Canada.

    PubMed

    Woudneh, Million B; Sekela, Mark; Tuominen, Taina; Gledhill, Melissa

    2007-01-12

    In the period 2003-2005 a study was conducted to determine the occurrence, spatial and temporal distribution of five acidic herbicides in the Lower Fraser Valley (LFV) region of British Columbia, Canada. A high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS) method capable of detecting analytes at the sub ng/L level was developed for this study. Samples were collected and analyzed from two references, five agricultural, two urban and five agricultural and urban mixed sites. Only (4-chloro-2-methylphenoxy)acetic acid and triclopyr were detected at the reference sites. The highest concentration of herbicide detected at the reference sites was 0.109ng/L for (4-chloro-2-methylphenoxy)acetic acid. Varying levels of all of the herbicides monitored were detected at the urban, agricultural and the mixed sites. For the urban sites the highest concentration of herbicide detected was 66.6ng/L for 2-(4-chloro-2-methylphenoxy)propanoic acid. For the agricultural sites the highest concentration of herbicide detected was 345ng/L for (2,4-dichlorophenoxy)acetic acid (2,4-D). For the mixed sites the highest concentration of herbicide detected was 1230ng/L for 2,4-D. Overall the mixed sites showed highest concentrations and detection frequencies followed by the agricultural and urban sites. With few exceptions higher concentrations of herbicides were observed for samples collected during spring than for samples collected during fall. The detected concentrations of herbicides were evaluated against established water quality criteria. Herbicide data presented in this study provide reference levels for future pesticide monitoring programs in the region.

  2. Renal and Vascular Effects of Uric Acid Lowering in Normouricemic Patients With Uncomplicated Type 1 Diabetes.

    PubMed

    Lytvyn, Yuliya; Har, Ronnie; Locke, Amy; Lai, Vesta; Fong, Derek; Advani, Andrew; Perkins, Bruce A; Cherney, David Z I

    2017-07-01

    Higher plasma uric acid (PUA) levels are associated with lower glomerular filtration rate (GFR) and higher blood pressure (BP) in patients with type 1 diabetes (T1D). Our aim was to determine the impact of PUA lowering on renal and vascular function in patients with uncomplicated T1D. T1D patients (n = 49) were studied under euglycemic and hyperglycemic conditions at baseline and after PUA lowering with febuxostat (FBX) for 8 weeks. Healthy control subjects were studied under normoglycemic conditions (n = 24). PUA, GFR (inulin), effective renal plasma flow (para-aminohippurate), BP, and hemodynamic responses to an infusion of angiotensin II (assessment of intrarenal renin-angiotensin-aldosterone system [RAAS]) were measured before and after FBX treatment. Arterial stiffness, flow-mediated dilation (FMD), nitroglycerin-mediated dilation (GMD), urinary nitric oxide (NO), and inflammatory markers were measured before and after FBX treatment. Gomez equations were used to estimate arteriolar afferent resistance, efferent resistance (RE), and glomerular hydrostatic pressure (PGLO). FBX had a modest systolic BP-lowering effect in T1D patients (112 ± 10 to 109 ± 9 mmHg, P = 0.049) without impacting arterial stiffness, FMD, GMD, or NO. FBX enhanced the filtration fraction response to hyperglycemia in T1D patients through larger increases in RE, PGLO, and interleukin-18 but without impacting the RAAS. FBX lowered systolic BP and modulated the renal RE responses to hyperglycemia but without impacting the RAAS or NO levels, suggesting that PUA may augment other hemodynamic or inflammatory mechanisms that control the renal response to hyperglycemia at the efferent arteriole. Ongoing outcome trials will determine cardiorenal outcomes of PUA lowering in patients with T1D. © 2017 by the American Diabetes Association.

  3. Failure of various agents to decrease oleic acid pulmonary albumin leak.

    PubMed

    Sugerman, H J; Blocher, C R; Hirsch, J I; Strash, A M; Tatum, J L

    1983-05-01

    Computerized pulmonary gamma scintigraphy has been shown to be a sensitive technique for the measurement of albumin flux in oleic acid pulmonary microvascular injury. In this technique technetium-99m-tagged human serum albumin is administered intravenously and lung:heart radioactivity ratios are constructed. This ratio remains constant unless there is a net flux of albumin from the vascular space into the lung, when a rising ratio is seen, called the "slope of injury" or SI. Gamma scintigraphy provides a method to rapidly screen the ability of various possible therapeutic agents to reduce the flux of albumin in experimental ARDS. In this study, 0.05 ml/kg oleic acid produced a significant increase in the SI. None of the agents tested (30 mg/kg methylprednisolone, 12.5 mg/kg ibuprofen, 4 mg/kg MK-447, a superoxide radical scavenger, or 140 mg/kg calcium gluconate) were able to alter the scintigraphically measured increased albumin flux produced by 0.05 ml/kg oleic acid.

  4. 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.

  5. Assessment of ADRs associated with lipid-lowering agents recorded in the Department of Internal Medicine, University Hospital, Jena.

    PubMed

    Hippius, M; Farker, K; Helble, S; Hoffmann, A

    2002-03-01

    Drug-related illness is an important cause of admission to hospital. Little information is available regarding the frequency of ADRs caused by antilipidemic agents classified as HMG-CoA reductase inhibitors (statins). Treatment with statins has been associated with the occurrence of myopathy or liver toxicity in case reports. Recent lipid intervention studies have involved the implementation of lipid lowering therapy with HMG-CoA reductase inhibitors in cardiovascular risk management. Since January 1997 we have been involved in a study, the aim of which was to improve the spontaneous drug information reporting system in Germany. The study was supported by the German Federal Institute for Drugs and Medical Devices, the "Bundesinstitut für Arzneimittel und Medizinprodukte", Berlin BfArM. Between early 1997 and late 2000, as a result of this monitoring of ADRs, we analyzed all patient histories concerning therapy with statins. A total of 550 ADR patients were evaluated, (209 male, 341 female) with a mean age of 66.4 years. 27 (4.9%) of all patients had received statins (atorvastatin = 12, fluvastatin = 7, simvastatin as well as pravastatin = 3, lovastatin = 2). Only 2 of the 27 patients admitted to hospital for typical ADRs of statins such as skeletal muscle toxicity (e.g. myalgia, rhabdomyolysis) or disorders involving hepatic structure or function were receiving statins (atorvastatin). An increased risk of rhabdomyolysis has been reported in the case of several statins, following concomitant use with erythromycin, cyclosporine or itraconazole, all of which are potent inhibitors of CYP3A4 enzyme. But only 1 atorvastatin patient had received cyclosporine as a CYP3A4 inhibitor. After discontinuing medication, signs of intoxication disappeared. The antihyperlipidemic drugs available are generally safe and effective, and rate of ADRs is low if concomitant intake of other drugs and the differing pharmacokinetic profiles of the statins are considered.

  6. Phytic acid (IP6), novel broad spectrum anti-neoplastic agent: a systematic review.

    PubMed

    Fox, C H; Eberl, M

    2002-12-01

    Phytic acid or IP6 has been extensively studied in animals and is being promoted as an anti-cancer agent in health food stores. It is naturally found in legumes, wheat bran, and soy foods. It is believed to be the active ingredient that gives these substances their cancer fighting abilities. Proposed mechanisms of action include gene alteration, enhanced immunity, and anti-oxidant properties. A Medline search from 1966 to May 2002 using the keywords phytic acid and cancer, and limiting the search to the subheadings of therapeutic uses, prevention, and adverse effects revealed 28 studies. These studies were included in the review. A great majority of the studies were done in animals and showed that phytic acid had anti-neoplastic properties in breast, colon, liver, leukemia, prostate, sarcomas, and skin cancer. There were no human studies. Side effects included chelation of multivalent cations, and an increase in bladder and renal papillomas. This increase in papilloma formation only occurred with the sodium salt of phytic acid. It did not occur with either the potassium or magnesium salts. There is a large body of animal evidence to show that phytic acid may have a role in both the prevention and treatment of many forms of cancer. There is clearly enough evidence to justify the initiation of Phase I and Phase II clinical trials in humans.

  7. Acid reducing agents to neonates – lack of evidence and guidelines

    PubMed Central

    Paulsson, Stina; Eksborg, Staffan; Andersson, Åsa; Nydert, Per; Grahnquist, Lena

    2012-01-01

    Objective The aim of this retrospective study was to investigate the clinical practice, i.e. the frequency of use and the treatment strategies, for acid reducing drugs to neonates in a Swedish hospital. Methods Retrospective reviews of charts and interviews with nurses at the neonatal wards of Karolinska University Hospital were performed to identify difficulties that might occur with drug administration. All patients admitted over a 2-month period were included. Main outcome measure were the number of patients treated with acid reducing drugs and the dosages. Results Nine out of 215 patients (4.2%) received an acid reducing drug. Patients treated with acid reducing drugs had significantly lower birth weight, lower gestational age and longer duration of hospitalization. Eight of the patients were treated with omeprazole. One of these patients started treatment with omeprazole but continued later on with ranitidine. One patient was exclusively treated with ranitidine. The doses of omeprazole (intravenous or oral administration) were within the range 0.16–1.26 mg/kg/day. Conclusions A wide variation in treatment regimens of acid reducing drugs is given to newborn infants. The percentage of treated children was much lower than earlier reports from the US and UK. No conclusions can be drawn as to whether the doses and dosing intervals used give sufficient acid suppression, since the effect of the therapy was not recorded. The present study is only retrospective and data are not truly comparable with other studies. Further studies are therefore warranted to evaluate effective doses and pharmacokinetics of acid reducing drugs in newborn infants. PMID:27536424

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

    PubMed

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

    2014-06-01

    Unnatural cyclic amino acids (UNAAs) 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) were evaluted 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 (ICP-OES) at 2.5h following intraperitoneal (i.p.) injection of the test agents at a concentration equivalent to 24mg/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 could be potentially 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.

  9. Reaction of nucleic acids and cis-diamminedichloroplatinum(II) in the presence of intercalating agents.

    PubMed Central

    Malinge, J M; Leng, M

    1986-01-01

    The reaction of cis-diamminedichloroplatinum(II) and several synthetic or natural double-stranded polydeoxyribonucleotides has been carried out in the presence of such intercalating agents as ethidium bromide, proflavine, and acridine. After incubation of the reaction mixtures at 37 degrees C for 24 hr, some ethidium or proflavine, but no acridine, molecules are tightly bound to nucleic acids. Tight binding is defined by resistance to extraction with butanol, assayed by filtration at acid pH or by thin-layer chromatography at basic pH. In the ternary complexes, there is about one tightly bound ethidium (or proflavine) per platinum residue. At 37 degrees C, but not at 4 degrees C, tightly bound ethidium exchanges with free ethidium, whereas platinum residues do not exchange. The binding and the release of tightly bound ethidium are very slow (several hours). It is suggested that in the ternary complexes, nucleic acid-cis-Pt(NH3)2-intercalating agent, a bidentate adduct (guanine-ethidium or -proflavine)-cis-Pt(NH3)2, is formed. No tightly bound ethidium or proflavine is found when cis-diamminedichloroplatinum(II) is replaced by trans-diamminedichloroplatinum(II). Competition experiments between cis-diamminedichloroplatinum(II), poly(dG-dC), and poly(dG)-poly(dC) or poly(dA-dT) show that the presence of ethidium bromide, proflavine, or acridine interferes with the distribution of platinum between the polynucleotides. These results might help to explain the synergism for drugs used in combination with cis-diamminedichloroplatinum(II) and in the design of new chemotherapeutic agents. PMID:3462697

  10. Reduction of the surface-tension-lowering ability of surfactant after exposure to hypochlorous acid.

    PubMed Central

    Merritt, T A; Amirkhanian, J D; Helbock, H; Halliwell, B; Cross, C E

    1993-01-01

    The reactive species hypochlorous acid (HOCl/OCl-) is a major product of the respiratory burst in activated neutrophils. We studied the effects of HOCl/OCl- on human surfactant and upon surfactants Survanta, KL4 and Exosurf, utilizing a pulsating surfactometer for measuring surface tension. HOCl/OCl- induced a marked dose-dependent decrease in the surface-tension-lowering activity of human surfactant. The surfactant containing surfactant proteins B and C (Survanta) was less sensitive; however, synthetic surfactants with or without peptides were not affected by HOCl/OCl- (KL4, Exosurf). Ascorbic acid and GSH protected human surfactant against inactivation by HOCl/OC1-. We suggest that HOCl/OCl- produced by activated phagocytes in the alveolar compartment of the lung could damage endogenous surfactant and affect the function of exogenously administered natural or other surfactants, especially if ascorbic acid and GSH levels in the lung lining fluids are subnormal, as is known to be the case in some inflammatory lung diseases. PMID:8216215

  11. In vivo efficacy of the diuretic agent ethacrynic acid against multiple myeloma.

    PubMed

    Kim, Young; Gast, Sanna-Marie; Endo, Tomoyuki; Lu, Desheng; Carson, Dennis; Schmidt-Wolf, Ingo G H

    2012-05-01

    It was recently confirmed that the diuretic agent ethacrynic acid (EA) inhibits Wnt/beta catenin signaling in myeloma. This study investigated the antitumor effect of EA in vivo in a murine myeloma model. In vivo, tumor growth was significantly reduced and overall survival significantly prolonged in mice treated with EA as compared to untreated mice. Interestingly, this effect was higher as compared to the effect by lenalidomide, a commonly used drug against myeloma. These results reveal a significant in vivo effect by EA against myeloma.

  12. 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.

  13. Investigation of Changing Pore Topology and Porosity During Matrix Acidizing using Different Chelating Agents

    NASA Astrophysics Data System (ADS)

    Umer Shafiq, Mian; Khaled Ben Mahmud, Hisham; Rezaee, Reza; Testamanti, Nadia

    2017-07-01

    Core flooding acidizing experiments on sandstone/carbonate formation are usually performed in the laboratory to observe different physical phenomena and to design acidizing stimulation jobs for the field. During the tests, some key parameters are analyzed such as pore volume required for breakthrough as well as pressure. Hydrochloric acid (HCl) is commonly used in the carbonate matrix acidizing while Mud acid (HF: HCl) is usually applied during the sandstone acidizing to remove damage around the well bore. However, many problems are associated with the application of these acids, such as fast reaction, corrosion and incompatibility of HCl with some minerals (illite). To overcome these problems, chelating agents (HEDTA, EDTA and GLDA) were used in this research. Colton tight sandstone and Guelph Dolomite core samples were used in this study. The experiments usually are defined in terms of porosity, permeability, dissolution and pore topology. Effluent samples were analyzed to determine dissolved iron, sodium, potassium, calcium and other positive ions using Inductively Coupled Plasma (ICP). Meanwhile Nuclear Magnetic Resonance (NMR) was employed to determine porosity and pore structure of the core sample. Core flood experiments on Berea sandstone cores and dolomite samples with dimensions of 1.5 in × 3 in were conducted at a flow rate of 1 cc/min under 150oF temperature. NMR and porosity analysis concluded that applied chemicals are effective in creating fresh pore spaces. ICP analysis concluded that HEDTA showed good ability to chelate calcium, sodium, magnesium, potassium and iron. It can be established from the analysis that HEDTA can increase more amount of permeability as compared to other chelates.

  14. 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

  15. Conversion of glucose to fatty acids and methane: roles of two mycoplasmal agents

    SciTech Connect

    Rose, C.S.; Pirt, S.J.

    1981-07-01

    Two species of obligately anaerobic mycoplasmas were the major components of a methanogenic glucose-limited enrichment culture. In pure culture, one of these organisms, tentatively named Anaeroplasma sp. strain London, was shown to be responsible for the fermentation of glucose to fatty acids, hydrogen, and carbon dioxide; the other mycoplasma was shown to produce methane from hydrogen and carbon dioxide and was named Methanoplasma elizabethii. This same methanogenic mycoplasma contained a low-molecular-weight fluorescent cofactor which had a maximum light absorbance at 430 nm. When both species of mycoplasmas were grown together on glucose, fermentation products included fatty acids and methane. For the first time, mycoplasmas are implicated as agents of anaerobic degradation and methanogenesis in a sewage sludge digester.

  16. Antimicrobial peptides incorporating non-natural amino acids as agents for plant protection.

    PubMed

    Ng-Choi, Iteng; Soler, Marta; Güell, Imma; Badosa, Esther; Cabrefiga, Jordi; Bardaji, Eduard; Montesinos, Emilio; Planas, Marta; Feliu, Lidia

    2014-04-01

    The control of plant pathogens is mainly based on copper compounds and antibiotics. However, the use of these compounds has some limitations. They have a high environmental impact and the use of antibiotics is not allowed in several countries. Moreover, resistance has been developed to these pathogens. The identification of new agents able to fight plant pathogenic bacteria and fungi will represent an alternative to currently used antibiotics or pesticides. Antimicrobial peptides are widely recognized as promising candidates, however naturally occurring sequences present drawbacks that limit their development. These include susceptibility to protease degradation and low bioavailability. To overcome these problems, research has focused on the introduction of unnatural amino acids into lead peptide sequences. In particular, we have improved the biological profile of antimicrobial peptides active against plant pathogenic bacteria and fungi by incorporating triazolyl, biaryl and D-amino acids into their sequence. These modifications and their influence on the biological activity are summarized.

  17. Lignosulfonates carboxylated with chloroacetic acid as additives in oil recovery processes involving chemical recovery agents

    SciTech Connect

    Kalfoglou, G.

    1981-05-19

    A process for producing petroleum from subterranean formations is disclosed wherein production from the formation is obtained by driving a fluid from an injection well to a production well. The process involves injecting via the injection well into the formation an aqueous solution of lignosulfonates carboxylated with chloroacetic acid as a sacrificial agent to inhibit the deposition of surfactant and/or polymer on the reservoir matrix. The process may best be carried out by injecting the lignosulfonates carboxylated with chloroacetic acid into the formation through the injection well mixed with either a polymer, a surfactant solution and/or a micellar dispersion. This mixture would then be followed by a drive fluid such as water to push the chemicals to the production well.

  18. Lowered omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients.

    PubMed

    Maes, M; Christophe, A; Delanghe, J; Altamura, C; Neels, H; Meltzer, H Y

    1999-03-22

    Depression is associated with a lowered degree of esterification of serum cholesterol, an increased C20:4omega6/C20:5omega3 ratio and decreases in omega3 fractions in fatty acids (FAs) or in the red blood cell membrane. The aims of the present study were to examine: (i) serum phospholipid and cholesteryl ester compositions of individual saturated fatty acids (SFAs), monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs) in major depressed patients vs. healthy volunteers; (ii) the relationships between the above FAs and lowered serum zinc (Zn), a marker of the inflammatory response in depression; and (iii) the effects of subchronic treatment with antidepressants on FAs in depression. The composition of the FAs was determined by means of thin layer chromatography in conjunction with gas chromatography. Lipid concentrations were assayed by enzymatic colorimetric methods. The oxidative potential index (OPI) of FAs was computed in 34 major depressed inpatients and 14 normal volunteers. Major depression was associated with: increased MUFA and C22:5omega3 proportions and increased C20:4omega6/C20:5omega3 and C22:5omega6/C22:6omega3 ratios; lower C22:4omega6, C20:5omega3 and C22:5omega3 fractions in phospholipids; lower C18:3omega3, C20:5omega3 and total (sigma)omega3 FAs, and higher C20:4omega6/C20:5omega3 and sigmaomega6/sigmaomega3 ratios in cholesteryl esters; lower serum concentrations of phospholipids and cholesteryl esters; and a decreased OPI. In depression, there were significant and positive correlations between serum Zn and C20:5omega3 and C22:6omega3 fractions in phospholipids; and significant inverse correlations between serum Zn and the sigmaomega6/sigmaomega3, C20:4omega6/C20:5omega3, and C22:5omega6/C22:6omega3 ratios in phospholipids. There was no significant effect of antidepressive treatment on any of the FAs. The results show that, in major depression, there is a deficiency of omega3 PUFAs and a compensatory increase in MUFAs and C22:5omega6 in

  19. Icosapent ethyl: Eicosapentaenoic acid concentration and triglyceride-lowering effects across clinical studies.

    PubMed

    Bays, Harold E; Ballantyne, Christie M; Doyle, Ralph T; Juliano, Rebecca A; Philip, Sephy

    2016-09-01

    Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved at a dose of 4g/day as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500mg/dL) hypertriglyceridemia. This post-hoc exploratory analysis examined the relationship of icosapent ethyl dose with EPA concentrations in plasma and red blood cells (RBCs) across 3 clinical studies-a phase 1 pharmacokinetic study in healthy adult volunteers and 2 pivotal phase 3 studies (MARINE and ANCHOR) in adult patients with hypertriglyceridemia-and examined the relationship between EPA levels and TG-lowering effects in MARINE and ANCHOR. In all 3 studies, icosapent ethyl produced dose-dependent increases in the concentrations of EPA in plasma and RBCs. In both MARINE and ANCHOR, these dose-dependent EPA increases correlated with the degree of TG level lowering (all P<0.01). In patients with high TG levels (≥200mg/dL) and treated with icosapent ethyl 4g/day, the end-of-treatment plasma and RBC EPA concentrations were >170μg/mL and>70μg/mL, respectively. These studies support icosapent ethyl as producing predictable dose-dependent pharmacokinetics/pharmacodynamics, with TG level lowering dependent upon icosapent ethyl dose and EPA concentrations in plasma and RBCs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Potential of the chlorogenic acid as multitarget agent: Insulin-secretagogue and PPAR α/γ dual agonist.

    PubMed

    Sanchez, Maetzin Becerra; Miranda-Perez, Elizabeth; Verjan, Juan Carlos Gomez; de Los Angeles Fortis Barrera, Maria; Perez-Ramos, Julia; Alarcon-Aguilar, Francisco Javier

    2017-10-01

    The chlorogenic acid (CGA) is a natural product isolated from Cecropia obtusifolia, which possesses several pharmacological properties, such as: anti-carcinogenic, neuroprotective, antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic. In relation to its effects on the hyperglycemia and hypertriglyceridemia, few is known about the mechanisms in which this compound may be acting, therefore, the aim of the present study was to determine if CGA acts as an insulin secretagogue increasing intracellular calcium concentrations ([Ca(2+)]i) in RINm5F cells; or as an insulin sensitizer and lipid-lowering agent stimulating the expression of PPARγ and PPARα, respectively, in 3T3-L1 adipocytes. As results, RINm5F cells treated with 200μM of CGA showed an increase in [Ca(2+)]i of 9-times versus control and 4-times as compared to positive control; in addition, an increase in insulin secretion was observed similarly to those of positive control. CGA also significantly increased the mRNA expression of PPARγ (150%) and GLUT4 (220%), as well PPARα (40%) and FATP (25%) as it was appreciated by RT-PCR. Additionally, a chemoinformatic analysis suggested that CGA has suitable physicochemical properties to be considered as leader bioactive molecule for the development of novel agents with similar properties. Together, our results indicate that CGA possesses multiple mechanisms of action for the development of highly effective therapeutics in the treatment of metabolic diseases such as type 2 diabetes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. An Overview of Structurally Modified Glycyrrhetinic Acid Derivatives as Antitumor Agents.

    PubMed

    Xu, Bing; Wu, Gao-Rong; Zhang, Xin-Yu; Yan, Meng-Meng; Zhao, Rui; Xue, Nan-Nan; Fang, Kang; Wang, Hui; Chen, Meng; Guo, Wen-Bo; Wang, Peng-Long; Lei, Hai-Min

    2017-06-02

    Glycyrrhetinic Acid (GA), a triterpenoid aglycone component of the natural product glycyrrhizinic acid, was found to possess remarkable anti-proliferative and apoptosis-inducing activity in various cancer cell lines. Though GA was not as active as other triterpenes, such as betulinic acid and oleanolic acid, it could trigger apoptosis in tumor cells and it can be obtained easily and cheaply, which has stimulated scientific interest in using GA as a scaffold to synthesize new antitumor agents. The structural modifications of GA reported in recent decades can be divided into four groups, which include structural modifications on ring-A, ring-C, ring-E and multiple ring modifications. The lack of a comprehensive and recent review on this topic prompted us to gather more new information. This overview is dedicated to summarizing and updating the structural modification of GA to improve its antitumor activity published between 2005 and 2016. We reviewed a total of 210 GA derivatives that we encountered and compiled the most active GA derivatives along with their activity profile in different series. Furthermore, the structure activity relationships of these derivatives are briefly discussed. The included information is expected to be of benefit to further studies of structural modifications of GA to enhance its antitumor activity.

  2. 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.

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

    PubMed

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

    2015-07-21

    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.

  4. 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

  5. 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

    2012-07-06

    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.

  6. 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.

  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. RNA Preservation Agents and Nucleic Acid Extraction Method Bias Perceived Bacterial Community Composition

    PubMed Central

    McCarthy, Ann; Chiang, Edna; Schmidt, Marian L.; Denef, Vincent J.

    2015-01-01

    Bias is a pervasive problem when characterizing microbial communities. An important source is the difference in lysis efficiencies of different populations, which vary depending on the extraction protocol used. To avoid such biases impacting comparisons between gene and transcript abundances in the environment, the use of one protocol that simultaneously extracts both types of nucleic acids from microbial community samples has gained popularity. However, knowledge regarding tradeoffs to combined nucleic acid extraction protocols is limited, particularly regarding yield and biases in the observed community composition. Here, we evaluated a commercially available protocol for simultaneous extraction of DNA and RNA, which we adapted for freshwater microbial community samples that were collected on filters. DNA and RNA yields were comparable to other commonly used, but independent DNA and RNA extraction protocols. RNA protection agents benefited RNA quality, but decreased DNA yields significantly. Choice of extraction protocol influenced the perceived bacterial community composition, with strong method-dependent biases observed for specific phyla such as the Verrucomicrobia. The combined DNA/RNA extraction protocol detected significantly higher levels of Verrucomicrobia than the other protocols, and those higher numbers were confirmed by microscopic analysis. Use of RNA protection agents as well as independent sequencing runs caused a significant shift in community composition as well, albeit smaller than the shift caused by using different extraction protocols. Despite methodological biases, sample origin was the strongest determinant of community composition. However, when the abundance of specific phylogenetic groups is of interest, researchers need to be aware of the biases their methods introduce. This is particularly relevant if different methods are used for DNA and RNA extraction, in addition to using RNA protection agents only for RNA samples. PMID:25798612

  9. RNA preservation agents and nucleic acid extraction method bias perceived bacterial community composition.

    PubMed

    McCarthy, Ann; Chiang, Edna; Schmidt, Marian L; Denef, Vincent J

    2015-01-01

    Bias is a pervasive problem when characterizing microbial communities. An important source is the difference in lysis efficiencies of different populations, which vary depending on the extraction protocol used. To avoid such biases impacting comparisons between gene and transcript abundances in the environment, the use of one protocol that simultaneously extracts both types of nucleic acids from microbial community samples has gained popularity. However, knowledge regarding tradeoffs to combined nucleic acid extraction protocols is limited, particularly regarding yield and biases in the observed community composition. Here, we evaluated a commercially available protocol for simultaneous extraction of DNA and RNA, which we adapted for freshwater microbial community samples that were collected on filters. DNA and RNA yields were comparable to other commonly used, but independent DNA and RNA extraction protocols. RNA protection agents benefited RNA quality, but decreased DNA yields significantly. Choice of extraction protocol influenced the perceived bacterial community composition, with strong method-dependent biases observed for specific phyla such as the Verrucomicrobia. The combined DNA/RNA extraction protocol detected significantly higher levels of Verrucomicrobia than the other protocols, and those higher numbers were confirmed by microscopic analysis. Use of RNA protection agents as well as independent sequencing runs caused a significant shift in community composition as well, albeit smaller than the shift caused by using different extraction protocols. Despite methodological biases, sample origin was the strongest determinant of community composition. However, when the abundance of specific phylogenetic groups is of interest, researchers need to be aware of the biases their methods introduce. This is particularly relevant if different methods are used for DNA and RNA extraction, in addition to using RNA protection agents only for RNA samples.

  10. Seasonality and movement of adventive populations of the arundo wasp (Hymenoptera: Eurytomidae), a biological control agent of giant reed in the Lower Rio Grande Basin in south Texas

    USDA-ARS?s Scientific Manuscript database

    The arundo wasp, Tetramesa romana, has been permitted as a biological control agent for the invasive perennial grass, Arundo donax. Evidence of adventive populations of the arundo wasp in the Lower Rio Grande Basin was confirmed with a spatio-temporal survey spanning more than 350 river miles. A ...

  11. Possible formation of amino acid precursors in the lower atmosphere of Titan

    NASA Astrophysics Data System (ADS)

    Kobayashi, K.; Taniuchi, T.; Kaneko, T.; Al-Hanbali, H.; Yamori, A.; Miyakawa, S.; Takano, Y.

    Titan is a quite interesting satellite of Saturn from the point of view of astrobiology and origins of life It has ca 0 15 MPa atmosphere mainly composed of nitrogen and methane which can give us the possible implication of primitive Earth environments There have been a great number of experiments simulating chemical reactions in Titan atmosphere In most experiments electric discharges and ultraviolet light were used as energy sources The former is simulation of charged particles trapped in Saturn s magnetosphere and the latter is simulation of solar light Thus it can be said that these experiments simulate chemical reaction in the upper thin atmosphere Cosmic rays are another possible energy source available in Titan atmosphere Their energy is so high that they can penetrate into the lower atmosphere of Titan The energy flux of cosmic rays in the lower Titan atmosphere was estimated as to 9 0 x 10 -3 erg cm -2 s -1 Sagan and Thompson 1984 In order to simulate the action of cosmic rays in Titan atmosphere we irradiated simulated Titan atmosphere with high-energy protons A gas mixture of methane 1-10 and nitrogen balance total pressure was 700 Torr was sealed in a Pyrex tube with a window of Havar foil 0 01 mm thick It was irradiated with 3 MeV protons from a van de Graaff accelerator Tokyo Institute of Technology The products were dissolved in water dichloromethane tetrahydrofuran or benzene They were evaporated to dryness and then acid-hydrolyzed Amino acids were analyzed by cation exchange HPLC

  12. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria.

    PubMed

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-10-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UE(UA)) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UE(UA), suggesting that SUA decreased as a result of the increase in the UE(UA). The increase in UE(UA) was correlated with an increase in urinary D-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UE(UA) is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and D-glucose. It was observed that the efflux of [(14) C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm D-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [(14) C]UA by oocytes was cis-inhibited by 100 mm D-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UE(UA) could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose.

  13. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

    PubMed Central

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d-glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm d-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis-inhibited by 100 mm d-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. PMID:25044127

  14. Nitrilase-catalyzed production of pyrazinoic acid, an antimycobacterial agent, from cyanopyrazine by resting cells of Rhodococcus rhodochrous J1.

    PubMed

    Kobayashi, M; Yanaka, N; Nagasawa, T; Yamada, H

    1990-10-01

    Using resting cells of Rhodococcus rhodochrous J1, in which a large amount of nitrilase is induced, a simple and efficient bioconversion process for the production of pyrazinoic acid, an antimycobacterial agent, through catalysis by a nitrilase was developed. The reaction conditions for production of pyrazinoic acid were optimized. Under optimum conditions, 3.5 M cyanopyrazine was converted to pyrazinoic acid, with a molar conversion yield of 100%. The highest yield achieved corresponded to 434 g of pyrazinoic acid per liter of reaction mixture. The synthesized pyrazinoic acid was isolated and identified physico-chemically.

  15. ATP-dependent uptake of anti-neoplastic agents by acidic organelles.

    PubMed

    Moriyama, Y; Manabe, T; Yoshimori, T; Tashiro, Y; Futai, M

    1994-02-01

    Daunomycin, an anti-neoplastic agent, is known to be sequestered by acidic organelles in normal and multidrug-resistant cells [Willingham, M.C., Cornwell, M.M., Cardarelli, C.O., Gottesman, M.M., & Pastan, I. (1986) Cancer Res. 46, 5941-5946]. We studied the mechanism of accumulation of daunomycin into acidic organelles using chromaffin granule vesicles and proteoliposomes reconstituted with purified F-type H(+)-ATPase as model systems. Radiolabeled daunomycin was taken up by chromaffin vesicles upon addition of ATP. Its ATP-dependent uptake was stimulated about 1.4- to 1.8-fold by valinomycin plus K+, but was inhibited by ammonium chloride (10 mM) and nigericin plus K+. Quinidine (5 microM), verapamil (5 microM), or vanadate (0.5 mM), inhibitors of P-glycoprotein, had no effect on its uptake. Daunomycin was also taken up by liposomes reconstituted with F-type H(+)-ATPase. Furthermore, doxorubicin and vinblastine were taken up by these vesicles, whereas colchicine and rhodamine 123 were not. The accumulations of daunomycin and doxorubicin in acidic organelles of cultured cells were decreased by inhibiting vacuolar ATPase by addition of bafilomycin A1 or concanamycin A, or by increasing the internal pH by addition of nigericin. Melittin and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide dissipated the delta pH and inhibited accumulation of daunomycin in the membrane vesicles and acidic organelles in cultured cells. These results indicate that the delta pH established by vacuolar-type ATPase drives the uptake of daunomycin, doxorubicin or vinblastine into acidic organelles, and that no specific transporters are involved in their uptakes.

  16. Family history of exceptional longevity is associated with lower serum uric acid levels in Ashkenazi Jews.

    PubMed

    Lai, Jennifer Yi-Chun; Atzmon, Gil; Melamed, Michal L; Hostetter, Thomas H; Crandall, Jill P; Barzilai, Nir; Bitzer, Markus

    2012-04-01

    To test whether lower serum uric acid (UA) levels are associated with longevity independent of renal function. Cross-sectional cohort study. Ashkenazi Jewish individuals with exceptional longevity (Longevity Genes Project at Albert Einstein College of Medicine). Long-lived individuals (LLI) of Ashkenazi Jewish ethnicity (mean age ± standard deviation 97.7 ± 2.9, n = 365), their offspring (mean age ± standard deviation 68.2 ± 8.2, n = 593) and controls (without family history of longevity, mean age ± standard deviation 72.5 ± 9.9, n = 356). Association between UA levels and estimated glomerular filtration rate (eGFR) as well as chronic kidney disease (CKD) stage, and correlation of UA levels of LLI and offspring were determined. Because LLI lack an appropriate control group, UA levels, eGFR, and prevalence of hyperuricemia and CKD stages were compared between offspring and controls. Offspring were less likely to have hyperuricemia and had lower UA levels than controls. Despite negative correlation between UA levels and eGFR and positive correlation between UA levels and CKD stages, eGFR and the prevalence of CKD stage III to V were not found to be different between offspring and controls. Furthermore, significant association between UA levels in LLI and their offspring (β estimate 0.1544, 95% confidence interval = 0.08-0.23, P < .001) has been observed. Offspring had lower UA levels than controls despite similar renal function, suggesting that other factors such as UA metabolism or renal tubular transport determine UA levels. The association between UA levels and longevity is particularly intriguing because UA levels are potentially modifiable with diet and drugs. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

  17. Anthranilic acid analogs as diamagnetic CEST MRI contrast agents that feature an intramolecular-bond shifted hydrogen.

    PubMed

    Song, Xiaolei; Yang, Xing; Ray Banerjee, Sangeeta; Pomper, Martin G; McMahon, Michael T

    2015-01-01

    Diamagnetic chemical exchange saturation transfer (diaCEST) agents are a new class of imaging agents, which have unique magnetic resonance (MR) properties similar to agents used for optical imaging. Here we present a series of anthranilic acid analogs as examples of diaCEST agents that feature an exchangeable proton shifted downfield, namely, an intramolecular-bond shifted hydrogen (IM-SHY), which produces significant and tunable contrast at frequencies of 4.8-9.3 ppm from water. Five analogs of N-sulfonyl anthranilic acids are all highly soluble and produced similar CEST contrast at ~6-8 ppm. We also discovered that flufenamic acid, a commercial nonsteroidal anti-inflammatory drug, displayed CEST contrast at 4.8 ppm. For these N-H IM-SHY agents, the contrast produced was insensitive to pH, making them complementary to existing diaCEST probes. This initial IM-SHY library includes the largest reported shifts for N-H protons on small organic diaCEST agents, and should find use as multifrequency MR agents for in vivo applications.

  18. 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.

  19. 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.

  20. 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.

  1. Solubility of acetic acid and trifluoroacetic acid in low-temperature (207-245 k) sulfuric acid solutions: implications for the upper troposphere and lower stratosphere.

    PubMed

    Andersen, Mads P Sulbaek; Axson, Jessica L; Michelsen, Rebecca R H; Nielsen, Ole John; Iraci, Laura T

    2011-05-05

    The solubility of gas-phase acetic acid (CH(3)COOH, HAc) and trifluoroacetic acid (CF(3)COOH, TFA) in aqueous sulfuric acid solutions was measured in a Knudsen cell reactor over ranges of temperature (207-245 K) and acid composition (40-75 wt %, H(2)SO(4)). For both HAc and TFA, the effective Henry's law coefficient, H*, is inversely dependent on temperature. Measured values of H* for TFA range from 1.7 × 10(3) M atm(-1) in 75.0 wt % H(2)SO(4) at 242.5 K to 3.6 × 10(8) M atm(-1) in 40.7 wt % H(2)SO(4) at 207.8 K. Measured values of H* for HAc range from 2.2 × 10(5) M atm(-1) in 57.8 wt % H(2)SO(4) at 245.0 K to 3.8 × 10(8) M atm(-1) in 74.4 wt % H(2)SO(4) at 219.6 K. The solubility of HAc increases with increasing H(2)SO(4) concentration and is higher in strong sulfuric acid than in water. In contrast, the solubility of TFA decreases with increasing sulfuric acid concentration. The equilibrium concentration of HAc in UT/LS aerosol particles is estimated from our measurements and is found to be up to several orders of magnitude higher than those determined for common alcohols and small carbonyl compounds. On the basis of our measured solubility, we determine that HAc in the upper troposphere undergoes aerosol partitioning, though the role of H(2)SO(4) aerosol particles as a sink for HAc in the upper troposphere and lower stratosphere will only be discernible under high atmospheric sulfate perturbations.

  2. 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.

  3. Status of Waterhyacinth/Hydrilla Infestations and Associated Biological Control Agents in Lower Rio Grande Valley Cooperating Irrigation Districts

    DTIC Science & Technology

    2000-09-01

    During September 1999, surveys to quantify plant infestations and insect biological control agents of both Eichhornia crassipes and Hydrilla...from site to site and ranged from 3 kg/cu m to about 21 kg/cu m. Both Neochetina eichhorniae and N. bruchi were commonly collected from all

  4. 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

  5. Effect of chaotropic agents on reversible unfolding of a soybean (Glycine max) seed acid phosphatase.

    PubMed

    Cavagis, Alexandre Donizeti Martins; Granjeiro, Paulo Afonso; Ferreira, Carmen Veríssima; Aoyama, Hiroshi

    2004-04-01

    In this work we examined the effect of urea and guanidinium chloride on the structural stability of a single isoform of soybean seed acid phosphatase, based on the intensity of tryptophan fluorescence as a function of denaturant concentration. The free energy of unfolding, DeltaGu, was calculated at 25 degrees C as a function of the concentrations of both chaotropic agents; the conformational stability, DeltaG (H2O), was determined to be 2.48 kcal mol(-1). Center of mass, determined from analysis of fluorescence data, was used as a parameter to assess conformational changes. Our results indicate that complete enzyme inactivation occurred before full enzyme unfolding in both cases, and suggest that there are differences between the conformational flexibility of the active-site and that of the macromolecule as a whole.

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

    PubMed

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

    2015-03-06

    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.

  7. Evolution in Medicinal Chemistry of Ursolic Acid Derivatives as Anticancer Agents

    PubMed Central

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

    2015-01-01

    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. PMID:25617694

  8. 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

    2014-04-07

    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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Synthesis of novel 2'-fluoro-3'-hydroxymethyl-5'-deoxythreosyl phosphonic acid nucleoside analogues as antiviral agents.

    PubMed

    Kim, Kyung Mi; Hong, Joon Hee

    2014-01-01

    A series of purine 5'-deoxyphosphonate analogues were designed and synthesized to mimic naturally occurring purine monophosphate from 1,3-dihydroxyacetone as starting material. The discovery of threosyl phosphonate nucleoside (PMDTA, EC50 = 2.53 μM) as a potent anti-HIV agent has led to the synthesis and biological evaluation of 2',3'-modified 5'-deoxyversions of the threosyl phosphonate nucleosides. The synthesized 2'-fluoro-3'-hydroxymethyl 5'-deoxythreosyl phosphonic acid nucleoside analogues 14, 18, 23, and 27 were tested for anti-HIV activity as well as cytotoxicity. The adenine analogue 18 exhibits weak in vitro anti-HIV-1 activity (EC50 = 19.2 μM).

  10. 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.

  11. Environmentally relevant concentrations of aminopolycarboxylate chelating agents mobilize Cd from humic acid.

    PubMed

    North, Ashley E; Sarpong-Kumankomah, Sophia; Bellavie, Andrew R; White, Wade M; Gailer, Jürgen

    2017-07-01

    Although Cd is a pollutant of public health relevance, many dietary sources from which it can be absorbed into human tissues remain unknown. While it is well established that the biogeochemical cycle of Cd involves its complexation with environment-derived ligands (e.g., humic acids, HAs) and anthropogenic ones (e.g., chelating agents, CAs), the interaction of Cd with both of these ligands is less well understood. To gain insight, a HA-Cd complex was injected on a size-exclusion chromatography (SEC) column coupled on-line with a flame atomic absorption spectrometer (FAAS) using 10mmol/L Tris buffer (pH8.0) as the mobile phase. This approach allowed us to observe the intact HA-Cd complex and the retention behavior of Cd as a function of 2-20μmol/L concentrations of ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) or methylglycinediacetic acid (MGDA) that were added to the mobile phase. An increase of the retention time of Cd was indicative of a partial or complete abstraction of Cd from HA. Our results revealed that all CAs abstracted Cd from the HA-Cd complex at concentrations of 5μmol/L, while MGDA and DTPA were effective at 2μmol/L. The bioavailability of some of the on-column formed CA-Cd complexes explains the previously reported increased accumulation of Cd in periphyton in the ecosystem downstream of wastewater treatment plants. In addition, our results imply that the use of effluents which contain CAs and Cd for the irrigation of food crops can introduce Cd into the food supply and compromise food safety. Copyright © 2017. Published by Elsevier B.V.

  12. "On-off" thermoresponsive coating agent containing salicylic acid applied to maize seeds for chilling tolerance.

    PubMed

    Guan, Yajing; Li, Zhan; He, Fei; Huang, Yutao; Song, Wenjian; Hu, Jin

    2015-01-01

    Chilling stress is an important constraint for maize seed establishment in the field. In this study, a type of "on-off" thermoresponsive coating agent containing poly (N-isopropylacrylamide-co-butylmethacrylate) (Abbr. P(NIPAm-co-BMA)) hydrogel was developed to improve the chilling tolerance of coated maize seed. The P(NIPAm-co-BMA) hydrogel was synthesized by free-radical polymerization of N-isopropylacrylamide (NIPAm) and butylmethacrylate (BMA). Salicylic acid (SA) was loaded in the hydrogel as the chilling resistance agent. SA-loaded P(NIPAm-co-BMA) was used for seed film-coating of two maize varieties, Huang C (HC, chilling-tolerant) and Mo17 (chilling-sensitive), to investigate the coated seed germination and seedling growth status under chilling stress. The results showed that the hydrogel obtained a phase transition temperature near 12°C with a NIPAM to MBA weight ratio of 1: 0.1988 (w/w). The temperature of 12°C was considered the "on-off" temperature for chilling-resistant agent release; the SA was released from the hydrogel more rapidly at external temperatures below 12°C than above 12°C. In addition, when seedlings of both maize varieties suffered a short chilling stress (5°C), higher concentrations of SA-loaded hydrogel resulted in increased germination energy, germination percentage, germination index, root length, shoot height, dry weight of roots and shoots and protective enzyme activities and a decreased malondialdehyde content in coated maize seeds compared to single SA treatments. The majority of these physiological and biochemical parameters achieved significant levels compared with the control. Therefore, SA-loaded P(NIPAm-co-BMA), a nontoxic thermoresponsive hydrogel, can be used as an effective material for chilling tolerance in film-coated maize seeds.

  13. Plasma Sterilization of Poly Lactic Acid Ultrasound Contrast Agents: Surface Modification and Implications for Drug Delivery

    PubMed Central

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

    2013-01-01

    Poly lactic acid (PLA) ultrasound contrast agents (CA) have been previously developed 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 minutes) and intensity (low- 10 mA, 6.8 W; medium- 15 mA, 10.5 W; and high- 25 mA, 18W) on the CA’s 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 three minutes 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 minutes, 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 drug. PMID:19766380

  14. 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.

  15. 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.

  16. Folic Acid and Creatine as Therapeutic Approaches to Lower Blood Arsenic: A Randomized Controlled Trial

    PubMed Central

    Peters, Brandilyn A.; Hall, Megan N.; Liu, Xinhua; Parvez, Faruque; Sanchez, Tiffany R.; van Geen, Alexander; Mey, Jacob L.; Siddique, Abu B.; Shahriar, Hasan; Uddin, Mohammad Nasir; Islam, Tariqul; Balac, Olgica; Ilievski, Vesna; Factor-Litvak, Pam; Graziano, Joseph H.

    2015-01-01

    Background The World Health Organization estimates that > 140 million people worldwide are exposed to arsenic (As)–contaminated drinking water. As undergoes biologic methylation, which facilitates renal As elimination. In folate-deficient individuals, this process is augmented by folic acid (FA) supplementation, thereby lowering blood As (bAs). Creatinine concentrations in urine are a robust predictor of As methylation patterns. Although the reasons for this are unclear, creatine synthesis is a major consumer of methyl donors, and this synthesis is down-regulated by dietary/supplemental creatine. Objectives Our aim was to determine whether 400 or 800 μg FA and/or creatine supplementation lowers bAs in an As-exposed Bangladeshi population. Methods We conducted a clinical trial in which 622 participants were randomized to receive 400 μg FA, 800 μg FA, 3 g creatine, 3 g creatine+400 μg FA, or placebo daily. All participants received an As-removal filter on enrollment, and were followed for 24 weeks. After the 12th week, half of the two FA groups were switched to placebo to evaluate post-treatment bAs patterns. Results Linear models with repeated measures indicated that the decline in ln(bAs) from baseline in the 800-μg FA group exceeded that of the placebo group (weeks 1–12: β= –0.09, 95% CI: –0.18, –0.01; weeks 13–24: FA continued: β= –0.12, 95% CI: –0.24, –0.00; FA switched to placebo: β= –0.14, 95% CI: –0.26, –0.02). There was no rebound in bAs related to cessation of FA supplementation. Declines in bAs observed in the remaining treatment arms were not significantly different from those of the placebo group. Conclusions In this mixed folate-deficient/replete study population, 12- and 24-week treatment with 800 μg (but not 400 μg) FA lowered bAs to a greater extent than placebo; this was sustained 12 weeks after FA cessation. In future studies, we will evaluate whether FA and/or creatine altered As methylation profiles. Citation

  17. 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

  18. Folic Acid and Creatine as Therapeutic Approaches to Lower Blood Arsenic: A Randomized Controlled Trial.

    PubMed

    Peters, Brandilyn A; Hall, Megan N; Liu, Xinhua; Parvez, Faruque; Sanchez, Tiffany R; van Geen, Alexander; Mey, Jacob L; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad Nasir; Islam, Tariqul; Balac, Olgica; Ilievski, Vesna; Factor-Litvak, Pam; Graziano, Joseph H; Gamble, Mary V

    2015-12-01

    The World Health Organization estimates that > 140 million people worldwide are exposed to arsenic (As)-contaminated drinking water. As undergoes biologic methylation, which facilitates renal As elimination. In folate-deficient individuals, this process is augmented by folic acid (FA) supplementation, thereby lowering blood As (bAs). Creatinine concentrations in urine are a robust predictor of As methylation patterns. Although the reasons for this are unclear, creatine synthesis is a major consumer of methyl donors, and this synthesis is down-regulated by dietary/supplemental creatine. Our aim was to determine whether 400 or 800 μg FA and/or creatine supplementation lowers bAs in an As-exposed Bangladeshi population. We conducted a clinical trial in which 622 participants were randomized to receive 400 μg FA, 800 μg FA, 3 g creatine, 3 g creatine+400 μg FA, or placebo daily. All participants received an As-removal filter on enrollment, and were followed for 24 weeks. After the 12th week, half of the two FA groups were switched to placebo to evaluate post-treatment bAs patterns. Linear models with repeated measures indicated that the decline in ln(bAs) from baseline in the 800-μg FA group exceeded that of the placebo group (weeks 1-12: β= -0.09, 95% CI: -0.18, -0.01; weeks 13-24: FA continued: β= -0.12, 95% CI: -0.24, -0.00; FA switched to placebo: β= -0.14, 95% CI: -0.26, -0.02). There was no rebound in bAs related to cessation of FA supplementation. Declines in bAs observed in the remaining treatment arms were not significantly different from those of the placebo group. In this mixed folate-deficient/replete study population, 12- and 24-week treatment with 800 μg (but not 400 μg) FA lowered bAs to a greater extent than placebo; this was sustained 12 weeks after FA cessation. In future studies, we will evaluate whether FA and/or creatine altered As methylation profiles.

  19. Expression of lysophosphatidic acid receptors in the human lower esophageal sphincter

    PubMed Central

    FENG, YONG; LIU, JUN-FENG

    2014-01-01

    Lysophosphatidic acid (LPA) is a bioactive lipid that is involved in a variety of physiological and pathological processes occurring in the gastrointestinal tract. It acts via six distinct types of receptors, LPA1, LPA2, LPA3, LPA4, LPA5 and LPA6, which belong to the family of G protein-coupled receptors. The aim of the present study was to detect the expression of the LPA receptors in the human lower esophageal sphincter (LES). Quantitative polymerase chain reaction and western blotting were used to analyze the expression of LPA1-6 receptors in sling and clasp fibers from the human LES. The results showed that the protein and mRNA expression levels of various LPA receptors were significantly different. Specifically, the mRNA and protein expression levels of the LPA1 receptor were higher compared with those of the other receptors. The prevalence of the LPA1 receptor mRNA and protein indicates that the LPA1 receptor is likely to be involved in the regulation of human LES functions. PMID:24396418

  20. 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.

  1. Studies on the regulation of transient lower esophageal sphincter relaxations (TLESRs) by acid in the esophagus and stomach.

    PubMed

    Banovcin, P; Halicka, J; Halickova, M; Duricek, M; Hyrdel, R; Tatar, M; Kollarik, M

    2016-07-01

    Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism of gastroesophageal reflux, but the regulation of TLESR by stimuli in the esophagus is incompletely understood. We have recently reported that acid infusion in the esophagus substantially (by 75%) increased the number of meal-induced TLESR in healthy subjects. We concluded that the TLESR reflex triggered by gastric distention with meal was enhanced by the stimulation of esophageal nerves by acid. However, the possibilities that the acid infused into the esophagus acts after passing though lower esophageal sphincter in stomach to enhance TLESR, or that the acid directly initiates TLESR from the esophagus were not addressed. Here, we evaluated the effect of acid infusion into the proximal stomach on meal-induced TLESR (study 1) and the ability of acid infusion into the esophagus to initiate TLESR without prior meal (study 2). We analyzed TLESRs by using high-resolution manometry in healthy subjects in paired randomized studies. In study 1, we found that acid infusion into the proximal stomach did not affect TLESRs induced by standard meal. The number of meal-induced TLESRs following the acid infusion into the proximal stomach was similar to the number of meal-induced TLESRs following the control infusion. In study 2, we found that acid infusion into the esophagus without prior meal did not initiate TLESRs. We conclude that the increase in the meal-induced TLESRs by acid in the esophagus demonstrated in our previous study is not attributable to the action of acid in the stomach or to direct initiation of TLESR from the esophagus by acid. Our studies are consistent with the concept that the stimuli in the esophagus can influence TLESRs. The enhancement of TLESR by acid in the esophagus may contribute to pathogenesis of gastroesophageal reflux in some patients. © 2015 International Society for Diseases of the Esophagus.

  2. Dynamic wettability of wood surface modified by acidic dyestuff and fixing agent

    NASA Astrophysics Data System (ADS)

    Wei, Shuangying; Shi, Junyou; Gu, Jiyou; Wang, Di; Zhang, Yanhua

    2012-01-01

    Acidic dyestuffs can bring brilliant colors to the wood and fixing agents can avoid the color loss. They could change the surface wettability of wood, which impact the gluing process of veneers. In condition of the higher moisture content of wood, the rare veneers, the veneers dyed by acidic dyestuffs and the dyed veneers fixed by Chitosan were glued respectively by one-component wet-curing isocyanate adhesive and the contact angles (θ) of the different gluing interfaces were measured. The dynamic wettability of these gluing interfaces was characterized by both the contact angle θ and the spreading-penetration parameter (K) calculated by θ. The results showed that the θ-values decreased significantly with the extension of time and the initial contact angles (θi) decreased with the moisture contents of veneers increasing, but the variation of the balance contact angles (θe) was reversed with θi. When the moisture contents of veneers were same, the variation of θ of the rare veneers was minimal and the variation of θ of the fixed veneers was maximal. The K-values of these gluing interfaces all decreased significantly with the moisture contents of veneers increasing, but the variations of K were different. The wetting model describing the dynamic wetting process was established on the basis of these variations.

  3. 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).

  4. 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).

  5. Twelve-week, prospective, open-label, randomized trial on the effects of an anticholinergic agent or antidiuretic agent as add-on therapy to an alpha-blocker for lower urinary tract symptoms

    PubMed Central

    Shin, Yu Seob; Zhang, Li Tao; Zhao, Chen; Kim, Young Gon; Park, Jong Kwan

    2014-01-01

    Purpose The effects of an anticholinergic or antidiuretic agent as add-on therapy to an alpha-blocker for lower urinary tract symptoms (LUTS) according to a voiding diary in 3 days are unknown. We prospectively investigated the efficacy of an anticholinergic or antidiuretic agent as add-on therapy for nocturia in men previously treated with an alpha-blocker for LUTS. Subjects and methods Patients were randomly subdivided into two groups. All patients had a 4-week washout. Group A had alpha-blocker for 4 weeks, then an alpha-blocker plus an anticholinergic agent for 4 weeks, and, finally, 4 weeks of an alpha-blocker plus an antidiuretic agent. Group B had an alpha-blocker for 4 weeks, then an alpha-blocker plus an antidiuretic agent for 4 weeks, and, finally, 4 weeks of an alpha-blocker plus an anticholinergic agent. In both groups, patients were subdivided into nocturnal polyuria, decreased nocturnal bladder capacity (NBC), or nocturia by both causes subgroups. A 3-day voiding diary, total International Prostate Symptom Score (IPSS), IPSS sub-scores, Overactive Bladder Symptom Score, uroflowmetry, and post-void residual urine volume, were assessed at baseline, and at 4, 8, and 12 weeks. Results A total of 405 patients completed the study. During treatment, the changes from baseline in total IPSS and IPSS sub-scores were significantly decreased at 4 weeks and were maintained for 12 weeks. In the nocturnal polyuria subgroup of Groups A and B, the number of episodes of nocturia in 3 days, nocturnal urine volume, and nocturnal index were significantly decreased using an alpha-blocker plus an antidiuretic agent. In the decreased NBC subgroup of Groups A and B, IPSS storage sub-score, Overactive Bladder Symptom Score, number of episodes of nocturia in 3 days, number of episodes of urgency in 3 days, and NBC index were all significantly decreased using an alpha-blocker plus an anticholinergic agent. Conclusion An anticholinergic agent or antidiuretic agent as an add

  6. Twelve-week, prospective, open-label, randomized trial on the effects of an anticholinergic agent or antidiuretic agent as add-on therapy to an alpha-blocker for lower urinary tract symptoms.

    PubMed

    Shin, Yu Seob; Zhang, Li Tao; Zhao, Chen; Kim, Young Gon; Park, Jong Kwan

    2014-01-01

    The effects of an anticholinergic or antidiuretic agent as add-on therapy to an alpha-blocker for lower urinary tract symptoms (LUTS) according to a voiding diary in 3 days are unknown. We prospectively investigated the efficacy of an anticholinergic or antidiuretic agent as add-on therapy for nocturia in men previously treated with an alpha-blocker for LUTS. Patients were randomly subdivided into two groups. All patients had a 4-week washout. Group A had alpha-blocker for 4 weeks, then an alpha-blocker plus an anticholinergic agent for 4 weeks, and, finally, 4 weeks of an alpha-blocker plus an antidiuretic agent. Group B had an alpha-blocker for 4 weeks, then an alpha-blocker plus an antidiuretic agent for 4 weeks, and, finally, 4 weeks of an alpha-blocker plus an anticholinergic agent. In both groups, patients were subdivided into nocturnal polyuria, decreased nocturnal bladder capacity (NBC), or nocturia by both causes subgroups. A 3-day voiding diary, total International Prostate Symptom Score (IPSS), IPSS sub-scores, Overactive Bladder Symptom Score, uroflowmetry, and post-void residual urine volume, were assessed at baseline, and at 4, 8, and 12 weeks. A total of 405 patients completed the study. During treatment, the changes from baseline in total IPSS and IPSS sub-scores were significantly decreased at 4 weeks and were maintained for 12 weeks. In the nocturnal polyuria subgroup of Groups A and B, the number of episodes of nocturia in 3 days, nocturnal urine volume, and nocturnal index were significantly decreased using an alpha-blocker plus an antidiuretic agent. In the decreased NBC subgroup of Groups A and B, IPSS storage sub-score, Overactive Bladder Symptom Score, number of episodes of nocturia in 3 days, number of episodes of urgency in 3 days, and NBC index were all significantly decreased using an alpha-blocker plus an anticholinergic agent. An anticholinergic agent or antidiuretic agent as an add-on therapy in men previously treated with an alpha

  7. In Vitro and In Situ evaluation of pH-dependence of atazanavir intestinal permeability and interactions with acid-reducing agents.

    PubMed

    Kis, Olena; Walmsley, Sharon L; Bendayan, Reina

    2014-09-01

    The objectives of this study were to evaluate the effects of intestinal lumen pH, food intake, and acid-reducing agents on the intestinal permeability of atazanavir, an HIV-1 protease inhibitor. Atazanavir permeability across Caco-2 cell monolayers (P app) and in situ steady-state permeability across rat jejunum and ileum (P eff) were evaluated in buffers of varied pH (4.5-8.5), in fasted- or fed-state simulated intestinal fluid, or in presence of acid-reducing drugs (e.g., omeprazole). In vitro accumulation and apical-to-basolateral P app of atazanavir increased with decreasing pH. This effect appeared to be associated with lower atazanavir efflux by P-glycoprotein at acidic pH (5.5) compared to neutral pH. In situ atazanavir P eff across rat jejunum and ileum also decreased 2.7 and 2.3-fold, respectively, when pH was increased from 4.5 to 8.5. Several acid-reducing agents (e.g., omeprazole) moderately inhibited atazanavir efflux in Caco-2 monolayers; however, this effect was not observed in situ. Fed-state buffer significantly increased atazanavir apical-to-basolateral P app (p < 0.001) and in situ P eff (p < 0.05) compared to fasted-state buffer. Atazanavir permeability is sensitive to changes in intestinal lumen pH. This pH-sensitivity may contribute to atazanavir clinical interactions with acid-reducing agents and variable oral bioavailability.

  8. The Effects of Lowering Uric Acid Levels Using Allopurinol on Components of Metabolic Syndrome

    PubMed Central

    Heimbach, Esther J.; Bowden, Rodney G.; Griggs, Jackson O.; Beaujean, A. Alexander; Doyle, Eva I.; Doyle, Robert D.

    2012-01-01

    Background Researchers have reported an independent direct relationship between lipid levels and hyperuricemia with MetS. The purpose of this study was to determine the relationship between serum uric acid levels and lipids among patients on allopurinol. Methods A retrospective secondary data analysis was conducted on 66 adult patients from a family health clinic in Central Texas. Medical records used were recorded during a nine year period (2002 - 2010) ascertaining the relationship between uric acid and lipids. Results Spearman correlations revealed a weak correlation between uric acid and total cholesterol, a weak correlation between uric acid and triglycerides and LDL-C. A weak inverse correlation was discovered between uric acid and HDL-C. A moderate correlation was discovered when all lipid variables combined were compared to uric acid. Conclusions We discovered LDL-C and triglycerides to be significant predictors of uric acid with weak correlations. Additionally, weak correlations existed between uric acid and total cholesterol and HDL-C with an inverse relationship discovered with HDL-C. These findings support the literature suggesting that uric acid is more likely to be associated with total cholesterol and triglycerides. In addition, new discoveries serve as an indication that LDL-C may also be associated with uric acids levels. The mechanism by which uric acid may regulate lipids is elusive but suggestions have included suppression of lipid peroxidase and decreases in critical lipase activity.

  9. Synthesis of Sugar-Boronic Acid Derivatives: A Class of Potential Agents for Boron Neutron Capture Therapy.

    PubMed

    Imperio, Daniela; Del Grosso, Erika; Fallarini, Silvia; Lombardi, Grazia; Panza, Luigi

    2017-04-07

    To date, sugar analogues that contain boronic acids as substitutes for hydroxyl groups are a class of compounds nearly unknown in the literature. The challenging synthesis of two sugar-boronic acid analogues is described, and data are retrieved on their solution behavior, stability, and toxicity. As these compounds were expected to mimic the behavior of carbohydrates, they were tested in regards to their future development as potential boron neutron capture therapy agents.

  10. Use of Magnetic Bead Resin and Automated Liquid Handler Extraction Methods to Robotically Isolate Nucleic Acids of Biological Agent Simulates

    DTIC Science & Technology

    2003-09-01

    allows the ABATS to use a CORE system to link the Applied Biosystems ABI Prism® 7900HT thermocycler and the ORIGEN ® M8 Analyzer (IGEN, Gaithersburg, MD) to...measures pertaining to nucleic acid extraction of two accepted biological agent simulants in an effort to reduce labor and speed analysis of unknown...sites. As part of the labor reduction effort, we have developed a hybrid protocol for extraction of nucleic acids from environmental samples that can

  11. Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype

    PubMed Central

    Huertas, Ismael; Jesús, Silvia; Lojo, José Antonio; García-Gómez, Francisco Javier; Cáceres-Redondo, María Teresa; Oropesa-Ruiz, Juan Manuel; Carrillo, Fátima; Vargas-Gonzalez, Laura; Martín Rodríguez, Juan Francisco; Gómez-Garre, Pilar; García-Solís, David; Mir, Pablo

    2017-01-01

    Parkinson’s disease (PD) patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA), a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT) availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36), intermediate (I, n = 22), and tremor-dominant (TD, n = 17) subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001) and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25%) and I (45%) patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype. PMID:28358829

  12. Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype.

    PubMed

    Huertas, Ismael; Jesús, Silvia; Lojo, José Antonio; García-Gómez, Francisco Javier; Cáceres-Redondo, María Teresa; Oropesa-Ruiz, Juan Manuel; Carrillo, Fátima; Vargas-Gonzalez, Laura; Martín Rodríguez, Juan Francisco; Gómez-Garre, Pilar; García-Solís, David; Mir, Pablo

    2017-01-01

    Parkinson's disease (PD) patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA), a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT) availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36), intermediate (I, n = 22), and tremor-dominant (TD, n = 17) subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001) and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25%) and I (45%) patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.

  13. 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

  14. α-Linolenic acid (ALA) is an anti-inflammatory agent in inflammatory bowel disease.

    PubMed

    Reifen, Ram; Karlinsky, Anna; Stark, Aliza H; Berkovich, Zipi; Nyska, Abraham

    2015-12-01

    Studies suggest that consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFA) plays a protective role in inflammatory bowel disease; however, the use of plant-derived oils rich in α-linolenic acid (ALA) has not been widely investigated. The aims of this study were to test the effects of two different sources of (n-3) PUFA, fish and plant-derived oils, in two animal models of experimental colitis and to determine whether the (n-3) PUFA-enriched diets could ameliorate the inflammatory status. Rats were fed diets rich in corn, fish or sage oil with or without vitamin A supplementation for 3weeks then colitis was induced by adding dextran sodium sulfate to the drinking water or by injecting 2,4,6-trinitrobenzene sulfonic acid. We show that colitic rats fed the sage oil diets had a lower inflammatory response, improved histological repair and had less necrotic damage in the mucosa when compared to the corn and fish oil groups. Colonic damage and myeloperoxidase activity were significantly lower. Colonic mRNA levels of pro-inflammatory genes including interleukin IL-6, cyclooxygenase 2 and tumor necrosis factor α were markedly down-regulated in rats fed fish and sage oils compared to control. These results were supported by experiments in the human colonic epithelial cell line Caco-2, where ALA supplementation was shown to be effective in inhibiting inflammation induced by IL-1β by down-regulating mRNA levels of pro-inflammatory genes including IL-8, COX2 and inducible nitric oxide synthase. Taken together, these results suggest that plant-derived oil rich in ALA could ameliorate the inflammatory damage in colitis.

  15. Acute intestinal obstruction due to Kalimate, a potassium-lowering agent: a case report and literature review.

    PubMed

    Tongyoo, Assanee; Sriussadaporn, Ekkapak; Limpavitayaporn, Palin; Mingmalairak, Chatchai

    2013-12-01

    Sodium polystyrene sulfonate (Kayexalate) and calcium polystyrene sulfonate (CPS, Kalimate) are commonly used to reduce serum potassium. There were some published evidences of severe gastrointestinal complications from the administration of these agents such as colonic necrosis with or without perforation and acute obstruction. The authors reported a 52-year-old male patient being critically ill from severe soft tissue infection of the right leg and sepsis. Hyperkalemia had occurred due to renal insufficiency and required several doses of Kalimate to reduce the serum potassium level. Subsequently, the patient developed complete intestinal obstruction and an exploratory laparotomy was performed. The intra-operative findings were distended stomach and the small bowel contained a large amount of intraluminal affected Kalimate that was removed via gastrotomy and enterotomy. These findings suggested that the inspissated Kalimate could lead to significant obstruction of the gastrointestinal tract in some groups of patient.

  16. Clinical Comparison of Two Contrast Agents for Oral Cholecystography: Radiologic Efficacy and Drug Safety of Iopanoic Acid and Iopronic Acid 1

    PubMed Central

    Hedlund, Laurence; Putman, Charles E.; Burrell, Morton

    1979-01-01

    Oral doses of either iopronic acid (4.5 g Oravue, Squibb) or iopanoic acid (3 g Telepaque, Winthrop) were given to 98 patients requiring cholecystography. Radiographs were taken 13 to 16 hours after treatment showed good to excellent gallbladder opacification in 44 percent of patients after the first dose of iopronic acid and in an additional 29 percent after a second dose. Similar opacification occurred in 42 percent of patients after the first dose of iopanoic acid and in 34 percent after a second dose. Drug-related abnormalities in blood and urine tests occurred about equally in both groups and one patient in each group exhibited a clinically adverse reaction (diarrhea). Thus, the performance (radiographic efficacy and drug safety) of the new contrast agent, iopronic acid, was similar to a widely used drug, iopanoic acid. PMID:380184

  17. Dumb and dumber--the potential waste of a useful antistaphylococcal agent: emerging fusidic acid resistance in Staphylococcus aureus.

    PubMed

    Howden, Benjamin P; Grayson, M Lindsay

    2006-02-01

    Fusidic acid has activity against a range of pathogens but has mainly been used to treat staphylococcal infections. Fusidic acid monotherapy, especially topical preparations, has been strongly associated with the emergence of fusidic acid resistance among both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus. Key resistance determinants include mutations in the fusA gene, which encodes elongation factor G, and plasmid-mediated resistance (i.e., acquisition of resistance gene fusB). Clonal outbreaks of fusidic acid-resistant S. aureus have been noted throughout the United Kingdom and Europe, such that the efficacy of fusidic acid is threatened. Fusidic acid in combination with other agents, such as rifampicin, has proven effective for difficult-to-treat MRSA infections and provides a convenient oral alternative to oxazolidinones. Ensuring that systemic fusidic acid is always used in combination and that the use of topical fusidic acid is either abolished or restricted will be vital if we are to prevent the loss of this potentially useful agent.

  18. 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.

  19. In vitro studies on ultrasmall superparamagnetic iron oxide nanoparticles coated with gummic acid for T2 MRI contrast agent

    PubMed Central

    Rabias, I.; Pratsinis, H.; Drossopoulou, G.; Fardis, M.; Maris, T.; Boukos, N.; Tsotakos, N.; Kletsas, D.; Tsilibary, E.; Papavassiliou, G.

    2007-01-01

    Ultrasmall superparamagnetic iron oxide nanoparticles coated with gummic acid have been investigated as possible constituents of aqueous ferrofluids for biomedical applications and especially for MRI contrast agent. The structural characteristics and the size of the nanoparticles have been analyzed as well as the magnetic properties. In order to evaluate any possible capabilities as a contrast agent, the relaxation time, T2, of hydrogen protons in the colloidal solutions of nanoparticles have been measured in order to gain information on the relaxation behavior compared to other MRI contrast agents. The in vitro cytotoxicity of the obtained magnetic nanoparticles of iron oxide coated with gummic acid was investigated by two separate methods (MTT and FACS analysis) and by using three different normal and transformed cell lines. Our results showed that the synthesized nanoparticles had no toxic effect on any of the cell lines used. PMID:19693403

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

    PubMed Central

    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

    2014-01-01

    Increasing evidence supports the contention that many malignancies, including sporadic colorectal cancer (CRC), are driven by the self-renewing, chemotherapy-resistant cancer stem/stem-like cells (CSCs/CSLCs) 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 un-explored. The primary objectives of this investigation are 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 (b) whether EPA by itself or in combination with conventional chemotherapy prevents the recurrence of colon cancer via eliminating/suppressing CSCs/CSLCs. FuOx-resistant (chemo-resistant; CR) colon cancer cells, highly enriched in CSCs, were utilized for this study. While EPA alone was effective, combination of EPA and FuOx was more potent in (a) inhibiting cell growth, colonosphere formation and sphere-forming frequency, (b) increasing sphere disintegration, (c) suppressing the growth of SCID mice xenografts of CR colon cancer cells, and (d) decreasing pro-inflammatory metabolites in mice. Additionally, 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 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 CRC. PMID:25193342

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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…

  6. 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…

  7. 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

    2006-03-05

    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.

  8. 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

  9. Can we consider zoledronic acid a new antitumor agent? Recent evidence in clinical setting.

    PubMed

    Santini, Daniele; Virzi, Vladimir; Fratto, Maria Elisabetta; Bertoldo, Francesco; Sabbatini, Roberto; Berardi, Rossana; Calipari, Nicola; Ottaviani, Davide; Ibrahim, Toni

    2010-02-01

    New emerging data suggest that bisphosphonates may exert antitumor properties. Preclinical studies have demonstrated that zoledronic acid (ZA) can induce direct and indirect antitumor activities such as inhibition of angiogenesis, invasion and adhesion of tumor cells, and overall tumor progression, stimulation of adoptive and innate immunity and emerging evidence suggests that the use of these agents may prevent the development of skeletal and extra skeletal metastases. This review will critically describe the new growing evidence of antitumor activity exerted by bisphosphonates in cancer patients, both in metastatic disease and in the adjuvant setting. The effects of bisphosphonates on survival in metastatic cancer patients will be described and evidence from retrospective analyses and prospective studies will be critically reported. The early evidence from prospective analyses of survival impact by ZA in the adjuvant setting in breast cancer will be discussed together with the recently published results of the ABCSG-12 study. A new "era" for bisphosphonates in the oncological setting is opening. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of adjuvant and metastatic cancer therapies.

  10. 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.

  11. 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

  12. The uncoupling agent 2,4-dinitrophenol improves mitochondrial homeostasis following striatal quinolinic acid injections.

    PubMed

    Korde, Amit S; Sullivan, Patrick G; Maragos, William F

    2005-10-01

    It is now generally accepted that excitotoxic cell death involves bioenergetic failure resulting from the cycling of Ca2+ and the generation of reactive oxygen species (ROS) by mitochondria. Both Ca2+ cycling and ROS formation by mitochondria are dependent on the mitochondrial membrane potential (Deltapsi(m)) that results from the proton gradient that is generated across the inner membrane. Mitochondrial uncoupling refers to a condition in which protons cross the inner membrane back into the matrix while bypassing the ATP synthase. As a consequence of this "short-circuit," there is a reduction in Deltapsi(m). We have previously demonstrated that animals treated with the classic uncoupling agent 2,4-dinitrophenol (DNP) show significant protection against brain damage following striatal injections of the NMDA agonist quinolinic acid (QA). In an effort to elucidate the mechanism of neuroprotection, we have assessed the effects of DNP on several parameters of mitochondrial function caused by QA. The results presented herein demonstrate that treatment with DNP attenuates QA-induced increases in mitochondrial Ca2+ levels and ROS formation and also improves mitochondrial respiration. Our findings indicate that DNP may confer protection against acute brain injury involving excitotoxic pathways by mechanisms that maintain mitochondrial function.

  13. Evaluating the efficacy of amino acids as CO2 capturing agents: a first principles investigation.

    PubMed

    Hussain, M Althaf; Soujanya, Yarasi; Sastry, G Narahari

    2011-10-01

    Comprehension of the basic concepts for the design of systems for CO2 adsorption is imperative for increasing interest in technology for CO2 capture from the effluents. The efficacy of 20 naturally occurring amino acids (AAs) is demonstrated as the most potent CO2 capturing agents in the process of chemical absorption and physisorption through a systematic computational study using highly parametrized M05-2X/6-311+G(d,p) method. The ability of AAs to bind CO2 both in the noncovalent and covalent fashion and presence of multiple adsorption sites with varying magnitude of binding strengths in all 20 AAs makes them as most promising materials in the process of physisorption. The binding energies (BEs) estimating the strength of noncovalent interaction of AAs and CO2 are calculated and results are interpreted in terms of the nature and strength of the various types of cooperative interactions which are present. The study underlines the possibility to engineer the porous solid materials with extended networks by judiciously employing AA chains as linkers which can substantially augment their efficacy. Results show that a significant increase in the CO2···AA affinity is achieved in the case of AAs with polar neutral side chains. Furthermore, the study proposes AAs as effective alternatives to alkanolamines in chemical dissolution of CO2.

  14. Competitive FRET-aptamer-based detection of methylphosphonic acid, a common nerve agent metabolite.

    PubMed

    Bruno, John G; Carrillo, Maria P; Phillips, Taylor; Vail, Neal K; Hanson, Douglas

    2008-09-01

    Competitive fluorescence resonance energy transfer (FRET)-aptamer-based assay formats are described for one-step detection of methylphosphonic acid (MPA; a metabolite of several organophosphorus (OP) nerve agents). AminoMPA was attached to tosyl-magnetic beads and used for DNA aptamer selection from which one dominant aptamer sequence emerged. Two different FRET approaches were attempted. In one approach, the complementary DNA sequence was used as a template for labeling the aptamer with Alexa Fluor 546 (AF 546)-14-dUTP by asymmetric PCR. Following 3-dimensional (3-D), molecular modeling of the aptamer-MPA complex, a series of three fluoresceinated aptamers labeled at positions 50, 51, and 52 in the putative optimal binding pocket were synthesized. In both FRET formats, aminoMPA was linked to Black Hole Quencher (BHQ-1 or BHQ-2)-succinimides and allowed to bind the fluorescein or AF 546-labeled MPA aptamer. Following gel filtration to purify the labeled MPA aptamer-BHQ-aminoMPA FRET complexes, the complexes were competed against various concentrations of unlabeled MPA, MPA derivatives, and unrelated compounds in titration and cross-reactivity studies. Both approaches yielded low microgram per milliliter detection limits for MPA with generally low levels of cross-reactivity for unrelated compounds. However, the data suggest a pattern of traits that may effect the direction (lights on or off) and intensity of the FRET.

  15. Salvianolic Acid B, a Potential Chemopreventive Agent, for Head and Neck Squamous Cell Cancer

    PubMed Central

    Zhao, Yuan; Guo, Yinhan; Gu, Xinbin

    2011-01-01

    Head and neck squamous cell cancer (HNSCC) is one of the top ten cancers in the United States. The survival rate of HNSCC has only marginally improved over the last two decades. In addition, African-American men bear a disproportionate burden of this preventable disease. Therefore, a critical challenge of preventive health approaches is warranted. Salvianolic acid B (Sal-B) isolated from Salvia miltiorrhiza Bge, which is a well-know Chinese medicines has been safely used to treat and prevent aging diseases for thousand of years. Recently, the anticancer properties of Sal-B have received more attention. Sal-B significantly inhibits or delays the growth of HNSCC in both cultured HNSCC cells and HNSCC xenograft animal models. The following anticancer mechanisms have been proposed: the inhibition of COX-2/PGE-2 pathway, the promotion of apoptosis, and the modulation of angiogenesis. In conclusion, Sal-B is a potential HNSCC chemopreventive agent working through antioxidation and anti-inflammation mechanisms. PMID:21209716

  16. Cell morphology of extrusion foamed poly(lactic acid) using endothermic chemical foaming agent.

    PubMed

    Matuana, Laurent M; Faruk, Omar; Diaz, Carlos A

    2009-12-01

    Poly(lactic acid) (PLA) was foamed with an endothermic chemical foaming agent (CFA) through an extrusion process. The effects of polymer melt flow index, CFA content, and processing speed on the cellular structures, void fraction, and cell-population density of foamed PLA were investigated. The apparent melt viscosity of PLA was measured to understand the effect of melt index on the cell morphology of foamed PLA samples. The void fraction was strongly dependent on the PLA melt index. It increased with increasing melt index, reaching a maximum value, after which it decreased. Melt index showed no significant effect on the cell-population density of foamed samples within the narrow range studied. A gas containment limit was observed in PLA foamed with CFA. Both the void fraction and cell-population density increased with an initial increase in CFA content, reached a maximum value, and then decreased as CFA content continued to increase. The processing speed also affected the morphology of PLA foams. The void fraction reached a maximum value as the extruder's screw speed increased to 40 rpm and a further increase in the processing speed tended to reduce the void fraction of foamed samples. By contrast, cell-population density increased one order of magnitude by increasing the screw speed from 20 to 120 rpm. The experimental results indicate that a homogeneous and finer cellular morphology could be successfully achieved in PLA foamed in an extrusion process with a proper combination of polymer melt flow index, CFA content, and processing speed.

  17. Protection afforded by sunscreens containing inorganic sunscreening agents against blue light sensitivity induced by aminolevulinic acid.

    PubMed

    Bissonnette, Robert; Nigen, Simon; Bolduc, Chantal; Méry, Sophie; Nocera, Thérèse

    2008-11-01

    Application of aminolevulinic acid (ALA) for photodynamic therapy induces significant sensitivity to visible light. To determine whether sunscreens containing inorganic agents are effective against sensitivity to blue light induced by ALA application. Twenty subjects received application of ALA on the arm. Thirty minutes before blue light exposure, two sun protection factor 50 inorganic-based sunscreens containing iron oxide 3.2% and 0.2% were applied on separate areas where ALA was applied; a third area received no sunscreen. Small areas of skin were exposed to increasing fluences of blue light 3 or 18 hours later, and the minimal phototoxic dose (MPD) was noted. Three hours after ALA application MPD was 29.2 and 22.6 J/cm(2) for skin protected with sunscreen containing iron oxide 3.2% and 0.2%, respectively, and 10.6 J/cm(2) for unprotected skin (p=.003 and .0497 respectively). At 18 hours after ALA application, MPD for sunscreen containing iron oxide 3.2% was 5.78, compared with 0.33 for unprotected skin (p<.001) with a blue light protection factor of 21. The sunscreen containing iron oxide 3.2% afforded significant protection against blue light sensitivity induced by ALA application.

  18. Hypochlorous Acid: an ideal wound care agent with powerful microbicidal, antibiofilm, and wound healing potency.

    PubMed

    Sakarya, Serhan; Gunay, Necati; Karakulak, Meltem; Ozturk, Barcin; Ertugrul, Bulent

    2014-12-01

    Chronic wounds and the infections associated with them are responsible for a considerable escalation in morbidity and the cost of health care. Infection and cellular activation and the relation between cells are 2 critical factors in wound healing. Since chronic wounds offer ideal conditions for infection and biofilm production, good wound care strategies are critical for wound healing. Topical antiseptics in chronic wounds remain in widespread use today. These antiseptics are successful in microbial eradication, but their cytotoxcity is a controversial issue in wound healing. The aim of this study was to investigate the effect of stabilized hypochlorous acid solution (HOCl) on killing rate, biofilm formation, antimicrobial activity within biofilm against frequently isolated microorganisms and migration rate of wounded fibroblasts and keratinocytes. Minimal bactericidal concentration of stabilized HOCl solution for all standard microorganisms was 1/64 dilution and for clinical isolates it ranged from 1/32 to 1/64 dilutions. All microorganisms were killed within 0 minutes and accurate killing time was 12 seconds. The effective dose for biofilm impairment for standard microorganisms and clinical isolates ranged from 1/32 to 1/16. Microbicidal effects within the biofilm and antibiofilm concentration was the same for each microorganism. The stabilized HOCl solution had dose-dependent favorable effects on fibroblast and keratinocyte migration compared to povidone iodine and media alone. These features lead to a stabilized HOCl solution as an ideal wound care agent.

  19. Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis.

    PubMed

    Pardi, Darrell S; Loftus, Edward V; Kremers, Walter K; Keach, Jill; Lindor, Keith D

    2003-04-01

    Ursodeoxycholic acid (UDCA) has shown effectiveness as a colon cancer chemopreventive agent in preclinical studies. In addition, a recent report suggests that it also may decrease the risk for developing colorectal dysplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We sought to evaluate the effect of UDCA on colorectal neoplasia in a group of patients with UC and PSC enrolled in a randomized, placebo-controlled trial. From a prior, randomized, placebo-controlled trial of UDCA therapy in PSC at our center, we followed-up patients with concomitant UC to assess the effect of UDCA on the development of colorectal dysplasia and cancer as compared with placebo. Fifty-two subjects were followed-up for a total of 355 person-years. Those originally assigned to receive UDCA had a relative risk of 0.26 for developing colorectal dysplasia or cancer (95% confidence interval, 0.06-0.92; P = 0.034). Many of the patients originally assigned to the placebo group eventually received open-label UDCA. Assigning these patients to the UDCA group from the time they began active therapy did not change the magnitude of the protective effect (relative risk, 0.26; 95% confidence interval, 0.07-0.99; P = 0.049). UDCA significantly decreases the risk for developing colorectal dysplasia or cancer in patients with UC and PSC.

  20. Nicotinic acid (niacin) receptor agonists: will they be useful therapeutic agents?

    PubMed

    Kamanna, Vaijinath S; Kashyap, Moti L

    2007-12-03

    niacin receptor agonists as therapeutic agents. Several niacin receptor agonists have been developed and patented, but their clinical effects have not been described. Future research is needed to determine whether niacin receptor agonists will demonstrate all the beneficial properties of nicotinic acid on atherosclerosis and without significant adverse effects.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  2. Effect of Uric Acid Lowering on Renin-Angiotensin-System Activation and Ambulatory BP: A Randomized Controlled Trial.

    PubMed

    McMullan, Ciaran J; Borgi, Lea; Fisher, Naomi; Curhan, Gary; Forman, John

    2017-05-08

    Higher serum uric acid levels, even within the reference range, are strongly associated with increased activity of the renin-angiotensin system (RAS) and risk of incident hypertension. However, the effect of lowering serum uric acid on RAS activity in humans is unknown, although the data that lowering serum uric acid can reduce BP are conflicting. In a double-blind placebo-controlled trial conducted from 2011 to 2015, we randomly assigned 149 overweight or obese adults with serum uric acid ≥5.0 mg/dl to uric acid lowering with either probenecid or allopurinol, or to placebo. The primary endpoints were kidney-specific and systemic RAS activity. Secondary endpoints included mean 24-hour systolic BP, mean awake and asleep BP, and nocturnal dipping. Allopurinol and probenecid markedly lowered serum uric acid after 4 and 8 weeks compared with placebo (mean serum uric acid in allopurinol, probenecid, and placebo at 8 weeks was 2.9, 3.5, and 5.6 mg/dl, respectively). The change in kidney-specific RAS activity, measured as change in the median (interquartile range) renal plasma flow response to captopril (in ml/min per 1.73 m(2)) from baseline to 8 weeks, was -4 (-25 to 32) in the probenecid group (P=0.83), -4 (-16 to 9) in the allopurinol group (P=0.32), and 1 (-21 to 17) in the placebo group (P=0.96), with no significant treatment effect (P=0.77). Similarly, plasma renin activity and plasma angiotensin II levels did not significantly change with treatment. The change in mean (±SD) 24-hour systolic BPs from baseline to 8 weeks was -1.6±10.1 with probenecid (P=0.43), -0.4±6.1 with allopurinol (P=0.76), and 0.5±6.0 with placebo (P=0.65); there was no significant treatment effect (P=0.58). Adverse events occurred in 9%, 12%, and 2% of those given probenecid, allopurinol, or placebo, respectively. In contrast to animal experiments and observational studies, this randomized, placebo-controlled trial found that uric acid lowering had no effect on kidney-specific or

  3. Severe muscle symptoms with lipid-lowering agents may be confused with neurogenic claudication associated with spinal canal stenosis.

    PubMed

    Savage, Ruth L; Star, Kristina; Hill, Richard

    2012-01-01

    Screening of the WHO global individual case safety report database (VigiBase) has recently identified case reports with HMG CoA reductase inhibitors and muscle symptoms co-reported with spinal stenosis. In some reports spinal stenosis appears to have been listed as a coincidental finding. To assess reports with sufficient information to ascertain if they suggested that there may have been diagnostic confusion between muscle symptoms attributable to HMG CoA reductase inhibitors with or without ezetimibe and symptoms of spinal stenosis. Reports were examined for patient demographics, past history, clinical and investigational findings, co-prescribed medicines and outcomes. Three case histories recorded details suggestive of diagnostic confusion between severe and disabling muscle symptoms affecting the lower limbs attributable to an HMG CoA reductase inhibitor with and without ezetimbe and symptoms of neurogenic claudication due to spinal stenosis. The statins were not discontinued promptly leading to prolonged morbidity. Serum creatine kinase levels (CK) were normal in two patients and not recorded for the third. The reports include two safety issues, firstly the need to consider HMG CoA reductase inhibitors as a cause of severe lower limb muscle symptoms even in the presence of spinal stenosis and normal CK levels and the second, the need to measure serum creatine kinase when these symptoms occur to detect progression of myopathy and potentially serious outcomes.

  4. 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.

  5. 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.

  6. Metabolism of fatty acid in yeast: addition of reducing agents to the reaction medium influences beta-oxidation activities, gamma-decalactone production, and cell ultrastructure in Sporidiobolus ruinenii cultivated on ricinoleic acid methyl ester.

    PubMed

    Feron, Gilles; Mauvais, Geneviève; Lherminier, Jeanine; Michel, Joël; Wang, Xiao-Dong; Viel, Christophe; Cachon, Rémy

    2007-06-01

    The sensitivity of Sporidiobolus ruinenii yeast to the use of reducing agents, reflected in changes in the oxidoreduction potential at pH 7 (Eh7) environment, ricinoleic acid methyl ester catabolism, gamma-decalactone synthesis, cofactor level, beta-oxidation activity, and ultrastructure of the cell, was studied. Three environmental conditions (corresponding to oxidative, neutral, and reducing conditions) were fixed with the use of air or air and reducing agents (hydrogen and dithiothreitol). Lowering Eh7 to neutral conditions (Eh7 = +30 mV and +2.5 mV) favoured the production of lactone more than the more oxidative condition (Eh7 = +350 mV). In contrast, when a reducing condition was used (Eh7 = -130 mV), the production of gamma-decalactone was very low. These results were linked to changes in the cofactor ratio during lactone production, to the beta-oxidation activity involved in decanolide synthesis, and to ultrastructural modification of the cell.

  7. 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.

  8. 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

  9. Effects of Lowering Glycemic Index of Dietary Carbohydrate on Plasma Uric Acid: The OmniCarb Randomized Clinical Trial

    PubMed Central

    Juraschek, Stephen P; McAdams-Demarco, Mara; Gelber, Allan C; Sacks, Frank M.; Appel, Lawrence J; White, Karen; Miller, Edgar R

    2017-01-01

    Objective The effects of carbohydrates on plasma uric acid levels are controversial. We determined the individual and combined effects of carbohydrate quality (glycemic index, GI) and quantity (proportion of total daily energy, %carb) on uric acid. Methods We conducted a randomized, crossover feeding trial in overweight or obese adults without cardiovascular disease (N=163). Participants were fed each of four diets over 5-week periods separated by 2-week washout periods. Body weight was kept constant. The four diets were: high GI (GI ≥65) with high %carb (58% kcal), low GI (GI ≤45) with low %carb (40% kcal), low GI with high %carb; and high GI with low %carb. Plasma uric acid was measured at baseline and after each feeding period for comparison between the 4 diets. Results Study participants were 52% women and 50% non-Hispanic black with a mean age of 52.6 years and a mean uric acid of 4.7 (SD, 1.2) mg/dL. Reducing GI lowered uric acid when the %carb was low (−0.24 mg/dL; P <0.001) or high (−0.17 mg/dL; P <0.001). Reducing the %carb marginally increased uric acid only when GI was high (P = 0.05). The combined effect of lowering GI and increasing the %carb was −0.27 mg/dL (P <0.001). This effect was observed even after adjustment for concurrent changes in kidney function, insulin sensitivity, and products of glycolysis. Conclusions Reducing GI lowers uric acid. Future studies should examine whether reducing GI can prevent gout onset or flares. TRIAL REGISTRATION clinicaltrials.gov, Identifier: NCT00608049 PMID:26636424

  10. 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.

  11. 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.

  12. Development of Novel Radiogallium-Labeled Bone Imaging Agents Using Oligo-Aspartic Acid Peptides as Carriers

    PubMed Central

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

    2013-01-01

    68Ga (T1/2 = 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 68Ga-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 67Ga, with the previously described 67Ga-DOTA complex conjugated bisphosphonate, 67Ga-DOTA-Bn-SCN-HBP. After synthesizing DOTA-(Asp)n by a Fmoc-based solid-phase method, complexes were formed with 67Ga, resulting in 67Ga-DOTA-(Asp)n with a radiochemical purity of over 95% after HPLC purification. In hydroxyapatite binding assays, the binding rate of 67Ga-DOTA-(Asp)n increased with the increase in the length of the conjugated aspartate peptide. Moreover, in biodistribution experiments, 67Ga-DOTA-(Asp)8, 67Ga-DOTA-(Asp)11, and 67Ga-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 67Ga-DOTA-(Asp)n was lower than that of 67Ga-DOTA-Bn-SCN-HBP, blood clearance of 67Ga-DOTA-(Asp)n was more rapid. Accordingly, the bone/blood ratios of 67Ga-DOTA-(Asp)11 and 67Ga-DOTA-(Asp)14 were comparable with those of 67Ga-DOTA-Bn-SCN-HBP. In conclusion, these data provide useful insights into the drug design of 68Ga-PET tracers for the diagnosis of bone disorders, such as bone metastases. PMID:24391942

  13. 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.

  14. Caffeic acid: potential applications in nanotechnology as a green reducing agent for sustainable synthesis of gold nanoparticles.

    PubMed

    Seo, Yu Seon; Cha, Song-Hyun; Yoon, Hye-Ran; Kang, Young-Hwa; Park, Youmie

    2015-04-01

    The sustainable synthesis of gold nanoparticles from gold ions was conducted with caffeic acid as a green reducing agent. The formation of gold nanoparticles was confirmed by spectroscopic and microscopic methods. Spherical nanoparticles with an average diameter of 29.99 ± 7.43 nm were observed in high- resolution transmission electron microscopy and atomic force microscopy images. The newly prepared gold nanoparticles exhibited catalytic activity toward the reduction of 4-nitrophenol to 4-aminophenol in the presence of sodium borohydride. This system enables the preparation of green catalysts using plant natural products as reducing agents, which fulfills the growing need for sustainability initiatives.

  15. Microwave Treated Rapid Hydrothermal Synthesis Of Zno Nano-Flakes Array: The Effect Of Citric Acid As Capping Agent

    NASA Astrophysics Data System (ADS)

    Gopal Ram, S. D.; Ravi, G.; Kulandainathan, M. Anbu

    2010-10-01

    Microwave assisted hydrothermal synthesis of ZnO nanostructures with improved surface area by the addition of Citric Acid (CA) as a metal capping agent is reported. Citric acid is added to the mother precursor in three different concentrations for the preparation of ZnO nanostructure. The influence of the citric acid as a capping agent has been studied both in the preparation of ZnO nanopowders and in the ordered array formation on the precoated ZnO seed layer over glass substrates. The addition of this capping agent has shown up clearly in the morphology of the nanostructures. The X-ray diffraction patterns has shown a diminished crystallinity and a increased full width half maximum (FWHM) in the preferred oriented diffraction peak. The peak broadening is an indication of the reduced crystallite size. This cause of the inhibition in growth is realized to be the effect of capping action of citric acid. The optical property of the ZnO nanostructure was characterized by UV-vis-NIR spectroscopy.

  16. 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

  17. Acetic Acid as a Sclerosing Agent for Renal Cysts: Comparison with Ethanol in Follow-Up Results

    SciTech Connect

    Seo, Tae-Seok; Oh, Joo Hyeong; Yoon, Yup; Lim, Joo Won; Park, Seong Jin; Chang, Sung-Goo; Jeon, Yang Hyeon

    2000-03-15

    Purpose: To compare follow-up results of sclerotherapy for renal cyst using 50% acetic acid with those using 99% ethanol as sclerosing agents.Methods: Eighty-one patients underwent sclerotherapy and 58 patients, 23 males, 35 females, aged 6-76 years, having a total of 60 cysts, were included in this study; the others were lost to follow-up. The renal cysts were diagnosed by sonography, computed tomography (CT), or magnetic resonance imaging (MRI). Sclerotherapy was performed using 50% acetic acid for 32 cysts in 31 patients and 99% ethanol for 28 cysts in 27 patients. Under fluoroscopic guidance, cystic fluid was aspirated as completely as possible. After instillation of a sclerosing agent corresponding to 11.7%-25% (4-100 ml) of the aspirated volume, the patient changed position for 20 min and then the agent was removed. Patients were followed up by sonography for a period of 1-49 months. The volume of the renal cyst after sclerotherapy was compared with that of the renal cyst calculated before sclerotherapy. Medical records were reviewed to analyze complications.Results: The mean volume after sclerotherapy of the 17 cysts followed for 3-4 months in the acetic acid group was 5.1% of the initial volume, and for the 14 cysts in the ethanol group it was 10.2%. Complete regression during follow-up was shown in 21 cysts (66%) in the acetic acid group; the mean volume of these cysts before the procedure was 245 ml. The mean volume of the nine (32%) completely regressed cysts in the ethanol group was 184 ml. Mild flank pain, which occurred in three patients in each group, was the only complication and resolved the next day.Conclusion: Acetic acid was an effective and safe sclerosing agent for renal cysts, tending to induce faster and more complete regression than ethanol.

  18. Ultrasound triggered cell death in vitro with doxorubicin loaded poly lactic-acid contrast agents.

    PubMed

    Eisenbrey, J R; Huang, P; Hsu, J; Wheatley, M A

    2009-12-01

    Traditional chemotherapy generally results in systemic toxicity, which also limits drug levels at the area of need. Two ultrasound contrast agents (UCA), with diameters between 1-2 microm in diameter and shell thicknesses of 100-200 nm, composed of poly lactic-acid (PLA), one loaded by surface adsorption and the other loaded by drug incorporation in the shell, were compared in vitro for potential use in cancer therapy. These poly lactic-acid (PLA) UCA platforms contain a gas core that in an ultrasound (US) field can cause the UCA to oscillate or rupture. Following a systemic injection of drug loaded UCA with external application of US focused at the area of interest, this platform could potentially increase drug toxicity at the area of need, while protecting healthy tissue through microencapsulation of the drug. In vitro toxicity in MDA-MB-231 breast cancer cells of the surface-adsorbed and shell-incorporated doxorubicin (Dox) loaded UCA were examined at 5 MHz insonation using a pulse repetition frequency of 100 Hz at varying pressure amplitudes. Both platforms resulted in equivalent cell death compared to free Dox and US when insonated at peak positive pressure amplitudes of 1.26 MPa and above. While no significant changes in cell death were seen for surface adsorbed Dox-UCA with or without insonation, cell death using the platform with Dox incorporated within the shell increased from 16.12% to 25.78% (p=0.0272), approaching double the potency of the platform when insonated at peak positive pressure amplitudes of 1.26 MPa and above. This mechanism is believed to be the result of UCA rupture at higher insonation pressure amplitudes, resulting in more exposed drug and shell surface area as well as increased cellular uptake of Dox containing polymer shell fragments. This study has shown that a polymer UCA with drug housed within the shell may be used for US-triggered cell death. US activation can be used to make a carrier significantly more potent once in the area of

  19. Evaluation of 9-cis retinoic acid and mitotane as antitumoral agents in an adrenocortical xenograft model.

    PubMed

    Nagy, Zoltán; Baghy, Kornélia; Hunyadi-Gulyás, Éva; Micsik, Tamás; Nyírő, Gábor; Rácz, Gergely; Butz, Henriett; Perge, Pál; Kovalszky, Ilona; Medzihradszky, Katalin F; Rácz, Károly; Patócs, Attila; Igaz, Peter

    2015-01-01

    The available drug treatment options for adrenocortical carcinoma (ACC) are limited. In our previous studies, the in vitro activity of 9-cis retinoic acid (9-cisRA) on adrenocortical NCI-H295R cells was shown along with its antitumoral effects in a small pilot xenograft study. Our aim was to dissect the antitumoral effects of 9-cisRA on ACC in a large-scale xenograft study involving mitotane, 9-cisRA and their combination. 43 male SCID mice inoculated with NCI-H295R cells were treated in four groups (i. control, ii. 9-cisRA, iii. mitotane, iv. 9-cisRA + mitotane) for 28 days. Tumor size follow-up, histological and immunohistochemical (Ki-67) analysis, tissue gene expression microarray, quantitative real-time-PCR for the validation of microarray results and to detect circulating microRNAs were performed. Protein expression was studied by proteomics and Western-blot validation. Only mitotane alone and the combination of 9-cisRA and mitotane resulted in significant tumor size reduction. The Ki-67 index was significantly reduced in both 9-cisRA and 9-cisRA+mitotane groups. Only modest changes at the mRNA level were found: the 9-cisRA-induced overexpression of apolipoprotein A4 and down-regulation of phosphodiesterase 4A was validated. The expression of circulating hsa-miR-483-5p was significantly reduced in the combined treatment group. The SET protein was validated as being significantly down-regulated in the combined mitotane+9-cisRA group. 9-cisRA might be a helpful additive agent in the treatment of ACC in combination with mitotane. Circulating hsa-miR-483-5p could be utilized for monitoring the treatment efficacy in ACC patients, and the treatment-induced reduction in protein SET expression might raise its relevance in ACC biology.

  20. Evaluation of 9-cis retinoic acid and mitotane as antitumoral agents in an adrenocortical xenograft model

    PubMed Central

    Nagy, Zoltán; Baghy, Kornélia; Hunyadi-Gulyás, Éva; Micsik, Tamás; Nyírő, Gábor; Rácz, Gergely; Butz, Henriett; Perge, Pál; Kovalszky, Ilona; Medzihradszky, Katalin F; Rácz, Károly; Patócs, Attila; Igaz, Peter

    2015-01-01

    The available drug treatment options for adrenocortical carcinoma (ACC) are limited. In our previous studies, the in vitro activity of 9-cis retinoic acid (9-cisRA) on adrenocortical NCI-H295R cells was shown along with its antitumoral effects in a small pilot xenograft study. Our aim was to dissect the antitumoral effects of 9-cisRA on ACC in a large-scale xenograft study involving mitotane, 9-cisRA and their combination. 43 male SCID mice inoculated with NCI-H295R cells were treated in four groups (i. control, ii. 9-cisRA, iii. mitotane, iv. 9-cisRA + mitotane) for 28 days. Tumor size follow-up, histological and immunohistochemical (Ki-67) analysis, tissue gene expression microarray, quantitative real-time-PCR for the validation of microarray results and to detect circulating microRNAs were performed. Protein expression was studied by proteomics and Western-blot validation. Only mitotane alone and the combination of 9-cisRA and mitotane resulted in significant tumor size reduction. The Ki-67 index was significantly reduced in both 9-cisRA and 9-cisRA+mitotane groups. Only modest changes at the mRNA level were found: the 9-cisRA-induced overexpression of apolipoprotein A4 and down-regulation of phosphodiesterase 4A was validated. The expression of circulating hsa-miR-483-5p was significantly reduced in the combined treatment group. The SET protein was validated as being significantly down-regulated in the combined mitotane+9-cisRA group. 9-cisRA might be a helpful additive agent in the treatment of ACC in combination with mitotane. Circulating hsa-miR-483-5p could be utilized for monitoring the treatment efficacy in ACC patients, and the treatment-induced reduction in protein SET expression might raise its relevance in ACC biology. PMID:26885453

  1. Susceptibility of lactic acid bacteria, bifidobacteria and other bacteria of intestinal origin to chemotherapeutic agents.

    PubMed

    Flórez, Ana B; Sierra, Marta; Ruas-Madiedo, Patricia; Mayo, Baltasar

    2016-11-01

    Chemotherapy is a cornerstone of cancer treatment but it can have serious side effects, such as intestinal mucositis. This work reports the susceptibility/resistance profiles of 34 species of lactic acid bacteria (LAB), bifidobacteria and other intestinal bacteria from different collections to various chemotherapeutic agents (CAs) currently used in cancer treatments in an attempt to identify microorganisms that could prevent or treat mucositis symptoms. The highest concentrations of the CAs tested were equal to or higher than those reached in plasma during anticancer treatments. All 34 species proved to be resistant at the highest concentrations assayed [minimum inhibitory concentrations (MICs) > 128 µg/mL] to capecitabine, cyclophosphamide, docetaxel, erlotinib, gefitinib, irinotecan and paclitaxel. For doxorubicin, 5-fluorouracil, gemcitabine and, especially, afatinib and pemetrexed, interspecies variation in the MIC was observed. In further work to assess the interspecies and intraspecies variability, MICs of the CAs pemetrexed and afatinib were determined for 32 strains belonging to four Bifidobacterium spp. of intestinal origin. For pemetrexed, a bimodal MIC curve was obtained (modes <2-8 µg/mL and >256 µg/mL), whilst a normal unimodal curve was obtained for afatinib (mode 128 µg/mL). Altogether, these results suggest that the majority of CAs should not, by themselves, perturb the microbial populations of the gut microbiota (but considering that they could be transformed in vivo into more toxic compounds). However, LAB and bifidobacteria, which are key players in the intestinal microbial balance of the healthy state, might be particularly inhibited by CAs such as gemcitabine or doxorubicin. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  2. Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register.

    PubMed

    Ekström, Nils; Svensson, Ann-Marie; Miftaraj, Mervete; Franzén, Stefan; Zethelius, Björn; Eliasson, Björn; Gudbjörnsdottir, Soffia

    2016-10-01

    To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers. Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score. Of the 20 422 patients included in the study, 43% started on second-line treatment with sulphonylurea (SU), 21% basal insulin, 12% thiazolidinedione (TZD), 11% meglitinide, 10% dipeptidyl peptidase-4 (DPP-4) inhibitor, 1% glucagon-like peptide-1 (GLP-1) receptor agonist and 1% acarbose. At the index date, the mean patient age was ~60 years for all groups except the GLP-1 receptor agonist (56.0 years) and SU (62.9 years) groups. Diabetes duration and glycated haemoglobin levels were similar in all groups. When compared with SU, basal insulin was associated with an 18% higher risk and TZD with a 24% lower risk of mortality [HR 1.18 (95% CI 1.03-1.36) and 0.76 (95% CI 0.62-0.94)], respectively. DPP-4 inhibitor treatment was associated with significantly lower risks of CVD, fatal CVD, CHD, fatal CHD and CHF. This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality. © 2016 John Wiley & Sons Ltd.

  3. Lipid lowering agents use and systemic and oral inflammation in overweight or obese adult Puerto Ricans: the San Juan Overweight Adults Longitudinal Study (SOALS)

    PubMed Central

    Andriankaja, Oelisoa M.; Jiménez, James J.; Muñoz-Torres, Francisco J.; Pérez, Cynthia M.; Vergara, José L.; Joshipura, Kaumudi

    2015-01-01

    The effects of lipid-lowering agents (LLA) on reducing systemic and oral inflammation have not been evaluated. Objective To assess the association of LLA use with high-sensitivity C-reactive protein (hs-CRP) and oral inflammation. Design Cross-sectional analysis using baseline data from 1,300 overweight/obese participants aged 40–65 years, recruited for the ongoing San Juan Overweight Adults Longitudinal Study. Serum hs-CRP was measured by ELISA, gingival/periodontal inflammation was evaluated as bleeding upon probing (BOP), and LLA was self-reported. Separate logistic models were performed for systemic and oral inflammation. Results 24% participants reported history of dyslipidemia, of which, 50.3% self-reported LLA use. Sixty percent of the participants had elevated hs-CRP (>3 mg/dL) and 50% had high BOP (defined as at or above the median: 21%). After adjusting for age, gender, smoking, HDL-C, physical activity, diabetes, blood pressure medications, and percent body fat composition, LLA users had significantly lower odds of elevated hs-CRP compared to LLA non-users (OR=0.58; 95% CI: 0.39–0.85). After adjusting for age, gender, smoking status, educational level, mean plaque index, and percent body fat, LLA users had significantly lower odds of high BOP compared to LLA non-users (OR= 0.62; 95% CI: 0.42–0.91). Conclusions Lipid-lowering agents may reduce both systemic and oral inflammatory responses. PMID:26407668

  4. Erythrocyte very long-chain saturated fatty acids associated with lower risk of incident sudden cardiac arrest.

    PubMed

    Lemaitre, Rozenn N; King, Irena B; Rice, Kenneth; McKnight, Barbara; Sotoodehnia, Nona; Rea, Thomas D; Johnson, Catherine O; Raghunathan, Trivellore E; Cobb, Leonard A; Mozaffarian, Dariush; Siscovick, David S

    2014-10-01

    Prior studies suggest that circulating n-3 and trans-fatty acids influence the risk of sudden cardiac arrest (SCA). Yet, while other fatty acids also differ in their membrane properties and biological activities which may influence SCA, little is known about the associations of other circulating fatty acids with SCA. The aim of this study was to investigate the associations of 17 erythrocyte membrane fatty acids with SCA risk. We used data from a population-based case-control study of SCA in the greater Seattle, Washington, area. Cases, aged 25-74 years, were out-of-hospital SCA patients, attended by paramedics (n=265). Controls, matched to cases by age, sex and calendar year, were randomly identified from the community (n=415). All participants were free of prior clinically-diagnosed heart disease. Blood was obtained at the time of cardiac arrest by attending paramedics (cases) or at the time of an interview (controls). Higher levels of erythrocyte very long-chain saturated fatty acids (VLSFA) were associated with lower risk of SCA. After adjustment for risk factors and levels of n-3 and trans-fatty acids, higher levels of 20:0 corresponding to 1 SD were associated with 30% lower SCA risk (13-43%, p=0.001). Higher levels of 22:0 and 24:0 were associated with similar lower SCA risk (ORs for 1 SD-difference: 0.71 [95% CI: 0.57-0.88, p=0.002] for 22:0; and 0.79 [95% CI: 0.63-0.98, p=0.04] for 24:0). These novel findings support the need for investigation of biologic effects of circulating VLSFA and their determinants.

  5. Erythrocyte Very Long-Chain Saturated Fatty Acids Associated with Lower Risk of Incident Sudden Cardiac Arrest

    PubMed Central

    Lemaitre, Rozenn N.; King, Irena B.; Rice, Kenneth; McKnight, Barbara; Sotoodehnia, Nona; Rea, Thomas D; Johnson, Catherine O; Raghunathan, Trivellore E.; Cobb, Leonard A.; Mozaffarian, Dariush; Siscovick, David S.

    2014-01-01

    Prior studies suggest that circulating n-3 and trans-fatty acids influence the risk of sudden cardiac arrest (SCA). Yet, while other fatty acids also differ in their membrane properties and biological activities which may influence SCA, little is known about the associations of other circulating fatty acids with SCA. The aim of this study was to investigate the associations of 17 erythrocyte membrane fatty acids with SCA risk. We used data from a population-based case-control study of SCA in the greater Seattle, Washington, area. Cases, aged 25–74 years, were out-of-hospital SCA patients, attended by paramedics (n=265). Controls, matched to cases by age, sex and calendar year, were randomly identified from the community (n=415). All participants were free of prior clinically-diagnosed heart disease. Blood was obtained at the time of cardiac arrest by attending paramedics (cases) or at the time of an interview (controls). Higher levels of erythrocyte very long-chain saturated fatty acids (VLSFA) were associated with lower risk of SCA. After adjustment for risk factors and levels of n-3 and trans-fatty acids, higher levels of 20:0 corresponding to 1 SD were associated with 30% lower SCA risk (13%-43%, p=0.001). Higher levels of 22:0 and 24:0 were associated with similar lower SCA risk (ORs for 1 SD-difference: 0.71 [95% CI: 0.57–0.88, p=0.002] for 22:0; and 0.79 [95% CI: 0.63–0.98, p=0.04] for 24:0). These novel findings support the need for investigation of biologic effects of circulating VLSFA and their determinants. PMID:25107579

  6. [Folic acid supplementation as prophylaxis of neural tube defect in the Lower Silesia region: fact or fiction?].

    PubMed

    Bagłaj, Maciej; Wojtyłko, Anna

    2011-01-01

    To assess the efficacy of nationwide programme of prophylaxis of neural tube defects in the Lower Silesia region. A questionnaire study was conducted among all mothers of infants admitted between 2001 and 2010 to the Department of Pediatric Surgery and Urology in Wroclaw Medical Academy. The data regarding pregnancy and delivery, newborn's medical condition, family history, parental health, profession and education, and finally folic acid supplementation by mothers were analysed. Among 1278 newborn infants, in 148 children (11.6%) central nervous system (CNS) defects were diagnosed. Among 894 mothers (69.9%) who took part in the study, 159 of them (17.8%) confirmed taking folic acid before becoming pregnant. The rate of supplementation with folic acid showed a rising trend in the study period and increased from 7.1% in 2001 to 35.8% in 2010. Folic acid was taken more frequently by the women living in urban areas (24.2%) than by those living in rural regions (9.2%). With regard to the educational level, the highest rate of supplementation with folic acid was noted among the women with high education (37.8%). Forty-eight percent of mothers were informed about prevention of neural tube defects by their physician, while in 32% of them the family or media were the source of information. Mothers of 255 infants confirmed that they knew about prevention of congenital defects by vitamin intake, but they had not taken folic acid before pregnancy. 1. Realization of the programme of prevention of neural tube defects in Lower Silesia region is highly unsatisfactory. 2. The actions undertaken on the national and local level and aimed to popularize the knowledge about prevention of CNS defects among women are assessed to be ineffective in the Lower Silesia region and need urgent verification.

  7. 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.

  8. 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.

  9. Synthesis and biological relationships of 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives as antimitotic agents.

    PubMed

    Lai, Ya-Yun; Huang, Li-Jiau; Lee, Kuo-Hsiung; Xiao, Zhiyan; Bastow, Kenneth F; Yamori, Takao; Kuo, Sheng-Chu

    2005-01-03

    As part of a continuing search for potential anticancer drug candidates in the 2-phenyl-4-quinolone series, 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives and their salts were synthesized and evaluated. Preliminary screening showed that carboxylic acid analogs containing a m-fluoro substituted 2-phenyl group displayed the highest in vitro anticancer activity. Activity decreased significantly if a chlorine or methoxy group replaced the fluorine atom. 3'-Fluoro-6-methoxy-2-phenyl-4-quinolone-3-carboxylic acid (68) had the highest in vitro cytotoxic activity among all tested carboxylic acid derivatives and their salts. The mechanism of action may be similar, but not identical, to that of tubulin binding drugs, such as navelbine and taxol. Compound 68 merits further investigation as a novel hydrophilic antimitotic agent.

  10. 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.

  11. Curcumin Targeted, Polymalic Acid-Based MRI Contrast Agent for the Detection of Aβ Plaques in Alzheimer's Disease.

    PubMed

    Patil, Rameshwar; Gangalum, Pallavi R; Wagner, Shawn; Portilla-Arias, Jose; Ding, Hui; Rekechenetskiy, Arthur; Konda, Bindu; Inoue, Satoshi; Black, Keith L; Ljubimova, Julia Y; Holler, Eggehard

    2015-09-01

    Currently, there is no gadolinium-based contrast agent available for conventional magnetic resonance imaging (MRI) detection of amyloidal beta (Aβ) plaques in Alzheimer's disease (AD). Its timely finding would be vital for patient survival and quality of life. Curcumin (CUR), a common Indian spice effectively binds to Aβ plaques which is a hallmark of AD. To address this binding, we have designed a novel nanoimaging agent (NIA) based on nature-derived poly(β-l-malic acid) (PMLA) containing covalently attached gadolinium-DOTA(Gd-DOTA) and nature-derived CUR. The all-in-one agent recognizes and selectively binds to Aβ plaques and is detected by MRI. It efficiently detected Aβ plaques in human and mouse samples by an ex vivo staining. The method can be useful in clinic for safe and noninvasive diagnosis of AD.

  12. Effects of Citric Acid and Desensitizing Agent Application on Nonfluorosed and Fluorosed Dentin: An In Vitro Sem Study

    PubMed Central

    Neha, Mahajan; Vandana, Laxman K

    2015-01-01

    Fluorosis is one of the factors which bring about mineralisation changes in a dentinal structure leading to dentin. The purpose of the present study was to compare and evaluate the dentinal tubular changes in fluorosed and nonfluorosed teeth subsequent to the application of citric acid,strontium acetate based sodium fluoride (SAF) using scanning electron microscopy (SEM). Dentin specimens from healthy fluorosed and nonfluorosed teeth were included in the study. Each of them was grouped into acid treated and SAF treatment groups. Using SEM, the photomicrographs (3500x) of dentin specimens were evaluated. Results showed while there was a significant difference in tubular width of partial occlusion ≤ 25%, being more in fluorosed group compared to nonfluorosed group after application SAF. Application of desensitising agents demonstrated higher number of dentinal tubular occlusion and diameter reduction in nonfluorosed dentin compared to fluorosed dentin. Summary: Root biomodification and desensitising agent procedure brings in definite difference between fluorosed and non-fluorosed dentin specimens. PMID:25870716

  13. 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.

  14. Quinolone antimicrobial agents. 1. Versatile new synthesis of 1-alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids.

    PubMed

    Mitscher, L A; Gracey, H E; Clark, G W; Suzuki, T

    1978-05-01

    A flexible reaction sequence has been developed which starts with readily available anthranilic acids or isatoic anhydrides and leads regiospecifically to 1-alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids after reaction with 1,3-dicarbonyl compounds. The sequence is superior to earlier published methods by allowing electron-releasing and -withdrawing groups in any position on the aro;atic ring, by allowing convenient substitution at C2, and better overall yield. A number of new and known antimicrobial agents were prepared and tested in vitro, demonstrating, inter alia, that substitution of the H at C2 abolished antibacterial activity.

  15. Knockdown of Pyruvate Carboxylase or Fatty Acid Synthase Lowers Numerous Lipids and Glucose-Stimulated Insulin Release in Insulinoma Cells

    PubMed Central

    MacDonald, Michael J.; Hasan, Noaman M.; Dobrzyn, Agnieszka; Stoker, Scott W.; Ntambi, James M.; Liu, Xueqing; Sampath, Harini

    2013-01-01

    We previously showed that knockdown of the anaplerotic enzyme pyruvate carboxylase in the INS-1 832/13 insulinoma cell line inhibited glucose-stimulated insulin release and glucose carbon incorporation into lipids. We now show that knockdown of fatty acid synthase (FAS) mRNA and protein also inhibits glucose-stimulated insulin release in this cell line. Levels of numerous phospholipids, cholesterol esters, diacylglycerol, triglycerides and individual fatty acids with C14-C24 side chains were acutely lowered about 20% in glucose-stimulated pyruvate carboxylase knockdown cells over a time course that coincides with insulin secretion. In FAS knockdown cells glucose carbon incorporation into lipids and the levels of the subclasses of phospholipids and cholesterol ester species were lower by 20–30% without inhibition of glucose oxidation. These studies suggest that rapid lipid modification is essential for normal glucose-stimulated insulin secretion. PMID:23357280

  16. Omega-3 Fatty Acid Supplementation Lowers Serum FSH in Normal Weight But Not Obese Women

    PubMed Central

    Al-Safi, Zain A.; Liu, Huayu; Carlson, Nichole E.; Chosich, Justin; Harris, Mary; Bradford, Andrew P.; Robledo, Celeste; Eckel, Robert H.

    2016-01-01

    Context: Dietary omega-3 fatty acids delay ovarian aging and promote oocyte quality in mice. Objective: To test whether dietary supplementation with omega-3 polyunsaturated fatty acids (PUFA) modulates reproductive hormones in reproductive-age women. Design: Prospective interventional study. Setting: Academic center. Participants: Fifteen obese and 12 normal-weight (NW) eumenorrheic women, ages 28–34 years. Intervention: Two frequent blood-sampling studies were performed before and after 1 month of omega-3 PUFA supplementation with 4 g of eicosapentaenoic acid and docosahexaenoic acid daily. Main Outcome Measures: Serum LH and FSH (basal and after GnRH stimulation). Results: The ratio of omega-6 to omega-3 PUFA was significantly reduced in plasma and red blood cell components for both groups after treatment (both P < .01). Omega-3 PUFA supplementation resulted in reduction of FSH and FSH response to GnRH by 17% on average (P = .06 and P = .03, respectively) in NW but not obese women. Serum levels of IL-1β and TNF-α were reduced after omega-3 PUFA supplementation (−72% for IL-1β; −56% for TNF-α; both, P < .05) in obese but not in NW women. This reduction, however, was not associated with a hormonal change in obese women. Conclusions: Dietary administration with omega-3 PUFA decreased serum FSH levels in NW but not in obese women with normal ovarian reserve. This effect is intriguing and is directionally consistent with murine data whereby higher dietary omega-3 PUFA extends reproductive lifespan. Our results imply that this nutritional intervention should be tested in women with diminished ovarian reserve in an attempt to delay ovarian aging. PMID:26523525

  17. 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

  18. 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

  19. Cholesterol-Lowering Effects and Mechanisms in View of Bile Acid Pathway of Resveratrol and Resveratrol Glucuronides.

    PubMed

    Shao, Dongyan; Wang, Yilin; Huang, Qingsheng; Shi, Junling; Yang, Hui; Pan, Zhongli; Jin, Mingliang; Zhao, Haobin; Xu, Xiaoguang

    2016-10-13

    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 metabolites of Res in the liver, resveratrol glucuronides (Gres) is suspected to also contribute to the overall cholestrol-lowering activity of Res, which needs to be studied. In this research, when HepG2 steatosis hepatic cells were treated with Res and Gres at different concentration levels, Res and Gres showed similar activity in lowering cellular TC content. The presence of Res and Gres caused a significant increase in hepatic CYP7A1 and BSEP, indicating the increase in the synthesis and efflux of bile acids, respectively. The reduction of HMG-CoAR tied to a decrease in de novo synthesis of cholesterol and the increase of ABCG5 suggested the increase of direct efflux of cholesterol. All above variations reduced the hepatic cholesterol level, which triggered the significant enhancement of LDLR, illustrating the improvement of clearance of LDL-C from the plasma and prevention of atherosclerosis. Overall, this study demonstrated both Res and Gres might have capabilities in lowering hepatic cholesterol through increasing in the synthesis and efflux of bile acids, and decreasing in synthesis and increasing in the efflux of cholesterol. Gres would have preferred potential than Res because of its lower cytotoxicity, which indicated that the action of the metabolites should also be considered in the future studies. © 2016 Institute of Food Technologists®.

  20. Suberoylanilide hydroxamic acid as a potential therapeutic agent for human breast cancer treatment.

    PubMed Central

    Huang, L.; Pardee, A. B.

    2000-01-01

    BACKGROUND: Suberoylanilide hydroxamic acid (SAHA) is a prototype of the newly developed, second-generation, hybrid polar compounds. It is a novel histone deacetylase inhibitor with high potency for inducing cell differentiation of cultured murine erythroleukemia cells. Studies with SAHA have primarily been performed with hematopoietic tumor cells. Here we extent these studies with SAHA to human breast cancer cell lines in an attempt to find better therapeutic agents for breast cancer treatment. MATERIALS AND METHODS: Human breast cancer cell lines, MCF7, MDA-MB-231, and MDA-MB-435, as well as normal cells, including the normal breast epithelial cell line MCF-10A, and fibroblasts, were treated with SAHA. Cells assayed for cell survival by using trypan blue exclusion assay, colony formation assay, and cell cycle and apoptosis analysis. The effects of SAHA on cell cycle and apoptosis regulatory proteins were examined by Western blots analysis. The identification of additional target genes was carried out by differential display (DD) and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: SAHA inhibited clonogenic growth of MCF7, MDA-MB-231, and MDA-MB-435 breast cancer cells. These cells were more sensitive to SAHA-mediated cytotoxic effects than normal breast epithelial cells and fibroblasts. The cytotoxic effects of SAHA on breast cancer cells were manifested by G1 and G2/M cell cycle arrest and eventual apoptosis. The pan-caspase inhibitor, Z-VAD.fmk, blocked SAHA-induced cell death, DNA laddering, and cleavage of poly(ADP-ribose) polymerase, indicating the involvement of caspases in SAHA-mediated apoptosis. In addition, SAHA modulated cell cycle and apoptosis regulatory proteins. For example, cyclin-dependent kinase (CDK) inhibitors p21WAF1/Cip1 and p27Kip1 were induced, and retinoblastoma protein pRb was hypophosphorylated. Moreover, SAHA induced several genes associated with differentiation and/ or growth inhibition. These genes encode gelsolin

  1. Usefulness of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) in Women to Lower Triglyceride Levels (Results from the MARINE and ANCHOR Trials).

    PubMed

    Mosca, Lori; Ballantyne, Christie M; Bays, Harold E; Guyton, John R; Philip, Sephy; Doyle, Ralph T; Juliano, Rebecca A

    2017-02-01

    There are limited data on the efficacy and safety of triglyceride (TG)-lowering agents in women. We conducted subgroup analyses of the effects of icosapent ethyl (a high-purity prescription form of the ethyl ester of the omega-3 fatty acid, eicosapentaenoic acid) on TG levels (primary efficacy variable) and other atherogenic and inflammatory parameters in a total of 215 women with a broad range of TG levels (200-2000 mg/dl) enrolled in two 12-week placebo-controlled trials: MARINE (n = 18; placebo, n = 18) and ANCHOR (n = 91; placebo, n = 88). Icosapent ethyl 4 g/day significantly reduced TG levels from baseline to week 12 versus placebo in both MARINE (-22.7%; p = 0.0327) and ANCHOR (-21.5%; p <0.0001) without increasing low-density lipoprotein cholesterol levels. Significant improvements were also observed in non-high-density lipoprotein cholesterol levels in MARINE (-15.7%; p = 0.0082) and ANCHOR (-14.2%; p <0.0001) and total cholesterol levels in MARINE (-14.9%; p = 0.0023) and ANCHOR (-12.1%; p <0.0001), along with significant increases of >500% in eicosapentaenoic acid levels in plasma and red blood cells (all p <0.001). Icosapent ethyl was well tolerated, with adverse-event profiles comparable with findings in the overall studies. In conclusion, icosapent ethyl 4 g/day significantly reduced TG levels and other atherogenic parameters in women without increasing low-density lipoprotein cholesterol levels compared with placebo; the clinical implications of these findings are being evaluated in the REDUCtion of Cardiovascular Events With Eicosapentaenoic Acid [EPA]-Intervention Trial (REDUCE-IT) cardiovascular outcomes study.

  2. A short synthetic route to biologically active (+/-)-daurichromenic acid as highly potent anti-HIV agent.

    PubMed

    Lee, Yong Rok; Wang, Xue

    2005-11-07

    The efficient total synthesis of biologically interesting (+/-)-daurichromenic acid is accomplished starting from 2,4-dihydroxy-6-methylbenzoic acid or 2,4-dihydroxy-6-methylbenzaldehyde in one or two steps.

  3. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis.

    PubMed

    Palmer, Suetonia C; Mavridis, Dimitris; Navarese, Eliano; Craig, Jonathan C; Tonelli, Marcello; Salanti, Georgia; Wiebe, Natasha; Ruospo, Marinella; Wheeler, David C; Strippoli, Giovanni F M

    2015-05-23

    The comparative efficacy and safety of pharmacological agents to lower blood pressure in adults with diabetes and kidney disease remains controversial. We aimed to investigate the benefits and harms of blood pressure-lowering drugs in this population of patients. We did a network meta-analysis of randomised trials from around the world comparing blood pressure-lowering agents in adults with diabetic kidney disease. Electronic databases (the Cochrane Collaboration, Medline, and Embase) were searched systematically up to January, 2014, for trials in adults with diabetes and kidney disease comparing orally administered blood pressure-lowering drugs. Primary outcomes were all-cause mortality and end-stage kidney disease. We also assessed secondary safety and cardiovascular outcomes. We did random-effects network meta-analysis to obtain estimates for primary and secondary outcomes and we presented these estimates as odds ratios or standardised mean differences with 95% CIs. We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking (SUCRA) probabilities. 157 studies comprising 43,256 participants, mostly with type 2 diabetes and chronic kidney disease, were included in the network meta-analysis. No drug regimen was more effective than placebo for reducing all-cause mortality. However, compared with placebo, end-stage renal disease was significantly less likely after dual treatment with an angiotensin-receptor blocker (ARB) and an angiotensin-converting-enzyme (ACE) inhibitor (odds ratio 0·62, 95% CI 0·43-0·90) and after ARB monotherapy (0·77, 0·65-0·92). No regimen significantly increased hyperkalaemia or acute kidney injury, although combined ACE inhibitor and ARB treatment had the lowest rank among all interventions because of borderline increases in estimated risks of these harms (odds ratio 2·69, 95% CI 0·97-7·47 for hyperkalaemia; 2·69, 0·98-7·38 for acute kidney injury). No blood pressure-lowering strategy

  4. Higher docosahexaenoic acid, lower arachidonic acid and reduced lipid tolerance with high doses of a lipid emulsion containing 15% fish oil: a randomized clinical trial.

    PubMed

    D'Ascenzo, Rita; Savini, Sara; Biagetti, Chiara; Bellagamba, Maria P; Marchionni, Paolo; Pompilio, Adriana; Cogo, Paola E; Carnielli, Virgilio P

    2014-12-01

    Lipid emulsions containing fish oil, as source of long chain omega 3 fatty acids, have recently became available for parenteral nutrition in infants, but scanty data exist in extremely low birth weight preterms. The objective of this study was to compare plasma fatty acids and lipid tolerance in preterm infants receiving different doses of a 15% fish oil vs. a soybean oil based lipid emulsion. Preterm infants (birth weight 500-1249 g) were randomized to receive parenteral nutrition with MOSF (30% Medium-chain triglycerides, 25% Olive oil, 30% Soybean oil, 15% Fish oil) or S (S, 100% Soybean oil) both at two levels of fat intake: 2.5 or 3.5 g kg(-1) d(-1), named 2.5Fat and 3.5Fat respectively. Plasma lipid classes and their fatty acid composition were determined on postnatal day 7 and 14 by gas chromatography together with routine biochemistry. We studied 80 infants. MOSF infants had significantly higher plasma phospholipid Docosahexaenoic acid and Eicosapentaenoic and lower Arachidonic acid. Plasma phospholipids, triglycerides and free cholesterol were all significantly higher in the MOSF-3.5Fat group, while cholesterol esters were lower with MOSF than with S. The area under the curve of total bilirubin was significantly lower with MOSF than with S. The use of a lipid emulsion with 15% FO resulted in marked changes of plasma long-chain fatty acids. Whether the benefits of increasing Docosahexaenoic acid outweigh the potential negative effect of reduced Arachidonic acid should be further studied. MOSF patients exhibited reduced lipid tolerance at 3.5 g kg(-1) d(-1) fat intake. The trial was conducted between January 2008 and December 2012 so we had not registered it in a public trials registry as it is now required for trials that started after July 2008. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  5. 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.

  6. Application of chiral derivatizing agents in the high-performance liquid chromatographic separation of amino acid enantiomers: a review.

    PubMed

    Ilisz, István; Berkecz, Robert; Péter, Antal

    2008-05-12

    The past 20 years has seen an explosive growth in the field of chirality, as illustrated by the rapid progress in the various facets of this intriguing field. The impetus for advances in chiral separation has been highest in the past decade and this still continues to be an area of high focus. This paper reviews indirect separation approaches, i.e. derivatization reactions aimed at creating the basis for the chromatographic resolution of biologically and pharmaceutically important enantiomers, with emphasis on the literature published in the last 12 years. The main aspects of the chiral derivatization of amino acids are discussed, i.e. derivatization on the amino group, transforming the molecules into covalently bonded diastereomeric derivatives through the use of homochiral derivatizing agents. The diastereomers formed (amides, urethanes, urea, thiourea derivatives, etc.) can be separated on achiral stationary phases. The applications are considered, and in some cases different derivatizing agents for the resolution of complex mixtures of proteinogenic d,l-amino acids, non-proteinogenic amino acids and peptides/amino acids from peptide syntheses or microorganisms are compared.

  7. Comparison of natural humic substances and synthetic ethylenediaminetetraacetic acid and nitrilotriacetic acid as washing agents of a heavy metal-polluted soil.

    PubMed

    Soleimani, Mohsen; Hajabbasi, Mohammad A; Afyuni, Majid; Akbar, Samira; Jensen, Julie K; Holm, Peter E; Borggaard, Ole K

    2010-01-01

    Ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), and other synthetic polycarboxylic acids have been shown to possess substantial capacity as washing agents of heavy metal-polluted soils, but they are environmentally problematic. Therefore, a sample of natural soluble humic substances (HS) was tested as a possible substitute. The efficiency of HS to extract cadmium (Cd), copper (Cu), and lead (Pb) from a strongly polluted calcareous urban soil was compared with that of EDTA and NTA. The influence of extractant concentration (25-100 mmol L(-1) C), solution/soil ratio (5-100 L kg(-1)), and single-step vs. multistep extraction on heavy metal removal from the soil was investigated. The extracted pools were assessed by sequential extraction. Ethylenediaminetetraacetic acid and NTA extracted up to 86, 77, and 30% of total soil Cd, Cu, and Pb, respectively, whereas HS extracted 44, 53, and 4%. Extracted amounts of Cd, Cu, and Pb increased with increasing extractant concentration and solution/soil ratio in the range 5 to 100 L kg(-1). Single-step extraction removed about the same amounts of the three metals as multiple-step extraction. The metal-extracted pools of the soil depended on the metal and on the extractant. The overall conclusion is that soluble HS can replace synthetic EDTA and NTA as washing agents for Cd- and Cu-polluted soils, whereas HS is not a promising substitute of EDTA or NTA for cleaning Pb-polluted, calcareous soils.

  8. The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans.

    PubMed

    Berkenstam, Anders; Kristensen, Jens; Mellström, Karin; Carlsson, Bo; Malm, Johan; Rehnmark, Stefan; Garg, Neeraj; Andersson, Carl Magnus; Rudling, Mats; Sjöberg, Folke; Angelin, Bo; Baxter, John D

    2008-01-15

    Atherosclerotic cardiovascular disease is a major problem despite the availability of drugs that influence major risk factors. New treatments are needed, and there is growing interest in therapies that may have multiple actions. Thyroid hormone modulates several cardiovascular risk factors and delays atherosclerosis progression in humans. However, use of thyroid hormone is limited by side effects, especially in the heart. To overcome this limitation, pharmacologically selective thyromimetics that mimic metabolic effects of thyroid hormone and bypass side effects are under development. In animal models, such thyromimetics have been shown to stimulate cholesterol elimination through LDL and HDL pathways and decrease body weight without eliciting side effects. We report here studies on a selective thyromimetic [KB2115; (3-[[3,5-dibromo-4-[4-hydroxy-3-(1-methylethyl)-phenoxy]-phenyl]-amino]-3-oxopropanoic acid)] in humans. In moderately overweight and hypercholesterolemic subjects KB2115 was found to be safe and well tolerated and elicited up to a 40% lowering of total and LDL cholesterol after 14 days of treatment. Bile acid synthesis was stimulated without evidence of increased cholesterol production, indicating that KB2115 induced net cholesterol excretion. KB2115 did not provoke detectable effects on the heart, suggesting that the pharmacological selectivity observed in animal models translates to humans. Thus, selective thyromimetics deserve further study as agents to treat dyslipidemia and other risk factors for atherosclerosis.

  9. Aircraft measurements of ammonia and nitric acid in the lower troposphere

    NASA Technical Reports Server (NTRS)

    Lebel, P. J.; Hoell, J. M.; Levine, J. S.; Vay, S. A.

    1985-01-01

    The first simultaneous measurements of ammonia and nitric acid in the troposphere have been made from an aircraft using a tungsten oxide denuder system. Vertical profiles of NH3 and HNO3 taken over coastal Virginia and Maryland in March and September, 1983, at altitudes from 150 m to 3000 m, show mixing ratios that decrease with altitude. Ammonia profiles show substantial seasonal variation, while nitric acid profiles do not. Using the measured profiles and a one-dimensional photochemical model, lifetimes due to heterogeneous loss of one day for HNO3 and ten days for NH3 are calculated. In contrast, NH3 profiles up to 5300 m over the North Atlantic Ocean during August 1982 show mixing ratios that increase slightly with altitude. These data represent the first ammonia profiles measured over the ocean. It is suggested that the increase in NH3 with altitude is a result of an ammonia-rich continental air mass advected over the ocean, followed by the dissolution of NH3 in the marine boundary layer on water-covered sea salt particles.

  10. Aircraft measurements of ammonia and nitric acid in the lower troposphere

    NASA Astrophysics Data System (ADS)

    Lebel, P. J.; Hoell, J. M.; Levine, J. S.; Vay, S. A.

    1985-06-01

    The first simultaneous measurements of ammonia and nitric acid in the troposphere have been made from an aircraft using a tungsten oxide denuder system. Vertical profiles of NH3 and HNO3 taken over coastal Virginia and Maryland in March and September, 1983, at altitudes from 150 m to 3000 m, show mixing ratios that decrease with altitude. Ammonia profiles show substantial seasonal variation, while nitric acid profiles do not. Using the measured profiles and a one-dimensional photochemical model, lifetimes due to heterogeneous loss of one day for HNO3 and ten days for NH3 are calculated. In contrast, NH3 profiles up to 5300 m over the North Atlantic Ocean during August 1982 show mixing ratios that increase slightly with altitude. These data represent the first ammonia profiles measured over the ocean. It is suggested that the increase in NH3 with altitude is a result of an ammonia-rich continental air mass advected over the ocean, followed by the dissolution of NH3 in the marine boundary layer on water-covered sea salt particles.

  11. Synthesis of novel oleanolic acid and ursolic acid in C-28 position derivatives as potential anticancer agents.

    PubMed

    Tian, Tian; Liu, Xinyu; Lee, Eung-Seok; Sun, Jingyang; Feng, Zhonghua; Zhao, Longxuan; Zhao, Chunhui

    2017-04-01

    A series of nitrogen-containing derivatives of oleanolic acid and ursolic acid were prepared by a modification at C-28 position via esterification with 2-hydroxyacetic acid followed by amidation with amines, such as piperazine, N-methylpiperazine, and alkane-1, 2-diamines, alkane-1, 4-diamines, alkane-1, 6-diamines. In vitro antiproliferative activities of the compounds prepared towards MCF-7, Hela and A549 cell lines were evaluated by a MTT method to show that OA-5a, OA-5b, OA-5c and UA-5a showed somewhat improved antiproliferative activities against MCF-7, Hela and A549 cells comparing to that of the positive control, gefitinib.

  12. Effects of Blood Pressure Lowering With Different Antihypertensive Agents on Cognitive Function and Plasma Brain-derived Neurotrophic Factor Levels: A Comparative Study.

    PubMed

    Demir, Meral; Gürol, Ali Osman; Özyiğit, Raşit Tolga; Üresin, Ali Yağz

    2016-06-01

    Hypertension is a risk factor for cognitive impairment (CI). However, the specific effect of antihypertensive therapy on cognitive function is still controversial. We aimed to investigate the effect of antihypertensive agents targeting the renin-angiotensin system (RAS) on CI and brain-derived neurotropic factor (BDNF). We included 62 patients who had been using the same antihypertensive agent for at least 3 months. Patients who had relevant conditions that could contribute to CI were excluded. After subjects were divided into 3 groups according to their current antihypertensive medication, the cognitive status of each patient was assessed by the mini-mental state examination (MMSE). BDNF and plasma renin activity were evaluated. There was a negative association between systolic blood pressure and MMSE independent of medication (rho = -0.251, P = 0.049). There was no significant correlation between MMSE and BDNF. The MMSE score was slightly higher in the non-RAS group, but the difference did not reach statistical significance (P = 0.09). There was also no significant difference in BDNF levels between study groups (P = 0.32). Mean plasma renin activity levels were significantly lower in the non-RAS group compared with the angiotensin converting enzyme inhibitor and angiotensin receptor blocker groups (P = 0.007). We suggest that the essential intervention for CI in hypertensive patients is appropriate for blood pressure control.

  13. 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

  14. Dietary intake of vitamin B12 and folic acid is associated with lower blood pressure in Japanese preschool children.

    PubMed

    Tamai, Yuya; Wada, Keiko; Tsuji, Michiko; Nakamura, Kozue; Sahashi, Yukari; Watanabe, Kaori; Yamamoto, Keiko; Ando, Kyoko; Nagata, Chisato

    2011-11-01

    An elevated plasma homocysteine level is an independent risk factor for high blood pressure and cardiovascular disease, and its level is regulated by three vitamins; vitamin B6, B12, and folic acid. Until now, the association between the intake of these vitamins and blood pressure has been examined only in adult populations. We purposed to examine the association between dietary intake of these three vitamins and blood pressure of young children. We conducted a cross-sectional study at Japanese preschools in 2006. Blood pressure was measured among 418 children aged 3-6 years. Diets including vitamins were assessed by a 3-day dietary record. We compared the blood pressure levels among the four groups defined according to quartile of energy-adjusted vitamin intake by using analysis of covariance after controlling for age, sex, and body mass index. The mean systolic blood pressure was 6.6 mm Hg lower and the mean diastolic blood pressure was 5.7 mm Hg lower in the highest quartile than in the lowest quartile of vitamin B12 intake (P for trend was <0.001 and 0.006, respectively). The mean systolic blood pressure was 4.1 mm Hg lower in the highest quartile than in the lowest quartile of folic acid intake (P for trend = 0.004). Vitamin B6 intake was not significantly associated with blood pressure. The data suggest that high intakes of folic acid and vitamin B12 are associated with lower levels of blood pressure among preschool children.

  15. Microcystins do not necessarily lower the sensitivity of Microcystis aeruginosa to tannic acid.

    PubMed

    Švanys, Algirdas; Eigemann, Falk; Grossart, Hans-Peter; Hilt, Sabine

    2016-01-01

    Different phytoplankton strains have been shown to possess varying sensitivities towards macrophyte allelochemicals, yet the reasons for this are largely unknown. To test whether microcystin (MC) is responsible for strain-specific sensitivities of Microcystis aeruginosa to macrophyte allelochemicals, we compared the sensitivity of 12 MC- and non-MC-producing M. aeruginosa strains, including an MC-deficient mutant and its wild type, to the polyphenolic allelochemical tannic acid (TA). Non-MC-producing strains showed a significantly higher sensitivity to TA than MC-producing strains, both in Chlorophyll a concentrations and quantum yields of photosystem II. In contrast, an MC-deficient mutant displayed a higher fitness against TA compared to its wild type. These results suggest that the resistance of M. aeruginosa to polyphenolic allelochemicals is not primarily related to MCs per se, but to other yet unknown protective mechanisms related to MCs.

  16. Incorporation of Exogenous Fatty Acids Protects Enterococcus faecalis from Membrane-Damaging Agents

    PubMed Central

    Saito, Holly E.; Harp, John R.

    2014-01-01

    Enterococcus faecalis is a commensal bacterium of the mammalian intestine that can persist in soil and aquatic systems and can be a nosocomial pathogen to humans. It employs multiple stress adaptation strategies in order to survive such a wide range of environments. Within this study, we sought to elucidate whether membrane fatty acid composition changes are an important component for stress adaptation. We noted that E. faecalis OG1RF was capable of changing its membrane composition depending upon growth phase and temperature. The organism also readily incorporated fatty acids from bile, serum, and medium supplemented with individual fatty acids, often dramatically changing the membrane composition such that a single fatty acid was predominant. Growth in either low levels of bile or specific individual fatty acids was found to protect the organism from membrane challenges such as high bile exposure. In particular, we observed that when grown in low levels of bile, serum, or the host-derived fatty acids oleic acid and linoleic acid, E. faecalis was better able to survive the antibiotic daptomycin. Interestingly, the degree of membrane saturation did not appear to be important for protection from the stressors examined here; instead, it appears that a specific fatty acid or combination of fatty acids is critical for stress resistance. PMID:25128342

  17. Chiral discrimination of α-hydroxy acids and N-Ts-α-amino acids induced by tetraaza macrocyclic chiral solvating agents by using (1)H NMR spectroscopy.

    PubMed

    Lv, Caixia; Feng, Lei; Zhao, Hongmei; Wang, Guo; Stavropoulos, Pericles; Ai, Lin

    2017-02-21

    In the field of chiral recognition, reported chiral discrimination by (1)H NMR spectroscopy has mainly focused on various chiral analytes with a single chiral center, regarded as standard chiral substrates to evaluate the chiral discriminating abilities of a chiral auxiliary. Among them, chiral α-hydroxy acids, α-amino acids and their derivatives are chiral organic molecules involved in a wide variety of biological processes, and also play an important role in the area of preparation of pharmaceuticals, as they are part of the synthetic process in the production of chiral drug intermediates and protein-based drugs. In this paper, several α-hydroxy acids and N-Ts-α-amino acids were used to evaluate the chiral discriminating abilities of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a-1d by (1)H NMR spectroscopy. The results indicate that α-hydroxy acids and N-Ts-α-amino acids were successfully discriminated in the presence of TAMCSAs 1a-1d by (1)H NMR spectroscopy in most cases. The enantiomers of the α-hydroxy acids and N-Ts-α-amino acids were assigned based on the change of integration of the (1)H NMR signals of the corresponding protons. The enantiomeric excesses (ee) of N-Ts-α-amino acids 11 with different optical compositions were calculated based on the integration of the (1)H NMR signals of the CH3 protons (Ts group) of the enantiomers of (R)- and (S)-11 in the presence of TAMCSA 1b. At the same time, the possible chiral discriminating behaviors have been discussed by means of the Job plots of (±)-2 with TAMCSAs 1b and proposed theoretical models of the enantiomers of 2 and 6 with TAMCSA 1a, respectively.

  18. Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke.

    PubMed

    Scherer, Gerhard; Urban, Michael; Hagedorn, Heinz-Werner; Serafin, Richard; Feng, Shixia; Kapur, Sunil; Muhammad, Raheema; Jin, Yan; Sarkar, Mohamadi; Roethig, Hans-Juergen

    2010-10-01

    Alkylating agents occur in the environment and are formed endogenously. Tobacco smoke contains a variety of alkylating agents or precursors including, among others, N-nitrosodimethylamine (NDMA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acrylonitrile and ethylene oxide. We developed and validated a method for the simultaneous determination of methylmercapturic acid (MMA, biomarker for methylating agents such as NDMA and NNK), 2-hydroxyethylmercapturic acid (HEMA, biomarker for ethylene oxide) and 2-cyanoethylmercapturic acid (CEMA, biomarker for acrylonitrile) in human urine using deuterated internal standards of each compound. The method involves liquid/liquid extraction of the urine sample, solid phase extraction on anion exchange cartridges, derivatization with pentafluorobenzyl bromide (PFBBr), liquid/liquid extraction of the reaction mixture and LC-MS/MS analysis with positive electrospray ionization. The method was linear in the ranges of 5.00-600, 1.00-50.0 and 1.50-900 ng/ml for MMA, HEMA and CEMA, respectively. The method was applied to two clinical studies in adult smokers of conventional cigarettes who either continued smoking conventional cigarettes, were switched to test cigarettes consisting of either an electrically heated cigarette smoking system (EHCSS) or having a highly activated carbon granule filter that were shown to have reduced exposure to specific smoke constituents, or stopped smoking. Urinary excretion of MMA was found to be unaffected by switching to the test cigarettes or stop smoking. Urinary HEMA excretion decreased by 46 to 54% after switching to test cigarettes and by approximately 74% when stopping smoking. Urinary CEMA excretion decreased by 74-77% when switching to test cigarettes and by approximately 90% when stopping smoking. This validated method for urinary alkylmercapturic acids is suitable to distinguish differences in exposure not only between smokers and nonsmokers but also between smoking of conventional and

  19. "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.

  20. 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

  1. 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.

  2. 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.

  3. trans-trans Conjugated linoleic acid enriched soybean oil reduces fatty liver and lowers serum cholesterol in obese zucker rats.

    PubMed

    Gilbert, William; Gadang, Vidya; Proctor, Andrew; Jain, Vishal; Devareddy, Latha

    2011-10-01

    Conjugated linoleic acid (CLA) is a collection of octadecadienoic fatty acids that have been shown to possess numerous health benefits. The CLA used in our study was produced by the photoisomerization of soybean oil and consists of about 20% CLA; this CLA consists of 75% trans-trans (a mixture of t8,t10; t9,t11; t10,t12) isomers. This method could be readily used to increase the CLA content of all soybean oil used as a food ingredient. The objective of this study was to determine the effects of trans-trans CLA-rich soy oil, fed as a dietary supplement, on body composition, dyslipidemia, hepatic steatosis, and markers of glucose control and liver function of obese fa/fa Zucker rats. The trans-trans CLA-rich soy oil lowered the serum cholesterol and low density lipoprotein-cholesterol levels by 41 and 50%, respectively, when compared to obese controls. Trans-trans CLA-rich soy oil supplementation also lowered the liver lipid content significantly (P < 0.05) with a concomitant decrease in the liver weight in the obese rats. In addition, glycated hemoglobin values were improved in the group receiving CLA-enriched soybean oil in comparison to the obese control. PPAR-γ expression in white adipose tissue was unchanged. In conclusion, trans-trans CLA-rich soy oil was effective in lowering total liver lipids and serum cholesterol.

  4. 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

  5. Inhibition of Thymidine Kinase Activity and Deoxyribonucleic Acid Synthesis in L Cells Infected with the Meningopneumonitis Agent

    PubMed Central

    Lin, Hsiu-San

    1968-01-01

    The activities of enzymes related to deoxyribonucleic acid (DNA) synthesis were studied in uninfected L cells and in L cells infected with Chlamydia psittaci (strain meningopneumonitis). The meningopneumonitis agent multiplied normally but failed to induce the synthesis of thymidine kinase in LM (TK−) cells which contain no thymidine kinase in the uninfected state. It was concluded that this microorganism has no thymidine kinase of its own and that it does not depend on the functioning of the host enzyme for synthesizing its DNA. Exposure of clone 5b L cells to the meningopneumonitis agent was followed by a decline in their thymidine kinase activity to nearly zero levels, whereas the levels of uridine kinase and thymidylate synthetase remained unchanged. Inhibition of thymidine kinase activity in L cells occurred soon after infection and required new protein synthesis by the meningopneumonitis agent. This inhibition occurred before inhibition of host DNA synthesis, but it was not an essential prelude to the latter inhibition. On the basis of this and previous investigations and in light of present knowledge of the mammalian cell cycle, it was postulated that the meningopneumonitis agent inhibits macromolecular synthesis in L cells by preventing the initiation of a new cell cycle. PMID:5724972

  6. Redistribution of nitric acid in the Arctic lower stratosphere during the winter of 1996-1997

    NASA Astrophysics Data System (ADS)

    Irie, H.; Koike, M.; Kondo, Y.; Bodeker, G. E.; Danilin, M. Y.; Sasano, Y.

    2001-10-01

    Vertical profiles of HNO3, N2O, O3, and the aerosol extinction coefficient at 780 nm were observed by the Improved Limb Atmospheric Spectrometer (ILAS) on board the Advanced Earth Observing Satellite (ADEOS) during the Arctic winter of 1996-1997. Irreversible redistribution of HNO3 is evaluated using HNO3-N2O and HNO3-O3 correlations. Denitrification and nitrification started to be observed just after the Arctic vortex cooled to below the ice frost point (TICE) on February 10. Trajectory analyses show that denitrification occurred only in air masses, which were once cooled to near TICE and were kept at temperatures below the nitric acid trihydrate saturation threshold continuously for more than 4 days. Such a temperature history provides the necessary conditions for nucleation and growth of particles causing denitrification. The average extent of denitrification at 19 km reached 43% at the center of the vortex, suggesting that stratospheric ozone could be affected by denitrification deep inside the vortex. Denitrification (>2 ppbv) and nitrification (>1 ppbv) covered 40±10% and 35±10% of the vortex area, respectively. Redistributed numbers of HNO3 molecules at each altitude were calculated by integrating the area-weighted changes in the HNO3 concentration. The decreases in total HNO3 concentration at 17-21 km in late February and early March agreed with the increases at 12-15 km to within 25%, confirming conservation of HNO3 during sedimentation and evaporation of HNO3-containing polar stratospheric cloud particles.

  7. Lower pressure heating steam is practical for the distributed dry dilute sulfuric acid pretreatment.

    PubMed

    Shao, Shuai; Zhang, Jian; Hou, Weiliang; Qureshi, Abdul Sattar; Bao, Jie

    2017-08-01

    Most studies paid more attention to the pretreatment temperature and the resulted pretreatment efficiency, while ignored the heating media and their scalability to an industry scale. This study aimed to use a relative low pressure heating steam easily provided by steam boiler to meet the requirement of distributed dry dilute acid pretreatment. The results showed that the physical properties of the pretreated corn stover were maintained stable using the steam pressure varying from 1.5, 1.7, 1.9 to 2.1MPa. Enzymatic hydrolysis and high solids loading simultaneous saccharification and fermentation (SSF) results were also satisfying. CFD simulation indicated that the high injection velocity of the low pressure steam resulted in a high steam holdup and made the mixing time of steam and solid corn stover during pretreatment much shorter in comparison with the higher pressure steam. This study provides a design basis for the boiler requirement in distributed pretreatment concept. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Selective inhibition of 20-hydroxyeicosatetraenoic acid lowers blood pressure in a rat model of preeclampsia.

    PubMed

    Faulkner, Jessica L; Plenty, Nicole L; Wallace, Kedra; Amaral, Lorena M; Cunningham, Mark W; Murphy, Sydney; LaMarca, Babbette

    2017-09-22

    Little is currently known of the role(s) of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) in hypertensive pregnancies. We hypothesized that specific inhibition of 20-HETE would attenuate increases in blood pressure in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. Specific 20-HETE synthesis inhibitor HET0016 (1mg/kg) was administered daily to RUPP rats from gestational days 14-18. Blood pressure (BP) increased in RUPP rats and was decreased with HET0016 administration. BP was unchanged in NP+HET0016 rats. Fetal death greatly increased in RUPP rats and was reduced in RUPP+HET0016 rats. 20-HETE levels increased modestly in RUPP rats compared to NP and was reduced in both NP+HET0016 and RUPP+HET0016 rats. Furthermore, circulating levels of HETEs, EET, and DHETE were significantly altered between groups. HET0016 shifted CYP metabolism toward EETs, as indicated by a decrease in plasma 20-HETE:EETs in RUPP+HET0016 rats compared to RUPP. In conclusion, 20-HETE inhibition in RUPP rats reduces BP and fetal death, and is associated with an increase in EET/20-HETE ratio. Copyright © 2017. Published by Elsevier Inc.

  9. Expanding the docosahexaenoic acid food web for sustainable production: engineering lower plant pathways into higher plants

    PubMed Central

    Petrie, James R.; Singh, Surinder P.

    2011-01-01

    Background Algae are becoming an increasingly important component of land plant metabolic engineering projects. Land plants and algae have similar enough genetics to allow relatively straightforward gene transfer and they also share enough metabolic similarities that algal enzymes often function in a plant cell environment. Understanding metabolic systems in algae can provide insights into homologous systems in land plants. As examples, algal models are currently being used by several groups to better understand starch and lipid metabolism and catabolism, fields which have relevance in land plants. Importantly, land plants and algae also have enough metabolic divergence that algal genes can often provide new metabolic traits to plants. Furthermore, many algal genomes have now been sequenced, with many more in progress, and this easy access to genome-wide information has revealed that algal genomes are often relatively simple when compared with plants. Scope One example of the importance of algal, and in particular microalgal, resources to land plant research is the metabolic engineering of long-chain polyunsaturated fatty acids into oilseed crops which typically uses microalgal genes to extend existing natural plant biosynthetic pathways. This review describes both recent progress and remaining challenges in this field. PMID:22476481

  10. Lowered fasting chenodeoxycholic acid correlated with the decrease of fibroblast growth factor 19 in Chinese subjects with impaired fasting glucose.

    PubMed

    Zhang, Jing; Li, Huating; Zhou, Hu; Fang, Li; Xu, Jingjing; Yan, Han; Chen, Shuqin; Song, Qianqian; Zhang, Yinan; Xu, Aimin; Fang, Qichen; Ye, Yang; Jia, Weiping

    2017-07-20

    The gut-derived hormone Fibroblast growth factor 19 (FGF19) could regulate glucose metabolism and is induced by bile acids (BAs) through activating Farnesoid X Receptor (FXR). FGF19 was found to decrease in subjects with isolated-impaired fasting glucose (I-IFG) and type 2 diabetes mellitus (T2DM). However, the reason for the change of FGF19 in subjects with different glucometabolic status remained unclear. Here we measured six BAs including chenodeoxycholic acid (CDCA), cholic acid, deoxycholic acid, their glycine conjugates and FGF19 levels during oral glucose tolerance test (OGTT) in normal glucose tolerance (NGT), isolated-impaired glucose tolerance, I-IFG, combined glucose intolerance (CGI) and T2DM subjects. After OGTT, serum FGF19 peaked at 120 min in all subjects. Glycine conjugated BAs peaked at 30 min, while free BAs did not elevated significantly. Consistent with the decrease trend in FGF19 levels, fasting serum CDCA levels in subjects with I-IFG, CGI and T2DM were significantly lower than NGT subjects (P < 0.05). Fasting serum CDCA was independently associated with FGF19. CDCA strongly upregulated FGF19 mRNA levels in LS174T cells in a dose- and time-dependent manner. These results suggest that the decrease of FGF19 in subjects with I-IFG was at least partially due to their decrease of CDCA acting via FXR.

  11. Molecular and Vibrational Dynamics in the Cholesterol-Lowering Agent Lovastatin: Solid-State NMR, Inelastic Neutron Scattering, and Periodic DFT Study.

    PubMed

    Bilski, Paweł; Drużbicki, Kacper; Jenczyk, Jacek; Mielcarek, Jadwiga; Wąsicki, Jan

    2017-04-06

    Molecular and vibrational dynamics of a widely used cholesterol-lowering agent, lovastatin, have been studied by combining nuclear magnetic resonance relaxation experiments ((1)H NMR) with inelastic neutron scattering (INS) and periodic density functional theory modeling (plane-wave DFT). According to a complementary experimental study, lovastatin shows no phase transitions down to cryogenic conditions, while a progressive, stepwise activation of several molecular motions is observed below room temperature. The molecular packing and intermolecular forces were analyzed theoretically, supported by a (13)C NMR study and further correlated with observed molecular dynamics. The NMR relaxation experiments combined with theoretical calculations disclose that molecular dynamics in solid lovastatin is related to methyl group motions and conformational disorder in the methylbutanoate fragment. This is precisely assigned and analyzed quantitatively from both experimental and theoretical perspectives. The neutron vibrational spectroscopy further corroborates that the methyl rotors have a classical nature. In addition to the intramolecular reorientations, the vibrational dynamics was analyzed with an emphasis on the low-wavenumber range. For the first time, the terahertz response of lovastatin was studied by confronting neutron and optical techniques and clearly illustrating their complementarity. The consistent picture of the molecular dynamics is provided, which may support further considerations on alternative drug formulations and the amorphization tendency in this important lipid-lowering drug.

  12. [Experimental model for the study of the teratogenic interaction of chemical agents and drugs (toluene and acetylsalicylic acid)].

    PubMed

    Tátrai, E; Hudák, A; Ungváry, G

    1979-10-01

    On the 10th-13th days of pregnancy toluene (3600 mg/m3) by inhalation) and on 12th day acetylsalicylic acid (500 mg/kg of body weight per os) were administered to CFY rats and the common effect of these agents was studied. It was established that: 1. the maternal toxicity increased, i.e. increased the mortality rate, decreased the consumption of the food and the gain of weight, increased the relative weight of the liver; 2. the foetal toxicity increased, i.e. increased the mortality rate of foetuses, the rate of the loss of the body weight, the number of the anomalies of the sternum and the incidence of the supernumerary ribs. It is believed, that the non-teratogenic toluene rises the utilization of the glycine and the level of the free salicylic-acid, consequently the embryotoxic effect of the acetylsalicylic-acid. The danger of the occurrence of malformations as an effect of interaction of chemical agents and drugs taken in therapeutic doses is stressed.

  13. 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.

  14. 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.

  15. Design, synthesis and molecular docking of salicylic acid derivatives containing metronidazole as a new class of antimicrobial agents.

    PubMed

    Guo, Zhi-Hua; Yin, Yong; Wang, Cong; Wang, Peng-Fei; Zhang, Xing-Tao; Wang, Zhong-Chang; Zhu, Hai-Liang

    2015-09-15

    A series of novel salicylic acid derivatives containing metronidazole as Staphylococcus aureus Tyrosyl-tRNA synthetase (TyrRS) inhibitors have been synthesized and evaluated their biology activities as potential antibacterial agents. Among these compounds, compound 5r exhibited the most potent antibacterial activity against Gram-positive (S. aureus ATCC 6538 and Bacillus subtilis ATCC 6633) and Gram-negative (Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 13525) with MICs of 0.39-1.57 μg/mL and showed the most potent S. aureus Tyrosyl-tRNA synthetase inhibitory with 2.3 μM. Docking simulation was performed to insert compound 5r into the crystal structure of S. aureus Tyrosyl-tRNA synthetase active site to determine the probable binding model. These results suggested that compound 5r may be a promising antibacterial agent.

  16. 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.

  17. 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

  18. 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

  19. Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca2+-dependent K+ channels

    PubMed Central

    Hoshi, Toshinori; Wissuwa, Bianka; Tian, Yutao; Tajima, Nobuyoshi; Xu, Rong; Bauer, Michael; Heinemann, Stefan H.; Hou, Shangwei

    2013-01-01

    Long-chain polyunsaturated omega-3 fatty acids such as docosahexaenoic acid (DHA), found abundantly in oily fish, may have diverse health-promoting effects, potentially protecting the immune, nervous, and cardiovascular systems. However, the mechanisms underlying the purported health-promoting effects of DHA remain largely unclear, in part because molecular signaling pathways and effectors of DHA are only beginning to be revealed. In vascular smooth muscle cells, large-conductance Ca2+- and voltage-activated K+ (BK) channels provide a critical vasodilatory influence. We report here that DHA with an EC50 of ∼500 nM rapidly and reversibly activates BK channels composed of the pore-forming Slo1 subunit and the auxiliary subunit β1, increasing currents by up to ∼20-fold. The DHA action is observed in cell-free patches and does not require voltage-sensor activation or Ca2+ binding but involves destabilization of the closed conformation of the ion conduction gate. DHA lowers blood pressure in anesthetized wild-type but not in Slo1 knockout mice. DHA ethyl ester, contained in dietary supplements, fails to activate BK channels and antagonizes the stimulatory effect of DHA. Slo1 BK channels are thus receptors for long-chain omega-3 fatty acids, and these fatty acids—unlike their ethyl ester derivatives—activate the channels and lower blood pressure. This finding has practical implications for the use of omega-3 fatty acids as nutraceuticals for the general public and also for the critically ill receiving omega-3–enriched formulas. PMID:23487785

  20. 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

  1. The Use of Oxalic Acid as a Chelating Agent in the Dissolution Reaction of Calcium Molybdate

    NASA Astrophysics Data System (ADS)

    Ilhan, Sedat; Kalpakli, Ahmet Orkun; Kahruman, Cem; Yusufoglu, Ibrahim

    2013-06-01

    In this study, the dissolution behavior of calcium molybdate (CaMoO4) was investigated in oxalic acid (H2C2O4) solution. The effects of stirring speed, temperature, H2C2O4 concentration, and particle size on the dissolution reaction of CaMoO4 were determined. The dissolved quantities of molybdenum and calcium were analyzed quantitatively by ICP-OES. Fractional conversion of CaMoO4 vs time and concentration of calcium vs time diagrams were plotted. It was observed that at constant temperatures and lower H2C2O4 concentrations, the dissolution increased by increasing H2C2O4 concentration, but at higher H2C2O4 concentrations, the effect of H2C2O4 concentrations was negligible. The dissolution reaction of CaMoO4 in H2C2O4 solution was performed in two steps as series-parallel type reaction. In the first step, CaMoO4 reacted with H2C2O4 to form the water-soluble calcium aqua oxalato molybdate (Ca[MoO3(C2O4)(H2O)]) intermediate chelate product. In the second step, the intermediate chelate, Ca[MoO3(C2O4)(H2O)], reacted with the reactant, H2C2O4, to yield water-soluble hydrogen oxalato dimolybdate chelate (H2[(MoO3)2(C2O4)]) and insoluble CaC2O4H2O as final products. It was found that 500 rpm was enough to eliminate the resistance of liquid film layer that surrounds the solid particles. It was concluded that the optimum temperature was 313 K (40 °C) and the optimum concentration of H2C2O4 was 1 kmol m-3 to obtain high conversion during the dissolution of CaMoO4.

  2. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability.

    PubMed

    Kim, Jeong S; Jang, Sun W; Son, Miwon; Kim, Byoung M; Kang, Myung J

    2016-01-20

    The oral bioavailability (BA) of risedronate sodium (RS), an antiresorptive agent, is less than 1% due to its low membrane permeability as well as the formation of non-absorbable complexes with multivalent cations such as calcium ion (Ca(2+)) in the gastrointestinal tract. In the present study, to increase oral BA of the bisphosphonate, a novel enteric-coated tablet (ECT) dosage form of RS in combination with phytic acid (IP6), a natural chelating agent recognized as safe, was formulated. The chelating behavior of IP6 against Ca(2+), including a stability constant for complex formulation was characterized using the continuous variation method. Subsequently, in vitro dissolution profile and in vivo pharmacokinetic profile of the novel ECT were evaluated comparatively with that of the marketed product (Altevia, Sanofi, US), an ECT containing ethylenediaminetetraacetic acid (EDTA) as a chelating agent, in beagle dogs. The logarithm of stability constant for Ca(2+)-IP6 complex, an equilibrium constant approximating the strength of the interaction between two chemicals to form complex, was 19.05, which was 3.9-fold (p<0.05) and 1.7-fold (p<0.05) higher than those of Ca(2+)-RS and Ca(2+)-EDTA complexes. The release profile of RS from both enteric-coated dosage forms was equivalent, regardless of the type of chelating agent. An in vivo absorption study in beagle dogs revealed that the maximum plasma concentration and area under the curve of RS after oral administration of IP6-containing ECT were approximately 7.9- (p<0.05) and 5.0-fold (p<0.05) higher than those of the marketed product at the same dose (35mg as RS). Therefore, our study demonstrates the potential usefulness of the ECT system in combination with IP6 for an oral therapy with the bisphosphonate for improved BA.

  3. 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.

  4. 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

  5. Removal of heavy metals from polluted soil using the citric acid fermentation broth: a promising washing agent.

    PubMed

    Zhang, Hongjiao; Gao, Yuntao; Xiong, Huabin

    2017-04-01

    The citric acid fermentation broth was prepared and it was employed to washing remediation of heavy metal-polluted soil. A well-defined washing effect was obtained, the removal percentages using citric acid fermentation broth are that 48.2% for Pb, 30.6% for Cu, 43.7% for Cr, and 58.4% for Cd and higher than that using citric acid solution. The kinetics of heavy metals desorption can be described by the double constant equation and Elovich equation and is a heterogeneous diffusion process. The speciation analysis shows that the citric acid fermentation broth can effectively reduce bioavailability and environmental risk of heavy metals. Spectroscopy characteristics analysis suggests that the washing method has only a small effect on the mineral composition and does not destroy the framework of soil system. Therefore, the citric acid fermentation broth is a promising washing agent and possesses a potential practical application value in the field of remediation of soils with a good washing performance.

  6. Synthesis and antitussive evaluation of verticinone-cholic acid salt, a novel and potential cough therapeutic agent.

    PubMed

    Xu, Fang-Zhou; Chen, Chang; Zhang, Yong-Hui; Ruan, Han-Li; Pi, Hui-Fang; Zhang, Pong; Wu, Ji-Zhou

    2007-10-01

    To seek a novel and potent antitussive drug based on Shedan-Chuanbei powder, a complex of traditional Chinese medicine preparation for cough therapy. Verticinone-cholic acid (Ver-CA) salt, a novel, salifying derivative of verticinone and cholic acid, both of which are the major bioactive components in Shedan-Chuanbei powder, was synthesized. We then evaluated the antitussive activity and the acute toxicity of the salt. The new compound, with good solubility in water, has much more potent antitussive activity in comparison with the same dose of single verticinone and single cholic acid. The administration 3 mg/kg of Ver-CA could result in over 50% reduction of a citric acid-induced cough. Pretreatment with naloxone (0.8 mg/kg, ip) can only partially antagonize its antitussive effect. On the other hand, glybenclamide (3 mg/kg, ip), an ATP-sensitive K+ channel blocker, can also significantly reduce the antitussive effect of Ver-CA. A further acute toxicity study showed that the LD(50) values of Ver-CA were 3 times that of verticinone. Based on the studies of pharmacology and acute toxicity, the salt has a synergic and attenuated toxicity compared with single verticinone and cholic acid. Moreover, the present study also suggests that Ver-CA, a potential novel antitussive agent, may exert its antitussive effect via both the peripheral (modulated by ATP-sensitive K+ channels) and central mechanisms (modulated by the opioid receptor).

  7. Improved Cycling Performance of a Si Nanoparticle Anode Utilizing Citric Acid as a Surface-Modifying Agent.

    PubMed

    Nguyen, Cao Cuong; Seo, Daniel M; Chandrasiri, K W D K; Lucht, Brett L

    2017-09-19

    Citric acid and its analogues have been investigated as surface-modifying agents for Si nanoparticle anodes using electrochemical cycling, attenuated total reflectance infrared (ATR IR), and X-ray photoelectron spectroscopy (XPS). A Si nanoparticle anode prepared with citric acid (CA) has better capacity retention than one containing 1,2,3,4-butanetetracarboxylic acid (BA), but both electrodes outperform Si-PVDF. The Si-CA anode has an initial specific capacity of 3530 mA h/g and a first cycle efficiency of 82%. Surprisingly, the Si-CA electrode maintains a high specific capacity of ∼2200 mA h/g after 250 cycles, corresponding to 64% capacity retention, which is similar to the Si prepared with long-chain poly(acrylic acid) (PAA). On the contrary, the silicon electrode prepared with PVDF has a fast capacity fade and retains only 980 mA h/g after 50 cycles. The IR and XPS data show that the Si-CA electrode has an SEI composed primarily of lithium citrate during the first 50 cycles, resulting from the electrochemical reduction of citric acid. Only low concentrations of electrolyte reduction products are observed. The lithium citrate layer derived from CA stabilizes the silicon surface and suppresses electrolyte reduction, which likely contributes to the enhanced cycling performance of the Si nanoparticle anode.

  8. Noncovalent modification of carbon nanotubes with ferrocene-amino acid conjugates for electrochemical sensing of chemical warfare agent mimics.

    PubMed

    Khan, Mohammad A K; Kerman, Kagan; Petryk, Michael; Kraatz, Heinz-Bernhard

    2008-04-01

    The electrochemical detection of chemical warfare agent (CWA) mimics was explored using multiwalled carbon nanotubes (MWCNTs) on indium tin oxide (ITO) surfaces in connection with ferrocene-amino acid conjugates. Various ferrocene-amino acid conjugates were synthesized and utilized as the recognition layer for the detection of CWA mimics. The ferrocene-amino acid conjugates were noncovalently attached to the pretreated MWCNTs on the ITO surface and reacted with CWA mimics, upon which the electrical properties of the MWCNTs and the Fc group were affected significantly. Alternating current voltammetry and capacitance-based detection offered large dynamic ranges for the detection of methylphosphonic acid, diethyl cyanophosphonate, ethylmethylphosphonate, and pinacolyl methylphosphonate in water. Electrochemical measurements showed dramatic changes upon the electrostatic interaction between the CWA mimics and the ferrocene-amino acid conjugates immobilized on MWCNTs on ITO surfaces. Electrochemical sensing in connection with MWCNTs is shown to be a promising analytical tool for the trace-level detection of CWA mimics in aqueous solutions.

  9. Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion.

    PubMed

    Toma, A; Kosmider, O; Chevret, S; Delaunay, J; Stamatoullas, A; Rose, C; Beyne-Rauzy, O; Banos, A; Guerci-Bresler, A; Wickenhauser, S; Caillot, D; Laribi, K; De Renzis, B; Bordessoule, D; Gardin, C; Slama, B; Sanhes, L; Gruson, B; Cony-Makhoul, P; Chouffi, B; Salanoubat, C; Benramdane, R; Legros, L; Wattel, E; Tertian, G; Bouabdallah, K; Guilhot, F; Taksin, A L; Cheze, S; Maloum, K; Nimuboma, S; Soussain, C; Isnard, F; Gyan, E; Petit, R; Lejeune, J; Sardnal, V; Renneville, A; Preudhomme, C; Fontenay, M; Fenaux, P; Dreyfus, F

    2016-04-01

    After failure of erythropoiesis-stimulating agents (ESAs), lenalidomide (LEN) yields red blood cell (RBC) transfusion independence (TI) in 20-30% of lower-risk non-del5q myelodysplastic syndrome (MDS). Several observations suggest an additive effect of ESA and LEN in this situation. We performed a randomized phase III study in 131 RBC transfusion-dependent (TD, median transfusion requirement six RBC units per 8 weeks) lower-risk ESA-refractory non-del5q MDS. Patients received LEN alone, 10 mg per day, 21 days per 4 weeks (L arm) or LEN (same schedule) + erythropoietin (EPO) beta, 60,000 U per week (LE arm). In an intent-to-treat (ITT) analysis, erythroid response (HI-E, IWG 2006 criteria) after four treatment cycles (primary end point) was 23.1% (95% CI 13.5-35.2) in the L arm and 39.4% (95% CI 27.6-52.2) in the LE arm (P=0.044), while RBC-TI was reached in 13.8 and 24.2% of the patients in the L and LE arms, respectively (P=0.13). Median response duration was 18.1 and 15.1 months in the L and LE arms, respectively (P=0.47). Side effects were moderate and similar in the two arms. Low baseline serum EPO level and a G polymorphism of CRBN gene predicted HI-E. Combining LEN and EPO significantly improves erythroid response over LEN alone in lower-risk non-del5q MDS patients with anemia resistant to ESA.

  10. Effects of skin preapplication treatments and postapplication cleansing agents on dermal absorption of 2,4-dichlorophenoxyacetic acid dimethylamine by Fischer 344 rats.

    PubMed

    Pelletier, O; Ritter, L; Caron, J

    1990-12-01

    Various methods of preparing dermal application sites in Fischer 344 rats prior to exposure to 2,4-dichlorophenoxyacetic acid dimethylamine salt (2,4-D amine) and the effect of various cleansing agents following exposure were examined by measuring recoveries of 14C-labeled 2,4-D amine in skin, postapplication cleansing solution, blood, and urine. The middorsal area of the rat was the site of application for four treatments tested: (1) hair clipping only, (2) hair clipping followed by an epilatory cream, (3) hair clipping plus shaving with an electrical razor, and (4) as in treatment 3 followed by washing with soap and water. A last preparation was the rat's tail thoroughly brushed with soap and water. The results indicated that the tail retained greater than 75% of the material, thus preventing its absorption into the blood stream and subsequent removal by cleansing. With treatment 1 the dense short hair remaining after clipping impaired the absorption of 2,4-D as evidenced by considerably lower blood and urinary levels than treatments 2-4. With preparations 1-4, 45-61% of the dose was removed with the 7-h postapplication cleansing and a further 5-6% with the subsequent 23-h cleansing. In other studies using preparation 3 above, the following cleansing agents were tested: soap and water, water, isopropanol, acetone, and Rad-Con, a foam-producing cleanser. Rad-Con removed more 2,4-D from the skin than other cleansing agents after 7 h of exposure and more than soap and water after 23 h. The percentages of 2,4-D left on the skin following either 7- or 23-h cleansing with Rad-Con were 8-12%, nearly half those following the other cleansing agents. Cleansing agents other than Rad-Con presented little advantage over soap and water. With all cleansing agents, delaying cleansing from 7 to 23 h after exposure resulted in higher blood and urinary levels of 2,4-D measured 24 h after application.

  11. 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.

  12. Delivery of selective agents via time-delayed release tablets improves recovery of Listeria monocytogenes injured by acid and nitrite.

    PubMed

    Nyarko, Esmond; D'Amico, Dennis; Mach, Patrick; Xia, Wensheng; Donnelly, Catherine

    2014-05-01

    Listeria selective enrichment media are designed to enhance the isolation of the organism and increase the chances of detection. Drawbacks include the requirements for prolonged sample incubation (48 to 72 h) and manual addition of selective agents, which may be a source of contamination. Modified Listeria recovery broth (mLRB) is a proprietary enrichment medium formulated to facilitate the recovery of injured cells; its selective agents are incorporated into a format that allows delayed release until 6 h of incubation. We evaluated the change in cell populations over time for acid- and nitrite-injured Listeria monocytogenes in mLRB with the selective agents added manually at 0 h (mLRBS0) and 6 h (mLRBS6). Recovery of injured cells in mLRB plus time-delayed tablets (mLRBTD) was also compared with that in enrichment media recommended by the U.S. Department of Agriculture (University of Vermont broth), the U.S. Food and Drug Administration (buffered Listeria enrichment broth), and the International Organization for Standardization (demi-Fraser broth). Nitrite- or acid-injured Listeria at approximately 10 CFU/ml were inoculated into each broth medium, and Listeria populations were enumerated at various times from 12 to 48 h of incubation at 37°C. Analysis of variance revealed that acid-injured Listeria populations in mLRBS6 at 24 h were significantly higher (P < 0.05) than those in mLRBS0; however, the differences in populations on these two media were not significant for nitrite-injured cells. Cell populations of four strains of Listeria inoculated into mLRBTD were significantly higher at 24 h than when those strains were enriched in buffered Listeria enrichment broth, demi-Fraser broth, and University of Vermont broth. Comparison between artificially contaminated milk and meat samples with a four-strain cocktail of Listeria resulted in cell populations that were significantly higher (P < 0.05) at 24 h on mLRBTD for contaminated meat than on mLRB for contaminated

  13. 4-Hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as potent anti-tumor agents.

    PubMed

    Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

    2004-01-19

    Based on the structure of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which exhibits selective cytotoxicity against a tumorigenic cell line, (2,4-dimethoxyphenyl)-(4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)-methanone (18m) was designed and synthesized as a biologically stable derivative containing no ester group. Although the potency of 18m was almost the same as our initial hit compound 1, 18m is expected to last longer in the human body as an anticancer agent.

  14. Novel conjugates of aspirin with phenolic acid as anti-inflammatory agents having significantly reduced gastrointestinal toxicity.

    PubMed

    Jiang, Shan; Ding, Ning; Zhang, Wei; Zhang, Yichun; Geng, Meiyu; Li, Yingxia

    2010-04-01

    A series of novel conjugates of aspirin with natural phenolic acid antioxidants connected through a diol linker were designed and synthesized as potential bifunctional agents combining antioxidant and anti-inflammatory activity for reducing gastrointestinal toxicity. In general, the conjugates were found to be efficient antioxidants and many of them demonstrated much more potent anti-inflammatory activity than aspirin. Among them, 5a and 5b which bear the best anti-inflammatory activity exhibited significantly reduced ulcerogenic potency and toxicity compared to aspirin. However, it is evident that the anti-inflammatory activity of these dual-acting molecules in vivo, was not simply consistent with their antioxidant ability in vitro.

  15. Synthesis and evaluation of novel 6',6'-difluoro 5'-deoxycarbocyclic phosphonic acid nucleosides as antiviral agents.

    PubMed

    Kim, Eunae; Shen, Guang Huan; Kang, Lien; Hong, Joon Hee

    2013-01-01

    The authors describe highly efficient synthetic routes for the preparation of novel 6',6'-difluoro 5'-deoxycarbocyclic phosphonic acid nucleosides from 1,4-dihydroxy-2-butene. The discovery that the 6'-fluorinated carbocyclic nucleoside (2, EC₅₀ = 0.16 μM) is a potent anti-HSV-1 agent led to the syntheses and biological evaluations of 6'-modified 5'-deoxyversions of carbocyclic phosphonate nucleosides. The synthesized nucleoside analogues 15, 18, 22, and 25 were tested for anti-HIV activity and for cytotoxicity. However, none of them showed significant anti-HIV-1 activity or cytotoxicity at concentrations up to 100 μM.

  16. Synthesis of Novel 4'-Trifluoromethyl-5'-Norcarbocyclic C-Nucleoside Phosphonic Acids as Potent Anti-Leukemic Agents.

    PubMed

    Kim, Seyeon; Hong, Joon Hee

    2015-01-01

    The syntheses of novel C-nucleoside phosphonic acids as potential antiviral agents are described. The sugar moiety that served as the nucleoside skeleton was produced starting from commercially available 1,3-dihydroxy cyclopentane. The key C-C bond formation from sugar to base precursor was performed using the Knoevenagel-type condensation. The synthesized compounds exhibited anti-HIV activity and cytotoxicity. Also, the synthesized compounds were screened in vitro for tumor growth inhibitory activity against mouse leukemia cell lines (L-1210, P-815).

  17. Synthesis and antiviral evaluation of novel 2',2'-difluoro 5'-norcarbocyclic phosphonic acid nucleosides as antiviral agents.

    PubMed

    Shen, Guang Huan; Hong, Joon Hee

    2014-01-01

    A very efficient synthetic route to novel 2',2'-difluoro 5'-norcarbocyclic phosphonic acid nucleosides from but-3-en-1-ol 5 is described. The discovery of 2'-fluorinated furanose nucleoside 1 as a potent anti-HIV-1 agent has led to the synthesis and biological evaluation of 2'-modified 5'-norversions of the carbocyclic phosphonate nucleosides. The synthesized nucleoside analogues 18, 19, 23a, 23b, and 24 were tested for anti-HIV activity as well as cytotoxicity. Adenine analogue 19 shows significant anti-HIV-1 activity (EC(50) = 13 μM).

  18. Lower Expression of Glutamic Acid Decarboxylase 67 in the Prefrontal Cortex in Schizophrenia: Contribution of Altered Regulation by Zif268

    PubMed Central

    Kimoto, Sohei; Bazmi, H. Holly; Lewis, David A.

    2015-01-01

    Objective Cognitive deficits of schizophrenia may be due at least in part to lower expression of the 67-kDa isoform of glutamic acid decarboxylase (GAD67), a key enzyme for GABA synthesis, in the dorsolateral prefrontal cortex of individuals with schizophrenia. However, little is known about the molecular regulation of lower cortical GAD67 levels in schizophrenia. The GAD67 promoter region contains a conserved Zif268 binding site, and Zif268 activation is accompanied by increased GAD67 expression. Thus, altered expression of the immediate early gene Zif268 may contribute to lower levels of GAD67 mRNA in the dorsolateral prefrontal cortex in schizophrenia. Method The authors used polymerase chain reaction to quantify GAD67 and Zif268 mRNA levels in dorsolateral pre-frontal cortex area 9 from 62 matched pairs of schizophrenia and healthy comparison subjects, and in situ hybridization to assess Zif268 expression at laminar and cellular levels of resolution. The effects of potentially confounding variables were assessed in human subjects, and the effects of antipsychotic treatments were tested in antipsychotic-exposed monkeys. The specificity of the Zif268 findings was assessed by quantifying mRNA levels for other immediate early genes. Results GAD67 and Zif268 mRNA levels were significantly lower and were positively correlated in the schizophrenia subjects. Both Zif268 mRNA-positive neuron density and Zif268 mRNA levels per neuron were significantly lower in the schizophrenia subjects. These findings were robust to the effects of the confounding variables examined and differed from other immediate early genes. Conclusions Deficient Zif268 mRNA expression may contribute to lower cortical GAD67 levels in schizophrenia, suggesting a potential mechanistic basis for altered cortical GABA synthesis and impaired cognition in schizophrenia. PMID:24874453

  19. 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

  20. [Amino acid chloramines and chlorimines as antiplatelet agents: reactive properties and mechanism of action].

    PubMed

    Murina, M A; Roshchupkin, D I; Petrova, A O; Sergienko, V I

    2009-01-01

    Oxidative modifications of thiols, disulfide, and thioester atomic groups in proteins, peptides, and amino acids induced by chloramines or chloramine derivatives of amino acids and other reactive oxidants are considered. In the case of disulfide and thiol groups, production of sulfur-reactive groups may take place, such as disulphide S-oxides and sulphenic groups. Various chloramines and chloramines differently modify sulfur-containing groups. For example, N,N-dichlorotaurine rapidly modifies the thiolgroup in reduced glutathione and N-chloroglycine readily oxidizes the thioester group in methionine. Amino acid chloramines inhibit platelet aggregation by modifying S-containing centres. Autodecay of amino acid chloramines does not affect aggregation as follows from the absence of positive correlation between chloramines decay rate and antiplatelet activity. N,N-dichlorotaurine and its chlorimine derivatives are characterized by high stability and have good prospects as potential antiaggregants.

  1. Poly (amido amine) and nano-calcium phosphate bonding agent to remineralize tooth dentin in cyclic artificial saliva/lactic acid.

    PubMed

    Liang, Kunneng; Weir, Michael D; Reynolds, Mark A; Zhou, Xuedong; Li, Jiyao; Xu, Hockin H K

    2017-03-01

    The objectives of this study were to develop a novel method to remineralize dentin lesions, and investigate the remineralization effects of poly (amido amine) (PAMAM) dendrimer plus a bonding agent with nanoparticles of amorphous calcium phosphate (NACP) in a cyclic artificial saliva/lactic acid environment for the first time. Dentin lesions were produced via phosphoric acid. Four groups were tested: (1) dentin control, (2) dentin with PAMAM, (3) dentin with NACP bonding agent, and (4) dentin with PAMAM plus NACP bonding agent. Specimens were treated with cyclic artificial saliva/lactic acid. The remineralized dentin was examined using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), hardness and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). NACP bonding agent yielded a dentin shear bond strength similar to commercial controls (Prime & Bond NT, Dentsply; Scotchbond Multi-purpose, 3M) (p>0.1). Increasing NACP in bonding agent from 0 to 40% did not affect bond strength. NACP bonding agent neutralized the acid and released Ca ions with concentrations of 4 to 20mmol/L, and P ions of 2 to 9mmol/L. PAMAM or NACP bonding agent alone achieved slight remineralization. The PAMAM+NACP group achieved the greatest dentin remineralization p<0.05). At 20days, PAMAM+NACP increased the hardness of pre-demineralized dentin to reach the normal dentin hardness (p>0.1). In conclusion, superior remineralization of PAMAM+NACP bonding agent was demonstrated for the first time. PAMAM+NACP bonding agent induced dentin remineralization under acid challenge, when conventional remineralization methods such as PAMAM alone did not work well. The novel PAMAM+NACP bonding agent method is promising to improve the longevity of resin-dentin bonds, inhibit caries, and protect teeth.

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

    PubMed Central

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

    2015-01-01

    A new strategy for synthesizing spherical nucleic acid (SNA) nanostructures from biodegradable DNA block copolymers is reported. Multiple DNA strands are grafted to one end of a polyester chain (poly-caprolactone) to generate an amphiphilic DNA brush block copolymer (DBBC) structure capable of assembling into spherical micelles in aqueous solution. These novel DBBC-based micelle-SNAs exhibit a higher surface density of nucleic acids compared to micelle structures assembled from an analogous linear DNA block copolymer (DBC), which endows them with the ability to more efficiently enter cells without the need for transfection agents. Importantly, the new SNAs show effective gene regulation without observable cellular toxicity in mammalian cell culture. PMID:26297167

  3. 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

  4. Formic acid as an alternative reducing agent for the catalytic nitrate reduction in aqueous media.

    PubMed

    Choi, Eun-Kyoung; Park, Kuy-Hyun; Lee, Ho-Bin; Cho, Misun; Ahn, Samyoung

    2013-08-01

    Formic acid was used for the nitrate reduction as a reductant in the presence of Pd:Cu/gamma-alumina catalysts. The surface characteristics of the bimetallic catalyst synthesized by wet impregnation were investigated by SEM, TEM-EDS. The metals were not distributed homogeneously on the surface of catalyst, although the total contents of both metals in particles agreed well with the theoretical values. Formic acid decomposition on the catalyst surface, its influence on solution pH and nitrate removal efficacy was investigated. The best removal of nitrate (50 ppm) was obtained under the condition of 0.75 g/L catalyst with Pd:Cu ratio (4:1) and two fold excess of formic acid. Formic acid decay patterns resembled those of nitrate removal, showing a linear relationship between k(f) (formic acid decay) and k (nitrate removal). Negligible amount of ammonia was detected, and no nitrite was detected, possibly due to buffering effect of bicarbonate that is in situ produced by the decomposition of formic acid, and due to the sustained release of H2 gas.

  5. Real-time monitoring of matrix acidizing including the effects of diverting agents

    SciTech Connect

    Hill, A.D.; Zhu, D.

    1996-05-01

    Real-time monitoring of the injection rate and pressure during matrix acidizing provides operators with a way to determine the changing skin factor as stimulation proceeds. Current methods are based either on the assumption of steady-state flow in the region around the wellbore affected by acid injection or on computer solution of the transient flow equations describing the unsteady reservoir flow process occurring during acidizing. In this paper, a new method for real-time monitoring of matrix acidizing, the inverse injectivity vs. superposition time function plot, is presented. This new method can be applied with a spreadsheet computer program or a programmable calculator and accounts for the transient flow effects occurring during matrix acidizing at multiple rates and injection pressures. The evolving skin factor during a matrix treatment is readily obtained from the diagnostic plot. Hypothetical examples show how the inverse injectivity plot can be used to assess the efficiency of stimulation and diversion. Comparisons with previously presented field cases show the new method to be a simple and accurate means of monitoring the evolving skin factor during matrix acidizing.

  6. Cloud Acidity and Acidic Deposition in the Lower Troposphere and Ozone Depletion in the Antarctic Stratosphere: Modeling and Data Analysis Regarding the Role of Atmospheric Aerosol.

    NASA Astrophysics Data System (ADS)

    Lin, Neng-Huei

    This study is focused on the role of atmospheric aerosols in determining the cloud acidity and acidic deposition in the lower troposphere and the ozone depletion in the Antarctic stratosphere. For the former, a cloud chemistry model is developed to study the in-cloud chemistry and acidity in cloud droplets. The cloud chemistry model includes the absorption of trace gases, the oxidation of aqueous phase SO_2, and the scavenging of atmospheric aerosols. A new scheme is developed to differentiate the acidity and chemical composition distributing in individual cloud droplets. The above cloud chemistry model is incorporated into a two-layer flow model in order to investigate the effects of mountain waves on the cloud acidity. Using the three-year (1986-1988) database acquired at Mt. Mitchell site, the in-cloud chemistry and acidic deposition through dry, wet and cloud deposition pathways are investigated. The in-cloud scavenging of submicron aerosols such as sulfates and nitrates is parameterized as a function of cloud deposition rate. The deposition fluxes of sulfur (S) compounds are found primarily contributed by cloud capture mechanism (60%) followed by incident precipitation (25%) and dry deposition (15%). A comparison of deposition estimates at Mt. Mitchell with those at other sites shows that the sulfate deposition at sites exceeding 1,200 m MSL in elevation in Bavaria (Germany) and eastern USA is almost identical within error limits. The features of the Antarctic stratospheric aerosols during the ozone depletion episode of October 1987 are investigated based on the SAGE II (Stratospheric Aerosol and Gas Experiment II) data. The study focuses on (1) inferring the aerosol size spectrum using a modified randomized minimization-search-technique (RMST), and (2) investigating the vertical, zonal and columnar averages of aerosol properties, together with the ozone concentration. The aerosol size distribution is found to be bimodal in several instances. An enhanced

  7. 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.

  8. Modifying the fatty acid profile of dairy products through feedlot technology lowers plasma cholesterol of humans consuming the products.

    PubMed

    Noakes, M; Nestel, P J; Clifton, P M

    1996-01-01

    Intake of milk and butter has been clearly associated with higher coronary heart disease rates in different countries and this is likely to be mediated by the hypercholesterolemic effect of dairy fat. Fat-modified dairy products are an innovation involving a technology in which protected unsaturated lipids are fed to ruminants resulting in milk and tissue lipids with reduced saturated fatty acids. We examined the impact of these novel dairy fats on plasma lipids in a human dietary trial. Thirty-three men and women participated in an 8-wk randomized crossover trial comparing fat-modified with conventional dairy products. The trial consisted of a 2-wk low-fat baseline period followed by two 3-wk intervention phases. During the test periods, the fat-modified products resulted in a significant 0.28-mmol/L (4.3%) lowering of total cholesterol (P < 0.001). Most of this decrease was in LDL cholesterol, which decreased by 0.24 mmol/L (P < 0.001) whereas HDL cholesterol and triacylglycerols remained essentially unchanged. This alteration in the fatty acid profile of dairy products, if applied to populations typical of developed Western countries, represents a potential strategy to lower the risk of coronary heart disease without any appreciable change in customary eating patterns.

  9. Design, Synthesis and Biological Evaluation of Sulfur-Containing 1,1-Bisphosphonic Acids as Antiparasitic Agents

    PubMed Central

    Recher, Marion; Barboza, Alejandro P.; Li, Zhu-Hong; Galizzi, Melina; Ferrer-Casal, Mariana; Szajnman, Sergio H.; Docampo, Roberto; Moreno, Silvia N. J.

    2013-01-01

    As part of our efforts aimed at searching for new antiparasitic agents, 2-alkylmercaptoethyl-1,1-bisphosphonate derivatives were synthesized and evaluated against Trypanosoma cruzi, the etiologic agent of Chagas disease, and Toxoplasma gondii, the responsible agent for toxoplasmosis. Many of these sulfur-containing bisphosphonates were potent inhibitors against the intracellular form of T. cruzi, the clinically more relevant replicative form of this parasite, and tachyzoites of T. gondii targeting T. cruzi or T. gondii farnesyl diphosphate synthases (FPPSs), which constitute valid targets for the chemotherapy of these parasitic diseases. Interestingly, long chain length sulfur-containing bisphosphonates emerged as relevant antiparasitic agents. Taking compounds 37, 38, and 39 as representative members of this class of drugs, they exhibited ED50 values of 15.8 μM, 12.8 μM, and 22.4 μM, respectively, against amastigotes of T. cruzi. These cellular activities matched the inhibition of the enzymatic activity of the target enzyme (TcFPPS) having IC50 values of 6.4 μM, 1.7 μM, and 0.097 μM, respectively. In addition, these compounds were potent anti-Toxoplasma agents. They had ED50 values of 2.6 μM, 1.2 μM, and 1.8 μM, respectively, against T. gondii tachyzoites, while they exhibited a very potent inhibitory action against the target enzyme (TgFPPS) showing IC50 values of 0.024 μM, 0.025 μM, and 0.021 μM, respectively. Bisphosphonates bearing a sulfoxide unit at C-3 were also potent anti-Toxoplasma agents, particularly those bearing long aliphatic chains such as 43–45, which were also potent antiproliferative drugs against tachyzoites of T. gondii. These compounds inhibited the enzymatic activity of the target enzyme (TgFPPS) at the very low nanomolar range. These bisphosphonic acids have very good prospective not only as lead drugs but also as potential chemotherapeutic agents. PMID:23318904

  10. Styrene lower catabolic pathway in Pseudomonas fluorescens ST: identification and characterization of genes for phenylacetic acid degradation.

    PubMed

    Di Gennaro, Patrizia; Ferrara, Silvia; Ronco, Ilaria; Galli, Enrica; Sello, Guido; Papacchini, Maddalena; Bestetti, Giuseppina

    2007-08-01

    Pseudomonas fluorescens ST is a styrene degrading microorganism that, by the sequential oxidation of the vinyl side chain, converts styrene to phenylacetic acid. The cluster of styrene upper pathway catabolic genes (sty genes) has been previously localized on a chromosomal region. This report describes the isolation, sequencing and analysis of a new chromosomal fragment deriving from the ST strain genomic bank that contains the styrene lower degradative pathway genes (paa genes), involved in the metabolism of phenylacetic acid. Analysis of the paa gene cluster led to the description of 14 putative genes: a gene encoding a phenylacetyl-CoA ligase (paaF), the enzyme required for the activation of phenylacetic acid; five ORFs encoding the subunits of a ring hydroxylation multienzymatic system (paaGHIJK); the gene paaW encoding a membrane protein of unknown function; five genes for a beta-oxidation-like system (paaABCDE), involved in the steps following the aromatic ring cleavage; a gene encoding a putative permease (paaL) and a gene (paaN) probably involved in the aromatic ring cleavage. The function of some of the isolated genes has been proved by means of biotransformation experiments.

  11. 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

    2012-03-08

    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.

  12. Multivalent Protein Polymer MRI Contrast Agents: Controlling Relaxivity via Modulation of Amino Acid Sequence

    PubMed Central

    Karfeld-Sulzer, Lindsay S.; Waters, Emily A.; Davis, Nicolynn E.; Meade, Thomas J.; Barron, Annelise E.

    2010-01-01

    Magnetic Resonance Imaging (MRI) is a noninvasive imaging modality with high spatial and temporal resolution. Contrast agents (CAs) are frequently used to increase the contrast between tissues of interest. To increase the effectiveness of MR agents, small molecule CAs have been attached to macromolecules. We have created a family of biodegradable, macromolecular CAs based on protein polymers, allowing control over the CA properties. The protein polymers are monodisperse, random coil, and contain evenly spaced lysines that serve as reactive sites for Gd(III) chelates. The exact sequence and length of the protein can be specified, enabling controlled variation in lysine spacing and molecular weight. Relaxivity could be modulated by changing protein polymer length and lysine spacing. Relaxivities of up to ∼14 mM-1s-1 per Gd(III) and ∼461 mM-1s-1 per conjugate were observed. These CAs are biodegradable by incubation with plasmin, such that they can be easily excreted after use. They do not reduce cell viability, a prerequisite for future in vivo studies. The protein polymer CAs can be customized for different clinical diagnostic applications, including biomaterial tracking, as a balanced agent with high relaxivity and appropriate molar mass. PMID:20420441

  13. 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

    2015-06-02

    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.

  14. 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

  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. 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

  17. 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.

  18. 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.

  19. 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

  20. Structural characterization of 1,3-propanedithiols that feature carboxylic acids: Homologues of mercury chelating agents.

    PubMed

    Sattler, Wesley; Palmer, Joshua H; Bridges, Christy C; Joshee, Lucy; Zalups, Rudolfs K; Parkin, Gerard

    2013-11-12

    The molecular structures of a series of 1,3-propanedithiols that contain carboxylic acid groups, namely rac- and meso-2,4-dimercaptoglutaric acid (H4DMGA) and 2-carboxy-1,3-propanedithiol (H3DMCP), have been determined by X-ray diffraction. Each compound exhibits two centrosymmetric intermolecular hydrogen bonding interactions between pairs of carboxylic acid groups, which result in a dimeric structure for H3DMCP and a polymeric tape-like structure for rac- and meso-H4DMGA. Significantly, the hydrogen bonding motifs observed for rac- and meso-H4DMGA are very different to those observed for the 1,2-dithiol, rac-2,3-dimercaptosuccinic acid (rac-H4DMSA), in which the two oxygen atoms of each carboxylic acid group hydrogen bond to two different carboxylic acid groups, thereby resulting in a hydrogen bonded sheet-like structure rather than a tape. Density functional theory calculations indicate that 1,3-dithiolate coordination to mercury results in larger S-Hg-S bond angles than does 1,2-dithiolate coordination, but these angles are far from linear. As such, κ(2)-S2 coordination of these dithiolate ligands is expected to be associated with mercury coordination numbers of greater than two. In vivo studies demonstrate that both rac-H 4 DMGA and H3DMCP reduce the renal burden of mercury in rats, although the compounds are not as effective as either 2,3-dimercaptopropane-1-sulfonic acid (H3DMPS) or meso-H4DMSA.

  1. The antiepileptic and anticancer agent, valproic acid, induces P-glycoprotein in human tumour cell lines and in rat liver

    PubMed Central

    Eyal, S; Lamb, J G; Smith-Yockman, M; Yagen, B; Fibach, E; Altschuler, Y; White, H S; Bialer, M

    2006-01-01

    Background and purpose: The antiepileptic drug valproic acid, a histone deacetylase (HDAC) inhibitor, is currently being tested as an anticancer agent. However, HDAC inhibitors may interact with anticancer drugs through induction of P-glycoprotein (P-gp, MDR1) expression. In this study we assessed whether valproic acid induces P-gp function in tumour cells. We also investigated effects of valproic acid on the mRNA for P-gp and the cytochrome P450, CYP3A, in rat livers. >Experimental approach: Effects of valproic acid on P-gp were assessed in three tumour cell lines, SW620, KG1a and H4IIE. Accumulation of acetylated histone H3 in rats' livers treated for two or seven days with valproic acid was evaluated using a specific antibody. Hepatic expression of the P-gp genes, mdr1a, mdr1b and mdr2, was determined by real-time polymerase chain reaction. The effects of valproic acid on CYP3A were assessed by Northern blot analysis and CYP3A activity assays. Key results: Valproic acid (0.5–2.0 mM) induced P-gp expression and function up to 4-fold in vitro. The effect of a series of valproic acid derivatives on P-gp expression in SW620 and KG1a cells correlated with their HDAC inhibition potencies. Treatment of rats with 1 mmol kg−1 valproic acid for two and seven days increased hepatic histone acetylation (1.3- and 3.5-fold, respectively) and the expression of mdr1a and mdr2 (2.2–4.1-fold). Valpromide (0.5–2.0 mM) did not increase histone acetylation or P-gp expression in rat livers, but induced CYP3A expression. Conclusions: Valproic acid increased P-gp expression and function in human tumour cell lines and in rat liver. The clinical significance of this increase merits further investigation. PMID:16894351

  2. Development and Evaluation of a Nanoemulsion Containing Ursolic Acid: a Promising Trypanocidal Agent : Nanoemulsion with Ursolic Acid Against T. cruzi.

    PubMed

    Vargas de Oliveira, Erika Cristina; Carneiro, Zumira Aparecida; de Albuquerque, Sérgio; Marchetti, Juliana Maldonado

    2017-02-21

    Over a hundred years after the discovery of Chagas disease, this ailment continues to affect thousands of people. For more than 40 years, only two drugs have been available to treat it. Ursolic acid is a naturally occurring terpene that has shown a good trypanocidal action. However, the hydrophobicity of this compound presents a challenge for the development of proper delivery systems. Nanostructured systems are a prominent in delivering lipophilic drugs. Thus, a nanoemulsion containing ursolic acid was developed and had its trypanocidal activity and cytotoxicity evaluated. Pseudo-ternary phase diagrams and hydrophilic-lipophilic balance (HLB) system were used in the development. The system was stable throughout 90 days of testing, as evidenced by turbidimetry analysis and measurements of the droplet size (57.3 nm) and polydispersity index (0.24). Fourier transform infrared spectroscopy and mass spectrometry evidenced drug's integrity in the formulation. An in vitro dissolution profile showed 75% of ursolic acid release after 5 min from the nanoemulsion into the alkaline dissolution medium, while only 20% could be released from a physical mixture after 2 h. Trypanocidal activity and cytotoxicity were evaluated on the CL Brener strain and LLC-MK2 (monkey kidney) fibroblast by chlorophenol red-β-D-galactoside (CPRG) method. Biological studies showed that the developed formulation was nontoxic and effective against replicant forms of the parasite. A stable and efficient nanoemulsion could be developed to improve the delivery of a promising drug to treat a threatening illness such as Chagas disease.

  3. 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.

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

    PubMed Central

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

    2016-01-01

    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

  5. Novel cytotoxic agents from an unexpected source: bile acids and ovarian tumor apoptosis.

    PubMed

    Horowitz, Neil S; Hua, Jun; Powell, Matthew A; Gibb, Randall K; Mutch, David G; Herzog, Thomas J

    2007-11-01

    Unique biologic activities have been identified for the 4 different bile acids: cholic acid (CA, chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and ursodeoxycholic acid (UDCA). The aim of this study was to examine and compare the effects of these 4 bile acids on the human ovarian cancer cell lines A2780 and A2780-CP-R(cisplatin-resistant) and to evaluate mechanisms of action. Antiproliferative effects were determined by the cytotoxic MTT assay. Cells undergoing apoptosis were identified by morphologic analysis of cells stained using Diff-Quick and nuclear staining with DAPI and by quantitative nucleosome ELISA assay. Cells were lysed in buffer after 24 h of exposure to three different concentrations of bile acid (50 mM, 200 mM, and 400 mM) and protein concentrations were determined. Cell extracts containing 25 mg of protein were assayed for protein kinase C (PKC) enzyme activity. None of the bile acids stimulated proliferation of ovarian cancer cells. CA and UDCA had only minimal cytotoxic effect even at maximum concentrations. In contrast, DCA and CDCA administration resulted in statistically significant dose-dependent cytotoxicity in both platinum sensitive and platinum-resistant cell lines (p<0.05). Cells incubated with DCA and CDCA exhibited morphologic features characteristic of apoptosis. The quantitative nucleosome ELISA assay demonstrated over 10 times increased nucleosome levels after cells were treated for 24 h by DCA and CDCA at 200 mM and 400 mM as compared to CA or UDCA treatment and to untreated controls (p<0.01). All 4 bile acids reduced PKC activity at concentrations of 200 and 400 mM (p<0.01). CDCA and DCA have significant cytotoxic activity in ovarian cancer cells via induction of apoptosis. The mechanism of apoptosis appears to be mediated by alternative kinases distinct from PKC. CDCA and DCA may have clinical utility in the treatment of ovarian cancer pending in vivo confirmation of activity especially in cisplatin-resistant disease.

  6. 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.

  7. Synthesis of Tryptoline-3-Carboxylic Acid Derivatives A Novel Antidiabetic Agent

    PubMed Central

    Choudhary, AN; Kohli, MS; Kumar, A; Joshi, A

    2011-01-01

    The compounds, 2-(methylsulfonyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic acid (DM3), 2-(phenylsulfonyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic acid (DM4), and 2-(p-toluenesulfonyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic acid (DM5) were synthesized by coupling of 1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic acid (DM2) with methanesulfonyl chloride, benzenesulfonyl chloride, and toluenesulfonyl chloride, which in turn, was synthesized by dissolving dilute aqueous ammonia with 2-(N-hydroxy methyl amino)-indol-3-yl-propanoic acid (DM1) which is the reaction product of l-tryptophan and formalin. All the intermediates and title compounds were characterized by physical, chemical, analytical, and spectral data. All the title compounds have been screened for in vivo antidiabetic activity in streptozotocin-induced diabetic rats, and serum glucose was estimated spectrophotometrically at 505 nm by glucose oxidase/peroxidase method. Compound DM5 showed potent antidiabetic activity. PMID:21731359

  8. 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

  9. Bioactivity and structure-activity relationship of cinnamic acid esters and their derivatives as potential antifungal agents for plant protection.

    PubMed

    Zhou, Kun; Chen, Dongdong; Li, Bin; Zhang, Bingyu; Miao, Fang; Zhou, Le

    2017-01-01

    A series of cinnamic acid esters and their derivatives were synthesized and evaluated for antifungal activities in vitro against four plant pathogenic fungi by using the mycelium growth rate method. Structure-activity relationship was derived also. Almost all of the compounds showed some inhibition activity on each of the fungi at 0.5 mM. Eight compounds showed the higher average activity with average EC50 values of 17.4-28.6 μg/mL for the fungi than kresoxim-methyl, a commercial fungicide standard, and ten compounds were much more active than commercial fungicide standards carbendazim against P. grisea or kresoxim-methyl against both P. grisea and Valsa mali. Compounds C1 and C2 showed the higher activity with average EC50 values of 17.4 and 18.5 μg/mL and great potential for development of new plant antifungal agents. The structure-activity relationship analysis showed that both the substitution pattern of the phenyl ring and the alkyl group in the alcohol moiety significantly influences the activity. There exists complexly comprehensive effect between the substituents on the phenyl ring and the alkyl group in the alcohol moiety on the activity. Thus, cinnamic acid esters showed great potential the development of new antifungal agents for plant protection due to high activity, natural compounds or natural compound framework, simple structure, easy preparation, low-cost and environmentally friendly.

  10. Bioactivity and structure-activity relationship of cinnamic acid esters and their derivatives as potential antifungal agents for plant protection

    PubMed Central

    Li, Bin; Zhang, Bingyu; Miao, Fang

    2017-01-01

    A series of cinnamic acid esters and their derivatives were synthesized and evaluated for antifungal activities in vitro against four plant pathogenic fungi by using the mycelium growth rate method. Structure−activity relationship was derived also. Almost all of the compounds showed some inhibition activity on each of the fungi at 0.5 mM. Eight compounds showed the higher average activity with average EC50 values of 17.4–28.6 μg/mL for the fungi than kresoxim-methyl, a commercial fungicide standard, and ten compounds were much more active than commercial fungicide standards carbendazim against P. grisea or kresoxim-methyl against both P. grisea and Valsa mali. Compounds C1 and C2 showed the higher activity with average EC50 values of 17.4 and 18.5 μg/mL and great potential for development of new plant antifungal agents. The structure−activity relationship analysis showed that both the substitution pattern of the phenyl ring and the alkyl group in the alcohol moiety significantly influences the activity. There exists complexly comprehensive effect between the substituents on the phenyl ring and the alkyl group in the alcohol moiety on the activity. Thus, cinnamic acid esters showed great potential the development of new antifungal agents for plant protection due to high activity, natural compounds or natural compound framework, simple structure, easy preparation, low-cost and environmentally friendly. PMID:28423022

  11. Influence of Glacial Acetic Acid and Nitric Acid as a Chelating Agent in Sol-gel Process to the Nanostructured Titanium Dioxide Thin Films

    NASA Astrophysics Data System (ADS)

    Ahmad, M. K.; Rusop, M.

    2009-06-01

    The comparison between different chelating agents in sol-gel process for deposition of nanostructured Titanium Dioxide (TiO2) thin film has been studied. Glacial Acetic Acid (GA) and Nitric Acid (NA) were used in 0.2 M of concentration. The effects to the structural, electrical and optical properties have been studied. The effects of these properties were characterized using X-Ray Diffractometer (XRD), 2-point probe I-V measurement and UV-Vis-NIR Spectrophotometer. For electrical properties, it showed that nanostructured TiO2 thin film that using GA (TF-GA) as chelating agent gives better low sheet resistance compare to nanostructured TiO2 thin film using NA (TF-NA). From XRD results, it indicates that no significantly different between both TiO2 thin film. Both of thin films have crystalline anatase phase at 2θ degree 25.8° which corresponded to (101) orientation. For optical properties, sol-gel using GA has slightly higher in transmittance spectra properties but both of films fully absorbed UV light at 300 nm of wavelength. As for optical band gap, both sol-gels using GA and NA has similar optical band gap which is 3.27 eV.

  12. Quantification of phosphatidylserine, phosphatidic acid and free fatty acids in an ultrasound contrast agent by normal-phase high-performance liquid chromatography with evaporative light scattering detection.

    PubMed

    Hvattum, Erlend; Uran, Steinar; Sandbaek, Anne Gunvor; Karlsson, Anders A; Skotland, Tore

    2006-10-11

    Sonazoid is a new contrast agent for ultrasound imaging. The product is an aqueous suspension of perfluorobutane microbubbles coated with phospholipids obtained from hydrogenated egg phosphatidylserine (H-EPS). A normal-phase high-performance liquid chromatographic (HPLC) method with evaporative light scattering detection was developed for quantification of free fatty acids, phosphatidylserine and phosphatidic acid in H-EPS and Sonazoid. Separation of the lipids was carried out on an HPLC diol column and a gradient of chloroform and methanol with 0.2% formic acid titrated to pH 7.5 with ammonia. The calibration standards contained stearic acid, distearoyl-phosphatidic acid (DSPA) and distearoyl-phosphatidylserine (DSPS) in the concentration range of 0.016-1.0mg/ml (0.4-25microg injected). The method was validated with a limit of quantification of the three lipids set to 0.4microg (approximately 20-60microM). The best fit of the three calibration curves were obtained when the logarithmic transformed theoretical lipid concentration was plotted against the logarithmic transformed area under the peak and fitted to a second order polynomial equation. Stearic acid, DSPA and DSPS were analysed with an intermediate precision ranging from 4.4% to 5.3% R.S.D. and they were extracted from an aqueous suspension with a recovery ranging from 103.3% to 113.3%. The sum of total phospholipid concentration determined in H-EPS ranged from 96.4% to 103.2% of the theoretical values. The lipids in the ultrasound product were quantitated with a repeatability ranging from 6.2% to 11.7% R.S.D.

  13. 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.

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

    DOEpatents

    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.

  15. 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.

  16. 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

  17. Synthesis and biological evaluation of new heteroaryl carboxylic acid derivatives as anti-inflammatory-analgesic agents.

    PubMed

    Abouzid, Khaled Abouzid Mohamed; Khalil, Nadia Abdalla; Ahmed, Eman Mohamed; Zaitone, Sawsan Abo-Bakr

    2013-01-01

    A series of nicotinic acid derivatives structurally related to niflumic acid and certain pyridazine-containing compounds have been synthesized and characterized by analytical and spectral data. All compounds were screened for their potential analgesic and anti-inflammatory activities. The compounds which displayed analgesic and anti-inflammatory activities were tested for ulcerogenicity and screened for in vivo inhibition of certain inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). Compounds 1c, 2a, 2b, and 5a have shown potent analgesic and anti-inflammatory activities.

  18. New tuberculostatic agents targeting nucleic acid biosynthesis: drug design using QSAR approaches.

    PubMed

    Bueno, Renata V; Braga, Rodolpho C; Segretti, Natanael D; Ferreira, Elizabeth I; Trossini, Gustavo H G; Andrade, Carolina H

    2014-01-01

    Worldwide, tuberculosis (TB) is the leading cause of death among curable infectious diseases. The emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) TB is a growing global health concern and there is an urgent need for new anti-TB drugs. Enzymes involved in DNA and ATP biosynthesis are potential targets for tuberculostatic drug design, since these enzymes are essential for Mycobacterium tuberculosis growth. This review presents the current progress and applications of structure-activity relationship analysis for the discovery of innovative tuberculostatic agents as inhibitors of ribonucleotide reductase, DNA gyrase, ATP synthase, and thymidylate kinase enzymes, highlighting present challenges and new opportunities in TB drug design.

  19. 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.

  20. Long-term intake of soyabean phytosterols lowers serum TAG and NEFA concentrations, increases bile acid synthesis and protects against fatty liver development in dyslipidaemic hamsters.

    PubMed

    Laos, Sirle; Caimari, Antoni; Crescenti, Anna; Lakkis, Jamileh; Puiggròs, Francesc; Arola, Lluís; del Bas, Josep Maria

    2014-09-14

    Various human trials and pre-clinical studies have suggested that dietary plant sterols possess hypotriacylglycerolaemic properties apart from their cholesterol-lowering properties. We hypothesised that phytosterols (PS) might attenuate triacylglycerolaemia by interfering with the deleterious effects of cholesterol overload in the liver. In the present study, twenty hamsters (Mesocricetus auratus) with diet-induced combined hyperlipidaemia were fed a high-fat diet (HFD, n 10) or a HFD supplemented with soyabean PS (n 10) for 40 d. In parallel, a healthy group was fed a standard diet (n 10). PS normalised fasting plasma cholesterol concentrations completely after 20 d and were also able to normalise serum TAG and NEFA concentrations after 40 d. HFD feeding caused microvesicular steatosis and impaired the expression of key genes related to fatty acid oxidation such as PPARA, carnitine palmitoyltransferase-Iα (CPT1A) and phosphoenolpyruvate carboxykinase 1 (PCK1) in the liver. PS treatment completely protected against HFD-induced steatosis and resulted in a normalised hepatic gene expression profile. The protection of the hepatic function by PS was paralleled by increased faecal cholesterol excretion along with a 2-fold increase in the biliary bile acid (BA):cholesterol ratio. The present study supports the conclusion that long-term consumption of PS can reduce serum TAG and NEFA concentrations and can protect against the development of fatty liver via different mechanisms, including the enhancement of BA synthesis. The results of the present study place these compounds as promising hepatoprotective agents against fatty liver and its derived pathologies.

  1. Synthesis and characteristics of (Hydrogenated) ferulic acid derivatives as potential antiviral agents with insecticidal activity

    PubMed Central

    2013-01-01

    Background Plant viruses cause many serious plant diseases and are currently suppressed with the simultaneous use of virucides and insecticides. The use of such materials, however, increases the amounts of pollutants in the environment. To reduce environmental contaminants, virucides with insecticidal activity is an attractive option. Results A series of substituted ferulic acid amide derivatives 7 and the corresponding hydrogenated ferulic acid amide derivatives 13 were synthesized and evaluated for their antiviral and insecticidal activities. The majority of the synthesized compounds exhibited good levels of antiviral activity against the tobacco mosaic virus (TMW), with compounds 7a, 7b and 7d in particular providing higher levels of protective and curative activities against TMV at 500 μg/mL than the control compound ribavirin. Furthermore, these compounds displayed good insecticidal activities against insects with piercing-sucking mouthparts, which can spread plant viruses between and within crops. Conclusions Two series of ferulic acid derivatives have been synthesized efficiently. The bioassay showed title compounds not only inhibit the plant viral infection, but also prevented the spread of plant virus by insect vectors. These findings therefore demonstrate that the ferulic acid amides represent a new template for future antiviral studies. PMID:23409923

  2. Long-acting contraceptive agents: esters of norethisterone with alkoxy- and halogeno-substituted carboxylic acids.

    PubMed

    Shafiee, A; Vossoghi, M; Francisco, C G; Freire, R; Hernandez, R; Salazar, J A; Suarez, E; Sotheeswaran, S

    1983-03-01

    The chemical synthesis and physical data of several new esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) are reported, which contain either a chloro- or an alkoxy-group as a substituent in the acid side-chain.

  3. Wood ants produce a potent antimicrobial agent by applying formic acid on tree-collected resin.

    PubMed

    Brütsch, Timothée; Jaffuel, Geoffrey; Vallat, Armelle; Turlings, Ted C J; Chapuisat, Michel

    2017-04-01

    Wood ants fight pathogens by incorporating tree resin with antimicrobial properties into their nests. They also produce large quantities of formic acid in their venom gland, which they readily spray to defend or disinfect their nest. Mixing chemicals to produce powerful antibiotics is common practice in human medicine, yet evidence for the use of such "defensive cocktails" by animals remains scant. Here, we test the hypothesis that wood ants enhance the antifungal activity of tree resin by treating it with formic acid. In a series of experiments, we document that (i) tree resin had much higher inhibitory activity against the common entomopathogenic fungus Metarhizium brunneum after having been in contact with ants, while no such effect was detected for other nest materials; (ii) wood ants applied significant amounts of endogenous formic and succinic acid on resin and other nest materials; and (iii) the application of synthetic formic acid greatly increased the antifungal activity of resin, but had no such effect when applied to inert glass material. Together, these results demonstrate that wood ants obtain an effective protection against a detrimental microorganism by mixing endogenous and plant-acquired chemical defenses. In conclusion, the ability to synergistically combine antimicrobial substances of diverse origins is not restricted to humans and may play an important role in insect societies.

  4. 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.

  5. Sugar beet pulp and poly(lactic acid) composites using methylene diphenyl diisocyanate as coupling agent

    USDA-ARS?s Scientific Manuscript database

    Composites from sugar beet pulp (SBP) and poly(lactic acid) (PLA) were extruded in the presence of polymeric methylene diphenyl diisocyanate (pMDI). SBP particles were evenly distributed within the PLA matrix phase as revealed by confocal fluorescence microscopic analysis. The resultant composites w...

  6. Lignin-coated cellulose nanocrystals as promising nucleating agent for poly(lactic acid)

    Treesearch

    Anju Gupta; William Simmons; Gregory T. Schueneman; Eric A. Mintz

    2016-01-01

    We report the effect of lignin-coated cellulose nanocrystals (L-CNCs) on the crystallization behavior of poly(lactic acid) (PLA). PLA/L-CNC nanocomposites were prepared by melt mixing, and the crystallization behavior of PLA was investigated using differential scanning calorimetry. Isothermal crystallization data were analyzed using Avrami and Lauritzen–Hoffman...

  7. The iron-chelating agent picolinic acid enhances transferrin receptors expression in human erythroleukaemic cell lines.

    PubMed

    Testa, U; Louache, F; Titeux, M; Thomopoulos, P; Rochant, H

    1985-07-01

    Picolinic acid, a metal chelating molecule, was administered to human erythroleukaemic cell lines (K 562 and HEL) that were grown in serum-containing media. Picolinic acid inhibited both iron uptake and cell growth. Furthermore, picolinic acid was shown to markedly decrease the level of ferritin in the cells. In spite of the inhibition of cell growth, picolinic acid induced a marked increase in the transferrin-binding capacity of the cells. This phenomenon was due to a two-five-fold enhancement of the rate of transferrin receptor biosynthesis. Other iron-chelating compounds, capable of reducing the level of intracellular iron, also elicited a marked enhancement of the transferrin-binding capacity of the cells. However, the addition of iron, as ferric ammonium citrate, in the culture medium elicited a marked increase in the level of ferritin and a strong decrease in the transferrin-binding capacity of the cells. On the basis of these data we propose that a feed-back mechanism is involved in the regulation of transferrin receptors: when the cells accumulate iron they decrease the number of transferrin receptors in order to prevent further accumulation of iron; when no or low iron is available to the cells, the number of transferrin receptors markedly increases as a compensatory mechanism.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  9. 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

  10. Influence of root-surface conditioning with acid and chelating agents on clot stabilization.

    PubMed

    Leite, Fábio Renato Manzolli; Sampaio, José Eduardo Cezar; Zandim, Daniela Leal; Dantas, Andréa Abi Rached; Leite, Elza Regina Manzolli; Leite, Amauri Antiquera

    2010-04-01

    To compare the adhesion and maturation of blood components on chemically conditioned root surfaces. Clinical root samples of human teeth were obtained (n = 150) and manually scaled. Five groups of 30 samples were treated as follows: (1) saline solution irrigation (control); (2) 24% EDTA gel; (3) 25% citric acid solution; (4) tetracycline solution (50 mg/mL); and (5) 30% sodium citrate solution. After these treatments, 15 samples of each group received a blood drop and were analyzed by SEM. The remaining 15 had their surface morphology evaluated for collagen fibrils exposure by SEM. Photomicrographs were analyzed according to the score of adhesion of blood components. Kruskal-Wallis and Dunn multiple comparison tests were employed. The control group was characterized by the absence of blood elements on the surface. The best result was observed in the citric acid group, which had a dense fibrin network with blood elements adhered. The EDTA group showed a moderate fibrin network formation. In contrast, a scarce fibrin network and a few cells were present in the tetracycline samples, and an absence of blood elements was found on sodium citrate specimens. The citric acid group was statistically different from the control group (P < .01). No differences were found among the control, EDTA, tetracycline, and sodium citrate groups (P > .05). Under these experimental conditions, citric acid is indicated to stabilize clots on the root surface, which act as a scaffold for connective tissue cell development.

  11. 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.

  12. 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.

  13. Studies on the oligosaccharide heterogeneity of the isoelectric forms of the lower molecular weight acid phosphatase of frog liver.

    PubMed

    Kubicz, A; Szalewicz, A; Chrambach, A

    1991-01-01

    1. The lower molecular weight, heterogeneous acid phosphatase (AcPase) from the frog liver (Rana esculenta) containing AcPase I, II, III and IV was separated into enzymatically active components by isoelectric focusing in an immobilized pH gradient. 2. The blotted enzyme bands were characterized by their different binding patterns obtained with the lectins concanavalin A, wheat germ agglutinin (WGA), Lens culinaris hemagglutinin (LcH) and peanut agglutinin (PNA). 3. In situ neuraminidase treatment reduced the staining intensity of some WGA-bands and increased that of PNA-bands. 4. The finding that AcPases I, II, III and IV differ in their carbohydrate chain composition, together with previous results showing different bioactivities of AcPases III and IV, indicates a correlation between the glycosylation state of enzyme forms and their physiological action.

  14. Carbohydrates blended with polydextrose lower gas production and short-chain fatty acid production in an in vitro system.

    PubMed

    Vester Boler, Brittany M; Hernot, David C; Boileau, Thomas W; Bauer, Laura L; Middelbos, Ingmar S; Murphy, Michael R; Swanson, Kelly S; Fahey, George C

    2009-09-01

    Maximizing health benefits of prebiotics, while limiting negative side effects, is of importance to the food industry. This study examined several oligosaccharides and their blends in an in vitro fermentation model. Substrates included medium- and long-chain fructooligosaccharides (FOS), oligofructose-enriched inulin, galactooligosaccharide, polydextrose (POL), and 50:50 substrate blends. Substrates and blends were fermented in vitro using human fecal inoculum, and fermentation characteristics were quantified at 0, 4, 8, and 12 hours. We hypothesized that mixtures of short- and long-chain oligosaccharides would generate less gas than do short-chain oligosaccharides and modulate gut microflora to a greater extent than do long-chain oligosaccharides. Carbohydrates blended with POL had decreased (P < .01) total gas volume and H(2) produced after 4, 8, and 12 hours of fermentation compared with individual carbohydrates. Mixing of 2 oligofructose-enriched inulin products led to less (P < .05) gas produced and a slower (P < .05) rate of production. When mixed with POL, all carbohydrates tested in the present study produced less total short-chain fatty acids (P < .04) and butyrate (P < .0001) after 12 hours of in vitro fermentation, compared with individual carbohydrates. The bifidogenic effect of medium-chain FOS and oligofructose-enriched inulin after 12 hours of in vitro fermentation was lower (P < .05) when mixed with POL. Mixing the pure carbohydrates with galactooligosaccharide increased (P < .05) bifidobacteria counts measured after 12 hours of in vitro fermentation, except when mixed with medium-chain FOS. In general, when mixed with POL, all carbohydrates had lower gas production, gas production rates, butyrate and total short-chain fatty acid production, and bifidobacteria counts than when fermented alone for 12 hours.

  15. The body fat-lowering effect of conjugated linoleic acid: a comparison between animal and human studies.

    PubMed

    Navarro, V; Fernández-Quintela, A; Churruca, I; Portillo, M P

    2006-06-01

    Different reasons which justify differences between rodents and humans in body fat reduction produced by conjugated linoleic acid (CLA) could be proposed. The doses used in humans are lower than those used in rodents. Human experiments have been performed with CLA isomer mixtures instead of isolated isomers. The variable dilution of t-10, c-12, the active isomer, among different preparations might explain the reduced responsiveness in humans. Diet composition may modulate CLA effects on body fat accumulation. As far as human studies are concerned, a specific dietary pattern has not been established. As a result differences among studies and also among subjects in the same study are likely. In rodents, the effects of CLA vary with genotype, suggesting that genetic predisposition to fat accumulation can play an important role in the effectiveness of CLA. Human volunteers with different body mass index have participated in the published studies and even in the same experiment. So, differences in lipid metabolism among subjects could help to explain the discrepancies observed in the literature. Age and maturity may also be crucial. Experiments using rodents have been conducted with growing animals and there is little evidence of CLA effectiveness in adult animals. By contrast, human studies have been performed with adults. Inhibition of lipogenesis in white adipose tissue is one of the mechanisms which have been proposed to explain the body-fat lowering effect of CLA, but lipogenesis in this tissue is very low in humans. Another mechanism suggested is increased fatty acid oxidation in the liver associated with peroxisome proliferation, but humans are relatively insensitive to this effect.

  16. A-ring modified betulinic acid derivatives as potent cancer preventive agents.

    PubMed

    Hung, Hsin-Yi; Nakagawa-Goto, Kyoko; Tokuda, Harukuni; Iida, Akira; Suzuki, Nobutaka; Bori, Ibrahim D; Qian, Keduo; Lee, Kuo-Hsiung

    2014-02-01

    Ten new 3,4-seco betulinic acid (BA) derivatives were designed and synthesized. Among them, compounds 7-15 exhibited enhanced chemopreventive ability in an in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation assay in Raji cells. Specifically, analogs with a free C-28 carboxylic acid, including 7, 8, 11, and 13, inhibited EBV-EA activation significantly. The most potent compound 8 displayed 100% inhibition at 1×10(3) mol ratio/TPA and 73.4%, 35.9%, and 8.4% inhibition at 5×10(2), 1×10(2), and 1×10 mol ratio/TPA, respectively, comparable with curcumin at high concentration and better than curcumin at low concentration. The potent chemopreventive activity of novel seco A-ring BAs (8 and 11) was further confirmed in an in vivo mouse skin carcinogenesis assay.

  17. Battery acid--an agent of attempted suicide in black South Africans.

    PubMed

    Wilson, D A; Wormald, P J

    1995-06-01

    Over a 36-month period 27 black adults, who had taken battery acid in apparent suicide attempts, were admitted to a major South African general hospital for assessment and treatment. There were no deaths. Patient features included limited schooling, unemployment and a male/female ratio of 2.4:1. Triggers were minor to moderate stressors (mainly domestic arguments) in 23 patients. Nine had a diagnosable psychiatric disorder and 5 required further psychiatric hospitalisation following discharge from the general hospital. The reported high mortality rate from acid ingestion was not observed; however, 4 patients required surgical intervention to deal with stricture formation. The average duration of stay was 7.6 days. There were no repeat suicide attempts during the study period.

  18. 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.

  19. 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.

  20. Molecular level interaction of the human acidic fibroblast growth factor with the antiangiogenic agent, inositol hexaphosphate .

    PubMed

    Kumar, Sriramoju M; Wang, Han-Min; Mohan, Sepuru K; Chou, Ruey-Hwang; Yu, Chin

    2010-12-21

    Acidic fibroblast growth factor (FGF1) regulates a wide array of important biological phenomena such as angiogenesis, cell differentiation, tumor growth, and neurogenesis. Generally, FGFs are known for their strong affinity for the glycosaminoglycan heparin, as a prerequisite for recognition of a specific tyrosine kinase on the cell surface and are responsible for the cell signal transduction cascade. Inositol hexaphosphate (IP6) is a natural antioxidant and is known for its antiangiogenic role, in addition to its ability to control tumor growth. In the present study, we investigated the interaction of IP6 with the acidic fibroblast growth factor (FGF1) using various biophysical techniques including isothermal calorimetry, circular dichroism, and multidimensional NMR spectroscopy. Herein, we have reported the three-dimensional solution structure of the FGF1-IP6 complex. These data show that IP6 binds FGF1 and enhances its thermal stability. In addition, we also demonstrate that IP6 acts as an antagonist to acidic fibroblast growth factor by inhibiting its receptor binding and subsequently decreasing the mitogenic activity. The inhibition likely results in the ability of IP6 to antagonize the angiogenic and mitogenic activity of FGF1.

  1. Xyloglucan from Hymenaea courbaril var. courbaril seeds as encapsulating agent of L-ascorbic acid.

    PubMed

    Farias, Mirla D P; Albuquerque, Priscilla B S; Soares, Paulo A G; de Sá, Daniele M A T; Vicente, António A; Carneiro-da-Cunha, Maria G

    2017-10-05

    This study evaluated the L-ascorbic acid (AA) encapsulation in microparticles of xyloglucan (XAA) extracted from Hymenaea courbaril seeds by spray drying (SD) and its application in tilapia fish burgers. The encapsulation efficiency was 96.34±1.6% and the retention of the antioxidant activity was of 89.48±0.88% after 60days at 25°C. SEM images showed microspheres with diameters ranging from 4.4 to 34.0μm. FTIR spectrum confirmed the presence of AA in xyloglucan microparticles, which was corroborated by DSC and TGA. The release of ascorbic acid was found to be pH-dependent. The application of XAA in tilapia fish burger did not change the pH after heating and the ascorbic acid retention was greater compared to its free form. The results indicate that xyloglucan can be used to encapsulate AA by SD and suggest that XAA was able to reduce undesirable organoleptic changes in fish burgers. Copyright © 2017. Published by Elsevier B.V.

  2. 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

  3. Graphene oxide as a nanocarrier for controlled release and targeted delivery of an anticancer active agent, chlorogenic acid.

    PubMed

    Barahuie, Farahnaz; Saifullah, Bullo; Dorniani, Dena; Fakurazi, Sharida; Karthivashan, Govindarajan; Hussein, Mohd Zobir; Elfghi, Fawzi M

    2017-05-01

    We have synthesized graphene oxide using improved Hummer's method in order to explore the potential use of the resulting graphene oxide as a nanocarrier for an active anticancer agent, chlorogenic acid (CA). The synthesized graphene oxide and chlorogenic acid-graphene oxide nanocomposite (CAGO) were characterized using Fourier transform infrared (FTIR) spectroscopy, thermogravimetry and differential thermogravimetry analysis, Raman spectroscopy, powder X-ray diffraction (PXRD), UV-vis spectroscopy and high resolution transmission electron microscopy (HRTEM) techniques. The successful conjugation of chlorogenic acid onto graphene oxide through hydrogen bonding and π-π interaction was confirmed by Raman spectroscopy, FTIR analysis and X-ray diffraction patterns. The loading of CA in the nanohybrid was estimated to be around 13.1% by UV-vis spectroscopy. The release profiles showed favourable, sustained and pH-dependent release of CA from CAGO nanocomposite and conformed well to the pseudo-second order kinetic model. Furthermore, the designed anticancer nanohybrid was thermally more stable than its counterpart. The in vitro cytotoxicity results revealed insignificant toxicity effect towards normal cell line, with a viability of >80% even at higher concentration of 50μg/mL. Contrarily, CAGO nanocomposite revealed enhanced toxic effect towards evaluated cancer cell lines (HepG2 human liver hepatocellular carcinoma cell line, A549 human lung adenocarcinoma epithelial cell line, and HeLa human cervical cancer cell line) compared to its free form. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. 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.

  5. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

    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.

  7. 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

  8. Lower dose of rhBMP-2 achieves spine fusion when combined with an osteoconductive bulking agent in non-human primates.

    PubMed

    Barnes, Bryan; Boden, Scott D; Louis-Ugbo, John; Tomak, Patrick R; Park, Jin-Soo; Park, Moon-Soo; Minamide, Akihito

    2005-05-15

    A non-human primate lumbar intertransverse process arthrodesis model was used to evaluate the effectiveness of different formulations of recombinant human bone morphogenetic protein-2 (rhBMP-2) to induce consistent bone formation. To determine if the combination of rhBMP-2/absorbable collagen sponge (ACS) wrapped around a bulking agent, consisting of a biphasic calcium phosphate/collagen composite, could achieve posterolateral spine fusion with a dose of rhBMP-2 (3.0 mg/side) that previously failed to induce posterolateral fusion in rhesus monkeys with other carriers. Successful bone induction in both human and non-human primates has required higher concentrations of BMP than were required in lower order models. The Food and Drug Administration approved concentration of rhBMP-2 for interbody fusion (1.5 mg/mL) when delivered on the ACS alone without a bulking agent (doses 3-9 mg/side) has failed to induce clinically relevant amounts of bone formation in a posterolateral spine fusion model in rhesus monkeys. Previously, a higher concentration of 2.0 mg/mL of rhBMP-2 delivered on stacked sheets of a biphasic calcium phosphate ceramic/collagen compression resistant matrix (CRM) was required to achieve fusion in the rhesus monkey and was the basis for this study (doses of 6-12 mg/side). Nine skeletally mature, rhesus macaque monkeys underwent single level posterolateral arthrodesis at L4-L5. Two different rhBMP-2 doses were evaluated in 3 delivery configurations. The first 3 monkeys received 10 mg/side (2.5 mL at 4.0 mg/mL) of rhBMP-2 loadeddirectly onto a CRM carrier (15% hydroxyapatite/85%beta-tricalcium phosphate ceramic/collagen matrix), resulting in a final concentration of 2.0 mg/mL. The second 3 monkeys received 3 mg/side (2.0 mL at 1.5 mg/mL) of rhBMP-2 loaded directly on the CRM carrier, resulting in a 0.6 mg/mL final concentration. Three additional monkeys also received the 3 mg/side (2.0 mL at 1.5 mg/mL) of rhBMP-2 delivered on an ACS, which was then wrapped

  9. I4, a synthetic anti-diabetes agent, attenuates atherosclerosis through its lipid-lowering, anti-inflammatory and anti-apoptosis properties.

    PubMed

    Ma, Lingman; Qian, Lifen; Ying, Qidi; Zhang, Yan; Zhou, Changlin; Wu, Guanzhong

    2017-01-15

    Here, we investigated whether I4, which was initially developed as a hypoglycemic agent, possesses anti-atherosclerotic activity and attempted to elucidate the probable mechanism of action underlying this activity. ApoE(-/-) mice were fed a Western diet and simultaneously administered I4, glimepiride, or pioglitazone once daily for 12 weeks, and the atherosclerotic vascular lesions, lipid content, and expression levels of LOX-1, ICAM-1, VCAM-1 and Bax/Bcl-2 in mouse aortas were assessed. RAW264.7 macrophage-derived foam cells were obtained via ox-LDL stimulation to investigate the lipid-lowering, anti-atherosclerotic inflammation and anti-apoptotic effect of I4. The data indicated that I4 significantly decreased the lipid accumulation in the circulation and tissue, especially for TG and FFA levels (p < 0.05 vs model group), alleviating the arterial and liver lesions induced by lipotoxicity. Its lipid-reducing effects may due to LOX-1and CD36 expression suppression. I4, at doses of 20 mg/kg and 10 mg/kg, significantly decreased serum IL-6, IL-1β, and TNF-α production and suppressed the expression of p-ERK, p-p38, VCAM-1 and ICAM-1 protein. I4 attenuated atherosclerotic inflammation by blocking NF-κB nuclear translocation, suppressing MAPK/NF-κB signaling pathway and diminishing NF-κB-VCAM-1 promoter region binding. Additionally, I4 suppressed p-p53 and cleaved-caspase-3 expression to inhibit foam cell apoptosis induced by ox-LDL uptake. Overall, I4 exerts potent inhibitory effects on atherosclerosis onset and development.

  10. Viral agents causing lower respiratory tract infections in hospitalized children: evaluation of the Speed-Oligo® RSV assay for the detection of respiratory syncytial virus.

    PubMed

    Sánchez-Yebra, W; Ávila-Carrillo, J A; Giménez-Sánchez, F; Reyes-Bertos, A; Sánchez-Forte, M; Morales-Torres, M; Rojas, A; Mendoza, J

    2012-03-01

    Respiratory syncytial virus (RSV) is the viral agent which is more frequently involved in lower respiratory tract infections (LRTIs) in infants under 1 year of age in developed countries. A new oligochromatographic assay, Speed-Oligo® RSV, was designed and optimized for the specific detection and identification of RSV subtypes A and B. The test was evaluated in 289 clinical samples from 169 hospitalized children using an immunochromatography (IC) test, virus isolation by culture, and an in-house real-time polymerase chain reaction (RT-PCR). Other viruses causing LRTIs were investigated by cell culture or PCR-based tests. Sixty-two patients were infected by RSV (36.7%). In addition, adenovirus, influenza B, parainfluenza 2, and human metapneumovirus were detected in rates ranging from 5 to 8%. A proportion of 10.1% of the patients had mixed infections. The sensitivity, specificity, and positive and negative predictive values were, respectively, 94.9, 99.4, 98.9, and 97.4% for Speed-Oligo® RSV, 92.9, 96.3, 92.9, and 96.3% for RT-PCR/RSV, and 58.4, 98.1, 93.3, and 82.6% for IC. Our rates of viral detection and co-infection were similar to those of previously reported series. Finally, we find that Speed-Oligo® RSV is a rapid and easy-to-perform technique for the detection of RSV and the identification of subtypes A and B.

  11. 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

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

    PubMed

    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

    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 (1)H 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

  13. 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

  14. 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

  15. ASSOCIATION OF BILE ACID RECEPTOR TGR5 VARIATION AND TRANSIT IN HEALTH AND LOWER FUNCTIONAL GASTROINTESTINAL DISORDERS

    PubMed Central

    Camilleri, Michael; Vazquez-Roque, Maria I.; Carlson, Paula; Burton, Duane; Wong, Banny S.; Zinsmeister, Alan R.

    2011-01-01

    Background The membrane bound bile acid (BA) receptor, TGR5, is located on myenteric, cholinergic and nitrergic neurons in colon and proximal small intestine. Our aim was to assess the association of genetic variation in TGR5 and small bowel (SBT) and colonic transit. Methods In 230 healthy controls and 414 patients with lower functional GI disorders (FGID: irritable bowel syndrome [IBS]-alternators [Alt] 84, IBS-constipation [IBS-C] 157, IBS-diarrhea [IBS-D] 173), we tested the association between TGR5 SNP rs11554825 (minor allele frequency 41%) with symptom phenotype (total cohort) and intermediate phenotype (SBT or colonic transit by radioscintigraphy) which was available in 213 people in this cohort. The association with symptom phenotype was assessed using logistic regression, while the association with colonic filling at 6h [CF6], and colonic transit (geometric center [GC] at 24h) was assessed using ANCOVA, in each instance assuming a dominant genetic model. Key Results There was no significant association with symptom phenotype. We observed a potential association of SNP rs11554825 with overall transit: CF6 (p=0.061) and GC24 (p=0.083). The association of the SNP with CF6 in the IBS-D subgroup (p=0.017) indicated the TC/CC subgroup had an average 50% faster SBT compared to the TT subgroup. In IBS-D patients, GC24 was not significantly associated with rs11554825 (TC/CC vs TT). Conclusions and Inferences Variation in TGR5 may contribute to altered SBT and colonic transit in lower FGID. Further studies are required to characterize the potential role of BA receptor TGR5 in the mechanism and treatment of bowel dysfunction in lower FGID. PMID:21883702

  16. Omega-3 fatty acid supply from milk associates with lower type 2 diabetes in men and coronary heart disease in women.

    PubMed

    Thorsdottir, Inga; Hill, Jeremy; Ramel, Alfons

    2004-09-01

    Omega-3 fatty acids may prevent type 2 diabetes and coronary heart disease (CHD). We investigated these fatty acids in Nordic cow's milk and whether their supply from milk associates with type 2 diabetes prevalence and CHD mortality in the Nordic countries. Samples (N = 84) of consumers' milk were collected in five Nordic countries four times during 1 year. Fatty acids were analyzed using gas chromatography. Fatty acids supply from milk fat was calculated using national food balance sheets. The omega-3 fatty acids content was higher and omega-6 fatty acid content was lower in Icelandic milk when compared with milk from other Nordic countries. Type 2 diabetes prevalence in men correlated inversely with the supply of omega-3 fatty acids and eicosapentaenic acid, but positively with omega-6/omega-3 ratio in milk. CHD mortality in women correlated inversely with the supply of eicosapentaenic acid but positively with the omega-6/omega-3 ratio. Milk fatty acids content can depend upon the origin of the milk. The higher supply of omega-3 fatty acids from milk might explain the lower type 2 diabetes prevalence and CHD mortality in Iceland compared to the other Nordic countries.

  17. Synthesis of novel 2',3'-difluorinated 5'-deoxythreosyl phosphonic acid nucleosides as antiviral agents.

    PubMed

    Kim, Eunae; Kim, Seyeon; Hong, Joon Hee

    2015-01-01

    A novel route for the synthesis of 2',3'-difluorinated 5'-deoxythreosyl phosphonic acid nucleosides from glyceraldehyde using the Horner-Emmons reaction in the presence of triethyl α-fluorophosphonoacetate is described. The second fluorination at the 2'-position was an electrophilic reaction performed using N-fluorodibenzenesulfonimide. Glycosylation reactions between the nucleosidic bases and glycosyl donor 9 generated nucleosides that were further phosphonated and hydrolyzed to produce the desired nucleoside analogues. The synthesized nucleoside analogues 13, 16, 20, and 23 were tested for anti- human immunodeficiency virus (HIV) activity as well as cytotoxicity. Adenine derivative 16 showed significant anti-HIV activity up to 100 μM.

  18. Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium-chain triglyceride ketogenic diet.

    PubMed

    Khabbush, Aziza; Orford, Michael; Tsai, Yi-Chen; Rutherford, Tricia; O'Donnell, Maura; Eaton, Simon; Heales, Simon J R

    2017-08-01

    The medium-chain triglyceride (MCT) ketogenic diet contains both octanoic (C8) and decanoic (C10) acids. The diet is an effective treatment for pharmacoresistant epilepsy. Although the exact mechanism for its efficacy is not known, it is emerging that C10, but not C8, interacts with targets that can explain antiseizure effects, for example, peroxisome proliferator-activated receptor-γ (eliciting mitochondrial biogenesis and increased antioxidant status) and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. For such effects to occur, significant concentrations of C10 are likely to be required in the brain. To investigate how this might occur, we measured the β-oxidation rate of (13) C-labeled C8 and C10 in neuronal SH-SY5Y cells using isotope-ratio mass spectrometry. The effects of carnitine palmitoyltransferase I (CPT1) inhibition, with the CPT1 inhibitor etomoxir, on C8 and C10 β-oxidation were also investigated. Both fatty acids were catabolized, as judged by (13) CO2 release. However, C10 was β-oxidized at a significantly lower rate, 20% that of C8. This difference was explained by a clear dependence of C10 on CPT1 activity, which is low in neurons, whereas 66% of C8 β-oxidation was independent of CPT1. In addition, C10 β-oxidation was decreased further in the presence of C8. It is concluded that, because CPT1 is poorly expressed in the brain, C10 is relatively spared from β-oxidation and can accumulate. This is further facilitated by the presence of C8 in the MCT ketogenic diet, which has a sparing effect upon C10 β-oxidation. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  19. [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.

  20. 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.

  1. 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.

  2. Screening of nerve agent markers with hollow fiber-chemosorption of phosphonic acids.

    PubMed

    Holmgren, Karin Höjer; Gustafsson, Tomas; Östin, Anders

    2016-10-15

    This report describes a method developed for extracting nerve gas markers such as phosphonic acids from urine and other aqueous samples. It involves single-step microextraction with chemosorption to hollow fibers that have been pre-soaked in a solution containing a derivatization reagent (3,5 triflouro methyl benzene diazomethane). The derivatives it forms with phosphonic acids can be sensitively detected by mass spectrometric detectors operating in negative chemical ionization (NCI) mode. Limits of quantification obtained in analyses of water and urine extracts by GC/MS in negative chemical ionization and selected ion monitoring mode were 0.1-10 and 0.5-10ng/mL, respectively. Pentaflourophenyl diazomethane can also be used as a derivatization reagent, and the micro-extracts (which generate low background signals) can be sensitively analyzed by GC-MS/MS in NCI selected reaction monitoring (SRM) mode, using two specific transitions for both reagents. Thus, this sensitive approach can be flexibly modified to obtain confirmatory information, or address potential problems caused by interferences in some samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Radiolabelling of ascorbic acid: a new clue to clarify its action as an anticancer agent?

    PubMed

    Mamede, A C; Abrantes, A M; Pires, A S; Tavares, S D; Serra, M E; Maia, J M; Botelho, M F

    2012-04-01

    Vitamin C exists in two forms: the reduced (ascorbic acid--AA) and oxidized form (dehydroascorbic acid--DHA). This is a nutrient whose benefits are long known and widely publicized, being most of them related to its antioxidant action. As an antioxidant, the main role of vitamin C is to neutralize free radicals, reducing oxidative stress. However, some controversial studies suggest that this nutrient may have a preventive and therapeutic role in cancer disease due to their possible pro-oxidant activity, promoting the formation of reactive oxygen species that can induce cell death in cancer cells. This factor, coupled with the decrease of antioxidant enzymes and increase of decompartmentalized transition metals in tumor cells may result in the selective cytotoxicity of vitamin C and the subsequent revelation of its therapeutic potential. In this way the first purpose of this work was radioactively label the reduced form of vitamin C with Tc-99m, its quality control by HPLC and the time stability. The second purpose was to use the radioactive complex 99mTc-AA in in vitro and in vivo studies in order to evaluate its uptake by colorectal cancer cells and biodistribution in mices, respectively. The results suggest that the pharmaceutical formulation developed, which was reproducible and stable over time, was residually taken up by colorectal cancer cells. Future studies are needed to deepen our understanding about the radioactive complex 99mTc-AA and clarify the mechanisms of action of vitamin C in oncologic disease.

  4. 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.

  5. “On-Off” Thermoresponsive Coating Agent Containing Salicylic Acid Applied to Maize Seeds for Chilling Tolerance

    PubMed Central

    He, Fei; Huang, Yutao; Song, Wenjian; Hu, Jin

    2015-01-01

    Chilling stress is an important constraint for maize seed establishment in the field. In this study, a type of “on-off” thermoresponsive coating agent containing poly (N-isopropylacrylamide-co-butylmethacrylate) (Abbr. P(NIPAm-co-BMA)) hydrogel was developed to improve the chilling tolerance of coated maize seed. The P(NIPAm-co-BMA) hydrogel was synthesized by free-radical polymerization of N-isopropylacrylamide (NIPAm) and butylmethacrylate (BMA). Salicylic acid (SA) was loaded in the hydrogel as the chilling resistance agent. SA-loaded P(NIPAm-co-BMA) was used for seed film-coating of two maize varieties, Huang C (HC, chilling-tolerant) and Mo17 (chilling-sensitive), to investigate the coated seed germination and seedling growth status under chilling stress. The results showed that the hydrogel obtained a phase transition temperature near 12°C with a NIPAM to MBA weight ratio of 1: 0.1988 (w/w). The temperature of 12°C was considered the “on-off” temperature for chilling-resistant agent release; the SA was released from the hydrogel more rapidly at external temperatures below 12°C than above 12°C. In addition, when seedlings of both maize varieties suffered a short chilling stress (5°C), higher concentrations of SA-loaded hydrogel resulted in increased germination energy, germination percentage, germination index, root length, shoot height, dry weight of roots and shoots and protective enzyme activities and a decreased malondialdehyde content in coated maize seeds compared to single SA treatments. The majority of these physiological and biochemical parameters achieved significant levels compared with the control. Therefore, SA-loaded P(NIPAm-co-BMA), a nontoxic thermoresponsive hydrogel, can be used as an effective material for chilling tolerance in film-coated maize seeds. PMID:25807522

  6. Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents.

    PubMed

    Koto, Kazutaka; Murata, Hiroaki; Kimura, Shinya; Horie, Naoyuki; Matsui, Takaaki; Nishigaki, Yasunori; Ryu, Kazuteru; Sakabe, Tomoya; Itoi, Megumi; Ashihara, Eishi; Maekawa, Taira; Fushiki, Shinji; Kubo, Toshikazu

    2010-07-01

    Third-generation bisphosphonates are known to inhibit bone resorption and also appear to exhibit direct anti-tumour activity. We previously reported that third-generation bisphosphonates such as zoledronic acid (ZOL) have a direct antitumour effect, and synergistically augment the effects of antitumor agents in osteosarcoma cells. There has been no report on the antitumor effect of ZOL against soft tissue sarcoma. The aim of this study was to evaluate the antitumor effect of this drug on a human fibrosarcoma cell line, in terms of proliferation and apoptosis, and, moreover, to evaluate the combined effects of ZOL with other antitumor drugs against the human fibrosarcoma cell line. HT1080 cells were treated with ZOL at various concentrations up to 10 microM, and then cell proliferation, cell cycle, nuclear morphology, and Western blot analyses were performed to study the antitumor effects of ZOL alone, and, moreover, HT1080 cells were treated with ZOL and other anticancer drugs such as paclitaxel, docetaxel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, cisplatin, or methotrexate to investigate the combined effects using proliferation and cell cycle analyses. We found that ZOL strongly inhibited in vitro proliferation, arrested the cell cycle between S and G2/M phases, and induced the apoptosis of human fibrosarcoma cells. Moreover, ZOL augmented the effect of antitumor agents when administered concurrently with paclitaxel, docetaxel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, and cisplatin in human fibrosarcoma cells. The treatment of fibrosarcoma with ordinary antitumor drugs is not fully effective. These findings suggest that ZOL directly affects the proliferation and survival of fibrosarcoma cells, and that the combined administration of ZOL with other antitumor agents may improve the efficacy of fibrosarcoma treatment. These results support the possibility that their combined use could be beneficial in the treatment of patients not only with

  7. Using poly-glutamic acid as soil-washing agent to remediate heavy metal-contaminated soils.

    PubMed

    Yang, Zong-Han; Dong, Cheng-Di; Chen, Chiu-Wen; Sheu, Yih-Terng; Kao, Chih-Ming

    2017-05-20

    The extraction efficiency of heavy metals from soils using three forms of gamma poly-glutamic acid (γ-PGA) as the washing agents was investigated. Controlling factors including agent concentrations, extraction time, pH, and liquid to soil ratio were evaluated to determine the optimum operational conditions. The distribution of heavy metal species in soils before and after extraction processes was analyzed. Up to 46 and 74% of heavy metal removal efficiencies were achieved with one round and a sequential extraction process using H-bonding form of γ-PGA (200 mM) with washing time of 40 min, liquid to solid ratio of 10 to 1, and pH of 6. Major heavy metal removal mechanisms were (1) γ-PGA-promoted dissolution and (2) complexation of heavy metal with free carboxyl groups in γ-PGA, which resulted in heavy metal desorption from soils. Metal species on soils were redistributed after washing, and soils were remediated without destruction of soil structures and productivity.

  8. Nucleic acid-binding molecules with high affinity and base sequence specificity: intercalating agents covalently linked to oligodeoxynucleotides.

    PubMed Central

    Asseline, U; Delarue, M; Lancelot, G; Toulmé, F; Thuong, N T; Montenay-Garestier, T; Hélène, C

    1984-01-01

    Oligodeoxyribonucleotides covalently linked to an intercalating agent via a polymethylene linker were synthesized. Oligothymidylates attached to an acridine dye (Acr) through the 3'-phosphate group [(Tp)n(CH2) mAcr ] specifically interact with the complementary sequence. The interaction is strongly stabilized by the intercalating agent. By using absorption and fluorescence spectroscopies, it is shown that complex formation between (Tp)n(CH2) mAcr and poly(rA) involves the formation of n A X T base pairs, where n is the number of thymines in the oligonucleotide. The acridine ring intercalates between A X T base pairs. Fluorescence excitation spectra reveal the existence of two environments for the acridine ring, whose relative contributions depend on the linker length (m). The binding of (Tp)4(CH2) mAcr to poly(rA) is analyzed in terms of site binding and cooperative interactions between oligonucleotides along the polynucleotide lattice. Thermodynamic parameters show that the covalent attachment of the acridine ring strongly stabilizes the binding of the oligonucleotide to its complementary sequence. The stabilization depends on the linker length; the compound with m = 5 gives a more stable complex than that with m = 3. These results open the way to the synthesis of a family of molecules exhibiting both high-affinity and high-specificity for a nucleic acid base sequence. PMID:6587350

  9. Synthesis and biological evaluation of strained unusual amino acid containing tetrapeptides as potential antidepressant agents.

    PubMed

    Mainkar, Prathama S; Chakravarty, Sumana; Srujana, Takkallapally; Vishwanathan, Libi Anandi; Prajapti, Santosh Kumar; Chandra, Karisetty Bhanu; Veeraval, Lenin; Babu, Bathini Nagendra

    2015-12-01

    Strained unusual amino acid derived tetrapeptides were synthesized as mimics of GLYX-13, a clinical candidate for neuroprotective and anti-depressant properties, were studied. The synthesized compounds were screened for neurite growth and anti-depressant properties in vitro and in vivo respectively comparing with the parent GLYX-13 compound. Neurite growth property was assessed by neurite length and anti-depressant property by percentage of immobility in forced swim test, a behavioural assay. Mechanistic insights about protein-ligand interactions were obtained using molecular docking study. Based on the in vitro and in vivo screening data and molecular docking study, a new analogue of GLYX-13, Compound 11a has been found to be as good as the parent compound in all respects.

  10. 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.

  11. 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.

  12. Synthesis of conjugated bile acids/azastilbenes as potential antioxidant and photoprotective agents.

    PubMed

    dos Santos, Juliana Alves; Polonini, Hudson Caetano; Suzuki, Érika Yoko; Raposo, Nádia R B; da Silva, Adilson David

    2015-06-01

    A series of 14 bile acids/azastilbenes conjugates (1a-g and 2a-g) was prepared through the condensation of bile amides (1 and 2) and aromatic aldehydes. The newly synthesized conjugates were evaluated in vitro for their antioxidant and photoprotective activities. Six compounds (1, 1a, 1b, 2, 2a and 2b) showed promising antioxidant activity with IC50 values of 19.60-31.83 μg mL(-1). The synthesized compounds presented a varied photoprotection profile, with the SPF ranging from 2 to 9. Among the 16 compounds tested for the protection against UVB sunrays, 3 compounds (2c, 2e and 2g) presented more significant protection than resveratrol and the free azastilbene 3; while the UVAPF increased from 2 in resveratrol and 5 in 3 to 5-11 in the majority of the conjugates.

  13. Design and synthesis of gambogic acid analogs as potent cytotoxic and anti-inflammatory agents

    PubMed Central

    Yen, Chiao-Ting; Nakagawa-Goto, Kyoko; Hwang, Tsong-Long; Morris-Natschke, Susan L.; Bastow, Kenneth F.; Wu, Yang-Chang; Lee, Kuo-Hsiung

    2012-01-01

    Prenyl- and pyrano-xanthones derived from 1,3,6-trihydroxy-9H-xanthen-9-one, a basic backbone of gambogic acid (GA), were synthesized and evaluated for in vitro cytotoxic effects against four human cancer cell lines (KB, KBvin, A549, and DU-145) and anti-inflammatory activity toward superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB. Among them, prenylxanthones 7-13 were generally less active than pyranoxanthones 14-21 in both anticancer and anti-inflammatory assays. Furthermore, two angular 3,3-dimethypyranoxanthones (16 and 20) showed the greatest and selective activity against the KBvin multidrug resistant (MDR) cell line with IC50 values of 0.9 and 0.8 μ g/mL, respectively. An angular 3-methyl-3-prenylpyranoxanthone (17) selectively inhibited elastase release with 200 times more potency than phenylmethylsulfonyl fluoride (PMSF), the positive control. PMID:22595179

  14. 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

  15. Influence of pH, bleaching agents, and acid etching on surface wear of bovine enamel.

    PubMed

    Soares, Ana Flávia; Bombonatti, Juliana Fraga Soares; Alencar, Marina Studart; Consolmagno, Elaine Cristina; Honório, Heitor Marques; Mondelli, Rafael Francisco Lia

    2016-01-01

    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. 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. 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). The pH showed a slight decrease, except for Group LPL15HL. Group LPS25HL showed the highest degree of wear, with and without etching. 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.

  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. Acridone acetic acid, sodium salt, as an agent to stop vitiligo progression: a pilot study.

    PubMed

    Korobko, Igor V; Lomonosov, Konstantin M

    2014-01-01

    Vitiligo progression is attributed to immune system malfunctioning, thus immunomodulating compounds might be beneficial in stopping vitiligo progression which is a prerequisite for successful repigmentation. The goal of this study was to assess efficacy of acridone acetic acid, sodium salt (Na-AAA), an immunomodulating compound with favorable safety profile, in stabilizing active vitiligo, and to reveal prognostic factors of treatment outcome. Sixty consecutive patients with progressing nonsegmental vitiligo were treated with 10 i.m. injections of Na-AAA every other day. Disease stability was assessed in 1, 3, 6, and 12 months post-treatment. Statistical analysis was applied to correlate treatment outcome and available clinical parameters. Of the 60 patients treated, vitiligo stopped progression in 44 patients (73.3%). Older age (p = 0.0219), age of 35 and older (p = 0.0189, odds ratio (OR) = 5.2, 95% confidence interval (CI) 1.30-20.84) or age of 40 and older (p = 0.0039, OR = 6.48, 95% CI 1.86-22.61), longer disease duration (p = 0.0234), pre-treatment interleukin-6 level over 2 pg/mL (p = 0.0005, OR = 13.7, 95% CI 2.97-63), and over the reference threshold value 5.9 pg/mL (p = 0.0009, OR = 25.8, 95% CI 2.8-239) as well as presence of other autoimmune diseases (p = 0.038, OR = 7.0, 95% CI 1.14-42.97) were negative prognostic factors of treatment success. In conclusion, acridone acetic acid, sodium salt, emerges as an efficient option for stopping vitiligo progression.

  18. Quercetin lowers plasma uric acid in pre-hyperuricaemic males: a randomised, double-blinded, placebo-controlled, cross-over trial.

    PubMed

    Shi, Yuanlu; Williamson, Gary

    2016-03-14

    Elevated plasma uric acid concentration is a risk factor for gout, insulin resistance and type 2 diabetes. Quercetin, a flavonoid found in high levels in onions, tea and apples, inhibits xanthine oxidoreductase in vitro, the final step in intracellular uric acid production, indicating that quercetin might be able to lower blood uric acid in humans. We determined the effects of 4 weeks of oral supplementation of quercetin on plasma uric acid, blood pressure and fasting glucose. This randomised, double-blinded, placebo-controlled, cross-over trial recruited twenty-two healthy males (19-60 years) with baseline plasma uric acid concentration in the higher, but still considered healthy, range (339 (SD 51) µmol/l). The intervention included one tablet containing 500 mg quercetin daily for 4 weeks, compared with placebo, with a 4-week washout period between treatments. The primary outcome was change in concentrations of plasma uric acid after 2 and 4 weeks; secondary outcome measures were changes in fasting plasma glucose, 24-h urinary excretion of uric acid and resting blood pressure. After quercetin treatment, plasma uric acid concentrations were significantly lowered by -26·5 µmol/l (95% CI, -7·6, -45·5; P=0·008), without affecting fasting glucose, urinary excretion of uric acid or blood pressure. Daily supplementation of 500 mg quercetin, containing the bioavailable amount of quercetin as present in approximately 100 g red onions, for 4 weeks, significantly reduces elevated plasma uric acid concentrations in healthy males.

  19. 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. Copyright 2010 Elsevier Ltd. All rights reserved.

  20. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Short-chain fatty acids and poly-beta-hydroxyalkanoates: (New) Biocontrol agents for a sustainable animal production.

    PubMed

    Defoirdt, Tom; Boon, Nico; Sorgeloos, Patrick; Verstraete, Willy; Bossier, Peter

    2009-01-01

    Because of the risk of antibiotic resistance development, there is a growing awareness that antibiotics should be used more carefully in animal production. However, a decreased use of antibiotics could result in a higher frequency of pathogenic bacteria, which in its turn could lead to a higher incidence of infections. Short-chain fatty acids (SCFAs) have long been known to exhibit bacteriostatic activity. These compounds also specifically downregulate virulence factor expression and positively influence the gastrointestinal health of the host. As a consequence, there is currently considerable interest in SCFAs as biocontrol agents in animal production. Polyhydroxyalkanoates (PHAs) are polymers of beta-hydroxy short-chain fatty acids. Currently, PHAs are applied as replacements for synthetic polymers. These biopolymers can be depolymerised by many different microorganisms that produce extracellular PHA depolymerases. Interestingly, different studies provided some evidence that PHAs can also be degraded upon passage through the gastrointestinal tract of animals and consequently, adding these compounds to the feed might result in biocontrol effects similar to those described for SCFAs.

  2. Versatile methods for synthesizing organic acid salts of quaternary berberine-type alkaloids as anti-ulcerative colitis agents.

    PubMed

    Zhang, Zhi-Hui; Li, Jing; Zhang, Hai-Jing; Deng, An-Jun; Wu, Lian-Qiu; Li, Zhi-Hong; Song, Hong-Rui; Wang, Wen-Jie; Qin, Hai-Lin

    2016-06-01

    Two versatile methods to synthesize kinds of organic acid salts of quaternary berberine-type alkaloids were investigated in order to determine which is more efficient to improve the liposolubility of the target compounds and to explore the efficacy of the target compounds as anti-ulcerative colitis (UC) agents. Overall evaluation according to the reaction results and yields of the final products indicated that the synthetic method using tertiary (±)-8-acylmethyldihydroberberine-type alkaloids as key intermediates is superior to that of using tertiary dihydroberberine-type alkaloids as intermediates. Ten target compounds were synthesized using quaternary berberine chloride and quaternary coptisine chloride as starting materials, respectively, and the anti-UC activity of some target compounds was evaluated in an in vitro x-box-binding protein 1 (XBP1) transcriptional activity assay using dual luciferase reporter detection. At 10 μM, the tested compounds were found to activate the transcription of XBP1 target at almost the same level as that of quaternary coptisine chloride. The synthesized target compounds were also found to share higher liposolubility than the inorganic acid salts of quaternary berberine-type alkaloid.

  3. 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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Percent reduction in LDL cholesterol following high-intensity statin therapy: potential implications for guidelines and for the prescription of emerging lipid-lowering agents

    PubMed Central

    Ridker, Paul M; Mora, Samia; Rose, Lynda

    2016-01-01

    % reduction directly relates to efficacy. These data support guideline approaches that incorporate % reduction targets for statin therapy as well as absolute targets, and might provide a structure for the allocation of emerging adjunctive lipid-lowering therapies such as PCSK9 inhibitors should these agents prove broadly effective for cardiovascular event reduction. PMID:26916794

  5. Indole carboxylic acid esters of melampomagnolide B are potent anticancer agents against both hematological and solid tumor cells.

    PubMed

    Bommagani, Shobanbabu; Ponder, Jessica; Penthala, Narsimha R; Janganati, Venumadhav; Jordan, Craig T; Borrelli, Michael J; Crooks, Peter A

    2017-08-18

    A series of novel, heteroaryl carboxylic acid conjugates of the sesquiterpene melampomagnolide-B (MMB, 3) has been evaluated as antitumor agents against an NCI panel of 64 human hematopoetic and solid tumor cell lines. The indole-3-acrylic acid conjugate 7j and the indole-3-carboxylic acid conjugate 7k were found to be the most potent analogs in the series. Compounds 7j and 7k exhibited remarkable growth inhibition, with GI50 values in the range 0.03-0.30 μM and 0.04-0.28 μM, respectively, against the cell lines in the leukemia sub-panel, and GI50 values of 0.05-0.40 μM and 0.04-0.61 μM, respectively, against 90% of the solid tumor cell lines in the NCI panel. Compound 7a was particularly effective against the sub-panel of breast cancer cell lines with GI50 values in the range <0.01-0.30 μM. Compounds 7j, 7a and its water soluble analog 7p also exhibited potent anticancer activity against rat 9L-SF gliosarcoma cells in culture. Compound 7j was the most potent compound in the series in the M9-ENL1 AML cell assay with a lethal dose concentration EC50 value of 720 nM, and exhibited the greatest cytotoxicity against a collection of primary AML stem cell specimens, which included a specimen that was unresponsive to PTL, affording EC50 values in the range 0.33-1.0 μM in three out of four specimens. The results from this study provide further evidence that analogs of the sesquiterpene MMB can be designed to afford molecules with significantly improved anticancer activity. Thus, both 7j and 7k are considered potential lead molecules in the search for new anticancer agents that can be used as treatments for both hematopoetic and solid tumors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Derivatives of caffeic acid, a natural a