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Sample records for a-lipoic acid prevents

  1. Stability, cutaneous delivery and antioxidant potential of a lipoic acid and α-tocopherol co-drug incorporated in microemulsions

    PubMed Central

    Thomas, Siji; Vieira, Camila S.; Hass, Martha A.; Lopes, Luciana B.

    2014-01-01

    The aim of this study was to assess the skin penetration, stability and antioxidant effects of a α-tocopherol-lipoic acid co-drug. To enhance penetration, we evaluated three microemulsions varying in water content and composition of the oil phase (isopropyl myristate with either monocaprylin or oleic acid). The co-drug was incorporated at 1% (w/w). Co-drug hydrolysis in the microemulsion increased with increases in time (up to 48 h) and formulation water content (10–30%, w/w). Microemulsions increased the co-drug delivery into viable layers of porcine ear skin by 2.9–7.8–fold compared to a control formulation (20% monocaprylin in isopropyl myristate) after 24 h. Penetration enhancement was influenced by the oil phase, with the formulation containing monocaprylin displaying the most pronounced effect. Antioxidant activity, assessed in skin bioequivalents using the thiobarbituric acid-reactive substances (TBARS) assay, demonstrated that TBARS levels decreased by 39% after treatment with the co-drug-containing microemulsion compared to the unloaded formulation. In addition to the co-drug, tocopherol (8.2 ± 0.6 μg/cm2) was detected in the viable bioequivalent tissues, suggesting that the co-drug was partly hydrolyzed after 12 h. Taken together, these results support the potential of nanodispersed formulations containing a tocopherol-lipoic acid co-drug to improve skin antioxidant activity. PMID:24961388

  2. The analysis and assessment of the effect of selected endo- and exogenous substances on prevention and treatment of selected conditions and injuries within the musculoskeletal system.

    PubMed

    Tomaszewski, Wiesław E; Obmiński, Zbigniew

    2017-04-12

    The aim of the presented report, prepared based on the results of the newest studies available in the reference sources, is the analysis and assessment of the important endo- and exogenous substances, whose role and significance in prevention and complex treatment of civilization-related diseases (including the pathological conditions and injuries of the musculoskeletal system) can be essential and significantly contribute to the improvement of the efficacy of the accepted treatment approach. Three substances, namely a-lipoic acid, y-linolenic acid and a-linoleic acid were subject to a detailed analysis and assessment.

  3. Folic acid and birth defect prevention

    MedlinePlus

    ... Women who have had a baby with a neural tube defect may need a higher dose of folic acid. If you have had a baby with a neural tube defect, you should take 400 micrograms of folic acid every day, even when you are not planning ...

  4. Prevention of acid drainage from stored coal

    SciTech Connect

    Olem, H.

    1983-01-01

    It was found that application of a 50-mg/l solution of the detergent sodium lauryl sulphate to a coal stockpile inhibited the activity of the bacteria causing acid formation and leaching and kept the drainage neutral for 60 days. The cost of a single application would be 0.4 cents/t of coal.

  5. Omega-3 fatty acids for breast cancer prevention and survivorship.

    PubMed

    Fabian, Carol J; Kimler, Bruce F; Hursting, Stephen D

    2015-05-04

    Women with evidence of high intake ratios of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid have been found to have a reduced risk of breast cancer compared with those with low ratios in some but not all case-control and cohort studies. If increasing EPA and DHA relative to arachidonic acid is effective in reducing breast cancer risk, likely mechanisms include reduction in proinflammatory lipid derivatives, inhibition of nuclear factor-κB-induced cytokine production, and decreased growth factor receptor signaling as a result of alteration in membrane lipid rafts. Primary prevention trials with either risk biomarkers or cancer incidence as endpoints are underway but final results of these trials are currently unavailable. EPA and DHA supplementation is also being explored in an effort to help prevent or alleviate common problems after a breast cancer diagnosis, including cardiac and cognitive dysfunction and chemotherapy-induced peripheral neuropathy. The insulin-sensitizing and anabolic properties of EPA and DHA also suggest supplementation studies to determine whether these omega-3 fatty acids might reduce chemotherapy-associated loss of muscle mass and weight gain. We will briefly review relevant omega-3 fatty acid metabolism, and early investigations in breast cancer prevention and survivorship.

  6. Yeast adaptation to weak acids prevents futile energy expenditure

    PubMed Central

    Ullah, Azmat; Chandrasekaran, Gayathri; Brul, Stanley; Smits, Gertien J.

    2013-01-01

    Weak organic acids (WOAs) are widely used preservatives to prevent fungal spoilage of foods and beverages. Exposure of baker's yeast Saccharomyces cerevisiae to WOA leads to cellular acidification and anion accumulation. Pre-adaptation of cultures reduced the rate of acidification caused by weak acid exposure, most likely as a result of changes in plasma membrane or cell wall composition. In order to adapt to sublethal concentrations of the acids and grow, yeast cells activate ATP consuming membrane transporters to remove protons and anions. We explored to what extent ATP depletion contributes to growth inhibition in sorbic or acetic acid treated cells. Therefore, we analyzed the effect of the reduction of proton and anion pumping activity on intracellular pH (pHi), growth, and energy status upon exposure to the hydrophilic acetic acid (HA) and the lipophilic sorbic acid (HS). ATP concentrations were dependent on the severity of the stress. Unexpectedly, we observed a stronger reduction of ATP with growth reducing than with growth inhibitory concentrations of both acids. We deduce that the not the ATP reduction caused by proton pumping, but rather the cost of sorbate anion pumping contributes to growth inhibition. A reduction of proton pumping activity may reduce ATP consumption, but the resulting decrease of pHi affects growth more. ATP utilization was differentially regulated during moderate and severe stress conditions. We propose that the energy depletion alone is not the cause of growth inhibition during HA or HS stress. Rather, the cells appear to reduce ATP consumption in high stress conditions, likely to prevent futile cycling and maintain energy reserves for growth resumption in more favorable conditions. The mechanism for such decision making remains to be established. PMID:23781215

  7. Chlorogenic acid and coffee prevent hypoxia-induced retinal degeneration.

    PubMed

    Jang, Holim; Ahn, Hong Ryul; Jo, Hyoung; Kim, Kyung-A; Lee, Eun Ha; Lee, Ki Won; Jung, Sang Hoon; Lee, Chang Y

    2014-01-08

    This study explored whether chlorogenic acid (CGA) and coffee have protective effects against retinal degeneration. Under hypoxic conditions, the viability of transformed retinal ganglion (RGC-5) cells was significantly reduced by treatment with the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP). However, pretreatment with CGA attenuated cell death in a concentration-dependent manner. In addition, CGA prevented the up-regulation of apoptotic proteins such as Bad and cleaved caspase-3. Similar beneficial effects of both CGA and coffee extracts were observed in mice that had undergone an optic nerve crush (ONC) procedure. CGA and coffee extract reduced cell death by preventing the down-regulation of Thy-1. Our in vitro and in vivo studies demonstrated that coffee and its major component, CGA, significantly reduce apoptosis of retinal cells induced by hypoxia and NO, and that coffee consumption may help in preventing retinal degeneration.

  8. [Folic acid: Primary prevention of neural tube defects. Literature Review].

    PubMed

    Llamas Centeno, M J; Miguélez Lago, C

    2016-03-01

    Neural tube defects (NTD) are the most common congenital malformations of the nervous system, they have a multifactorial etiology, are caused by exposure to chemical, physical or biological toxic agents, factors deficiency, diabetes, obesity, hyperthermia, genetic alterations and unknown causes. Some of these factors are associated with malnutrition by interfering with the folic acid metabolic pathway, the vitamin responsible for neural tube closure. Its deficit produce anomalies that can cause abortions, stillbirths or newborn serious injuries that cause disability, impaired quality of life and require expensive treatments to try to alleviate in some way the alterations produced in the embryo. Folic acid deficiency is considered the ultimate cause of the production of neural tube defects, it is clear the reduction in the incidence of Espina Bifida after administration of folic acid before conception, this leads us to want to further study the action of folic acid and its application in the primary prevention of neural tube defects. More than 40 countries have made the fortification of flour with folate, achieving encouraging data of decrease in the prevalence of neural tube defects. This paper attempts to make a literature review, which clarify the current situation and future of the prevention of neural tube defects.

  9. Lipoic acid prevents steroid-induced osteonecrosis in rabbits.

    PubMed

    Lu, Bang-Bao; Li, Kang-Hua

    2012-06-01

    The objective of this study was to investigate in vivo effects of lipoic acid (LA) in preventing steroid-induced osteonecrosis and the possible pathway in a rabbit model. Sixty rabbits were divided into 2 groups: rabbits were intraperitoneally injected with LA aqueous solution at 36 mg/kg of body weight per day for 4 weeks in Group A and rabbits were injected with physiologic saline (PS) as a control in Group B. At 2 weeks after starting treatment, they were intramuscularly injected once with 20 mg/kg of methylprednisolone acetate (MPSL). The femora were histopathologically examined for the presence of osteonecrosis. The plasma levels of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), glutathione (GSH), endothelin (ET) and malondialdehyde (MDA) were assayed at 2 weeks after the injection of MPSL. The incidence of osteonecrosis was significantly higher in Group B (73.1%) than in Group A (20.8%). The GSH level was higher in Group A than in Group B after the LA injection. The plasma MDA and ET levels were lower in Group A than in Group B at 2 weeks after the MPSL administration. Lipoic acid can prevent the development of steroid-induced osteonecrosis in rabbits. Inhibited oxidative stress and amendment of vascular endothelial dysfunction is a possible mechanism for this effect.

  10. Thrombosis Prevention by Acetylsalicylic Acid in Hyperlipemic Rats

    PubMed Central

    Renaud, S.; Godu, J.

    1970-01-01

    In rats, administration of acetylsalicylic acid (ASA) by stomach tube two hours before blood removal, or addition of the drug to platelet-rich plasma in vitro, markedly inhibited platelet aggregation induced by thrombin, ADP and collagen. Addition of ASA in vitro to human platelet-rich plasma also inhibited platelet aggregation by thrombin, ADP and collagen. In hyperlipemic rats, ASA (100 to 200 mg./kg.), administered by stomach tube once or five times, markedly inhibited the production of thrombosis initiated by intravenous injection of S. typhosa endotoxin. In these experiments, thrombosis prevention by ASA was associated with both a decrease in platelet aggregation and an increase in the recalcification plasma clotting time. PMID:5531310

  11. Skin tumorigenic potential of benzanthrone: prevention by ascorbic acid.

    PubMed

    Dwivedi, Neelam; Kumar, Sandeep; Ansari, Kausar M; Khanna, S K; Das, Mukul

    2013-09-01

    Benzanthrone (BA) exposed occupational workers have been found to exhibit toxicological manifestations in the skin, thus it is quite likely that long term exposure may lead to skin tumorigenicity. Thus, attempts were made to elucidate the tumor initiating and promoting potentials of pure (PBA) and commercial benzanthrone (CBA). Additionally, the preventive role of ascorbic acid (AsA) was also assessed. PBA showed tumor initiating activity while CBA demonstrated tumor initiating as well as promoting activities in two-stage mouse skin tumor protocol. Further, prior treatment of AsA to PBA and CBA followed by twice weekly application of 12-o-tetradecanoyl phorbal myristate acetate (TPA) resulted into delayed onset of tumor formation and similarly single application of 7,12-dimethylbenz [α] anthracene (DMBA) followed by twice weekly application of AsA and CBA showed an increase in the latency period. Thus, AsA showed a protective effect against CBA promoted skin tumor. Furthermore, the topical application of CBA significantly increased the levels of xenobiotic enzymes. The animals topically treated with AsA along with topical application of CBA, restored all the impairment observed in enzyme activities. Thus, this study suggested that AsA can be useful in preventing PBA and CBA induced skin tumorigenicity.

  12. Zoledronic acid for prevention and treatment of osteoporosis.

    PubMed

    Recknor, Chris

    2011-04-01

    Osteoporosis (OP) is associated with a high risk of fracture and disability and with substantial medical costs. This paper is a review of the intravenous (i.v.) bisphosphonate zoledronic acid 5 mg (ZOL), used in the treatment and prevention of OP. This is a review of the scientific literature, between 2003 and 2010, on the use of ZOL in patients with low bone mass or OP. ZOL, given as a single infusion once yearly, has proven efficacy in reducing risk of vertebral and hip fractures in postmenopausal women with OP. In men and women with a recent hip fracture, ZOL has been shown to reduce the incidence of future clinical fractures. Data also demonstrate an increase in bone mineral density in postmenopausal women with osteopenia, in men with OP, and in patients at risk for glucocorticoid-induced osteoporosis. The ZOL clinical program has shown this agent to be safe and generally well tolerated. Acute flu-like symptoms may occur following the first infusion of ZOL, but these are generally mild and transient, and decrease in frequency with subsequent infusions. Patients must have adequate renal function (creatinine clearance ≥ 35 ml/min) and be adequately hydrated prior to infusion. With orally administered bisphosphonates, patient compliance and persistence with weekly or monthly dosing are frequently suboptimal. The ability to administer i.v. ZOL once yearly over 15 min for the treatment of OP provides the advantage of guaranteeing medication compliance for the duration of the dosing interval.

  13. Cross-linked hyaluronic acid in pressure ulcer prevention.

    PubMed

    Beniamino, P; Vadalà, M; Laurino, C

    2016-07-02

    Long-term bedridden patients are at high risk of acquring pressure ulcers (PUs). In this group of patients, prevention is necessary to cut the health costs, improve quality of life and reduce the mortality. Here, we evaluated the effectiveness of a cross-linked hyaluronic acid (HA) as plastic bulking-agent filling and remodelling the deep dermis and subcutaneous space of the skin areas exposed to the risk of necrosis. Our work hypothesis has been to inflate a sub-dermal elastic cushion, filled with a natural ECM component, with the aim to induce a stronger tissue background resistant to the ulcerative process. All the patients had an increased risk of PUs, at the sacral, ileum or heel skin. Patients were being nursed accordingly to the standard orthopaedic ward management with a pressure relieveing air mattress. The standard protocol consisted in body mobilisation every 3 hours, 24 hours a day and accurate cleaning of the skin with liquid soap and water without any towel friction and without adding any cream or lotion for the skin protection. Our filling protocol enclosed: accurate disinfection of the skin to be injected with povidone-iodine solution, followed by a local anaesthesia with 28G 13 mm needle, injecting 1.5 ml of 1% xylocaine. Then slow, deep, subcutaneous injection of cross-linked HA was performed with a 18G long needle, in order to deliver a homogeneous, soft gel layer underneath and around the whitish erythematous skin edges at risk of ulceration. Patients' tolerability of the compound and adverse events were also recorded. There were 15 patients (78-94 years old) who participated in the study. All tolerated the procedure very well and no serious side effects were declared. No skin pressure ulceration was detected in the four weeks follow-up Conclusion: We have demonstrated the safety and tolerability of a cross-linked HA subdermal injection in PUs prevention. The compound stratifies in a soft, elastic, interstitial bulk into the deep dermis, thus

  14. Use of organic acids for prevention and removal of Bacillus subtilis biofilms on food contact surfaces.

    PubMed

    Akbas, Meltem Yesilcimen; Cag, Seyda

    2016-10-01

    The efficacies of organic acid (citric, malic, and gallic acids) treatments at 1% and 2% concentrations on prevention and removal of Bacillus subtilis biofilms were investigated in this study. The analyses were conducted on microtitration plates and stainless steel coupons. The biofilm removal activities of these organic acids were compared with chlorine on both surfaces. The results showed that citric acid treatments were as powerful as chlorine treatments for prevention and removal of biofilms. The antibiofilm effects of malic acid treatments were higher than gallic acid and less than citric acid treatment. When the antibiofilm effects of these acids and chlorine on the two surfaces were compared, the prevention and removal of biofilms were measured higher on microtitration plates than those on stainless steel coupons. Higher reductions were obtained by increasing concentrations of sanitizers on 24-hour biofilm with 20-minute sanitizer treatments for removal of biofilms. © The Author(s) 2016.

  15. Folic Acid Supplementation for the Prevention of Neural Tube Defects: US Preventive Services Task Force Recommendation Statement.

    PubMed

    Bibbins-Domingo, Kirsten; Grossman, David C; Curry, Susan J; Davidson, Karina W; Epling, John W; García, Francisco A R; Kemper, Alex R; Krist, Alex H; Kurth, Ann E; Landefeld, C Seth; Mangione, Carol M; Phillips, William R; Phipps, Maureen G; Pignone, Michael P; Silverstein, Michael; Tseng, Chien-Wen

    2017-01-10

    Neural tube defects are among the most common major congenital anomalies in the United States and may lead to a range of disabilities or death. Daily folic acid supplementation in the periconceptional period can prevent neural tube defects. However, most women do not receive the recommended daily intake of folate from diet alone. To update the 2009 US Preventive Services Task Force (USPSTF) recommendation on folic acid supplementation in women of childbearing age. In 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation. The USPSTF assessed the balance of the benefits and harms of folic acid supplementation in women of childbearing age and determined that the net benefit is substantial. Evidence is adequate that the harms to the mother or infant from folic acid supplementation taken at the usual doses are no greater than small. Therefore, the USPSTF reaffirms its 2009 recommendation. The USPSTF recommends that all women who are planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400-800 µg) of folic acid. (A recommendation).

  16. Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement.

    PubMed

    2009-05-05

    In 1996, the U.S. Preventive Services Task Force (USPSTF) recommended that all women planning or capable of pregnancy take a multivitamin supplement containing folic acid for the prevention of neural tube defects. This recommendation is an update of the 1996 USPSTF recommendation. The USPSTF reviewed the evidence on folic acid supplementation in women of childbearing age published since the 1996 USPSTF recommendation. The USPSTF did not review the evidence on folic acid food fortification, counseling to increase dietary intake, or screening for neural tube defects. The USPSTF recommends that all women planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400 to 800 microg) of folic acid. (Grade A recommendation).

  17. Prevention of spina bifida: folic acid intake during pregnancy in Gulu district, northern Uganda.

    PubMed

    Bannink, Femke; Larok, Rita; Kirabira, Peter; Bauwens, Lieven; van Hove, Geert

    2015-01-01

    The intake of folic acid before conception and during the first trimester of pregnancy can prevent spina bifida. This paper describes folic acid intake in women in Gulu district in northern Uganda. Structured interviews were held with 394 women attending antenatal care (ANC), 15 mothers of children with spina bifida, and 35 health workers in 2012 and 2013. SPSS16 was used for data analysis. 1/4 mothers of children with spina bifida took folic acid during late pregnancy, none preconception. None had knowledge about folic acid and spina bifida prevention. 33.5% of women attending ANC had ever heard about spina bifida, 1% knew folic acid intake can prevent spina bifida. 42.4% took folic acid supplements in late pregnancy, 8.1% during the first trimester, none preconception. All women said to have eaten food rich in folic acid. None were aware about fortified foods. 7% of health workers understood the importance of early folic acid intake. All health workers recommended folic acid intake to women attending ANC. 20% of the health workers and 25% of the women said folic acid supplements are not always available. Folic acid intake is limited in northern Uganda. This is attributed to limited education and understanding of women and health workers about the importance of early folic acid intake, late presentation of women at ANC, poor supply chain and dilapidated health services caused by war and poverty. A combination of food fortification, sensitization of health workers, women, and improving folic acid supply is recommended.

  18. Omega-3 Fatty Acids and Primary and Secondary Prevention of Cardiovascular Disease.

    PubMed

    Cao, Yong; Lu, Lei; Liang, Jun; Liu, Min; Li, Xianchi; Sun, RongRong; Zheng, Yi; Zhang, Peiying

    2015-05-01

    The prevalence of cardiovascular disease (CVD) is increasing dramatically especially in developing countries like India. CVD is a leading cause of morbidity and mortality. There has been a growing awareness of the role of nutrients in the prevention of CVD. One specific recommendation in the battle against CVD is the increased intake of omega-3 fatty acids, which are polyunsaturated fatty acids. Studies have reported inverse associations of CVD with dietary intake of omega-3 fatty acids, suggesting that omega-3 fatty acids supplementation might exert protective effects on CVD. They exert their cardioprotective effect through multiple mechanisms. Omega-3 fatty acid therapy has shown promise as a useful tool in the primary and secondary prevention of CVD. This review briefly summarizes the effects of omega-3 fatty acids in primary and secondary prevention of CVD.

  19. Prevention of Sports Injuries by Marine Omega-3 Fatty Acids.

    PubMed

    Bryhn, Morten

    2015-01-01

    Sport injuries are common and costly for the professional athlete, the "weekend warrior," and the community. Acute injuries are treated according to current guidelines with the aim of bringing the athlete back into the arena. These guidelines have not taken into account new scientific results of the inflammatory process following a trauma. The 4 hallmarks of inflammation, namely, pain, swelling, redness, and heat, are results of an adequate inflammatory response with the aim of bringing the affected tissue back to restitution (Latin: restitutio ad integrum). Cooling of the affected limb and anti-inflammatory drugs are widely used but may deter healing. The healing process is governed by fatty acids of the omega-3 and omega-6 series. In order to facilitate healing, these fatty acids have to be present in significant amounts in the affected tissues before the trauma occurs. This is particularly relevant for marine omega-3 fatty acids, which are often running low due to insignificant intake of seafood, common in individuals practicing sports. High-energy sports often lead to head and brain trauma. Continuous head traumata may even result in later mental defects. Saturation of brain cells with omega-3 fatty acids, in particular docosahexaenoic acid (DHA), may facilitate healing after brain trauma, thereby counteracting negative long-term results. The present understanding of a normal inflammatory process leading to restitution will be discussed along with data from recent scientific trials.

  20. MINE WASTE TECHNOLOGY PROGRAM PREVENTION OF ACID MINE DRAINAGE GENERATION FROM OPEN-PIT HIGHWALLS

    EPA Science Inventory

    This document summarizes the results of Mine Waste Technology Program Activity III, Project 26, Prevention of Acid Mine Drainage Generation from Open-Pit Highwalls. The intent of this project was to obtain performance data on the ability of four technologies to prevent the gener...

  1. MINE WASTE TECHNOLOGY PROGRAM PREVENTION OF ACID MINE DRAINAGE GENERATION FROM OPEN-PIT HIGHWALLS

    EPA Science Inventory

    This document summarizes the results of Mine Waste Technology Program Activity III, Project 26, Prevention of Acid Mine Drainage Generation from Open-Pit Highwalls. The intent of this project was to obtain performance data on the ability of four technologies to prevent the gener...

  2. [Role of omega-3 fatty acids in cardiovascular disease prevention].

    PubMed

    Piñeiro-Corrales, Guadalupe; Lago Rivero, N; Culebras-Fernández, Jesús M

    2013-01-01

    Fatty acids, in addition to its known energy value and its structural function, have other beneficial properties. In particular, the polyunsaturated fatty acids omega-3 acting on the cardiovascular apparatus through many channels exerting a protective effect against cardiovascular risk. The benefits associated with the reduction in cardiac mortality and sudden death particular, are related to the incorporation of EPA and DHA in phospholipid membrane of cardiomyocytes. An index is established that relates the percentage of EPA + DHA of total fatty acids in erythrocytes and risk of death from cardiovascular disease may layering in different degrees. Therefore, the primary source of fatty fish w-3 PUFA, behaves like a reference food in cardiosaludables diets.

  3. A 2015 global update on folic acid-preventable spina bifida and anencephaly.

    PubMed

    Arth, Annelise; Kancherla, Vijaya; Pachón, Helena; Zimmerman, Sarah; Johnson, Quentin; Oakley, Godfrey P

    2016-07-01

    Spina bifida and anencephaly are two major neural tube defects. They contribute substantially to perinatal, neonatal, infant, and under-five mortality and life-long disability. To monitor the progress toward the total prevention of folic acid-preventable spina bifida and anencephaly (FAP SBA), we examined their global status in 2015. Based on existing data, we modeled the proportion of FAP SBA that are prevented in the year 2015 through mandatory folic acid fortification globally. We included only those countries with mandatory fortification that added at least 1.0 ppm folic acid as a fortificant to wheat and maize flour, and had complete information on coverage. Our model assumed mandatory folic acid fortification at 200 μg/day is fully protective against FAP SBA, and reduces the rate of spina bifida and anencephaly to a minimum of 0.5 per 1000 births. Our estimates show that, in 2015, 13.2% (35,500 of approximately 268,700 global cases) of FAP SBA were prevented in 58 countries through mandatory folic acid fortification of wheat and maize flour. Most countries in Europe, Africa, and Asia were not implementing mandatory fortification with folic acid. Knowledge that folic acid prevents spina bifida and anencephaly has existed for 25 years, yet only a small fraction of FAP SBA is being prevented worldwide. Several countries still have 5- to 20-fold epidemics of FAP SBA. Implementation of mandatory fortification with folic acid offers governments a proven and rapid way to prevent FAP SBA-associated disability and mortality, and to help achieve health-related Sustainable Development Goals. Birth Defects Research (Part A) 106:520-529, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. [Neural tube defects and folic acid: a historical overview of a highly successful preventive intervention].

    PubMed

    Vásquez, Adriana Ordoñez; Suarez-Obando, Fernando

    2015-12-01

    This article gives a broad overview of part of the historical evolution of medical knowledge about neural tube defects (NTD) and the discovery of vitamin B9 or folic acid, as well as some relevant research events that, over the course of several centuries, defined the relationships between the understanding of central nervous system embryology, the discovery of the vitamin, the correlation between folic acid and cell proliferation and lastly the development of preventive measures for this type of defects. This narrative allows us to examine historically relevant concepts underlying clinical actions with a populational impact that prevent NTDs via folic acid consumption prior to conception.

  5. Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer

    PubMed Central

    Getino, María; Sanabria-Ríos, David J.; Fernández-López, Raúl; Campos-Gómez, Javier; Sánchez-López, José M.; Fernández, Antonio; Carballeira, Néstor M.

    2015-01-01

    ABSTRACT Bacterial conjugation constitutes a major horizontal gene transfer mechanism for the dissemination of antibiotic resistance genes among human pathogens. Antibiotic resistance spread could be halted or diminished by molecules that interfere with the conjugation process. In this work, synthetic 2-alkynoic fatty acids were identified as a novel class of conjugation inhibitors. Their chemical properties were investigated by using the prototype 2-hexadecynoic acid and its derivatives. Essential features of effective inhibitors were the carboxylic group, an optimal long aliphatic chain of 16 carbon atoms, and one unsaturation. Chemical modification of these groups led to inactive or less-active derivatives. Conjugation inhibitors were found to act on the donor cell, affecting a wide number of pathogenic bacterial hosts, including Escherichia, Salmonella, Pseudomonas, and Acinetobacter spp. Conjugation inhibitors were active in inhibiting transfer of IncF, IncW, and IncH plasmids, moderately active against IncI, IncL/M, and IncX plasmids, and inactive against IncP and IncN plasmids. Importantly, the use of 2-hexadecynoic acid avoided the spread of a derepressed IncF plasmid into a recipient population, demonstrating the feasibility of abolishing the dissemination of antimicrobial resistances by blocking bacterial conjugation. PMID:26330514

  6. Prevention of spina bifida: folic acid intake during pregnancy in Gulu district, northern Uganda

    PubMed Central

    Bannink, Femke; Larok, Rita; Kirabira, Peter; Bauwens, Lieven; van Hove, Geert

    2015-01-01

    Introduction The intake of folic acid before conception and during the first trimester of pregnancy can prevent spina bifida. This paper describes folic acid intake in women in Gulu district in northern Uganda. Methods Structured interviews were held with 394 women attending antenatal care (ANC), 15 mothers of children with spina bifida, and 35 health workers in 2012 and 2013. SPSS16 was used for data analysis. Results 1/4 mothers of children with spina bifida took folic acid during late pregnancy, none preconception. None had knowledge about folic acid and spina bifida prevention. 33.5% of women attending ANC had ever heard about spina bifida, 1% knew folic acid intake can prevent spina bifida. 42.4% took folic acid supplements in late pregnancy, 8.1% during the first trimester, none preconception. All women said to have eaten food rich in folic acid. None were aware about fortified foods. 7% of health workers understood the importance of early folic acid intake. All health workers recommended folic acid intake to women attending ANC. 20% of the health workers and 25% of the women said folic acid supplements are not always available. Conclusion Folic acid intake is limited in northern Uganda. This is attributed to limited education and understanding of women and health workers about the importance of early folic acid intake, late presentation of women at ANC, poor supply chain and dilapidated health services caused by war and poverty. A combination of food fortification, sensitization of health workers, women, and improving folic acid supply is recommended. PMID:26090048

  7. Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer.

    PubMed

    Getino, María; Sanabria-Ríos, David J; Fernández-López, Raúl; Campos-Gómez, Javier; Sánchez-López, José M; Fernández, Antonio; Carballeira, Néstor M; de la Cruz, Fernando

    2015-09-01

    Bacterial conjugation constitutes a major horizontal gene transfer mechanism for the dissemination of antibiotic resistance genes among human pathogens. Antibiotic resistance spread could be halted or diminished by molecules that interfere with the conjugation process. In this work, synthetic 2-alkynoic fatty acids were identified as a novel class of conjugation inhibitors. Their chemical properties were investigated by using the prototype 2-hexadecynoic acid and its derivatives. Essential features of effective inhibitors were the carboxylic group, an optimal long aliphatic chain of 16 carbon atoms, and one unsaturation. Chemical modification of these groups led to inactive or less-active derivatives. Conjugation inhibitors were found to act on the donor cell, affecting a wide number of pathogenic bacterial hosts, including Escherichia, Salmonella, Pseudomonas, and Acinetobacter spp. Conjugation inhibitors were active in inhibiting transfer of IncF, IncW, and IncH plasmids, moderately active against IncI, IncL/M, and IncX plasmids, and inactive against IncP and IncN plasmids. Importantly, the use of 2-hexadecynoic acid avoided the spread of a derepressed IncF plasmid into a recipient population, demonstrating the feasibility of abolishing the dissemination of antimicrobial resistances by blocking bacterial conjugation. Diseases caused by multidrug-resistant bacteria are taking an important toll with respect to human morbidity and mortality. The most relevant antibiotic resistance genes come to human pathogens carried by plasmids, mainly using conjugation as a transmission mechanism. Here, we identified and characterized a series of compounds that were active against several plasmid groups of clinical relevance, in a wide variety of bacterial hosts. These inhibitors might be used for fighting antibiotic-resistance dissemination by inhibiting conjugation. Potential inhibitors could be used in specific settings (e.g., farm, fish factory, or even clinical settings) to

  8. [Fatty acids in treatment and prevention of depression].

    PubMed

    Wilczyńska, Agnieszka

    2013-01-01

    The increase of incident rates for depression and other psychiatric disorders is a serious threat for all communities. The study presents data verifying the relationship between the level of omega-3 PUFAs in the blood and an increased risk of depression, including the parallel standard therapy with antidepressants or not. There is an increasing number of evidences that fatty acids like DHA, AA and EPA are linked to depression. In epidemiological studies and clinical trials a correlation between the decline of omega-3 PUFA intake and an increasing risk for developing depression is considered.

  9. Fish oil prevents essential fatty acid deficiency and enhances growth: clinical and biochemical implications.

    PubMed

    Strijbosch, Robert A M; Lee, Sang; Arsenault, Danielle A; Andersson, Charlotte; Gura, Kathleen M; Bistrian, Bruce R; Puder, Mark

    2008-05-01

    Fish oil, a rich source of omega-3 fatty acids, has never been used as the sole source of lipid in clinical practice for fear of development of essential fatty acid deficiency, as it lacks the believed requisite levels of linoleic acid, an omega-6 fatty acid. The objectives of this study were to establish biochemical standards for fish oil as the sole fat and to test the hypothesis that fish oil contains adequate amounts of omega-6 fatty acids to prevent essential fatty acid deficiency. Forty mice were divided into 2 groups that were either pair fed or allowed to eat ad libitum. In each group, 4 subgroups of 5 mice were fed 1%, 5%, and 10% fish oil diets by weight or a control soybean diet for 9 weeks. Blood was collected at 4 time points, and fatty acid analysis was performed. Food intake and weight status were monitored. All groups but the pair-fed 1% fish oil group gained weight, and the 5% fish oil group showed the highest caloric efficiency in both pair-fed and ad libitum groups. Fatty acid profiles for the 1% fish oil group displayed clear essential fatty acid deficiency, 5% fish oil appeared marginal, and 10% and soybean oil diets were found to prevent essential fatty acid deficiency. Fish oil enhances growth through higher caloric efficiency. We established a total omega-6 fatty acid requirement of between 0.30% and 0.56% of dietary energy, approximately half of the conventionally believed 1% as linoleic acid. This can presumably be attributed to the fact that fish oil contains not only a small amount of linoleic acid, but also arachidonic acid, which has greater efficiency to meet omega-6 fatty acid requirements.

  10. Oleic acid prevents detrimental effects of saturated fatty acids on bovine oocyte developmental competence.

    PubMed

    Aardema, Hilde; Vos, Peter L A M; Lolicato, Francesca; Roelen, Bernard A J; Knijn, Hiemke M; Vaandrager, Arie B; Helms, J Bernd; Gadella, Bart M

    2011-07-01

    Mobilization of fatty acids from adipose tissue during metabolic stress will increase the amount of free fatty acids in blood and follicular fluid and, thus, may affect oocyte quality. In this in vitro study, the three predominant fatty acids in follicular fluid (saturated palmitic and stearic acid and unsaturated oleic acid) were presented to maturing oocytes to test whether fatty acids can affect lipid storage of the oocyte and developmental competence postfertilization. Palmitic and stearic acid had a dose-dependent inhibitory effect on the amount of fat stored in lipid droplets and a concomitant detrimental effect on oocyte developmental competence. Oleic acid, in contrast, had the opposite effect, causing an increase of lipid storage in lipid droplets and an improvement of oocyte developmental competence. Remarkably, the adverse effects of palmitic and stearic acid could be counteracted by oleic acid. These results suggest that the ratio and amount of saturated and unsaturated fatty acid is relevant for lipid storage in the maturing oocyte and that this relates to the developmental competence of maturing oocytes.

  11. Superiority of zinc complex of acetylsalicylic acid to acetylsalicylic acid in preventing postischemic myocardial dysfunction

    PubMed Central

    Korkmaz, Sevil; Atmanli, Ayhan; Li, Shiliang; Radovits, Tamás; Hegedűs, Peter; Hirschberg, Kristóf; Loganathan, Sivakkanan; Yoshikawa, Yutaka; Yasui, Hiroyuki; Karck, Matthias; Szabó, Gábor

    2015-01-01

    The pathophysiology of ischemic myocardial injury involves cellular events, reactive oxygen species, and an inflammatory reaction cascade. The zinc complex of acetylsalicylic acid (Zn(ASA)2) has been found to possess higher anti-inflammatory and lower ulcerogenic activities than acetylsalicylic acid (ASA). Herein, we studied the effects of both ASA and Zn(ASA)2 against acute myocardial ischemia. Rats were pretreated with ASA (75 mg/kg) or Zn(ASA)2 (100 mg/kg) orally for five consecutive days. Isoproterenol (85 mg/kg, subcutaneously [s.c.]) was applied to produce myocardial infarction. After 17–22 h, animals were anesthetized with sodium pentobarbital (60 mg/kg, intraperitoneally [i.p.]) and both electrical and mechanical parameters of cardiac function were evaluated in vivo. Myocardial histological and gene expression analyses were performed. In isoproterenol-treated rats, Zn(ASA)2 treatment normalized significantly impaired left-ventricular contractility index (Emax 2.6 ± 0.7 mmHg/µL vs. 4.6 ± 0.5 mmHg/µL, P < 0.05), increased stroke volume (30 ± 3 µL vs. 50 ± 6 µL, P < 0.05), decreased systemic vascular resistance (7.2 ± 0.7 mmHg/min/mL vs. 4.2 ± 0.5 mmHg/min/mL, P < 0.05) and reduced inflammatory infiltrate into the myocardial tissues. ECG revealed a restoration of elevated ST-segment (0.21 ± 0.03 mV vs. 0.09 ± 0.02 mV, P < 0.05) and prolonged QT-interval (79.2 ± 3.2 ms vs. 69.5 ± 2.5 ms, P < 0.05) by Zn(ASA)2. ASA treatment did not result in an improvement of these parameters. Additionally, Zn(ASA)2 significantly increased the mRNA-expression of superoxide dismutase 1 (+73 ± 15%), glutathione peroxidase 4 (+44 ± 12%), and transforming growth factor (TGF)-β1 (+102 ± 22%). In conclusion, our data demonstrate that oral administration of zinc and ASA in the form of bis(aspirinato)zinc(II) complex is superior to ASA in preventing electrical

  12. Superiority of zinc complex of acetylsalicylic acid to acetylsalicylic acid in preventing postischemic myocardial dysfunction.

    PubMed

    Korkmaz, Sevil; Atmanli, Ayhan; Li, Shiliang; Radovits, Tamás; Hegedűs, Peter; Barnucz, Enikő; Hirschberg, Kristóf; Loganathan, Sivakkanan; Yoshikawa, Yutaka; Yasui, Hiroyuki; Karck, Matthias; Szabó, Gábor

    2015-09-01

    The pathophysiology of ischemic myocardial injury involves cellular events, reactive oxygen species, and an inflammatory reaction cascade. The zinc complex of acetylsalicylic acid (Zn(ASA)2) has been found to possess higher anti-inflammatory and lower ulcerogenic activities than acetylsalicylic acid (ASA). Herein, we studied the effects of both ASA and Zn(ASA)2 against acute myocardial ischemia. Rats were pretreated with ASA (75 mg/kg) or Zn(ASA)2 (100 mg/kg) orally for five consecutive days. Isoproterenol (85 mg/kg, subcutaneously [s.c.]) was applied to produce myocardial infarction. After 17-22 h, animals were anesthetized with sodium pentobarbital (60 mg/kg, intraperitoneally [i.p.]) and both electrical and mechanical parameters of cardiac function were evaluated in vivo. Myocardial histological and gene expression analyses were performed. In isoproterenol-treated rats, Zn(ASA)2 treatment normalized significantly impaired left-ventricular contractility index (Emax 2.6 ± 0.7 mmHg/µL vs. 4.6 ± 0.5 mmHg/µL, P < 0.05), increased stroke volume (30 ± 3 µL vs. 50 ± 6 µL, P < 0.05), decreased systemic vascular resistance (7.2 ± 0.7 mmHg/min/mL vs. 4.2 ± 0.5 mmHg/min/mL, P < 0.05) and reduced inflammatory infiltrate into the myocardial tissues. ECG revealed a restoration of elevated ST-segment (0.21 ± 0.03 mV vs. 0.09 ± 0.02 mV, P < 0.05) and prolonged QT-interval (79.2 ± 3.2 ms vs. 69.5 ± 2.5 ms, P < 0.05) by Zn(ASA)2. ASA treatment did not result in an improvement of these parameters. Additionally, Zn(ASA)2 significantly increased the mRNA-expression of superoxide dismutase 1 (+73 ± 15%), glutathione peroxidase 4 (+44 ± 12%), and transforming growth factor (TGF)-β1 (+102 ± 22%). In conclusion, our data demonstrate that oral administration of zinc and ASA in the form of bis(aspirinato)zinc(II) complex is superior to ASA in preventing electrical

  13. Folic acid supplement use in the prevention of neural tube defects.

    PubMed

    Delany, C; McDonnell, R; Robson, M; Corcoran, S; Fitzpatrick, C; De La Harpe, D

    2011-01-01

    In 2008, planned folic acid fortification for the prevention of Neural Tube Defects (NTD) was postponed. Concurrently, the economic recession may have affected dietary folic acid intake, placing increased emphasis on supplement use. This study examined folic acid supplement use in 2009. A cross-sectional survey of 300 ante-natal women was undertaken to assess folic acid knowledge and use. Associations between demographic, obstetric variables and folic acid knowledge and use were examined. A majority, 284/297 (96%), had heard of folic acid, and 178/297 (60%) knew that it could prevent NTD. Most, 270/297 (91%) had taken it during their pregnancy, but only 107/297 (36%) had used it periconceptionally. Being older, married, planned pregnancy and better socioeconomic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from economic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from earlier years. Continuous promotion efforts are necessary. Close monitoring of folic acid intake and NTD rates is essential, particularly in the absence of fortification.

  14. Assessment of Turkish women's knowledge concerning folic acid and prevention of birth defects.

    PubMed

    Unusan, Nurhan

    2004-10-01

    In Turkey, the incidence of neural tube defects (NTDs) is 30.1 per 10,000 births. For this reason it seems an important problem for women of childbearing age. Adequate periconceptional consumption of folic acid could prevent NTDs. Most women are unaware of this recommendation. The objectives of this study were to evaluate women' knowledge and beliefs with regard to folic acid, and to estimate the consumption frequency of vitamin supplements periconceptionally and during the first trimester of pregnancy. Eight hundred and eighteen married women who had delivered a live-born infant within the previous 12 months completed the questionnaire. Each subject participated in a 20-minute interview, with the questionnaire comprising multiple-choice statements. A random sample of 10 public health centres was drawn from 27 in three districts in Konya where about 50% of the population lives. Only 22% of subjects had heard or read about folic acid. Thirteen per cent of women indicated knowledge of the direct link between folic acid supplementation and NTD prevention. The knowledge was greatest among 26- to 35-year-olds. Women with a university degree were more likely to have heard about folic acid than were less-educated women. The results indicate that further government efforts are needed to inform the population and promote the optimal use of folic acid supplements and folate-enriched foods. It is the responsibility of national authorities to increase health education concerning folic acid and the prevention of NTDs in their countries.

  15. Zoledronic acid infusion for prevention and treatment of osteoporosis.

    PubMed

    Sunyecz, John A

    2010-10-14

    Osteoporotic fractures are associated with significant morbidity, reduced quality of life, increased mortality, and high health care costs. Bisphosphonates are standard therapy for treatment of osteoporosis. However, patient compliance and persistence with oral weekly or monthly bisphosphonate therapy are suboptimal and may lead to reduced effectiveness. Zoledronic acid (ZOL) is an intravenous bisphosphonate that is given once yearly for the treatment of osteoporosis via a medically supervised 15-minute infusion. This ensures compliance for a full 12 months. In clinical trials, an annual infusion of ZOL 5 mg has shown sustained efficacy in reducing hip and spine fractures in postmenopausal women with osteoporosis. It has also been shown to increase bone density in postmenopausal women with osteopenia (low bone mass) and in men with osteoporosis. Transient flu-like symptoms are the most common adverse effects following ZOL infusion, and these can generally be managed with acetaminophen. The availability of an intravenous bisphosphonate that ensures compliance over a long dosing interval may help to overcome barriers to efficacy resulting from poor long-term compliance with oral agents.

  16. [Folic acid use by pregnant women in Israel for preventing neural tube defects].

    PubMed

    Gil, Z; Aran, A; Friedman, O; Beni-Adani, L; Constantini, S

    2000-12-01

    Spina bifida and anencephaly are the most common, serious malformations in neural tube defects (NTD). Randomized trials in the last 2 decades have demonstrated that folic acid, 0.4 mg/d, reduces the incidence of NTD by more than 50%. We investigated the use of folic acid and multivitamins containing folic acid in childbearing women. Of 221 women interviewed, 67 (30%) regularly took pills containing 0.4 mg folic acid. Women with higher educational levels were more likely to take multivitamins with folic acid than were the less educated (p = 0.05). Of the women who took folic acid, only 5 (7.5%) used separate folic acid tablets, before and during their pregnancy. The rest used multivitamins containing folic acid. The 5 women who took folic acid separately were college-educated and nonreligious, and they took multivitamins in addition (p > 0.05). Of the women interviewed, 58 (26.2%) were Bedouin of the Negev. 24 (41.4%) of them took pills containing folic acid on a regular basis. This percentage is higher than that in the Jewish women in the study who took folic acid for prevention of NTD (17%; p = 0.038). Most of the women took folic acid after the first trimester. Only a minority took daily periconceptional folic acid. Multivitamins containing 0.4 mg of folic acid were more popular than folic acid tablets alone. This study emphasizes the need for continuing efforts to increase consumption of folic acid and awareness of its benefits among women of childbearing age.

  17. Prevention of neural tube defects in Lrp2 mutant mouse embryos by folic acid supplementation.

    PubMed

    Sabatino, Julia A; Stokes, Bethany A; Zohn, Irene E

    2017-01-20

    Neural tube defects (NTDs) are among the most common structural birth defects in humans and are caused by the complex interaction of genetic and environmental factors. Periconceptional supplementation with folic acid can prevent NTDs in both mouse models and human populations. A better understanding of how genes and environmental factors interact is critical toward development of rational strategies to prevent NTDs. Low density lipoprotein-related protein 2 (Lrp2) is involved in endocytosis of the folic acid receptor among numerous other nutrients and ligands. We determined the effect of iron and/or folic acid supplementation on the penetrance of NTDs in the Lrp2(null) mouse model. The effects of supplementation on folate and iron status were measured in embryos and dams. Periconceptional dietary supplementation with folic acid did not prevent NTDs in Lrp2 mutant embryos, whereas high levels of folic acid supplementation by intraperitoneal injection reduced incidence of NTDs. Importantly, Lrp2(null/+) dams had reduced blood folate levels that improved with daily intraperitoneal injections of folate but not dietary supplementation. On the contrary, iron supplementation had no effect on the penetrance of NTDs in Lrp2 mutant embryos and negated the preventative effect of folic acid supplementation in Lrp2(null/null) mutants. Lrp2 is required for folate homeostasis in heterozygous dams and high levels of supplementation prevents NTDs. Furthermore, high levels of dietary iron supplementation interfered with folic acid supplementation negating the positive effects of supplementation in this model. Birth Defects Research 109:16-26, 2017. © 2016 The Authors Birth Defects Published by Wiley Periodicals, Inc. © 2016 The Authors Birth Defects Research Published by Wiley Periodicals, Inc.

  18. Economic burden of neural tube defects and impact of prevention with folic acid: a literature review.

    PubMed

    Yi, Yunni; Lindemann, Marion; Colligs, Antje; Snowball, Claire

    2011-11-01

    Neural tube defects (NTDs) are the second most common group of serious birth defects. Although folic acid has been shown to reduce effectively the risk of NTDs and measures have been taken to increase the awareness, knowledge, and consumption of folic acid, the full potential of folic acid to reduce the risk of NTDs has not been realized in most countries. To understand the economic burden of NTDs and the economic impact of preventing NTDs with folic acid, a systematic review was performed on relevant studies. A total of 14 cost of illness studies and 10 economic evaluations on prevention of NTDs with folic acid were identified. Consistent findings were reported across all of the cost of illness studies. The lifetime direct medical cost for patients with NTDs is significant, with the majority of cost being for inpatient care, for treatment at initial diagnosis in childhood, and for comorbidities in adult life. The lifetime indirect cost for patients with spina bifida is even greater due to increased morbidity and premature mortality. Caregiver time costs are also significant. The results from the economic evaluations demonstrate that folic acid fortification in food and preconception folic acid consumption are cost-effective ways to reduce the incidence and prevalence of NTDs. This review highlights the significant cost burden that NTDs pose to healthcare systems, various healthcare payers, and society and concludes that the benefits of prevention of NTDs with folic acid far outweigh the cost. Further intervention with folic acid is justified in countries where the full potential of folic acid to reduce the risk of NTDs has not been realized.

  19. In situ forming hydrogel composed of hyaluronate and polygalacturonic acid for prevention of peridural fibrosis.

    PubMed

    Lin, Cheng-Yi; Peng, Hsiu-Hui; Chen, Mei-Hsiu; Sun, Jui-Sheng; Liu, Tse-Ying; Chen, Ming-Hong

    2015-04-01

    Hyaluronic acid-based hydrogels can reduce postoperative adhesion. However, the long-term application of hyaluronic acid is limited by tissue mediated enzymatic degradation. To overcome this limitation, we developed a polygalacturonic acid and hyaluronate composite hydrogel by Schiff's base crosslinking reaction. The polygalacturonic acid and hyaluronate composite hydrogels had short gelation time (less than 15 s) and degraded by less than 50 % in the presence of hyaluronidase for 7 days. Cell adhesion and migration assays showed polygalacturonic acid and hyaluronate composite hydrogels prevented fibroblasts from adhesion and infiltration into the hydrogels. Compared to hyaluronate hydrogels and commercial Medishield™ gels, polygalacturonic acid and hyaluronate composite hydrogel was not totally degraded in vivo after 4 weeks. In the rat laminectomy model, polygalacturonic acid and hyaluronate composite hydrogel also had better adhesion grade and smaller mean area of fibrous tissue formation over the saline control and hyaluronate hydrogel groups. Polygalacturonic acid and hyaluronate composite hydrogel is a system that can be easy to use due to its in situ cross-linkable property and potentially promising for adhesion prevention in spine surgeries.

  20. Fatty acid bile acid conjugates (FABACs)—New molecules for the prevention of cholesterol crystallisation in bile

    PubMed Central

    Gilat, T; Somjen, G; Mazur, Y; Leikin-Frenkel, A; Rosenberg, R; Halpern, Z; Konikoff, F.

    2001-01-01

    BACKGROUND—Cholesterol gall stones are a frequent disease for which at present surgery is the usual therapy. Despite the importance of bile acids it has become evident that phospholipids are the main cholesterol solubilisers in bile. Even phospholipid components, such as fatty acids, have anticrystallising activity.
AIM—To synthesise fatty acid bile acid conjugates (FABACs) and study their effects on cholesterol crystallisation in bile in vitro and in vivo.
METHODS—FABACs were prepared by conjugation of cholic acid at position 3 with saturated fatty acids of variable chain length using an amide bond. Cholesterol crystallisation and its kinetics (crystal observation time, crystal mass) were studied in model bile, pooled enriched human bile, and fresh human bile using FABACs with saturated fatty acids of varying chain length (C-6 to C-22). Absorption of FABACs into blood and bile was tested in hamsters. Prevention of biliary cholesterol crystallisation in vivo was tested in hamsters and inbred mice.
RESULTS—FABACs strongly inhibited cholesterol crystallisation in model as well as native bile. The FABACs with longer acyl chains (C-16 to C-22) were more effective. At a concentration of 5 mM, FABACs almost completely inhibited cholesterol crystallisation in fresh human bile for 21 days. FABACs were absorbed and found in both portal and heart blood of hamsters. Levels in bile were 2-3 times higher than in blood, indicating active secretion. Appreciable levels were found in the systemic circulation 24-48 hours after a single administration. Ingested FABACs completely prevented the formation of cholesterol crystals in the gall bladders of hamsters and mice fed a lithogenic diet.
CONCLUSIONS—FABACs are potent inhibitors of cholesterol crystallisation in bile. They are absorbed and secreted into bile and prevent the earliest step of cholesterol gall stone formation in animals. These compounds may be of potential use in cholesterol gall stone disease in

  1. Preventive Effects of Folic Acid Supplementation on Adverse Maternal and Fetal Outcomes

    PubMed Central

    Kim, Min Woo; Ahn, Ki Hoon; Ryu, Ki-Jin; Hong, Soon-Cheol; Lee, Ji Sung; Nava-Ocampo, Alejandro A.; Oh, Min-Jeong; Kim, Hai-Joong

    2014-01-01

    Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL). In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL). The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09–0.76) and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18–0.99) were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes. PMID:24842467

  2. Breast Cancer Prevention by Fatty Acid Binding Protein MRG-Induced Pregnancy Like Mammary Gland Differentiation

    DTIC Science & Technology

    2005-08-01

    Annual Summary 3. DATES COVERED (From - To) 1 AUG 2004 - 31 JUL 2005 4. TITLE AND SUBTITLE Breast Cancer Prevention by Fatty Acid Binding Protein...differentiation. Overexpression of MRG in human breast cancer cells induced differentiation with changes in cellular morphology and a significant increase

  3. Salicylic acid: a link between aspirin, diet and the prevention of colorectal cancer.

    PubMed

    Paterson, J R; Lawrence, J R

    2001-08-01

    Aspirin was introduced into clinical practice more than 100 years ago. This unique drug belongs to a family of compounds called the salicylates, the simplest of which is salicylic acid, the principal metabolite of aspirin. Salicylic acid is responsible for the anti-inflammatory action of aspirin, and may cause the reduced risk of colorectal cancer observed in those who take aspirin. Yet salicylic acid and other salicylates occur naturally in fruits and plants, while diets rich in these are believed to reduce the risk of colorectal cancer. Serum salicylic acid concentrations are greater in vegetarians than non-vegetarians, and there is overlap between concentrations in vegetarians and those taking low-dose aspirin. We propose that the cancer-preventive action of aspirin is due to its principal metabolite, salicylic acid, and that dietary salicylates can have the same effect. It is also possible that natural salicylates contribute to the other recognized benefits of a healthy diet.

  4. Nucleotide precursors prevent folic acid-resistant neural tube defects in the mouse.

    PubMed

    Leung, Kit-Yi; De Castro, Sandra C P; Savery, Dawn; Copp, Andrew J; Greene, Nicholas D E

    2013-09-01

    Closure of the neural tube during embryogenesis is a crucial step in development of the central nervous system. Failure of this process results in neural tube defects, including spina bifida and anencephaly, which are among the most common birth defects worldwide. Maternal use of folic acid supplements reduces risk of neural tube defects but a proportion of cases are not preventable. Folic acid is thought to act through folate one-carbon metabolism, which transfers one-carbon units for methylation reactions and nucleotide biosynthesis. Hence suboptimal performance of the intervening reactions could limit the efficacy of folic acid. We hypothesized that direct supplementation with nucleotides, downstream of folate metabolism, has the potential to support neural tube closure. Therefore, in a mouse model that exhibits folic acid-resistant neural tube defects, we tested the effect of specific combinations of pyrimidine and purine nucleotide precursors and observed a significant protective effect. Labelling in whole embryo culture showed that nucleotides are taken up by the neurulating embryo and incorporated into genomic DNA. Furthermore, the mitotic index was elevated in neural folds and hindgut of treated embryos, consistent with a proposed mechanism of neural tube defect prevention through stimulation of cellular proliferation. These findings may provide an impetus for future investigations of supplemental nucleotides as a means to prevent a greater proportion of human neural tube defects than can be achieved by folic acid alone.

  5. Cancer Preventive Potential of Kimchi Lactic Acid Bacteria (Weissella cibaria, Lactobacillus plantarum).

    PubMed

    Kwak, Shin-Hye; Cho, Young-Mi; Noh, Geon-Min; Om, Ae-Son

    2014-12-01

    The number of death due to cancer has been increasing in Korea. Chemotherapy is known to cause side effects because it damages not only cancerous cells but healthy cells. Recently, attention has focused on food-derived chemopreventive and anti-tumor agents or formulations with fewer side effects. Kimchi, most popular and widely consumed in Korea, contains high levels of lactic acid bacteria and has been shown to possess chemopreventive effects. This review focuses on Weissella cibaria and Lactobacillus plantarum, the representatives of kimchi lactic acid bacteria, in terms of their abilities to prevent cancer. Further studies are needed to understand the mechanisms by which lactic acid bacteria in kimchi prevent carcinogenic processes and improve immune functions.

  6. Capacity of lactic acid bacteria in immunity enhancement and cancer prevention.

    PubMed

    Riaz Rajoka, Muhammad Shahid; Shi, Junling; Zhu, Jing; Shao, Dongyan; Huang, Qingsheng; Yang, Hui; Jin, Mingliang

    2017-01-01

    Lactic acid bacteria are associated with the human gastrointestinal tract. They are important for maintaining the balance of microflora in the human gut. An increasing number of published research reports in recent years have denoted the importance of producing interferon-gamma and IgA for treatment of disease. These agents can enhance the specific and nonspecific immune systems that are dependent on specific bacterial strains. The mechanisms of these effects were revealed in this investigation, where the cell walls of these bacteria were modulated by the cytokine pathways, while the whole bacterial cell mediated the host cell immune system and regulated the production of tumor necrosis factors and interleukins. A supplement of highly active lactic acid bacteria strains provided significant potential to enhance host's immunity, offering prevention from many diseases including some cancers. This review summarizes the current understanding of the function of lactic acid bacteria immunity enhancement and cancer prevention.

  7. Potential role of dietary n-3 fatty acids in the prevention of dementia and macular degeneration.

    PubMed

    Johnson, Elizabeth J; Schaefer, Ernst J

    2006-06-01

    Dementia and age-related macular degeneration (AMD) are major causes of disability in the elderly. n-3 Fatty acids, particularly docosahexaenoic acid (DHA), are highly concentrated in brain and retinal tissue and may prevent or delay the progression of dementia and AMD. Low dietary intakes and plasma concentrations have been reported to be associated with dementia, cognitive decline, and AMD risk. The major dietary sources of DHA are fish and fish oils, although dietary supplements are available. At this point, it is not possible to make firm recommendations regarding n-3 fatty acids and the prevention of dementia and AMD. Our own unpublished observations from the Framingham Heart Study suggest that > or =180 mg/d of dietary DHA (approximately 2.7 fish servings/wk) is associated with an approximately 50% reduction in dementia risk. At least this amount of DHA is generally found in one commercially available 1-g fish oil capsule given daily.

  8. Interactions between prebiotics, probiotics, polyunsaturated fatty acids and polyphenols: diet or supplementation for metabolic syndrome prevention?

    PubMed

    Peluso, Ilaria; Romanelli, Luca; Palmery, Maura

    2014-05-01

    The metabolic syndrome can be prevented by the Mediterranean diet, characterized by fiber, omega-3 polyunsaturated fatty acids and polyphenols. However, the composition of the Mediterranean diet, which can be viewed as a natural multiple supplement, is poorly controlled, and its beneficial effects poorly predictable. The metabolic syndrome is associated with intestinal dysbiosis and the gut microbioma seems to be the main target and player in the interactions occurring between probiotics, prebiotics, omega 3 polyunsaturated fatty acids, and polyphenols. From the reviewed evidence, it is reasonable to manage growth and metabolism of gut microflora with specific prebiotics and polyphenols. Even though the healthy properties of functional foods and nutraceuticals still need to be fully elucidated, available data suggest that well-designed supplements, containing the better ratio of omega-3 polyunsaturated fatty acids and antioxidants, specific probiotic strains, and selected polyphenols and prebiotics, could be useful in metabolic syndrome prevention and treatment.

  9. Nicotinic acid prevents experimental liver fibrosis by attenuating the prooxidant process.

    PubMed

    Arauz, Jonathan; Rivera-Espinoza, Yadira; Shibayama, Mineko; Favari, Liliana; Flores-Beltrán, Rosa Elena; Muriel, Pablo

    2015-09-01

    Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in most chronic liver diseases. Nicotinamide treatment has been shown to prevent collagen accumulation and fibrogenesis in a bleomycin model of lung fibrosis. In this study, we evaluated the effects of nicotinic acid (NA) on experimental liver fibrosis and investigated its underlying mechanism. Fibrosis was induced by chronic TAA administration and the effects of co-administration with NA for 8 weeks were evaluated, including control groups. TAA administration induced liver fibrosis, which was prevented by nicotinic acid. NA prevented the elevation of liver enzymes and prevented hepatic glycogen depletion. Liver histopathology and hydroxyproline levels were significantly lower in the rats treated with TAA plus NA compared with TAA only. NA demonstrated antioxidant properties by restoring the redox equilibrium (lipid peroxidation and GPx levels). Western blot assays showed decreased expression levels of TGF-β and its downstream inductor CTGF. Additionally, NA prevented hepatic stellate cell activation due by blocking the expression of α-SMA. Zymography assays showed that NA decreased the activity of matrix metalloproteinases 2 and 9. NA prevents experimental fibrosis; the mechanisms of action are associated with its antioxidant properties and the reduction in TGF-β expression. The decrease in TGF-β levels may be associated with the attenuation of the oxidative processes, thus resulting in a reduction in HSC activation and ECM deposition. The findings suggest a possible role for NA as an antifibrotic agent for liver injury. Copyright © 2015. Published by Elsevier B.V.

  10. Amino acid, mineral and vitamin levels in hydrous faeces obtained from coprophagy-prevented rats.

    PubMed

    Sukemori, S; Ikeda, S; Kurihara, Y; Ito, S

    2003-06-01

    Amino acid, mineral and vitamin levels in hydrous faeces obtained from coprophagy-prevented rats were examined. Two experiments were conducted with rats of different age, 4 weeks and 10 weeks. Six rats each were fed under coprophagy-prevented and coprophagy-allowed (conventional feeding) conditions, respectively. In the first experiment using 4-week-old rats, amino acid values were determined for hydrous faeces and usual faeces obtained in the above-mentioned conditions. In the second experiment using 10-week-old rats, mineral values were determined for both types of faeces. Vitamin values were determined in both experiments. In a comparison of amino acid values and their patterns, specific kinds of amino acids in hydrous faeces were not recognized as growth factors. Sodium and potassium levels in hydrous faeces were significantly higher than those for usual faeces, but those levels were 1/(18-20) of those derived from feed. Although cyanocobalamin and folic acid levels in hydrous faeces were two to three times higher than those for usual faeces, folic acid supplements from coprophagy were 1/8 of those derived from feed. Cyanocobalamin supplements from hydrous faeces were five times larger than those from feed. Therefore, it appears that cyanocobalamin was supplied by the ingestion of hydrous faeces and that this cyanocobalamin supports conventional growth in rats.

  11. Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation.

    PubMed

    Yamamoto, Tetsuo; Kinoshita, Manabu; Shinomiya, Nariyoshi; Hiroi, Sadayuki; Sugasawa, Hidekazu; Matsushita, Yoshitaro; Majima, Takashi; Saitoh, Daizoh; Seki, Shuhji

    2010-01-01

    While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome.

  12. Role of n-3 Polyunsaturated Fatty Acids and Exercise in Breast Cancer Prevention: Identifying Common Targets

    PubMed Central

    Abdelmagid, Salma A.; MacKinnon, Jessica L.; Janssen, Sarah M.; Ma, David W.L.

    2016-01-01

    Diet and exercise are recognized as important lifestyle factors that significantly influence breast cancer risk. In particular, dietary n-3 polyunsaturated fatty acids (PUFAs) have been shown to play an important role in breast cancer prevention. Growing evidence also demonstrates a role for exercise in cancer and chronic disease prevention. However, the potential synergistic effect of n-3 PUFA intake and exercise is yet to be determined. This review explores targets for breast cancer prevention that are common between n-3 PUFA intake and exercise and that may be important study outcomes for future research investigating the combined effect of n-3 PUFA intake and exercise. These lines of evidence highlight potential new avenues for research and strategies for breast cancer prevention. PMID:27812288

  13. Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids.

    PubMed

    Den Ruijter, Hester M; Verkerk, Arie O; Coronel, Ruben

    2010-01-01

    Increased consumption of fatty fish, rich in omega-3-polyunsaturated fatty acids (ω3-PUFAs) reduces the severity and number of arrhythmias. Long-term ω3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating ω3-PUFAs in the bloodstream and incorporated ω3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating ω3-PUFAs in the bloodstream enhance or diminish the effects of incorporated ω3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (ω3) or sunflower oil (ω9, as control) for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch-clamp technique in the absence and presence of acutely administered ω3-PUFAs. Plasma of ω3 fed rabbits contained more free eicosapentaenoic acid (EPA) and isolated myocytes of ω3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA) in their sarcolemma compared to control. In the absence of acutely administered fatty acids, ω3 myocytes had a shorter action potential with a more negative plateau than ω9 myocytes. In the ω9 myocytes, but not in the ω3 myocytes, acute administration of a mixture of EPA + DHA shortened the action potential significantly. From these data we conclude that incorporated ω3-PUFAs into the sarcolemma and acutely administered ω3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac ω3-PUFA status will probably not benefit from short term ω3 supplementation as an antiarrhythmic therapy.

  14. Incorporated Fish Oil Fatty Acids Prevent Action Potential Shortening Induced by Circulating Fish Oil Fatty Acids

    PubMed Central

    Ruijter, Hester M. Den; Verkerk, Arie O.; Coronel, Ruben

    2010-01-01

    Increased consumption of fatty fish, rich in omega-3-polyunsaturated fatty acids (ω3-PUFAs) reduces the severity and number of arrhythmias. Long-term ω3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating ω3-PUFAs in the bloodstream and incorporated ω3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating ω3-PUFAs in the bloodstream enhance or diminish the effects of incorporated ω3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (ω3) or sunflower oil (ω9, as control) for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch-clamp technique in the absence and presence of acutely administered ω3-PUFAs. Plasma of ω3 fed rabbits contained more free eicosapentaenoic acid (EPA) and isolated myocytes of ω3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA) in their sarcolemma compared to control. In the absence of acutely administered fatty acids, ω3 myocytes had a shorter action potential with a more negative plateau than ω9 myocytes. In the ω9 myocytes, but not in the ω3 myocytes, acute administration of a mixture of EPA + DHA shortened the action potential significantly. From these data we conclude that incorporated ω3-PUFAs into the sarcolemma and acutely administered ω3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac ω3-PUFA status will probably not benefit from short term ω3 supplementation as an antiarrhythmic therapy. PMID:21423389

  15. Preventive Effects of Zoledronic Acid on Bone Metastasis in Mice Injected with Human Breast Cancer Cells

    PubMed Central

    Jeong, Joon; Lee, Kyung Sun; Choi, Yang-Kyu; Oh, Young Ju

    2011-01-01

    Bisphosphonates are used routinely to reduce bone-related events in breast cancer patients with bone metastasis. We evaluated the effects of zoledronic acid, a third generation, nitrogen-containing bisphosphonate, to prevent bone metastasis in breast cancer. Zoledronic acid or vehicle alone was administered to nude mice either simultaneously or after intracardiac injection of human breast cancer MDA-MB-231 cells. Nude mice treated with zoledronic acid at early time points showed a lower incidence of bone metastases than did vehicle-treated nude mice, but these differences were not statistically significant. Only 37.5% of mice treated with zoledronic acid at the time of tumor cell inoculation developed bone metastases compared to over 51.8% of mice receiving vehicle alone (P = 0.304). Cell count of apoptosis confirmed by immunohistochemical staining in metastatic bone tissue significantly increased in the zoledronic acid-treated groups compared to non-treated group (1,018.3 vs 282.0; P = 0.046). However, metastatic tumor cells, which invade soft tissue around the bone, did not show extensive apoptosis; there were no differences between the zoledronic acid-treated and control groups. These results suggest that zoledronic acid increases apoptosis of metastatic breast tumor cells in the bone and could therefore reduce metastatic tumor burden. These results support the use of zoledronic acid to reduce the incidence of bone metastasis in breast cancer. PMID:22147993

  16. Ibuprofen-conjugated hyaluronate/polygalacturonic acid hydrogel for the prevention of epidural fibrosis.

    PubMed

    Lin, Cheng-Yi; Peng, Hsiu-Hui; Chen, Mei-Hsiu; Sun, Jui-Sheng; Chang, Chih-Ju; Liu, Tse-Ying; Chen, Ming-Hong

    2016-05-01

    The formation of fibrous tissue is part of the natural healing response following a laminectomy. Severe scar tissue adhesion, known as epidural fibrosis, is a common cause of failed back surgery syndrome. In this study, by combining the advantages of drug treatment with a physical barrier, an ibuprofen-conjugated crosslinkable polygalacturonic acid and hyaluronic acid hydrogel was developed for epidural fibrosis prevention. Conjugation was confirmed and measured by 1D(1)H NMR spectroscopy.In vitroanalysis showed that the ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel showed low cytotoxicity. In addition, the conjugated ibuprofen decreased prostaglandin E2production of the lipopolysaccharide-induced RAW264.7 cells. Histological data inin vivostudies indicated that the scar tissue adhesion of laminectomized male adult rats was reduced by the application of our ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel. Its use also reduced the population of giant cells and collagen deposition of scar tissue without inducing extensive cell recruitment. The results of this study therefore suggest that the local delivery of ibuprofenviaa polygalacturonic acid-hyaluronic acid-based hydrogel reduces the possibility of epidural fibrosis.

  17. Acute intestinal injury induced by acetic acid and casein: prevention by intraluminal misoprostol

    SciTech Connect

    Miller, M.J.; Zhang, x.J.; Gu, x.A.; Clark, D.A. )

    1991-07-01

    Acute injury was established in anesthetized rabbits by intraluminal administration of acetic acid with and without bovine casein, into loops of distal small intestine. Damage was quantified after 45 minutes by the blood-to-lumen movement of {sup 51}Cr-labeled ethylenediaminetetraacetic acid (EDTA) and fluorescein isothiocyanate-tagged bovine serum albumin as well as luminal fluid histamine levels. The amount of titratable acetic acid used to lower the pH of the treatment solutions to pH 4.0 was increased by the addition of calcium gluconate. Luminal acetic acid caused a 19-fold increase in {sup 51}Cr-EDTA accumulation over saline controls; casein did not modify this effect. In saline controls, loop fluid histamine levels bordered on the limits of detection (1 ng/g) but were elevated 19-fold by acetic acid exposure and markedly increased (118-fold) by the combination of acid and casein. Intraluminal misoprostol (3 or 30 micrograms/mL), administered 30 minutes before acetic acid, significantly attenuated the increase in epithelial permeability (luminal {sup 51}Cr-EDTA, fluorescein isothiocyanate-bovine serum albumin accumulation) and histamine release (P less than 0.05). Diphenhydramine, alone or in combination with cimetidine, and indomethacin (5 mg/kg IV) were not protective. It is concluded that exposure of the epithelium to acetic acid promotes the transepithelial movement of casein leading to enhanced mast cell activation and mucosal injury. Damage to the epithelial barrier can be prevented by misoprostol.

  18. Formic acid, a novel metabolite of chronic ethanol abuse, causes neurotoxicity, which is prevented by folic acid.

    PubMed

    Kapur, Bhushan M; Vandenbroucke, Arthur C; Adamchik, Yana; Lehotay, Denis C; Carlen, Peter L

    2007-12-01

    Methanol is endogenously formed in the brain and is present as a congener in most alcoholic beverages. Because ethanol is preferentially metabolized over methanol (MeOH) by alcohol dehydrogenase, it is not surprising that MeOH accumulates in the alcohol-abusing population. This suggests that the alcohol-drinking population will have higher levels of MeOH's neurotoxic metabolite, formic acid (FA). FA elimination is mediated by folic acid. Neurotoxicity is a common result of chronic alcoholism. This study shows for the first time that FA, found in chronic alcoholics, is neurotoxic and this toxicity can be mitigated by folic acid administration. To determine if FA levels are higher in the alcohol-drinking population and to assess its neurotoxicity in organotypic hippocampal rat brain slice cultures. Serum and CSF FA was measured in samples from both ethanol abusing and control patients, who presented to a hospital emergency department. FA's neurotoxicity and its reversibility by folic acid were assessed using organotypic rat brain hippocampal slice cultures using clinically relevant concentrations. Serum FA levels in the alcoholics (mean +/- SE: 0.416 +/- 0.093 mmol/l, n = 23) were significantly higher than in controls (mean +/- SE: 0.154 +/- 0.009 mmol/l, n = 82) (p < 0.0002). FA was not detected in the controls' CSF (n = 20), whereas it was >0.15 mmol/l in CSF of 3 of the 4 alcoholic cases. Low doses of FA from 1 to 5 mmol/l added for 24, 48 or 72 hours to the rat brain slice cultures caused neuronal death as measured by propidium iodide staining. When folic acid (1 micromol/l) was added with the FA, neuronal death was prevented. Formic acid may be a significant factor in the neurotoxicity of ethanol abuse. This neurotoxicity can be mitigated by folic acid administration at a clinically relevant dose.

  19. Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid isomers in obesity prevention?

    PubMed

    Miranda, Jonatan; Arias, Noemi; Fernández-Quintela, Alfredo; del Puy Portillo, María

    2014-04-01

    Despite its benefits, conjugated linoleic acid (CLA) may cause side effects after long-term administration. Because of this and the controversial efficacy of CLA in humans, alternative biomolecules that may be used as functional ingredients have been studied in recent years. Thus, conjugated linolenic acid (CLNA) has been reported to be a potential anti-obesity molecule which may have additional positive effects related to obesity. According to the results reported in obesity, CLNA needs to be given at higher doses than CLA to be effective. However, because of the few studies conducted so far, it is still difficult to reach clear conclusions about the potential use of these CLNAs in obesity and its related changes (insulin resistance, dyslipidemia, or inflammation).

  20. Folic Acid supplementation and pregnancy: more than just neural tube defect prevention.

    PubMed

    Greenberg, James A; Bell, Stacey J; Guan, Yong; Yu, Yan-Hong

    2011-01-01

    Folate (vitamin B(9)) is an essential nutrient that is required for DNA replication and as a substrate for a range of enzymatic reactions involved in amino acid synthesis and vitamin metabolism. Demands for folate increase during pregnancy because it is also required for growth and development of the fetus. Folate deficiency has been associated with abnormalities in both mothers (anemia, peripheral neuropathy) and fetuses (congenital abnormalities). This article reviews the metabolism of folic acid, the appropriate use of folic acid supplementation in pregnancy, and the potential benefits of folic acid, as well as the possible supplementation of l-methylfolate for the prevention of pregnancy-related complications other than neural tube defects.

  1. Taurocholic Acid Prevents Biliary Damage Induced by Hepatic Artery Ligation in Cholestatic Rats

    PubMed Central

    Glaser, Shannon; Onori, Paolo; Gaudio, Eugenio; Ueno, Yoshiyuki; Pannarale, Luigi; Franchitto, Antonio; Francis, Heather; Mancinelli, Romina; Carpino, Guido; Venter, Julie; White, Mellanie; Kopriva, Shelley; Vetuschi, Antonella; Sferra, Roberta; Alpini, Gianfranco

    2010-01-01

    Background Ischemic injury by hepatic artery ligation (HAL) during obstructive cholestasis induced by bile duct ligation (BDL) results in bile duct damage, which can be prevented by administration of VEGF-A. The potential regulation of VEGF and VEGF receptor expression and secretion by bile acids in BDL with HAL is unknown. Aims We evaluated whether taurocholic acid (TC) can prevent HAL-induced cholangiocyte damage via the alteration of VEGFR-2 and/or VEGF-A expression. Methods Utilizing BDL, BDL+TC, BDL+HAL, BDL+HAL+TC, and BDL+HAL+wortmannin+TC treated rats, we evaluated cholangiocyte apoptosis, proliferation, and secretion as well VEGF-A and VEGFR-2 expression by immunohistochemistry. In vitro, we evaluated the effects of TC on cholangiocyte secretion of VEGF-A and the dependence of TC-induced proliferation on the activity of VEGFR-2. Results In BDL rats with HAL, chronic feeding of TC prevented HAL-induced loss of bile ducts and HAL-induced decreased cholangiocyte secretion. TC also prevented HAL-inhibited VEGF-A and VEGFR-2 expression in liver sections and HAL-induced circulating VEGF-A levels, which were blocked by wortmannin administration. In vitro, TC stimulated increased VEGF-A secretion by cholangiocytes, which was blocked by wortmannin and stimulated cholangiocyte proliferation that was blocked by VEGFR-2 kinase inhibitor. Conclusion TC prevented HAL-induced biliary damage by upregulation of VEGF-A expression. PMID:20303838

  2. Prevention of neural tube defects by folic acid - awareness among women of childbearing age in Slovakia.

    PubMed

    Horn, F; Sabova, L; Pinterova, E; Hornova, J; Trnka, J

    2014-01-01

    Folic acid deficiency plays a central role in the aetiology of many congenital anomalies including neural tube defects. Protective effect of folic acid on embryo may be acquired only if taken periconceptionally. The aim of the study was to investigate the awareness about folic acid among women of childbearing age in Bratislava, Slovakia. There were 130 respondents involved in the research (106 pregnant women, 24 female students of medical faculty). Using questionnaire we acquired following data: pregnancy details, interest in diet before and during pregnancy, recommendations regarding nutrition and supplementation pre- and post-conception, knowledge about folic and other acid in 2004 and 2009. More than half of the respondents knew the sources of folic acid. The interest in the nutrition facts of the food dropped from 91 % to 58.5 %. The number of pregnant women advised about correct nutrition and folic acid supplementation before and during pregnancy increased from 16 % to 37 %. Planning the next gravidity with folic acid supplementation became greater than 21 % (38 % in 2009). Nevertheless, only 46 % of these women believed that proper food content with folic acid may prevent congenital anomalies. In a group of students planning to take folic acid periconceptionally the number raised up to 62.5 %. The results revealed low knowledge about the effect of folic acid on developing embryo among women of childbearing age. Effective intervention programs are needed with the aim to improve periconceptional intake of folic acid in 2004 and 2009. The results in both periods show low knowledge about this essential vitamin (Tab. 1, Fig. 8, Ref. 31).

  3. Prevention of photocarcinogenesis and UV-induced immunosuppression in mice by topical tannic acid.

    PubMed

    Gensler, H L; Gerrish, K E; Williams, T; Rao, G; Kittelson, J

    1994-01-01

    Topical application of tannic acid, a phenolic antioxidant derived from plants, was found to inhibit the cutaneous carcinogenesis and the immunosuppression induced by ultraviolet B (UVB) irradiation with no visible toxicity. BALB/cAnNTacfBR mice were treated with 200 micrograms of tannic acid three times weekly for two weeks before UV treatments began and throughout the experiment. UVB irradiation consisted of five 30-minute exposures per week to banks of six FS40 Westinghouse sunlamps. In the photocarcinogenesis study, mice received a total dose of approximately 1.09 x 10(6) J/m2. Skin cancer incidence in UV-irradiated mice was 75% at 26 weeks after the first UV exposure; tannic acid reduced this to 42%. Immunosuppression induced by UVB irradiation normally prevents the host from rejecting antigenic syngeneic UV-induced tumors. Immunosuppression in these experiments was measured by a passive transfer assay. Tumor challenges grew to an average of 88 +/- 20, 36 +/- 11, and 20 +/- 8 mm2 in naive recipients of splenocytes from UVB-irradiated mice, nonirradiated control mice, and UVB-irradiated mice treated with tannic acid, respectively. Thus topical tannic acid treatment prevented the transfer of enhanced tumor susceptibility with splenocytes from UVB-irradiated mice.

  4. Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications

    PubMed Central

    Adisakwattana, Sirichai

    2017-01-01

    With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications. Based on several in vitro studies and animal models, cinnamic acid and its derivatives act on different mechanism of actions, including stimulation of insulin secretion, improvement of pancreatic β-cell functionality, inhibition of hepatic gluconeogenesis, enhanced glucose uptake, increased insulin signaling pathway, delay of carbohydrate digestion and glucose absorption, and inhibition of protein glycation and insulin fibrillation. However, due to the limited intestinal absorption being a result of low bioavailability of cinnamic acid and its derivatives, current improvement efforts with entrapping into solid and liquid particles are highlighted. Further human clinical studies are needed to clarify the effects of cinnamic acid and its derivatives in diabetic patients. PMID:28230764

  5. Role of omega-3 Fatty acids for prevention or treatment of perinatal depression.

    PubMed

    Borja-Hart, Nancy L; Marino, Jehan

    2010-02-01

    Perinatal depression is a complex mental health disorder that can manifest during pregnancy or after childbirth. Women with perinatal depression may not receive proper medical treatment because of concerns over teratogenic effects related to drug therapy. Evidence suggests that low levels of omega-3 fatty acids are correlated with depressive symptoms during pregnancy and after delivery. Omega-3 fatty acids may produce antidepressant effects due to their role in serotonin functioning. A literature search identified seven clinical trials of omega-3 fatty acids for the prevention or treatment of perinatal depression. Depression rating scale scores used in the studies improved, but results were statistically significant in only three trials. Four studies were randomized and placebo controlled, and three were open label. One study evaluating the prevention of postpartum depression in women with a history of depression was discontinued early due to relapse of depressive symptoms. In the trials we evaluated, the most common adverse effects were foul breath and/or unpleasant taste, and gastrointestinal complaints; no serious adverse events were reported. The seven studies were limited by small sample sizes and variable dosing and study durations. In the studies that demonstrated statistical significance, improvement in depression rating scale scores for omega-3 fatty acids was comparable to placebo. Overall, results have been inconclusive, but further investigation of omega-3 fatty acids is warranted because they did improve depression scores and appeared to be safe during pregnancy.

  6. Pretreatment of solid carbonaceous material with dicarboxylic aromatic acids to prevent scale formation

    SciTech Connect

    Brunson, R.J.

    1982-06-01

    Scale formation during the liquefaction of lower ranking coals and similar carbonaceous materials is significantly reduced and/or prevented by pretreatment with a pretreating agent selected from the group consisting of phthalic acid, phthalic anhydride, pyromellitic acid and pyromellitic anhydride. The pretreatment is believed to convert the scale-forming components to the corresponding phthalate and/or pyromellitate prior to liquefaction. The pretreatment is accomplished at a total pressure within the range from about 1 to about 2 atmospheres. Temperature during pretreatment will generally be within the range from about 5 to about 80/sup 0/ C.

  7. Pretreatment of solid carbonaceous material with dicarboxylic aromatic acids to prevent scale formation

    SciTech Connect

    Brunson, Roy J.

    1982-01-01

    Scale formation during the liquefaction of lower ranking coals and similar carbonaceous materials is significantly reduced and/or prevented by pretreatment with a pretreating agent selected from the group consisting of phthalic acid, phthalic anhydride, pyromellitic acid and pyromellitic anhydride. The pretreatment is believed to convert the scale-forming components to the corresponding phthalate and/or pyromellitate prior to liquefaction. The pretreatment is accomplished at a total pressure within the range from about 1 to about 2 atmospheres. Temperature during pretreatment will generally be within the range from about 5.degree. to about 80.degree. C.

  8. The activity of ferulic and gallic acids in biofilm prevention and control of pathogenic bacteria.

    PubMed

    Borges, Anabela; Saavedra, Maria J; Simões, Manuel

    2012-01-01

    The activity of two phenolic acids, gallic acid (GA) and ferulic acid (FA) at 1000 μg ml(-1), was evaluated on the prevention and control of biofilms formed by Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Listeria monocytogenes. In addition, the effect of the two phenolic acids was tested on planktonic cell susceptibility, bacterial motility and adhesion. Biofilm prevention and control were tested using a microtiter plate assay and the effect of the phenolic acids was assessed on biofilm mass (crystal violet staining) and on the quantification of metabolic activity (alamar blue assay). The minimum bactericidal concentration for P. aeruginosa was 500 μg ml(-1) (for both phenolic acids), whilst for E. coli it was 2500 μg ml(-1) (FA) and 5000 μg ml(-1) (GA), for L. monocytogenes it was >5000 μg ml(-1) (for both phenolic acids), and for S. aureus it was 5000 μg ml(-1) (FA) and >5000 μg ml(-1) (GA). GA caused total inhibition of swimming (L. monocytogenes) and swarming (L. monocytogenes and E. coli) motilities. FA caused total inhibition of swimming (L. monocytogenes) and swarming (L. monocytogenes and E. coli) motilities. Colony spreading of S. aureus was completely inhibited by FA. The interference of GA and FA with bacterial adhesion was evaluated by the determination of the free energy of adhesion. Adhesion was less favorable when the bacteria were exposed to GA (P. aeruginosa, S. aureus and L. monocytogenes) and FA (P. aeruginosa and S. aureus). Both phenolics had preventive action on biofilm formation and showed a higher potential to reduce the mass of biofilms formed by the Gram-negative bacteria. GA and FA promoted reductions in biofilm activity >70% for all the biofilms tested. The two phenolic acids demonstrated the potential to inhibit bacterial motility and to prevent and control biofilms of four important human pathogenic bacteria. This study also emphasizes the potential of phytochemicals as an emergent source of biofilm

  9. Wall teichoic acids prevent antibody binding to epitopes within the cell wall of Staphylococcus aureus.

    PubMed

    Gautam, Samir; Kim, Taehan; Lester, Evan; Deep, Deeksha; Spiegel, David A

    2016-01-15

    Staphylococcus aureus is a Gram-positive bacterial pathogen that produces a range of infections including cellulitis, pneumonia, and septicemia. The principle mechanism in antistaphylococcal host defense is opsonization with antibodies and complement proteins, followed by phagocytic clearance. Here we use a previously developed technique for installing chemical epitopes in the peptidoglycan cell wall to show that surface glycopolymers known as wall teichoic acids conceal cell wall epitopes, preventing their recognition and opsonization by antibodies. Thus, our results reveal a previously unrecognized immunoevasive role for wall teichoic acids in S. aureus: repulsion of peptidoglycan-targeted antibodies.

  10. Hydroxycinnamic acids do not prevent aortic atherosclerosis in hypercholesterolemic golden Syrian hamsters.

    PubMed

    Auger, Cyril; Laurent, Nathalie; Laurent, Caroline; Besançon, Pierre; Caporiccio, Bertrand; Teissédre, Pierre Louis; Rouanet, Jean-Max

    2004-03-26

    The protective effect of hydroxycinnamic acids, i.e. caffeic acid (CA) and sinapic acid (SA) present in wine, and chlorogenic acid (CHA) present in apple, compared to a red wine phenolic extract (RWPE) was investigated in hamsters fed an atherogenic diet for 12 weeks. Five groups of 8 hamsters fed such a diet received by force-feeding RWPE, CA or SA in water, mimicking a moderate consumption of alcohol-free red wine. Controls received water and CHA force-feeding was extrapolated from apple consumption. Plasma cholesterol concentration was lower in group that received RWPE (-22%) and hydroxycinnamic acids had no effect. Plasma apolipoprotein Apo-A1 concentration was not affected; consumption of RWPE only decreased Apo-B concentration (-46%). Liver superoxide dismutase activity was 33% lower and glutathione peroxidase activity was 67% greater in the group receiving RWPE compared to controls; there was no effect when CA, SA or CHA were given. All the phenolic compounds significantly increased plasma antioxidant capacity (about 28% on average) compared with controls. Aortic fatty streak area was significantly reduced in the group receiving RWPE (-30%) in comparison with controls and hydroxycinnamic acids. Our findings demonstrate that chronic ingestion of the nonalcoholic components of red wine, mainly polyphenols, prevent the development of atherosclerosis in hamster and that wine hydroxycinnamic acids are not the phenolic compounds involved in such a beneficial effect.

  11. Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy.

    PubMed

    Melli, Giorgia; Taiana, Michela; Camozzi, Francesca; Triolo, Daniela; Podini, Paola; Quattrini, Angelo; Taroni, Franco; Lauria, Giuseppe

    2008-12-01

    The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.

  12. Prevention of volatile fatty acids production and limitation of odours from winery wastewaters by denitrification.

    PubMed

    Bories, André; Guillot, Jean-Michel; Sire, Yannick; Couderc, Marie; Lemaire, Sophie-Andréa; Kreim, Virginie; Roux, Jean-Claude

    2007-07-01

    The effect of the addition of nitrate to winery wastewaters to control the formation of VFA in order to prevent odours during storage and treatment was studied in batch bioreactors at different NO(3)/chemical oxygen demand (COD) ratios and at full scale in natural evaporation ponds (2 x 7000 m(2)) by measuring olfactory intensity. In the absence of nitrate, butyric acid (2304 mgL(-1)), acetic acid (1633 mgL(-1)), propionic acid (1558 mgL(-1)), caproic acid (499 mgL(-1)) and valeric acid (298 mgL(-1)) were produced from reconstituted winery wastewater. For a ratio of NO(3)/COD=0.4 gg(-1), caproic and valeric acids were not formed. The production of butyric and propionic acids was reduced by 93.3% and 72.5%, respectively, at a ratio of NO(3)/COD=0.8, and by 97.4% and 100% at a ratio of NO(3)/COD=1.2 gg(-1). Nitrate delayed and decreased butyric acid formation in relation to the oxidoreduction potential. Studies in ponds showed that the addition of concentrated calcium nitrate (NITCAL) to winery wastewaters (3526 m(3)) in a ratio of NO(3)/COD=0.8 inhibited VFA production, with COD elimination (94%) and total nitrate degradation, and no final nitrite accumulation. On the contrary, in ponds not treated with nitrate, malodorous VFA (from propionic to heptanoïc acids) represented up to 60% of the COD. Olfactory intensity measurements in relation to the butanol scale of VFA solutions and the ponds revealed the pervasive role of VFA in the odour of the untreated pond as well as the clear decrease in the intensity and not unpleasant odour of the winery wastewater pond enriched in nitrates. The results obtained at full scale underscored the feasibility and safety of the calcium nitrate treatment as opposed to concentrated nitric acid.

  13. A postulated role of garlic organosulfur compounds in prevention of valproic acid hepatotoxicity.

    PubMed

    Sabayan, Behnam; Foroughinia, Farzaneh; Chohedry, Abdolhamid

    2007-01-01

    Valproic acid (2-propyl-pentanoic acid, VPA) is well established as a first-line and widely used antiepileptic agent. VPA is well tolerated in most patients and has an impressive safety profile. VPA induced hepatotoxicity is rare, but often there is fatal complication of this drug and it is more frequent in children under 2 years of age and in those taking multiple drugs. Several findings showed that oxidative stress induced by reactive oxygen species (ROS) over production and/or compromised antioxidant capacity play an important role in the development of hepatotoxicity in VPA treated patients. Reduced glutathione (GSH) and its related enzymes are important cellular defense against oxidative stress in which VPA induced oxidative stress impairs their function in hepatocytes. Consequently any mechanism which removes ROS or prevents hepatic GSH depletion or induce activation and production of GSH dependent enzymes may provide protection for hepatotoxicity in VPA-treated patient. As garlic organosulfur compounds enhance cellular antioxidant activity by free radical scavenging and augmentation of endogenous antioxidants via prevention of GSH depletion and alteration of GSH dependent enzymes activity and/or their gene expression, we propose the hypothesis that garlic organosulfur compounds can prevent valproic acid hepatotoxicity.

  14. Docosahexaenoic acid prevents cognitive deficits in human apolipoprotein E epsilon 4-targeted replacement mice.

    PubMed

    Chouinard-Watkins, Raphaël; Vandal, Milène; Léveillé, Pauline; Pinçon, Anthony; Calon, Frédéric; Plourde, Mélanie

    2017-09-01

    At a population level, dietary consumption of fish rich in docosahexaenoic acid (DHA) is associated with prevention of cognitive decline but this association is not clear in carriers of the apolipoprotein E epsilon 4 allele (E4). Plasma and liver DHA concentrations show significant alterations in E4 carriers, in part corrected by DHA supplementation. However, whether DHA sufficiency in E4 carriers has consequences on cognition is unknown. Mice expressing human E4 or apolipoprotein E epsilon 3 allele (E3) were fed either a control diet or a diet containing DHA for 8 months and cognitive performance was tested using the object recognition test and the Barnes maze test. In E4 mice fed the control diet, impaired memory was detected and arachidonic acid concentrations were elevated in the hippocampus compared to E3 mice fed the control diet. DHA consumption prevented memory decline and restored arachidonic acid concentrations in the hippocampus of E4 mice. Our results suggest that long-term high-dose DHA intake may prevent cognitive decline in E4 carriers. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Soft coagulation, polyglycolic acid felt, and fibrin glue for prevention of pancreatic fistula after distal pancreatectomy.

    PubMed

    Ikegami, Toru; Maeda, Takashi; Kayashima, Hiroto; Oki, Eiji; Yoshizumi, Tomoharu; Sakaguchi, Yoshihisa; Toh, Yasushi; Shirabe, Ken; Maehara, Yoshihiko

    2011-09-01

    To evaluate the effectiveness of using soft coagulation followed by the application of polyglycolic acid (PGA) felt and fibrin glue to prevent pancreatic fistula (PF) after distal pancreatectomy (DP). A soft coagulation system was applied on the cut surface of the pancreas after ligating the main pancreatic duct, followed by the application of layers of PGA felt and fibrin glue on the layers, to prevent the development of a PF after DP. This technique was applied in nine patients, with mean drain amylase levels of 372 ± 296, 185 ± 209, 54 ± 40, and 47 ± 34 IU/l on days 1, 3, 5, and 7, respectively, after DP. Only one patient (11.1%) showed a Grade A PF on day 3 after surgery; none of the other patients developed a fistula. This technique is an effective prophylactic measure to prevent the development of a PF after DP.

  16. Prevention

    MedlinePlus

    ... Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  17. Rapid intravenous administration of amino acids prevents biliary sludge induced by total parenteral nutrition in humans.

    PubMed

    Wu, Z S; Yu, L; Lin, Y J; Jun, Z J; Min, W S; Jun, Y; Hua, Z B

    2000-01-01

    The aim of this study was to evaluate whether daily rapid intravenous administration of amino acids (IVAA) prevented the formation of biliary sludge in humans receiving long-term total parenteral nutrition (TPN). Thirty adult patients receiving TPN for more than 28 consecutive days were studied. They were randomized to receive either saline solution (placebo) intravenously (15 patients) or 6.9% branched chain amino acid (BCAA)-enriched amino acid (15 synthetic amino acids; Freamine HBC) solution given by administration rapid intravenous (15 patients). The groups were similar with respect to age, sex, diagnosis, liver function test results, amylase levels, TPN time, and time of study. All patients underwent weekly ultrasound studies. Volume and emptying studies of the gallbladder in response to the study drug were performed after 1 week. As a result, none of the patients receiving rapid IVAA had sludge, whereas 11 of the 15 patients receiving placebo had sludge (P < 0.01). Results of emptying studies showed significant contraction of the gallbladder in those in the rapid IVAA group, but not in the placebo group. Consequently, the data suggest that rapid IVAA given daily prevents TPN-induced stasis and sludge in the gallbladder. We conclude that rapid IVAA should be used as routine prophylaxis against biliary sludge and formation of gallstones in patients receiving long-term TPN.

  18. Ca2+ channel blockade prevents lysergic acid diethylamide-induced changes in dopamine and serotonin metabolism.

    PubMed

    Antkiewicz-Michaluk, L; Románska, I; Vetulani, J

    1997-07-30

    To investigate the effect of a single and multiple administration of lysergic acid diethylamide (LSD) on cerebral metabolism of dopamine and serotonin, male Wistar rats were treated with low and high doses (0.1 and 2.0 mg/kg i.p.) of LSD and the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxytyramine, serotonin and 5-hydroxyindoleacetic acid were assayed by HPLC in the nucleus accumbens, striatum and frontal cortex. Some rats received nifedipine, 5 mg/kg i.p., before each injection of LSD to assess the effect of a Ca2+ channel blockade. High-dose LSD treatment (8 x 2 mg/kg per day) caused a strong stimulation of dopamine metabolism in the nucleus accumbens and striatum, and serotonin metabolism in the nucleus accumbens: the changes were observed 24 (but not 1 h) after the last dose. The changes induced by the low-dose treatment (8 x 0.1 mg/kg per day) had a different pattern, suggesting the release of dopamine from vesicles to cytoplasm. Co-administration of nifedipine completely prevented the LSD-induced biochemical changes. The results suggest that Ca2+ channel blocking agents may prevent development of some behavioral consequences of chronically used LSD.

  19. Preoperative zoledronic acid therapy prevent hungry bone syndrome in patients with primary hyperparathyroidism

    PubMed Central

    Mayilvaganan, Sabaretnam; Vijaya Sarathi, H. A.; Shivaprasad, C.

    2017-01-01

    Background: Hungry bone syndrome is a common complication of surgery for primary hyperparathyroidism in India which often leads to prolonged hospitalization. There are varying reports on the use and efficacy of bisphosphonates in the prevention of hungry bone syndrome. Methods: We retrospectively analyzed the effect of preoperative bisphosphonate therapy on rates of hungry bone syndrome in our patients with primary hyperparathyroidism. A total of 19 patients underwent surgery for primary hyperparathyroidism at our institute between January 2013 and June 2015 among whom eight did not receive preoperative bisphosphonates and 11 received intravenous zoledronic acid 4 mg, 24–48 h preoperatively. Results: There was no significant difference between the two groups with respect to age, gender, duration of symptoms, preoperative serum calcium, phosphorus, parathyroid hormone, alkaline phosphatase, and the presence of radiological evidence of hyperparathyroid bone disease also did not differ between the groups. Three out of the eight patients who did not receive preoperative zoledronic acid therapy had hungry bone syndrome but none in the zoledronic acid group. The prevalence of hungry bone syndrome tended to be lower in the zoledronic acid group (P = 0.058). The need for intravenous calcium and duration of postoperative hospital stay were significantly lesser in the zoledronic acid group. Conclusion: Preoperative intravenous zoledronic acid significantly reduces the need for intravenous calcium therapy and duration of postoperative hospital stay and seems a promising option to reduce the rate of hungry bone syndrome in patients with primary hyperparathyroidism. PMID:28217502

  20. Folic acid prevents neural tube defects: international comparison of awareness among obstetricians/gynecologists and urologists.

    PubMed

    Kondo, Atsuo; Kamihira, Osamu; Gotoh, Momokazu; Ozawa, Hideo; Lee, Tchun Yong; Lin, Alex T-L; Kim, Seung-Ryong; Lin, Ho-Hsiung

    2007-02-01

    It has been suggested that periconceptional intake of folic acid prevents risks of having fetuses afflicted with neural tube defects. We aim to internationally investigate knowledge of the role of folic acid and attitudes toward the life-style of young women of child-bearing age among obstetricians/gynecologists and urologists. A questionnaire was sent to obstetricians/gynecologists and urologists residing in Japan, South Korea, Taiwan, North America, Europe, Australia and New Zealand by post or e-mail. The investigation was conducted between December 2002 and November 2004. A mean of 91% of obstetricians/gynecologists and 56% of urologists are aware of the role of folic acid, where Asian urologists knew less compared to those of North America, Europe, Australia and New Zealand. A majority of doctors always, or occasionally, recommend folic acid supplements or multivitamins, well-balanced meals, and the cessation of smoking and drinking. An average of 85% of doctors believes information on folic acid should be disseminated to young women. A majority of obstetricians/gynecologists and urologists know the importance of periconceptional folic acid in reducing the risk of neural tube defects and have been advising young women to improve their lifestyle.

  1. Prevention of neural tube defects with folic acid: The Chinese experience.

    PubMed

    Ren, Ai-Guo

    2015-08-08

    Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28(th) day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a post-program survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs.

  2. [Folic acid and prevention of neural tube closure defects: the question is not solved yet].

    PubMed

    Vidailhet, M; Bocquet, A; Bresson, J-L; Briend, A; Chouraqui, J-P; Dupont, C; Darmaun, D; Frelut, M-L; Ghisolfi, J; Girardet, J-P; Goulet, O; Putet, G; Rieu, D; Rigo, J; Turck, D

    2008-07-01

    Between 1981 and 1996, several interventional studies proved the efficacy of periconceptional folic acid supplementation in the prevention of neural tube closure defects (NTCD), first in women at risk (with a previous case of NTCD) and also in women of the general population in age to become pregnant. The poor observance of this supplementation led several countries (USA, Canada, Chile...) to decide mandatory folic acid fortification of cereals, which permitted a 30% (USA) to 46% (Canada) reduction in the incidence of NTCD. Moreover, this benefit was accompanied by a diminished incidence of several other malformations and of stroke and coronary accidents in elderly people. However, several papers drew attention to an increased risk of colorectal and breast cancer in relation with high blood folate levels and the use of folic acid supplements. A controlled interventional study showed a higher rate of recurrence of colic adenomas and a higher percentage of advanced adenomas in subjects receiving 1mg/day of folic acid. A recent study demonstrated an abrupt reversal of the downward trend in colorectal cancer 1 year after the beginning of cereal folic acid fortification in the USA and Canada. Two studies also reported impaired cognitive functions in elder persons with defective vitamin B(12) status. Taken in aggregate, these studies question the wisdom of a nationwide, mandatory, folic acid fortification of cereals. As of today, despite their limited preventive efficacy, a safe approach is to keep our current French recommendations and to increase the awareness of all caregivers, so as to improve the observance of these recommendations.

  3. Puerto Rican primary physicians' knowledge about folic acid supplementation for the prevention of neural tube defects.

    PubMed

    Miranda, Ana; Dávila Torres, René R; Gorrín Peralta, José J; Montes de Longo, Idalina

    2003-12-01

    We conducted a study of a group of primary physicians in Puerto Rico to evaluate their knowledge about folic acid supplementation to prevent neural tube defects. The study design was transverse-correlational. A total of 66 primary physicians in two hospitals (public and private) participated in the study. The sample was nonrandom and opportunistic, and only those physicians present in the hospitals at the moment of distribution of the questionnaires participated. A self-administered and anonymous questionnaire was used. Descriptive statistics and cross-tabular analysis were used to describe the results of this study. Inferential statistics were also used, including Chi square and t-tests to establish the associations/differences between physician knowledge and the independent variables. Of the participants, 87.9% demonstrated an inadequate knowledge about folic acid supplementation for the prevention of neural tube defects as part of preconception care and only 12.1% demonstrated adequate knowledge. Older physicians had greater knowledge about folic acid. Also, women demonstrated greater knowledge about folic acid than did men. Most of the physicians who always recommend supplementation to their patients demonstrated a greater knowledge about folic acid, and all participants with adequate knowledge came from the public hospital. Despite a concerted effort by the Health Department of Puerto Rico to provide education in the importance of folic acid supplementation to reduce the incidence of neural tube defects, primary physicians in two Puerto Rican hospitals generally have not availed themselves of this training and showed a lack of knowledge on this important clinical issue. Copyright 2003 Wiley-Liss, Inc.

  4. Probiotic lactic acid bacteria and their potential in the prevention and treatment of allergic diseases

    PubMed Central

    Wróblewska, Paula; Adamczuk, Piotr; Silny, Wojciech

    2014-01-01

    Allergy is one of the most important and very common health problems worldwide. To reduce the proportion of people suffering from allergy, alternative methods of prevention and treatment are sought. The aim of this paper is to present the possibilities of probiotics in the prevention and treatment of allergic diseases. Probiotics are live microorganisms belonging mainly to the lactic acid bacteria. They modify the microflora of the human digestive system, especially the intestinal microflora. Prophylactic administration of probiotics in the early stages of life (naturally in breast milk or milk substitute synthetic compounds) is very important because intestinal microflora plays a huge role in the development of the immune system. Prevention of allergies as early as in the prenatal and postnatal periods provides huge opportunities for inhibiting the growing problem of allergy in emerging and highly developed societies. Effects of probiotic therapy depend on many factors such as the species of the microorganism used, the dose size and characteristics of the bacteria such as viability and capacity of adhesion to the intestinal walls. Authors of several studies showed beneficial effects of probiotics in the perinatal period, infancy, and also in adults in the prevention of atopic dermatitis or allergic rhinitis. Probiotics, due to their immunomodulatory properties and safety of use are a good, natural alternative for the prevention and treatment of many diseases including allergies. It is therefore important to explore the knowledge about their use and to carry out further clinical trials. PMID:26155109

  5. Prevention of cultured rat stellate cell transformation and endothelin-B receptor upregulation by retinoic acid.

    PubMed

    Chi, Xuedong; Anselmi, Kristin; Watkins, Simon; Gandhi, Chandrashekhar R

    2003-06-01

    1 Physiologically, perisinusoidal hepatic stellate cells (HSC) are quiescent and store retinoids. During liver injury and in cell culture, HSC transform into proliferating myofibroblast-like cells that express alpha-smooth muscle actin (alpha-sma) and produce excessive amounts of extracellular matrix. During transformation (also known as activation), HSC are depleted of the retinoid stores, and their expression of the endothelin-1 (ET-1) system is increased. ET-1 causes contraction of transformed HSC and is implicated in their proliferation and fibrogenic activity. In order to understand the association between retinoids, ET-1 and the activation of HSC, we investigated the effect of 13-cis-retinoic acid on the transformation of cultured HSC and the expression of ET-1 system. 2 HSC derived from normal rat liver were maintained for 10-12 days in a medium supplemented with 5% serum and containing 2.5 micro M retinoic acid without or with 50 nM ET-1 (ETA+ETB agonist) or sarafotoxin S6c (ETB agonist). In another set of experiments, cells treated for 10-12 days with vehicle (ethanol) or retinoic acid were challenged with ET-1 or sarafotoxin S6c, and various determinations were made at 24 h. 3 Retinoic acid inhibited transformation and proliferation of HSC as assessed by morphological characteristics, expression of alpha-sma, bromodeoxyuridine incorporation and cell count. Retinoic acid also prevented upregulation of ETB receptors without affecting ET-1 or ETA expression. Total protein synthesis ([(3)H]leucine incorporation), collagen alpha types I mRNA expression and collagen synthesis ([(3)H]proline incorporation) were lower in retinoic acid-treated cells. Although ET-1-treated cells were morphologically similar to the control cells, their expression of alpha-smooth muscle actin was significantly inhibited. The presence of retinoic acid in the medium during treatment with ET-1 caused further reduction in the expression of alpha-smooth muscle actin. ET-1 and sarafotoxin

  6. Glutamic Acid Not Beneficial for the Prevention of Vincristine Neurotoxicity in Children with Cancer

    PubMed Central

    Bradfield, Scott M.; Sandler, Eric; Geller, Thomas; Tamura, Roy N.; Krischer, Jeffrey P.

    2014-01-01

    Background Vincristine causes known side effects of peripheral sensory, motor, autonomic and cranial neuropathies. No preventive interventions are known. Procedure We performed a randomized, placebo-controlled, double-blind trial of oral glutamic acid as a preventive agent in pediatric patients with cancer who would be receiving vincristine therapy for at least 9 consecutive weeks (Stratum 1= Wilms tumor and rhabdomyosarcoma) or 4 consecutive weeks in conjunction with steroids (Stratum 2=Acute lymphoblastic leukemia and Non-Hodgkin lymphoma). At designated time points, a scored neurologic exam using the Modified Balis Pediatric Scale of Peripheral Neuropathies was performed to document neurologic toxicity. Results Between 2007–12, 250 patients were enrolled (Stratum 1=50, Stratum 2=200). The glutamic acid treated group did not have a significantly lower percentage of neurotoxicity compared to placebo treated group either overall or within stratum or age subgroups. The only subgroup which was suggestive of treatment effect was for age. Patients 13 years or older showed a larger benefit in favor of glutamic acid (p=0.055) compared to patients less than 13 years (p=1.00). Constipation was the most frequently reported (14%) Grade II or higher neurotoxicity. Conclusion Vincristine-associated neurotoxicity in pediatric oncology remains a frequent complication of chemotherapy for multiple diagnoses with an approximate 30% of patients affected. Glutamic acid is not effective for prevention in pre-adolescents. There is a suggestion of benefit in patients 13 years or older, but the study was not designed to provide adequate power to test the treatment effect within this age group alone. PMID:25545757

  7. Lipoic acid prevents fructose-induced changes in liver carbohydrate metabolism: role of oxidative stress.

    PubMed

    Castro, María C; Francini, Flavio; Gagliardino, Juan J; Massa, María L

    2014-03-01

    Fructose administration rapidly induces oxidative stress that triggers compensatory hepatic metabolic changes. We evaluated the effect of an antioxidant, R/S-α-lipoic acid on fructose-induced oxidative stress and carbohydrate metabolism changes. Wistar rats were fed a standard commercial diet, the same diet plus 10% fructose in drinking water, or injected with R/S-α-lipoic acid (35mg/kg, i.p.) (control+L and fructose+L). Three weeks thereafter, blood samples were drawn to measure glucose, triglycerides, insulin, and the homeostasis model assessment-insulin resistance (HOMA-IR) and Matsuda indices. In the liver, we measured gene expression, protein content and activity of several enzymes, and metabolite concentration. Comparable body weight changes and calorie intake were recorded in all groups after the treatments. Fructose fed rats had hyperinsulinemia, hypertriglyceridemia, higher HOMA-IR and lower Matsuda indices compared to control animals. Fructose fed rats showed increased fructokinase gene expression, protein content and activity, glucokinase and glucose-6-phosphatase gene expression and activity, glycogen storage, glucose-6-phosphate dehydrogenase mRNA and enzyme activity, NAD(P)H oxidase subunits (gp91(phox) and p22(phox)) gene expression and protein concentration and phosphofructokinase-2 protein content than control rats. All these changes were prevented by R/S-α-lipoic acid co-administration. Fructose induces hepatic metabolic changes that presumably begin with increased fructose phosphorylation by fructokinase, followed by adaptive changes that attempt to switch the substrate flow from mitochondrial metabolism to energy storage. These changes can be effectively prevented by R/S-α-lipoic acid co-administration. Control of oxidative stress could be a useful strategy to prevent the transition from impaired glucose tolerance to type 2 diabetes. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

    PubMed

    Yarla, Nagendra Sastry; Bishayee, Anupam; Sethi, Gautam; Reddanna, Pallu; Kalle, Arunasree M; Dhananjaya, Bhadrapura Lakkappa; Dowluru, Kaladhar S V G K; Chintala, Ramakrishna; Duddukuri, Govinda Rao

    2016-10-01

    Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A2s (PLA2s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA2s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Clofibric and ethacrynic acids prevent experimental pyelonephritis by Escherichia coli in mice.

    PubMed

    Balagué, Claudia E; de Ruiz, Clara Silva; Rey, Rosario; de Duffard, Ana María Evangelista; Nader-Macías, María Elena

    2004-11-01

    Interfering Escherichia coli attachment to the urinary tract, using P-fimbriation inhibitors, can prevent pyelonephritis. Clofibric and ethacrynic acids are organic compounds structurally related, but with different pharmacological uses. These agents are potentially active in the urinary tract due to its elimination in an unaltered form by the renal route. This study described a pyelonephritogenic E. coli strain, grown in the presence of sub-inhibitory concentrations of clofibric or ethacrynic acids (0.1 and 1 mM, respectively), which exhibits inhibition of P1 erythrocytes agglutination and a drastic decrease in fimbriation, using electron microscopy and quantitative analyses of superficial proteins (decrease to a 17-25% in comparison with the control). In vivo assays were performed using ascending urinary tract infection in mice. The treatment with therapeutic doses of the drugs, administered 2 days before the bacterial challenge and daily until the end of the experiment (22 days), abolished renal infection after 7-10 days of drug exposure. Within this period clofibric acid did not produce adverse effects on the renal parenchyma. However, ethacrynic acid caused pyelitis and tubular cellular desquamation. These results suggested that clofibric acid might be useful in the short-term prophylaxis of urinary tract infection.

  10. Low molecular weight hyaluronic acid prevents oxygen free radical damage to granulation tissue during wound healing.

    PubMed

    Trabucchi, E; Pallotta, S; Morini, M; Corsi, F; Franceschini, R; Casiraghi, A; Pravettoni, A; Foschi, D; Minghetti, P

    2002-01-01

    Hyaluronic acid protects granulation tissue from oxygen free radical damage and stimulates wound healing, but its molecular weight prevents it from permeating the epidermal barrier A low molecular weight hyaluronic acid preparation is able to permeate the skin, but it is unknown whether or not it retains the scavenging effects of oxygen free radicals in granulation tissue. Our experiments were conducted in rats with excisional or incisional wounds. Wound contraction over 11 days and breaking strength on the fifth day were measured. Oxygen free radical production was induced by intraperitoneal administration of two different xenobiotics: phenazine methosulfate and zymosan. The wounds were treated topically with low molecular weight hyaluronic acid (0.2%) cream or placebo. In the incisional wound group, the effects of superoxide dismutase were also determined. Absolute controls received wounds and placebo but no xenobiotics. Wound healing was significantly slower in the xenobiotic group than in the control groups. These effects were strongly reduced by topical administration of low molecular weight hyaluronic acid (0.2%) cream and in incisional wounds by topically injected superoxide dismutase. Low molecular weight hyaluronic acid is effective as the native compound against oxygen free radicals. Its pharmacological effects through transdermal administration should be tested in appropriate models.

  11. Effects of pyruvate salts, pyruvic acid, and bicarbonate salts in preventing experimental oxalate urolithiasis in rats.

    PubMed

    Ogawa, Y; Yamaguchi, K; Tanaka, T; Morozumi, M

    1986-05-01

    Sodium pyruvate, potassium pyruvate, pyruvic acid, sodium bicarbonate and potassium bicarbonate were added to a calcium-oxalate lithogenic diet (a glycolic-acid diet) in order to determine their effects in preventing lithogenicity. Male Wistar-strain rats who had been fed the glycolic-acid diet developed marked urinary calculi within four weeks. Rats in the sodium and potassium pyruvate groups had, however, almost no stones in the urinary system. Rats in the bicarbonate and pyruvic-acid groups showed slightly less effect than those in the pyruvate groups. Urinary oxalate excretion was high in all the groups during the experiment. The urinary oxalate concentration was relatively higher in the sodium-pyruvate group, and significantly higher in the potassium-pyruvate group, than in the glycolic-acid group. Urinary citrate excretion was high both in the pyruvate and bicarbonate groups; the urinary citrate concentration was, however, significantly higher in the pyruvate groups than in the bicarbonate groups at the fourth experimental week. The urinary calcium and magnesium concentrations were irrelevant to the diets administered. Therefore, it can be concluded that pyruvate salts inhibit urinary calculi formation, not by decreasing oxalate synthesis, but by increasing the urinary citrate concentration; bicarbonate salts work in the same manner, but a little less effectively.

  12. Preventive Effect of Phytic Acid on Isoproterenol-Induced Cardiotoxicity in Wistar Rats

    PubMed Central

    Brindha, E.; Rajasekapandiyan, M.

    2015-01-01

    This study was aimed to evaluate the preventive role of phytic acid on membrane bound enzymes such as sodium potassium- dependent adenosine triphosphatase (Na+ /K+ ATPase), calcium-dependent adenosine triphosphatase (Ca2+ ATPase) and magnesium- dependent adenosine triphosphatase (Mg2+ ATPase) and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats were pretreated with phytic acid (25 and 50 mg/kg, respectively) for a period of 56 days. After the treatment period, ISO (85 mg/kg) was subcutaneously injected to rats at an interval of 24 h for 2 days. ISO-induced rats showed a significant decrease in the activity of Na+ /K+ ATPase and increase in the activities of Ca2+ and Mg2+ ATPase in the heart and a significant (P<0.05) increase in the levels of glycoproteins in serum and the heart were also observed in ISO-induced rats. Pretreatment with phytic acid for a period of 56 days exhibited a significant (P<0.05) effect and altered these biochemical parameters positively in ISO-induced rats. Thus, our study shows that phytic acid has cardioprotective role in ISO-induced MI in rats.

  13. RETRACTED: Curcumin restores Nrf2 levels and prevents quinolinic acid-induced neurotoxicity.

    PubMed

    Carmona-Ramírez, Iván; Santamaría, Abel; Tobón-Velasco, Julio C; Orozco-Ibarra, Marisol; González-Herrera, Irma G; Pedraza-Chaverrí, José; Maldonado, Perla D

    2013-01-01

    Neurological diseases comprise a group of heterogeneous disorders characterized by progressive brain dysfunction and cell death. In the next years, these diseases are expected to constitute a world-wide health problem. Because excitotoxicity and oxidative stress are involved in neurodegenerative diseases, it becomes relevant to describe pharmacological therapies designed to activate endogenous cytoprotective systems. Activation of transcription factor Nrf2 stimulates cytoprotective vitagenes involved in antioxidant defense. In this work, we investigated the ability of the antioxidant curcumin to induce transcription factor Nrf2 in a neurodegenerative model induced by quinolinic acid in rats. Animals were administered with curcumin (400 mg/kg, p.o.) for 10 days, and then intrastriatally infused with quinolinic acid (240 nmol) on day 10 of treatment. Curcumin prevented rotation behavior (6 days post-lesion), striatal morphological alterations (7 days post-lesion) and neurodegeneration (1 and 3 days post-lesion) induced by quinolinic acid. Curcumin also reduced quinolinic acid-induced oxidative stress (measured as protein carbonyl content) at 6 h post-lesion. The protective effects of curcumin were associated to its ability to prevent the quinolinic acid-induced decrease of striatal intra-nuclear Nrf2 levels (30 and 120 min post-lesion), and total superoxide dismutase and glutathione peroxidase activities (1 day post-lesion). Therefore, results of this study support the concept that neuroprotection induced by curcumin is associated with its ability to activate the Nrf2 cytoprotective pathway and to increase the total superoxide dismutase and glutathione peroxidase activities. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. n-3 Polyunsaturated Fatty Acids: Promising Nutrients for Preventing Cardiovascular Disease.

    PubMed

    Yagi, Shusuke; Fukuda, Daiju; Aihara, Ken-Ichi; Akaike, Masashi; Shimabukuro, Michio; Sata, Masataka

    2017-08-24

    The adoption of the Western-style diet, with decreased fish intake and lack of exercise, has increased the prevalence of cardiovascular disease (CVD) in Japan. Statin treatment has been established to reduce the risk of cardiovascular events; however, 60%-70% of these events occur despite its use. Thus, the residual risk for CVD should be identified and resolved to reduce further cardiovascular events. The serum levels of n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid and docosahexaenoic acid, are reportedly associated with an increased incidence of cardiovascular events and mortality, whereas the addition of n-3 PUFA treatment to the statin treatment decreases cardiovascular events. Similar to statins, n-3 PUFAs have pleiotropic effects in addition to lipid-modifying effects. Pre-clinical and clinical studies have shown that n-3 PUFAs prevent cardiovascular events by ameliorating endothelial function and attenuating lipid accumulation, vascular inflammation, and macrophage recruitment, thereby causing coronary plaque development and rupture. Taken together, n-3 PUFAs are comprehensively able to attenuate the atherogenic response. Therefore, n-3 PUFA intake is recommended to prevent cardiovascular events, particularly in patients with multiple cardiovascular risk factors.

  15. alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells.

    PubMed

    Sabharwal, Anup K; May, James M

    2008-02-01

    Both alpha-lipoic acid (LA) and ascorbic acid (vitamin C) have been shown to improve endothelial dysfunction, a precursor of atherosclerosis. Since oxidant stress can cause endothelial dysfunction, we tested the interaction and efficacy of these antioxidants in preventing oxidant damage to lipids due to both intra- and extracellular oxidant stresses in EA.hy926 endothelial cells. LA spared intracellular ascorbate in culture and in response to an intracellular oxidant stress induced by the redox cycling agent menadione. Extracellular oxidant stress generated by incubating cells for 2 h in with 0.2 mg/ml LDL and 5 muM Cu2+ caused a time-dependent increase of the lipid peroxidation product malondialdehyde in both cells and LDL, preceded by rapid disappearance of; alpha-tocopherol in LDL. alpha-Lipoic acid at concentrations of 40-80 microM blunted these effects. Similarly, intracellular ascorbate concentrations of 1-2 mM also prevented Cu2+-induced lipid peroxidation in LDL and cells. Cu2+-dependent oxidation of LDL in the presence of ascorbate-loaded cells decreased intracellular ascorbate by 20%, but this decrease was not reversed by LA. Both LA and ascorbate protect endothelial cells and LDL from either intra- or extracellular oxidant stress, but that LA does not spare ascorbate in oxidatively stressed cells.

  16. Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer's Disease

    PubMed Central

    Thomas, J.; Thomas, C. J.; Radcliffe, J.; Itsiopoulos, C.

    2015-01-01

    Alzheimer's disease (AD) is the leading cause of dementia and the most common neurodegenerative disease in the elderly. Furthermore, AD has provided the most positive indication to support the fact that inflammation contributes to neurodegenerative disease. The exact etiology of AD is unknown, but environmental and genetic factors are thought to contribute, such as advancing age, family history, presence of chronic diseases such as cardiovascular disease (CVD) and diabetes, and poor diet and lifestyle. It is hypothesised that early prevention or management of inflammation could delay the onset or reduce the symptoms of AD. Normal physiological changes to the brain with ageing include depletion of long chain omega-3 fatty acids and brains of AD patients have lower docosahexaenoic acid (DHA) levels. DHA supplementation can reduce markers of inflammation. This review specifically focusses on the evidence in humans from epidemiological, dietary intervention, and supplementation studies, which supports the role of long chain omega-3 fatty acids in the prevention or delay of cognitive decline in AD in its early stages. Longer term trials with long chain omega-3 supplementation in early stage AD are warranted. We also highlight the importance of overall quality and composition of the diet to protect against AD and dementia. PMID:26301243

  17. Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer's Disease.

    PubMed

    Thomas, J; Thomas, C J; Radcliffe, J; Itsiopoulos, C

    2015-01-01

    Alzheimer's disease (AD) is the leading cause of dementia and the most common neurodegenerative disease in the elderly. Furthermore, AD has provided the most positive indication to support the fact that inflammation contributes to neurodegenerative disease. The exact etiology of AD is unknown, but environmental and genetic factors are thought to contribute, such as advancing age, family history, presence of chronic diseases such as cardiovascular disease (CVD) and diabetes, and poor diet and lifestyle. It is hypothesised that early prevention or management of inflammation could delay the onset or reduce the symptoms of AD. Normal physiological changes to the brain with ageing include depletion of long chain omega-3 fatty acids and brains of AD patients have lower docosahexaenoic acid (DHA) levels. DHA supplementation can reduce markers of inflammation. This review specifically focusses on the evidence in humans from epidemiological, dietary intervention, and supplementation studies, which supports the role of long chain omega-3 fatty acids in the prevention or delay of cognitive decline in AD in its early stages. Longer term trials with long chain omega-3 supplementation in early stage AD are warranted. We also highlight the importance of overall quality and composition of the diet to protect against AD and dementia.

  18. Folic acid and prevention of colorectal adenomas: a combined analysis of randomized clinical trials.

    PubMed

    Figueiredo, Jane C; Mott, Leila A; Giovannucci, Edward; Wu, Kana; Cole, Bernard; Grainge, Matthew J; Logan, Richard F; Baron, John A

    2011-07-01

    Observational data suggest that lower folate status is associated with an increased risk of colorectal neoplasia, implying that folate may be useful as a chemopreventive agent. We conducted a combined analysis of three large randomized trials of folic acid supplementation for the prevention of metachronous adenomas in patients with an adenoma history. Participants included 2,632 men and women who had a history of adenomas randomized to either 0.5 or 1.0 mg/day of folic acid or placebo and who had a follow-up endoscopy 6 to 42 months after randomization [mean = 30.6 (standard deviation = 8.1) months]. We used random-effects meta-analysis to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The RR comparing folic acid versus placebo was 0.98 (95% CI = 0.82-1.17) for all adenomas and 1.06 (95% CI = 0.81-1.39) for advanced lesions. Folic acid was associated with a nonsignificant decreased risk of any adenoma among subjects in the lowest quartile of baseline plasma folate (≤ 11 nmol/L) and no effect among individuals in the highest quartile (> 29 nmol/L, p for trend = 0.17). There was a nonsignificant trend of decreasing risk of any adenoma associated with folic acid supplements with increasing alcohol intake. During the early follow-up reported here, more deaths occurred in the placebo group than in the folic acid group (1.7% vs. 0.5%, p = 0.002). In conclusion, after up to 3.5 years of folic acid use, there is no clear decrease or increase in the occurrence of new adenomas in patients with a history of adenoma. Copyright © 2010 UICC.

  19. Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

    PubMed Central

    Brasky, Theodore M.; Till, Cathee; White, Emily; Neuhouser, Marian L.; Song, Xiaoling; Goodman, Phyllis; Thompson, Ian M.; King, Irena B.; Albanes, Demetrius; Kristal, Alan R.

    2011-01-01

    Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55–84 years, in the Prostate Cancer Prevention Trial during 1994–2003. Cases (n = 1,658) were frequency matched to controls (n = 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were extracted from serum, and concentrations of ω-3, ω-6, and trans-fatty acids (TFAs) were expressed as proportions of the total. Logistic regression models estimated odds ratios and 95% confidence intervals of associations of fatty acids with prostate cancer by grade. No fatty acids were associated with low-grade prostate cancer risk. Docosahexaenoic acid was positively associated with high-grade disease (quartile 4 vs. 1: odds ratio (OR) = 2.50, 95% confidence interval (CI): 1.34, 4.65); TFA 18:1 and TFA 18:2 were linearly and inversely associated with risk of high-grade prostate cancer (quartile 4 vs. 1: TFA 18:1, OR = 0.55, 95% CI: 0.30, 0.98; TFA 18:2, OR = 0.48, 95% CI: 0.27, 0.84). The study findings are contrary to those expected from the pro- and antiinflammatory effects of these fatty acids and suggest a greater complexity of effects of these nutrients with regard to prostate cancer risk. PMID:21518693

  20. Hyaluronic acid prevents immunosuppressive drug-induced ovarian damage via up-regulating PGRMC1 expression

    PubMed Central

    Zhao, Guangfeng; Yan, Guijun; Cheng, Jie; Zhou, Xue; Fang, Ting; Sun, Haixiang; Hou, Yayi; Hu, Yali

    2015-01-01

    Chemotherapy treatment in women can frequently cause damage to the ovaries, which may lead to primary ovarian insufficiency (POI). In this study, we assessed the preventative effects of hyaluronic acid (HA) in immunosuppressive drug-induced POI-like rat models and investigated the possible mechanisms. We found that HA, which was reduced in primary and immunosuppressant-induced POI patients, could protect the immunosuppressant-induced damage to granulosa cells (GCs) in vitro. Then we found that HA blocked the tripterygium glycosides (TG) induced POI-like presentations in rats, including delayed or irregular estrous cycles, reduced 17 beta-estradiol(E2) concentration, decreased number of follicles, destruction of follicle structure, and damage of reproductive ability. Furthermore, we investigated the mechanisms of HA prevention effects on POI, which was associated with promotion of GC proliferation and PGRMC1 expression. In conclusion, HA prevents chemotherapy-induced ovarian damage by promoting PGRMC1 in GCs. This study may provide a new strategy for prevention and treatment of POI. PMID:25558795

  1. Omega-3 Polyunsaturated Fatty Acids in Prevention of Mood and Anxiety Disorders

    PubMed Central

    Su, Kuan-Pin; Matsuoka, Yutaka; Pae, Chi-Un

    2015-01-01

    Psychiatric disorders in general, and major depression and anxiety disorders in particular, account for a large burden of disability, morbidity and premature mortality worldwide. Omega-3 polyunsaturated fatty acids (PUFAs) have a range of neurobiological activities in modulation of neurotransmitters, anti-inflammation, anti-oxidation and neuroplasticity, which could contribute to psychotropic effects. Here we reviewed recent research on the benefits of omega-3 PUFA supplements in prevention against major depression, bipolar disorders, interferon-α-induced depression patients with chronic hepatitis C viral infection, and posttraumatic stress disorder. The biological mechanisms underlying omega-3 PUFAs’ psychotropic effects are proposed and reviewed. Nutrition is a modifiable environmental factor that might be important in prevention medicine, which have been applied for many years in the secondary prevention of heart disease with omega-3 PUFAs. This review extends the notion that nutrition in psychiatry is a modifiable environmental factor and calls for more researches on prospective clinical studies to justify the preventive application of omega-3 PUFAs in daily practice. PMID:26243838

  2. Prevention

    Treesearch

    Kerry Britton; Barbara Illman; Gary Man

    2010-01-01

    Prevention is considered the most cost-effective element of the Forest Service Invasive Species Strategy (USDA Forest Service 2004). What makes prevention difficult is the desire to maximize free trade and the resulting benefits to society while, at the same time, protecting natural resources. The role of science is to first identify which commodities pose an...

  3. Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy.

    PubMed

    Žiberna, Lovro; Šamec, Dunja; Mocan, Andrei; Nabavi, Seyed Fazel; Bishayee, Anupam; Farooqi, Ammad Ahmad; Sureda, Antoni; Nabavi, Seyed Mohammad

    2017-03-16

    Nowadays, much attention has been paid to diet and dietary supplements as a cost-effective therapeutic strategy for prevention and treatment of a myriad of chronic and degenerative diseases. Rapidly accumulating scientific evidence achieved through high-throughput technologies has greatly expanded the understanding about the multifaceted nature of cancer. Increasingly, it is being realized that deregulation of spatio-temporally controlled intracellular signaling cascades plays a contributory role in the onset and progression of cancer. Therefore, targeting regulators of oncogenic signaling cascades is essential to prevent and treat cancer. A plethora of preclinical and epidemiological evidences showed promising role of phytochemicals against several types of cancer. Oleanolic acid, a common pentacyclic triterpenoid, is mainly found in olive oil, as well as several plant species. It is a potent inhibitor of cellular inflammatory process and a well-known inducer of phase 2 xenobiotic biotransformation enzymes. Main molecular mechanisms underlying anticancer effects of oleanolic acid are mediated by caspases, 5' adenosine monophosphate-activated protein kinase, extracellular signal-regulated kinase 1/2, matrix metalloproteinases, pro-apoptotic Bax and bid, phosphatidylinositide 3-kinase/Akt1/mechanistic target of rapamycin, reactive oxygen species/apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase, nuclear factor-κB, cluster of differentiation 1, CKD4, s6k, signal transducer and activator of transcription 3, as well as aforementioned signaling pathways . In this work, we critically review the scientific literature on the molecular targets of oleanolic acid implicated in the prevention and treatment of several types of cancer. We also discuss chemical aspects, natural sources, bioavailability, and safety of this bioactive phytochemical.

  4. Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy

    PubMed Central

    Žiberna, Lovro; Šamec, Dunja; Mocan, Andrei; Nabavi, Seyed Fazel; Bishayee, Anupam; Farooqi, Ammad Ahmad; Sureda, Antoni; Nabavi, Seyed Mohammad

    2017-01-01

    Nowadays, much attention has been paid to diet and dietary supplements as a cost-effective therapeutic strategy for prevention and treatment of a myriad of chronic and degenerative diseases. Rapidly accumulating scientific evidence achieved through high-throughput technologies has greatly expanded the understanding about the multifaceted nature of cancer. Increasingly, it is being realized that deregulation of spatio-temporally controlled intracellular signaling cascades plays a contributory role in the onset and progression of cancer. Therefore, targeting regulators of oncogenic signaling cascades is essential to prevent and treat cancer. A plethora of preclinical and epidemiological evidences showed promising role of phytochemicals against several types of cancer. Oleanolic acid, a common pentacyclic triterpenoid, is mainly found in olive oil, as well as several plant species. It is a potent inhibitor of cellular inflammatory process and a well-known inducer of phase 2 xenobiotic biotransformation enzymes. Main molecular mechanisms underlying anticancer effects of oleanolic acid are mediated by caspases, 5′ adenosine monophosphate-activated protein kinase, extracellular signal–regulated kinase 1/2, matrix metalloproteinases, pro-apoptotic Bax and bid, phosphatidylinositide 3-kinase/Akt1/mechanistic target of rapamycin, reactive oxygen species/apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase, nuclear factor-κB, cluster of differentiation 1, CKD4, s6k, signal transducer and activator of transcription 3, as well as aforementioned signaling pathways . In this work, we critically review the scientific literature on the molecular targets of oleanolic acid implicated in the prevention and treatment of several types of cancer. We also discuss chemical aspects, natural sources, bioavailability, and safety of this bioactive phytochemical. PMID:28300756

  5. A Peculiar Formula of Essential Amino Acids Prevents Rosuvastatin Myopathy in Mice

    PubMed Central

    D'Antona, Giuseppe; Tedesco, Laura; Ruocco, Chiara; Corsetti, Giovanni; Ragni, Maurizio; Fossati, Andrea; Saba, Elisa; Fenaroli, Francesca; Montinaro, Mery; Carruba, Michele O.; Valerio, Alessandra

    2016-01-01

    Abstract Aims: Myopathy, characterized by mitochondrial oxidative stress, occurs in ∼10% of statin-treated patients, and a major risk exists with potent statins such as rosuvastatin (Rvs). We sought to determine whether a peculiar branched-chain amino acid-enriched mixture (BCAAem), found to improve mitochondrial function and reduce oxidative stress in muscle of middle-aged mice, was able to prevent Rvs myopathy. Results: Dietary supplementation of BCAAem was able to prevent the structural and functional alterations of muscle induced by Rvs in young mice. Rvs-increased plasma 3-methylhistidine (a marker of muscular protein degradation) was prevented by BCAAem. This was obtained without changes of Rvs ability to reduce cholesterol and triglyceride levels in blood. Rather, BCAAem promotes de novo protein synthesis and reduces proteolysis in cultured myotubes. Morphological alterations of C2C12 cells induced by statin were counteracted by amino acids, as were the Rvs-increased atrogin-1 mRNA and protein levels. Moreover, BCAAem maintained mitochondrial mass and density and citrate synthase activity in skeletal muscle of Rvs-treated mice beside oxygen consumption and ATP levels in C2C12 cells exposed to statin. Notably, BCAAem assisted Rvs to reduce oxidative stress and to increase the anti-reactive oxygen species (ROS) defense system in skeletal muscle. Innovation and Conclusions: The complex interplay between proteostasis and antioxidant properties may underlie the mechanism by which a specific amino acid formula preserves mitochondrial efficiency and muscle health in Rvs-treated mice. Strategies aimed at promoting protein balance and controlling mitochondrial ROS level may be used as therapeutics for the treatment of muscular diseases involving mitochondrial dysfunction, such as statin myopathy. Antioxid. Redox Signal. 25, 595–608. PMID:27245589

  6. Long chain N-3 polyunsaturated fatty acids in the prevention of allergic and cardiovascular disease.

    PubMed

    van den Elsen, Lieke; Garssen, Johan; Willemsen, Linette

    2012-01-01

    The diet is considered to have a major impact on human health. Dietary lipids including long chain polyunsaturated fatty acids (LCPUFA) possess potent immunomodulatory activities. Over the last decades the incidence of inflammatory disorders including allergic and cardiovascular diseases (CVD) has been rising. This phenomenon is associated with deficiencies in N-3 LCPUFA, found in fatty fish, and increased content of N-6 LCPUFA in the Western diet. LCPUFA act via different mechanisms including membrane fluidity, raft composition, lipid mediator formation, signaling pathways and transmembrane receptors. N-3 LCPUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce the development of allergic disease by affecting both the innate and adaptive immune system involved in the initiation and persistence of allergic disease. Fish oil has been shown to be effective in the primary prevention of allergic disease in infants at risk when supplemented during pregnancy and lactation. Subtle effects of N-3 LCPUFA on the outcome of the immune response may underlie these protective effects. This review describes the currently reported effects of LCPUFA on dendritic cells, T cells, B cells and mast cells. Also CVD are positively affected by N-3 LCPUFA. Populations consuming high amounts of oily fish are protected against CVD. Moreover N-3 LCPUFA are effective in the secondary prevention of cardiovascular events. Amongst other effects, EPA and DHA have been shown to suppress endothelial cell activation hereby reducing adhesion molecule expression and endothelial cell - leukocyte interactions. This review describes the mechanistic basis of the preventive role for N-3 LCPUFA in allergic disease and CVD.

  7. 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

  8. 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.

  9. Probiotic Lactobacillus casei strain Shirota prevents indomethacin-induced small intestinal injury: involvement of lactic acid.

    PubMed

    Watanabe, Toshio; Nishio, Hikaru; Tanigawa, Tetsuya; Yamagami, Hirokazu; Okazaki, Hirotoshi; Watanabe, Kenji; Tominaga, Kazunari; Fujiwara, Yasuhiro; Oshitani, Nobuhide; Asahara, Takashi; Nomoto, Koji; Higuchi, Kazuhide; Takeuchi, Koji; Arakawa, Tetsuo

    2009-09-01

    Inflammatory responses triggered by activation of the lipopolysaccharide (LPS)/Toll-like receptor (TLR) 4 signaling pathway are a key mechanism in nonsteroidal anti-inflammatory drug-induced enteropathy. The aim of this study was to investigate the probiotic effect of Lactobacillus casei strain Shirota (LcS) on indomethacin-induced small intestinal injury. Rats pretreated with viable LcS or heat-killed LcS once or once daily for a week were administered indomethacin by gavage to induce injury. Anti-inflammatory effects of L-lactic acid (1-15 mM) were evaluated in vitro by use of THP-1 cells. One-week treatment with viable LcS prevented indomethacin-induced intestinal injury with increase in the concentration of lactic acid in small intestinal content and inhibited increases in myeloperoxidase activity and expression of mRNA for tumor necrosis factor-alpha (TNF-alpha) while affecting neither TLR4 expression nor the number of gram-negative bacteria in intestinal content, whereas neither heat-killed LcS nor a single dose of viable LcS inhibited intestinal injury. Prevention of this injury was also observed in rats given l-lactic acid in drinking water. Both L-lactic acid and LcS culture supernatant containing 10 mM lactic acid inhibited NF-kappaB activation and increases in TNF-alpha mRNA expression and TNF-alpha protein secretion in THP-1 cells treated with LPS. Western blot analyses showed that both L-lactic acid and LcS culture supernatants suppressed phosphorylation and degradation of I-kappaB-alpha induced by LPS without affecting expression of TLR4. These findings suggest that LcS exhibits a prophylactic effect on indomethacin-induced enteropathy by suppressing the LPS/TLR4 signaling pathway and that this probiotic effect of LcS may be mediated by L-lactic acid.

  10. α-Lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria.

    PubMed

    Zee, Tiffany; Bose, Neelanjan; Zee, Jarcy; Beck, Jennifer N; Yang, See; Parihar, Jaspreet; Yang, Min; Damodar, Sruthi; Hall, David; O'Leary, Monique N; Ramanathan, Arvind; Gerona, Roy R; Killilea, David W; Chi, Thomas; Tischfield, Jay; Sahota, Amrik; Kahn, Arnold; Stoller, Marshall L; Kapahi, Pankaj

    2017-03-01

    Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutritional supplement α-lipoic acid inhibits cystine stone formation in the Slc3a1(-/-) mouse model of cystinuria by increasing the solubility of urinary cystine. These findings identify a novel therapeutic strategy for the clinical treatment of cystinuria.

  11. Prevention by lactic acid bacteria of the oxidation of human LDL.

    PubMed

    Terahara, M; Kurama, S; Takemoto, N

    2001-08-01

    Ether extracts of lactic acid bacteria were analyzed for prevention of the oxidation of erythrocyte membrane and human low-density lipoprotein in vivo. Streptococcus thermophilus 1131 and Lactobacillus delbrueckii subsp. bulgaricus 2038, yogurt starters, were chosen as test-strains, and ether extracts of these cultures were used as samples. Both strain 1131 and strain 2038 produced radical scavengers and inhibited oxidation of erythrocyte membranes and low-density lipoproteins. The antioxidative activity of strain 2038 was higher than that of strain 1131.

  12. Sulforaphane prevents quinolinic acid-induced mitochondrial dysfunction in rat striatum.

    PubMed

    Luis-García, Erika Rubí; Limón-Pacheco, Jorge Humberto; Serrano-García, Norma; Hernández-Pérez, Alma Delia; Pedraza-Chaverri, José; Orozco-Ibarra, Marisol

    2017-02-01

    Quinolinic acid (QA) triggers striatal neuronal death by an excitotoxic cascade that involves oxidative stress, which in turns is tightly linked to mitochondria. Mitochondrial dysfunction is a molecular feature described in several brain pathologies. In this work, we determined whether the sulforaphane-neuroprotective effect in the rodent experimental model of Huntington's disease induced by QA is associated with mitochondrial function preservation. We found that QA impaired mitochondrial function within 24 h post-lesion. Sulforaphane effectively disrupted the mitochondrial dysfunction by preventing the decrease in respiratory control ratio, transmembrane potential, ability to synthetize ATP, and the activity of mitochondrial complexes I, II, and IV. © 2016 Wiley Periodicals, Inc.

  13. Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

    PubMed Central

    2011-01-01

    The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis. PMID:21375761

  14. 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.

  15. Antimicrobial activity of transition metal acid MoO(3) prevents microbial growth on material surfaces.

    PubMed

    Zollfrank, Cordt; Gutbrod, Kai; Wechsler, Peter; Guggenbichler, Josef Peter

    2012-01-01

    Serious infectious complications of patients in healthcare settings are often transmitted by materials and devices colonised by microorganisms (nosocomial infections). Current strategies to generate material surfaces with an antimicrobial activity suffer from the consumption of the antimicrobial agent and emerging multidrug-resistant pathogens amongst others. Consequently, materials surfaces exhibiting a permanent antimicrobial activity without the risk of generating resistant microorganisms are desirable. This publication reports on the extraordinary efficient antimicrobial properties of transition metal acids such as molybdic acid (H(2)MoO(4)), which is based on molybdenum trioxide (MoO(3)). The modification of various materials (e.g. polymers, metals) with MoO(3) particles or sol-gel derived coatings showed that the modified materials surfaces were practically free of microorganisms six hours after contamination with infectious agents. The antimicrobial activity is based on the formation of an acidic surface deteriorating cell growth and proliferation. The application of transition metal acids as antimicrobial surface agents is an innovative approach to prevent the dissemination of microorganisms in healthcare units and public environments. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. The potential role of boswellic acids in cancer prevention and treatment.

    PubMed

    Roy, Nand Kishor; Deka, Anindita; Bordoloi, Devivasha; Mishra, Srishti; Kumar, Alan Prem; Sethi, Gautam; Kunnumakkara, Ajaikumar B

    2016-07-10

    Despite the extensive research carried out in the field of cancer therapeutics, cancer is one of the most dreadful diseases in the world with no definitive treatment to date. The key attributes responsible for this are the various limiting factors associated with conventional chemotherapeutics that primarily include adverse side-effects and development of chemoresistance. Hence, there is an utter need to find compounds that are highly safe and efficacious for the prevention and treatment of cancer. Boswellic acid, a group of pentacyclic compounds, seems to be promising enough due to its inherent anti-cancerous properties. Considering this perspective, the present review highlights the established studies related to the anti-cancer potential of boswellic acid against different cancer types. The molecular mechanisms underlying the targets of boswellic acid that are accountable for its potent anti-cancer effect are also discussed. Overall, this review projects the pieces of evidence that reveal the potential of boswellic acid as a suitable candidate that can be appropriately developed and designed into a promising anti-cancer drug. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Acetylsalicylic Acid and Eflornithine in Treating Patients at High Risk for Colorectal Cancer | Division of Cancer Prevention

    Cancer.gov

    This phase II trial is studying how well giving acetylsalicylic acid together with eflornithine works in treating patients at high risk for colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acetylsalicylic acid and eflornithine may prevent colorectal cancer. |

  18. Docosahexaenoic acid supplementation early in pregnancy may prevent deep placentation disorders.

    PubMed

    Carvajal, Jorge A

    2014-01-01

    Uteroplacental ischemia may cause preterm birth, either due to preterm labor, preterm premature rupture of membranes, or medical indication (in the presence of preeclampsia or fetal growth restriction). Uteroplacental ischemia is the product of defective deep placentation, a failure of invasion, and transformation of the spiral arteries by the trophoblast. The failure of normal placentation generates a series of clinical abnormalities nowadays called "deep placentation disorders"; they include preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, in utero fetal death, and placental abruption. Early reports suggested that a LC-PUFAs (long chain polyunsaturated fatty acids) rich diet reduces the incidence of deep placentation disorders. Recent randomized controlled trials are inconsistent to show the benefit of docosahexaenoic acid (DHA) supplementation during pregnancy to prevent deep placentation disorders, but most of them showed that DHA supplementation was associated with lower risk of early preterm birth. We postulate that DHA supplementation, early in pregnancy, may reduce the incidence of deep placentation disorders. If our hypothesis is correct, DHA supplementation, early in pregnancy, will become a safe and effective strategy for primary prevention of highly relevant pregnancy diseases, such as preterm birth, preeclampsia, and fetal growth restriction.

  19. Docosahexaenoic Acid Supplementation Early in Pregnancy May Prevent Deep Placentation Disorders

    PubMed Central

    Carvajal, Jorge A.

    2014-01-01

    Uteroplacental ischemia may cause preterm birth, either due to preterm labor, preterm premature rupture of membranes, or medical indication (in the presence of preeclampsia or fetal growth restriction). Uteroplacental ischemia is the product of defective deep placentation, a failure of invasion, and transformation of the spiral arteries by the trophoblast. The failure of normal placentation generates a series of clinical abnormalities nowadays called “deep placentation disorders”; they include preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, in utero fetal death, and placental abruption. Early reports suggested that a LC-PUFAs (long chain polyunsaturated fatty acids) rich diet reduces the incidence of deep placentation disorders. Recent randomized controlled trials are inconsistent to show the benefit of docosahexaenoic acid (DHA) supplementation during pregnancy to prevent deep placentation disorders, but most of them showed that DHA supplementation was associated with lower risk of early preterm birth. We postulate that DHA supplementation, early in pregnancy, may reduce the incidence of deep placentation disorders. If our hypothesis is correct, DHA supplementation, early in pregnancy, will become a safe and effective strategy for primary prevention of highly relevant pregnancy diseases, such as preterm birth, preeclampsia, and fetal growth restriction. PMID:25019084

  20. Alpha-lipoic acid and alpha-lipoamide prevent oxidant-induced lysosomal rupture and apoptosis.

    PubMed

    Persson, H L; Svensson, A I; Brunk, U T

    2001-01-01

    Alpha-lipoic acid (LA) and its corresponding derivative, alpha-lipoamide (LM), have been described as antioxidants, but the mechanisms of their putative antioxidant effects remain largely uncharacterised. The vicinal thiols present in the reduced forms of these compounds suggest that they might possess metal chelating properties. We have shown previously that cell death caused by oxidants may be initiated by lysosomal rupture and that this latter event may involve intralysosomal iron which catalyzes Fenton-type chemistry and resultant peroxidative damage to lysosomal membranes. Here, using cultured J774 cells as a model, we show that both LA and LM stabilize lysosomes against oxidative stress, probably by chelating intralysosomal iron and, consequently, preventing intralysosomal Fenton reactions. In preventing oxidant-mediated apoptosis, LM is significantly more effective than LA, as would be expected from their differing capacities to enter cells and concentrate within the acidic lysosomal compartment. As previously reported, the powerful iron-chelator, desferrioxamine (Des) (which also locates within the lysosomal compartment), also provides protection against oxidant-mediated cell death. Interestingly, although Des enhances the partial protection afforded by LA, it confers no additional protection when added with LM. Therefore, the antioxidant actions of LA and LM may arise from intralysosomal iron chelation, with LM being more effective in this regard.

  1. Ursolic Acid Inhibits Na+/K+-ATPase Activity and Prevents TNF-α-Induced Gene Expression by Blocking Amino Acid Transport and Cellular Protein Synthesis

    PubMed Central

    Yokomichi, Tomonobu; Morimoto, Kyoko; Oshima, Nana; Yamada, Yuriko; Fu, Liwei; Taketani, Shigeru; Ando, Masayoshi; Kataoka, Takao

    2011-01-01

    Pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, induce the expression of a wide variety of genes, including intercellular adhesion molecule-1 (ICAM-1). Ursolic acid (3β-hydroxy-urs-12-en-28-oic acid) was identified to inhibit the cell-surface ICAM-1 expression induced by pro-inflammatory cytokines in human lung carcinoma A549 cells. Ursolic acid was found to inhibit the TNF-α-induced ICAM-1 protein expression almost completely, whereas the TNF-α-induced ICAM-1 mRNA expression and NF-κB signaling pathway were decreased only partially by ursolic acid. In line with these findings, ursolic acid prevented cellular protein synthesis as well as amino acid uptake, but did not obviously affect nucleoside uptake and the subsequent DNA/RNA syntheses. This inhibitory profile of ursolic acid was similar to that of the Na+/K+-ATPase inhibitor, ouabain, but not the translation inhibitor, cycloheximide. Consistent with this notion, ursolic acid was found to inhibit the catalytic activity of Na+/K+-ATPase. Thus, our present study reveals a novel molecular mechanism in which ursolic acid inhibits Na+/K+-ATPase activity and prevents the TNF-α-induced gene expression by blocking amino acid transport and cellular protein synthesis. PMID:24970122

  2. Beta-aminoisobutyric acid prevents diet-induced obesity in mice with partial leptin deficiency.

    PubMed

    Begriche, Karima; Massart, Julie; Abbey-Toby, Adjé; Igoudjil, Anissa; Lettéron, Philippe; Fromenty, Bernard

    2008-09-01

    Beta-Aminoisobutyric acid (BAIBA), a thymine catabolite, increases fatty acid oxidation (FAO) in liver and reduces the gain of body fat mass in Swiss (lean) mice fed a standard chow. We determined whether BAIBA could prevent obesity and related metabolic disorders in different murine models. To this end, BAIBA (100 or 500 mg/kg/day) was administered for 4 months in mice totally deficient in leptin (ob/ob). BAIBA (100 mg/kg/day) was also given for 4 months in wild-type (+/+) mice and mice partially deficient in leptin (ob/+) fed a high-calorie (HC) diet. BAIBA did not limit obesity and hepatic steatosis in ob/ob mice, but reduced liver cytolysis and inflammation. In ob/+ mice fed the HC diet, BAIBA fully prevented, or limited, the gain of body fat, steatosis and necroinflammation, glucose intolerance, and hypertriglyceridemia. Plasma beta-hydroxybutyrate was increased, whereas expression of carnitine palmitoyltransferase-1 was augmented in liver and white adipose tissue. Acetyl-CoA carboxylase was more phosphorylated, and de novo lipogenesis was less induced in liver. These favorable effects of BAIBA in ob/+ mice were associated with a restoration of plasma leptin levels. The reduction of body adiposity afforded by BAIBA was less marked in +/+ mice. Finally, BAIBA significantly stimulated the secretion of leptin in isolated ob/+ adipose cells, but not in +/+ cells. Thus, BAIBA could limit triglyceride accretion in tissues through a leptin-dependent stimulation of FAO. As partial leptin deficiency is not uncommon in the general population, supplementation with BAIBA may help to prevent diet-induced obesity and related metabolic disorders in low leptin secretors.

  3. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

    PubMed Central

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

    2013-01-01

    In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  4. Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis

    PubMed Central

    Shirkhani, Khojasteh; Teo, Ian; Armstrong-James, Darius; Shaunak, Sunil

    2015-01-01

    Aspergillus species are the major life threatening fungal pathogens in transplant patients. Germination of inhaled fungal spores initiates infection, causes severe pneumonia, and has a mortality of > 50%. This is leading to the consideration of pre-exposure prophylaxis to prevent infection. We made a very low MWt amphotericin B-polymethacrylic acid nanoparticle. It was not toxic to lung epithelial cells or monocyte-derived-macrophages in-vitro, or in an in-vivo transplant immuno-suppression mouse model of life threatening invasive aspergillosis. Three days of nebuliser based prophylaxis delivered the nanoparticle effectively to lung and prevented both fungal growth and lung inflammation. Protection from disease was associated with > 99% killing of the Aspergillus and a 90% reduction in lung TNF-α; the primary driver of tissue destructive immuno-pathology. This study provides in-vivo proof-of-principle that very small and cost-effective nanoparticles can be made simply, and delivered safely and effectively to lung by the aerosol route to prevent fungal infections. From the Clinical Editor Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The authors here made PMA based anionic hydrogels carrying amphotericin B, with mucoadhesive behavior. They showed that aerosol route of the drug was very effective in protecting against the disease in an in-vivo model and should provide a stepping-stone towards clinical trials in the future. PMID:25791815

  5. Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models

    PubMed Central

    Li, Shunan; Abedin, Md. Joynal; Noppakun, Kajohnsak; Wang, Lawrence; Kaur, Tarundeep; Najafian, Behzad; Rodrigues, Cecília M. P.

    2012-01-01

    Background Acute kidney injury (AKI) has grave short- and long-term consequences. Often the onset of AKI is predictable, such as following surgery that compromises blood flow to the kidney. Even in such situations, present therapies cannot prevent AKI. As apoptosis is a major form of cell death following AKI, we determined the efficacy and mechanisms of action of tauroursodeoxycholic acid (TUDCA), a molecule with potent anti-apoptotic and pro-survival properties, in prevention of AKI in rat and cell culture models. TUDCA is particularly attractive from a translational standpoint, as it has a proven safety record in animals and humans. Methodology/Principal Findings We chose an ischemia-reperfusion model in rats to simulate AKI in native kidneys, and a human kidney cell culture model to simulate AKI associated with cryopreservation in transplanted kidneys. TUDCA significantly ameliorated AKI in the test models due to inhibition of the mitochondrial pathway of apoptosis and upregulation of survival pathways. Conclusions This study sets the stage for testing TUDCA in future clinical trials for prevention of AKI, an area that needs urgent attention due to lack of effective therapies. PMID:23152827

  6. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid.

    PubMed

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E; Redhi, Godfrey H; Panlilio, Leigh V; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R

    2013-11-01

    In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse.

  7. Allergy-preventive effects of chlorogenic acid and iridoid derivatives from flower buds of Lonicera japonica.

    PubMed

    Oku, Hisae; Ogawa, Yuko; Iwaoka, Emiko; Ishiguro, Kyoko

    2011-01-01

    Allergy-preventive activity of flower buds of Lonicera japonica THUNB. was found in the 35% EtOH extract (LJ) using an in vivo assay, The assay system uses monitoring of a decrease in blood flow (BF) in the tail vein of mice subjected to sensitization with hen-egg white lysozyme (HEL). Bioassay-guided fractionation of the 35% EtOH extract led to isolation of chlorogenic acid (1) and three known iridoid derivatives, loganin (2), secoxyloganin (3) and sweroside (4), all of which inhibited the BF decrease. This suggested that the flower buds of L. japonica and compounds isolated from them have allergy-preventive properties. The structure-activity relationship of iridoid derivatives, morroniside (5), geniposide (6), asperuloside (7), aucubin (8) and catalpol (9), were also tested using the same bioassay method. Compounds 2-5 and 9 having the sp(3) atom at C-8 showed an allergy-preventive effect, while compounds 6, 7 and 8 having a double bond at C-7, C-8 did not.

  8. Valproic Acid Prevents Renal Dysfunction and Inflammation in the Ischemia-Reperfusion Injury Model

    PubMed Central

    Costalonga, Elerson C.; Silva, Filipe M. O.; Noronha, Irene L.

    2016-01-01

    Ischemia-reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI). At present, there are no effective therapies to prevent AKI. The aim of this study was to analyse whether valproic acid (VPA), a histone deacetylase inhibitor with anti-inflammatory properties, prevents renal IRI. Male Wistar rats were divided into three groups: SHAM rats were subjected to a SHAM surgery, IRI rats underwent bilateral renal ischemia for 45 min, and IRI + VPA rats were treated with VPA at 300 mg/kg twice daily 2 days before bilateral IRI. Animals were euthanized at 48 hours after IRI. VPA attenuated renal dysfunction after ischemia, which was characterized by a decrease in BUN (mg/dL), serum creatinine (mg/dL), and FENa (%) in the IRI + VPA group (39 ± 11, 0.5 ± 0.05, and 0.5 ± 0.06, resp.) compared with the IRI group (145 ± 35, 2.7 ± 0.05, and 4.9 ± 1, resp.; p < 0.001). Additionally, significantly lower acute tubular necrosis grade and number of apoptotic cells were found in the IRI + VPA group compared to the IRI group (p < 0.001). Furthermore, VPA treatment reduced inflammatory cellular infiltration and expression of proinflammatory cytokines. These data suggest that VPA prevents the renal dysfunction and inflammation that is associated with renal IRI. PMID:27195290

  9. [THE INFLUENCE OF THE POLYUNSATURATED FATTY ACIDS IN THE PREVENTION AND PROMOTION OF CANCER].

    PubMed

    Cabo-García, Liliana; Achón-Tuñón, María; González-González, M Purificación

    2015-07-01

    each year, almost eight million people die in the world due to cancer. Carcinogenesis is a process that involves a series of structural alterations of the DNA which affect its stability and prevents proper cell reproduction and development. There are many factors that influence the cancer etiology. Nutritional factors are included among them. The polyunsaturated fatty acids (PUFA) intake is associated more and more with the prevention and development of chronic diseases with an inflammatory component such as cancer. this work reviews the latest bibliography on the PUFA and its relationship with the cancer, mainly of prostate, breast and colon cancer. the preliminary search resulted in 92 selected references. But, after their review, 40 experimental studies, in animals and in vitro, and epidemiological studies have been included. experimental studies in animals and in vitro reviewed show a protective effect of ω3 PUFA against cancer. However, human studies are contradictory; although it is clear there is evidence of the protective effect of the ω3 PUFA in colon cancer prevention. the relationship between ω6 and ω3 PUFA of the diet against the cancer risk is becoming increasingly important, but further studies are needed to confirm their influence on the development of this disease. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  10. Zoledronic acid at the time of castration prevented castration-induced bone metastasis in mice.

    PubMed

    Ghosh, Paramita M; Gao, Allen C

    2014-10-01

    Androgen deprivation therapy (ADT) is known to cause bone loss in a majority of patients with castration-resistant prostate cancer (CRPC). A study published in this issue of Endocrine-Related Cancer by Ottewell and colleagues shows that ADT increased bone resorption and triggered growth of disseminated prostate cancer (CaP) cells to form bone metastasis using an in vivo model. However, prevention of bone decay by weekly administration of zoledronic acid (ZOL) at the time of castration prevented ADT-induced tumor growth in bone. Recently, two publications from Japan have demonstrated that ZOL combined with ADT improved outcomes for patients with treatment-naïve CaP with bone metastasis. The mechanistic cause for these patients having an improved overall survival compared with those who were treated with ZOL after ADT initiation or before metastasis development was never explained. Ottewell and colleague's study now suggests that it is the bone loss caused by ADT that promoted bone metastasis, and if ZOL is administered at the time of ADT initiation, it would prevent this bone loss and prolong skeletal-related event-free survival.

  11. The use of folic acid for the prevention of neural tube defects and other congenital anomalies.

    PubMed

    Wilson, R Douglas; Davies, Gregory; Désilets, Valérie; Reid, Gregory J; Summers, Anne; Wyatt, Philip; Young, David

    2003-11-01

    To provide information regarding the use of folic acid for the prevention of neural tube defects (NTDs) and other congenital anomalies, in order that physicians, midwives, nurses, and other health-care workers can assist in the education of women in the preconception phase of their health care. OPTION: Folic acid supplementation is problematic, since 50% of pregnancies are unplanned and the health status of women may not be optimal. Folic acid supplementation has been proven to decrease or minimize specific birth defects. A systematic review of the literature, including review and peer-reviewed articles, government publications, the previous Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of March 1993, and statements from the American College of Obstetrics and Gynecology, was used to develop a new clinical practice guideline for the SOGC. Peer-review process within the committee structure. The benefit is reduced lethal and severe morbidity birth defects and the harm is minimal. The personal cost is of vitamin supplementation on a daily basis and eating a healthy diet. 1. Women in the reproductive age group should be advised about the benefits of folic acid supplementation during wellness visits (birth control renewal, Pap testing, yearly examination), especially if pregnancy is contemplated. (III-A) 2. Women should be advised to maintain a healthy nutritional diet, as recommended in Canada's Food Guide to Healthy Eating (good or excellent sources of folic acid: broccoli, spinach, peas, Brussels sprouts, corn, beans, lentils, oranges). (III-A) 3. Women who could become pregnant should be advised to take a multivitamin containing 0.4 mg to 1.0 mg of folic acid daily. (II-1A) 4. Women taking a multivitamin with folic acid supplement should be advised not to take more than 1 daily dose of vitamin supplement, as indicated on the product label. (II-2A) 5. Women in intermediate- to high-risk categories for NTDs (NTD-affected previous

  12. Omega-3 fatty acid oxidation products prevent vascular endothelial cell activation by coplanar polychlorinated biphenyls

    SciTech Connect

    Majkova, Zuzana; Layne, Joseph; Sunkara, Manjula; Morris, Andrew J.; Toborek, Michal; Hennig, Bernhard

    2011-02-15

    Coplanar polychlorinated biphenyls (PCBs) may facilitate development of atherosclerosis by stimulating pro-inflammatory pathways in the vascular endothelium. Nutrition, including fish oil-derived long-chain omega-3 fatty acids, such as docosahexaenoic acid (DHA, 22:6{omega}-3), can reduce inflammation and thus the risk of atherosclerosis. We tested the hypothesis that cyclopentenone metabolites produced by oxidation of DHA can protect against PCB-induced endothelial cell dysfunction. Oxidized DHA (oxDHA) was prepared by incubation of the fatty acid with the free radical generator 2,2-azo-bis(2-amidinopropane) dihydrochloride (AAPH). Cellular pretreatment with oxDHA prevented production of superoxide induced by PCB77, and subsequent activation of nuclear factor-{kappa}B (NF-{kappa}B). A{sub 4}/J{sub 4}-neuroprostanes (NPs) were identified and quantitated using HPLC ESI tandem mass spectrometry. Levels of these NPs were markedly increased after DHA oxidation with AAPH. The protective actions of oxDHA were reversed by treatment with sodium borohydride (NaBH{sub 4}), which concurrently abrogated A{sub 4}/J{sub 4}-NP formation. Up-regulation of monocyte chemoattractant protein-1 (MCP-1) by PCB77 was markedly reduced by oxDHA, but not by un-oxidized DHA. These protective effects were proportional to the abundance of A{sub 4}/J{sub 4} NPs in the oxidized DHA sample. Treatment of cells with oxidized eicosapentaenoic acid (EPA, 20:5{omega}-3) also reduced MCP-1 expression, but less than oxDHA. Treatment with DHA-derived cyclopentenones also increased DNA binding of NF-E2-related factor-2 (Nrf2) and downstream expression of NAD(P)H:quinone oxidoreductase (NQO1), similarly to the Nrf-2 activator sulforaphane. Furthermore, sulforaphane prevented PCB77-induced MCP-1 expression, suggesting that activation of Nrf-2 mediates the observed protection against PCB77 toxicity. Our data implicate A{sub 4}/J{sub 4}-NPs as mediators of omega-3 fatty acid-mediated protection against the

  13. Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: Prevention with folic acid

    PubMed Central

    Sarmah, Swapnalee; Marrs, James A.

    2014-01-01

    BACKGROUND Fetal alcohol spectrum disorder (FASD) describes a range of birth defects including various congenital heart defects (CHDs). Mechanisms of FASD-associated CHDs are not understood. Whether alcohol interferes with a single critical event or with multiple events in heart formation is not known. RESULTS Our zebrafish embryo experiments showed that ethanol interrupts different cardiac regulatory networks and perturbed multiple steps of cardiogenesis (specification, myocardial migration, looping, chamber morphogenesis and endocardial cushion formation). Ethanol exposure during gastrulation until cardiac specification or during myocardial midline migration did not produce severe or persistent heart development defects. However, exposure comprising gastrulation until myocardial precursor midline fusion or during heart patterning stages produced aberrant heart looping and defective endocardial cushions. Continuous exposure during entire cardiogenesis produced complex cardiac defects leading to severely defective myocardium, endocardium, and endocardial cushions. Supplementation of retinoic acid with ethanol partially rescued early heart developmental defects, but the endocardial cushions did not form correctly. In contrast, supplementation of folic acid rescued normal heart development, including the endocardial cushions. CONCLUSIONS Our results indicate that ethanol exposure interrupted divergent cardiac morphogenesis events causing heart defects. Folic acid supplementation was effective in preventing a wide spectrum of ethanol-induced heart developmental defects. PMID:23832875

  14. Conjugated linoleic acid prevents high glucose-induced hypertrophy and contractile dysfunction in adult rat cardiomyocytes.

    PubMed

    Aloud, Basma Milad; Raj, Pema; O'Hara, Kimberley; Shao, Zongjun; Yu, Liping; Anderson, Hope D; Netticadan, Thomas

    2016-02-01

    Diabetes mellitus is associated with increased risk and incidence of cardiovascular morbidity and mortality, independently of other risk factors typically associated with diabetes such as coronary artery disease and hypertension. This promotes the development of a distinct condition of the heart muscle known as diabetic cardiomyopathy. We have previously shown that conjugated linoleic acid (CLA) prevents endothelin-1-induced cardiomyocyte hypertrophy. However, the effects of CLA in preventing alterations in cardiomyocyte structure and function due to high glucose are unknown. We therefore hypothesized that CLA will have protective effects in an in vitro model of diabetic cardiomyopathy using adult rat cardiomyocytes exposed to high glucose. Our results demonstrate that subjecting adult rat cardiomyocytes to high glucose (25 mmol/L) for 24 hours significantly impaired the contractile function as evidenced by decreases in maximal velocity of shortening, peak shortening, and maximal velocity of relengthening. High glucose-induced contractile dysfunction was inhibited by pretreatment with CLA (30 μmol/L; 1 hour). In addition to contractile aberrations, exposing adult rat cardiomyocytes to high glucose for 48 hours induced cardiomyocyte hypertrophy. High glucose-induced cardiomyocyte hypertrophy was likewise prevented by CLA. The antihypertrophic effects of CLA were abolished when cardiomyocytes were pretreated with the pharmacologic inhibitor of peroxisome proliferator-activated receptor γ, GW9662 (1 μmol/L). In conclusion, our findings show that exposing cardiomyocytes to high glucose results in cardiomyocyte functional and structural abnormalities, and these abnormalities are prevented by pretreatment with CLA and mediated, in part, by peroxisome proliferator-activated receptor γ activation. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  15. Dietary n-3 long chain polyunsaturated fatty acids in allergy prevention and asthma treatment.

    PubMed

    Willemsen, Linette E M

    2016-08-15

    The rise in non-communicable diseases, such as allergies, in westernized countries links to changes in lifestyle and diet. N-3 long chain polyunsaturated fatty acids (LCPUFA) present in marine oils facilitate a favorable milieu for immune maturation and may contribute to allergy prevention. N-3 LCPUFA can suppress innate and adaptive immune activation and induce epigenetic changes. Murine studies convincingly show protective effects of fish oil, a source of n-3 LCPUFA, in food allergy and asthma models. Observational studies in human indicate that high dietary intake of n-3 LCPUFA and low intake of n-6 PUFA may protect against the development of allergic disease early in life. High n-6 PUFA intake is also associated with an increased asthma risk while n-3 LCPUFA may be protective and reduce symptoms. The quality of the marine oil used has impact on efficacy of allergy prevention and several observations link in particular n-3 LCPUFA DHA to allergy suppression. Randomized controlled trials indicate that optimal timing, duration and dosage of n-3 LC-PUFA is required to exert an allergy protective effect. Supplementation during early pregnancy and lactation has shown promising results regarding allergy prevention. However these findings should be confirmed in a larger cohort. Although clinical trials in asthma patients reveal no consistent clinical benefits of n-3 LCPUFA supplementation on lung function, it can suppress airway inflammation. Future food-pharma approaches may reveal whether adjunct therapy with dietary n-3 LCPUFA can improve allergy prevention or immunotherapy via support of allergen specific oral tolerance induction or contribute to the efficacy of drug therapy for asthma patients.

  16. Sodium 4-phenylbutyric acid prevents murine acetaminophen hepatotoxicity by minimizing endoplasmic reticulum stress.

    PubMed

    Kusama, Hiromi; Kon, Kazuyoshi; Ikejima, Kenichi; Arai, Kumiko; Aoyama, Tomonori; Uchiyama, Akira; Yamashina, Shunhei; Watanabe, Sumio

    2017-05-01

    Acetaminophen (APAP) overdose induces severe oxidative stress followed by hepatocyte apoptosis/necrosis. Previous studies have indicated that endoplasmic reticulum (ER) stress is involved in the cell death process. Therefore, we investigated the effect of the chemical chaperone 4-phenyl butyric acid (PBA) on APAP-induced liver injury in mice. Eight-week-old male C57Bl6/J mice were given a single intraperitoneal (i.p.) injection of APAP (450 mg/kg body weight), following which some were repeatedly injected with PBA (120 mg/kg body weight, i.p.) every 3 h starting at 0.5 h after the APAP challenge. All mice were then serially euthanized up to 12 h later. PBA treatment dramatically ameliorated the massive hepatocyte apoptosis/necrosis that was observed 6 h after APAP administration. PBA also significantly prevented the APAP-induced increases in cleaved activating transcription factor 6 and phosphorylation of c-Jun N-terminal protein kinase and significantly blunted the increases in mRNA levels for binding immunoglobulin protein, spliced X-box binding protein-1, and C/EBP homologous protein. Moreover, PBA significantly prevented APAP-induced Bax translocation to the mitochondria, and the expression of heme oxygenase-1 mRNA and 4-hydroxynonenal. By contrast, PBA did not affect hepatic glutathione depletion following APAP administration, reflecting APAP metabolism. PBA prevents APAP-induced liver injury even when an APAP challenge precedes its administration. The underlying mechanism of action most likely involves the prevention of ER stress-induced apoptosis/necrosis in the hepatocytes during APAP intoxication.

  17. Vitamin E supplementation does not prevent ethanol-reduced hepatic retinoic acid levels in rats.

    PubMed

    Chung, Jayong; Veeramachaneni, Sudipta; Liu, Chun; Mernitz, Heather; Russell, Robert M; Wang, Xiang-Dong

    2009-09-01

    Chronic, excessive ethanol intake can increase retinoic acid (RA) catabolism by inducing cytochrome P450 2E1 (CYP2E1). Vitamin E (VE) is an antioxidant implicated in CYP2E1 inhibition. In the current study, we hypothesized that VE supplementation inhibits CYP2E1 and decreases RA catabolism, thereby preventing ethanol-induced hepatocyte hyperproliferation. For 1 month, 4 groups of Sprague-Dawley rats were fed a Lieber-DeCarli liquid ethanol (36% of the total energy) diet as follows: either ethanol alone (Alc group) or ethanol in combination with 0.1 mg/kg body weight of all-trans-RA (Alc + RA group), 2 mg/kg body weight of VE (Alc + VE group), or both together (Alc + RA + VE group). Control rats were pair-fed a liquid diet with an isocaloric amount of maltodextrin instead of ethanol. The ethanol-fed groups had 3-fold higher hepatic CYP2E1 levels, 50% lower hepatic RA levels, and significantly increased hepatocyte proliferation when compared with the controls. The ethanol-fed rats given VE had more than 4-fold higher hepatic VE concentrations than the ethanol-fed rats without VE, but this did not prevent ethanol induction of CYP2E1, lower hepatic retinoid levels, or hepatocellular hyperproliferation. Furthermore, VE supplementation could not prevent RA catabolism in liver microsomal fractions of the ethanol-fed rats in vitro. These results show that VE supplementation can neither inhibit ethanol-induced changes in RA catabolism nor prevent ethanol-induced hepatocyte hyperproliferation in the rat liver.

  18. Doubling the number of women consuming vitamin supplement pills containing folic acid: an urgently needed birth defect prevention complement to the folic acid fortification of cereal grains.

    PubMed

    Oakley, G P

    1997-01-01

    The major known environmental causes of birth defects are ancient agents that have been in the environment for centuries but have been only recently discovered-rubella, alcohol, and folic acid deficiency. In the United States, we have made great progress in preventing congenital rubella syndrome. We also have a great opportunity to prevent spina bifida and anencephaly (SBA) by increasing the number of women who daily consume vitamin supplements containing folic acid. Even with the recently announced grain fortification regulations, there are 45 million women unprotected from an SBA-affected pregnancy. This article suggests that a substantial educational campaign could, over a 5-year period, double the number of women consuming folic acid supplement pills and make a substantial contribution toward preventing SBA.

  19. Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer's disease.

    PubMed

    Cornejo, Alberto; Aguilar Sandoval, Felipe; Caballero, Leonardo; Machuca, Luis; Muñoz, Patricio; Caballero, Julio; Perry, George; Ardiles, Alejandro; Areche, Carlos; Melo, Francisco

    2017-12-01

    Alzheimer's disease is a common tauopathy where fibril formation and aggregates are the hallmark of the disease. Efforts targeting amyloid-β plaques have succeeded to remove plaques but failed in clinical trials to improve cognition; thus, the current therapeutic strategy is at preventing tau aggregation. Here, we demonstrated that four phenolic diterpenoids and rosmarinic acid inhibit fibrillization. Since, rosmarinic acid was the most active compound, we observe morphological changes in atomic force microscopy images after treatment. Hence, rosmarinic acid leads to a decrease in amide regions I and III, indicating that rosmarinic acid prevents β-sheet assembly. Molecular docking study inside the steric zipper model of the hexapeptide (306)VQIVYK(311) involved in fibrillization and β sheet formation, suggests that rosmarinic acid binds to the steric zipper with similar chemical interactions with respect to those observed for orange G, a known pharmacofore for amyloid.

  20. Zoledronic acid prevents loss of trabecular bone after focal irradiation in mice.

    PubMed

    Keenawinna, Lihini; Oest, Megan E; Mann, Kenneth A; Spadaro, Joseph; Damron, Timothy A

    2013-07-01

    Radiation therapy for soft tissue sarcomas and metastatic disease can adversely affect bone, leading to late-onset fragility fractures. Adjunct administration of bisphosphonates has been postulated as means of minimizing these adverse effects. Using a murine model of focal hindlimb irradiation, we examined the potential for zoledronic acid treatment to minimize the deleterious effects of localized radiotherapy (RTx) on bone. Mice received a single, unilateral hindlimb exposure of 20 Gy. Beginning 4 days prior to irradiation, and at 1, 2 and 3 weeks post-irradiation, animals were treated with zoledronic acid or saline/vehicle injections. Areal bone mineral density was assessed at 4 days, and 2, 4 and 12 weeks post-irradiation by dual-energy X-ray absorptiometry (DXA). Micro-computed tomography and axial compression testing were used to quantify changes in morphological and mechanical properties of femurs at 4 and 12 weeks post-irradiation. Radiation had differential effects on cortical and trabecular bone, increasing cortical bone mineral content (BMC), cortical bone volume (BV) and trabecular separation (Tb.Sp) while decreasing trabecular number (Tb.N) by 12 weeks after localized radiotherapy. Administration of zoledronic acid increased hindlimb areal bone mineral density in both the presence and absence of radiotherapy, increased cortical bone mineral content and bone volume, increased trabecular bone volume (BV/TV), increased trabecular number, increased trabecular thickness (Tb.Th), and decreased trabecular separation compared to irradiated and vehicle control femurs. Despite these improvements in morphology with zoledronic acid, no biomechanical advantage was observed. Further work is needed to define the role of bisphosphonates in prevention of post-irradiation fragility fractures.

  1. ω-3 fatty acids in the prevention of cognitive decline in humans.

    PubMed

    Cederholm, Tommy; Salem, Norman; Palmblad, Jan

    2013-11-01

    The brain is a lipid-rich organ where docosahexaenoic acid (DHA) is enriched and where eicosapentaenoic acid (EPA) may have anti-inflammatory effects. The potential role for n-3 (ω-3) fatty acids such as DHA and EPA in the prevention of cognitive decline, including Alzheimer's disease (AD) has attracted major interest for the past 20 y. This review presents our understanding of recent observational, interventional, and experimental studies, with the aim of providing some answers to the following question: Can n-3 FA intake modulate cognitive function during aging? In longitudinal observation studies we mainly observe inverse relations between fish intake or serum concentrations of DHA and cognitive impairment. Intervention studies of EPA and DHA supplementation in healthy old individuals have been negative so far (i.e., after up to 2 years of treatment, no differences in cognitive decline between treated and nontreated participants have been observed). In studies that provided EPA and DHA to adults with mild cognitive impairment or age-related cognitive impairment the data seem to be positive. However, when patients with established AD were supplemented with EPA and DHA it appears no benefit was gained. For studies on healthy individuals, a major concern is that the treatment periods may have been too short. There might also be subgroup effects because of the carriage of apolipoprotein Eε4 alleles or risk factor burden. Experimental studies appear to be consistently positive (i.e., n-3 FA supplementation in rodents over a substantial portion of their lives reduces amyloid-β deposition and hippocampal neuron loss and improves cognitive functioning). We are getting closer to providing evidence-based recommendations on fish and fish oil intake to facilitate memory function during old age. In the meantime it is advised to follow the general CDC dietary recommendations of 2-3 fish meals per week or the equivalent intake of long chain n-3 fatty acids, particularly DHA.

  2. Medium-chain fatty acids: functional lipids for the prevention and treatment of the metabolic syndrome.

    PubMed

    Nagao, Koji; Yanagita, Teruyoshi

    2010-03-01

    Metabolic syndrome is a cluster of metabolic disorders, such as abdominal obesity, dyslipidemia, hypertension and impaired fasting glucose, that contribute to increased cardiovascular morbidity and mortality. Although the pathogenesis of metabolic syndrome is complicated and the precise mechanisms have not been elucidated, dietary lipids have been recognized as contributory factors in the development and the prevention of cardiovascular risk clustering. This review explores the physiological functions and molecular actions of medium-chain fatty acids (MCFAs) and medium-chain triglycerides (MCTs) in the development of metabolic syndrome. Experimental studies demonstrate that dietary MCFAs/MCTs suppress fat deposition through enhanced thermogenesis and fat oxidation in animal and human subjects. Additionally, several reports suggest that MCFAs/MCTs offer the therapeutic advantage of preserving insulin sensitivity in animal models and patients with type 2 diabetes.

  3. Use of a Gluconobacter frateurii mutant to prevent dihydroxyacetone accumulation during glyceric acid production from glycerol.

    PubMed

    Habe, Hiroshi; Shimada, Yuko; Fukuoka, Tokuma; Kitamoto, Dai; Itagaki, Masayuki; Watanabe, Kunihiro; Yanagishita, Hiroshi; Yakushi, Toshiharu; Matsushita, Kazunobu; Sakaki, Keiji

    2010-01-01

    To prevent dihydroxyacetone (DHA) by-production during glyceric acid (GA) production from glycerol using Gluconobacter frateurii, we used a G. frateurii THD32 mutant, ΔsldA, in which the glycerol dehydrogenase subunit-encoding gene (sldA) was disrupted, but ΔsldA grew much more slowly than the wild type, growth starting after a lag of 3 d under the same culture conditions. The addition of 1% w/v D-sorbitol to the medium improved both the growth and the GA productivity of the mutant, and ΔsldA produced 89.1 g/l GA during 4 d of incubation without DHA accumulation.

  4. Dehydroepiandrosterone prevents linoleic acid-induced endothelial cell senescence by increasing autophagy.

    PubMed

    Lee, Min Jung; Kim, Eun Hee; Lee, Sang Ah; Kang, Yu Mi; Jung, Chang Hee; Yoon, Hae Kyeong; Seol, So Mi; Lee, Yoo La; Lee, Woo Je; Park, Joong-Yeol

    2015-09-01

    Autophagy has emerged as a potentially important factor in the pathogenesis of atherosclerosis. Dehydroepiandrosterone (DHEA) is an adrenal steroid of great recent interest due to its anti-aging and anti-atherogenic effects; however, little is known about its role in autophagy and endothelial senescence. The aim of this study was to investigate whether DHEA prevents linoleic acid (LA)-induced endothelial senescence by enhancing autophagy. After pre-treatement with or without DHEA prior to LA treatment in human aortic endothelial cells (HAECs), the level of senescence was compared by senescence-associated acidic β-galactosidase (SA-β-Gal) staining and hyperphosphorylated pRB (ppRB) protein level. Autophagy was detected by LC3 conversion and measuring the level of p62/SQSTM1 (sequestosome 1), a protein degraded by autophagy. The fusion of autophagosome and lysosome was confirmed by fluorescence microscopy. Pre-treatment with DHEA inhibited LA-induced endothelial senescence. DHEA increased the conversion of LC3-I to LC3-II and decreased the level of p62 in a time- and dose-dependent manner. Although both DHEA and LA treatment increased the conversion of LC3-I to LC3-II, treatment of LA increased p62 and decreased fusion of autophagosome and lysosome, which reflected decreased autophagic flux. However, pre-treatment with DHEA restored autophagic flux inhibited by LA. When we evaluated signaling pathways, we found that JNK activation involved in LC3 conversion induced by DHEA. DHEA prevents LA-induced endothelial senescence by restoring autophagy and autophagic flux through JNK activation. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. [Analysis of the Spanish situation regarding folic acid/calcic folinate consumption for birth defects prevention].

    PubMed

    Martínez-Frías, M Luisa; Rodríguez-Pinilla, Elvira; Bermejo, Eva

    2003-12-06

    Since 1992, the recommendation on the ingestion of folic acid (FA) to prevent congenital defects has become general in developed countries. In this paper, we analyze such a situation in Spain in most recent years. We used the information concerning mothers of infants selected as controls in the ECEMC database. These mothers make up a sample of pregnant women of the general population. We analyzed the evolution of the consumption of FA/calcic folinate (CF) by pregnant women over the last 22 years, considering the period of pregnancy during which this vitamin was taken and the dosage. The proportion of women who take FA/CF during the first trimester of pregnancy increased dramatically in the last 9 years, up to 80% in 2002. However, only about 9% took the vitamin before becoming pregnant. Moreover, many daily doses are much higher than those internationally recommended for the general population of women planning pregnancy. In our country, the use of FA/CF to prevent congenital defects is correct in a small part of the population of pregnant women. Therefore, it is necessary to continue disseminating appropriate guidelines not only among gynecologists but also among family and general practitioners and health professionals working at family planning centers. Thus, they can transmit to women the need of using FA/CF and the right way to do it.

  6. Dietary docosahexaenoic acid supplementation prevents the formation of cholesterol oxidation products in arteries from orchidectomized rats.

    PubMed

    Villalpando, Diva M; Rojas, Mibsam M; García, Hugo S; Ferrer, Mercedes

    2017-01-01

    Testosterone deficiency has been correlated with increased cardiovascular diseases, which in turn has been associated with increased oxidative stress. Several studies have considered cholesterol oxidation products (COPs) as oxidative stress biomarkers, since some of them play pro-oxidant and pro-inflammatory roles. We have previously described the cardioprotective effects of a dosahexaenoic acid (DHA) supplemented diet on the aortic and mesenteric artery function of orchidectomized rats. The aim of this study was to investigate whether impaired gonadal function alters the formation of COPs, as well as the potential preventive role of a DHA-supplemented diet on that effect. For this purpose, aortic and mesenteric artery segments obtained from control and orchidectomized rats, fed with a standard or supplemented with DHA, were used. The content of the following COPs: 7α-hydroxycholesterol, 7β-hydroxycholesterol, 7-ketocholesterol, 5,6α-epoxycholesterol, 5,6β-epoxycholesterol, cholestanetriol and 25-hydroxycholesterol, were analyzed by gas chromatography. The results showed that orchidectomy increased the formation of COPs in arteries from orchidectomized rats, which may participate in the orchidectomy-induced structural and functional vascular alterations already reported. The fact that the DHA-supplemented diet prevented the orchidectomy-induced COPs increase confirms the cardiovascular protective actions of DHA, which could be of special relevance in mesenteric arterial bed, since it importantly controls the systemic vascular resistance.

  7. Atorvastatin Prevents Glutamate Uptake Reduction Induced by Quinolinic Acid Via MAPKs Signaling.

    PubMed

    Vandresen-Filho, S; Martins, W C; Bertoldo, D B; Rieger, D K; Maestri, M; Leal, R B; Tasca, C I

    2016-08-01

    Statins have been shown to promote neuroprotection in a wide range of neurological disorders. However, the mechanisms involved in such effects of statins are not fully understood. Quinolinic acid (QA) is a neurotoxin that induces seizures when infused in vivo and promotes glutamatergic excitotoxicity in the central nervous system. The aim of this study was to evaluate the putative glutamatergic mechanisms and the intracellular signaling pathways involved in the atorvastatin neuroprotective effects against QA toxicity. Atorvastatin (10 mg/kg) treatment for 7 days prevented the QA-induced decrease in glutamate uptake, but had no effect on increased glutamate release induced by QA. Moreover, atorvastatin treatment increased the phosphorylation of ERK1 and prevented the decrease in Akt phosphorylation induced by QA. Neither atorvastatin treatment nor QA infusion altered glutamine synthetase activity or the levels of phosphorylation of p38(MAPK) or JNK1/2 during the evaluation. Inhibition of MEK/ERK signaling pathway, but not PI3K/Akt signaling, abolished the neuroprotective effect of atorvastatin against QA-induced decrease in glutamate uptake. Our data suggest that atorvastatin protective effects against QA toxicity are related to modulation of glutamate transporters via MAPK/ERK signaling pathway.

  8. Lactic acid bacteria in the prevention of pneumococcal respiratory infection: future opportunities and challenges.

    PubMed

    Villena, Julio; Oliveira, Maria Leonor S; Ferreira, Patricia C D; Salva, Susana; Alvarez, Susana

    2011-11-01

    Lactic acid bacteria (LAB) are technologically and commercially important and have various beneficial effects on human health. Several studies have demonstrated that certain LAB strains can exert their beneficial effect on the host through their immunomudulatory activity. Although most research concerning LAB-mediated enhanced immune protection is focused on gastrointestinal tract pathogens, recent studies have centered on whether these immunobiotics might sufficiently stimulate the common mucosal immune system to provide protection to other mucosal sites as well. In this sense, LAB have been used for the development of probiotic foods with the ability to stimulate respiratory immunity, which would increase resistance to infections, even in immunocompromised hosts. On the other hand, the advances in the molecular biology of LAB have enabled the development of recombinant strains expressing antigens from respiratory pathogens that have proved effective to induce protective immunity. In this review we examine the current scientific literature concerning the use of LAB strains to prevent respiratory infections. In particular, we have focused on the works that deal with the capacity of probiotic and recombinant LAB to improve the immune response against Streptococcus pneumoniae. Research from the last decade demonstrates that LAB represent a promising resource for the development of prevention strategies against respiratory infections that could be effective tools for medical application.

  9. Salvianolic acid B, an antioxidant from Salvia miltiorrhiza, prevents 6-hydroxydopamine induced apoptosis in SH-SY5Y cells.

    PubMed

    Tian, Lin-Lin; Wang, Xue-Jun; Sun, Yu-Ning; Li, Chun-Rong; Xing, Ya-Ling; Zhao, Hai-Bao; Duan, Ming; Zhou, Zhe; Wang, Sheng-Qi

    2008-01-01

    Oxidative stress caused by dopamine may play an important role in the pathogenesis of Parkinson's disease. Salvianolic acid B is an antioxidant derived from the Chinese herb, Salvia miltiorrhiza. In this study, we investigated the neuroprotective effect of salvianolic acid B against 6-hydroxydopamine-induced cell death in human neuroblastoma SH-SY5Y cells. Pretreatment of SH-SY5Y cells with salvianolic acid B significantly reduced 6-hydroxydopamine-induced generation of reactive oxygen species, and prevented 6-hydroxydopamine-induced increases in intracellular calcium. Our data demonstrated that 6-hydroxydopamine-induced apoptosis was reversed by salvianolic acid B treatment. Salvianolic acid B reduced the 6-hydroxydopamine-induced increase of caspase-3 activity, and reduced cytochrome C translocation into the cytosol from mitochondria. The 6-hydroxydopamine-induced decrease in the Bcl-x/Bax ratio was prevented by salvianolic acid B. Additionally, salvianolic acid B decreased the activation of extracellular signal-regulated kinase and induced the activation of 6-hydroxydopamine-suppressed protein kinase C. These results indicate that the protective function of salvianolic acid B is dependent upon its antioxidative potential. Our results strongly suggest that salvianolic acid B may be effective in treating neurodegenerative diseases associated with oxidative stress.

  10. Omega-3 fatty acids prevent the ketamine-induced increase in acetylcholinesterase activity in an animal model of schizophrenia.

    PubMed

    Zugno, Alexandra I; Chipindo, Helder; Canever, Lara; Budni, Josiane; Alves de Castro, Adalberto; Bittencourt de Oliveira, Mariana; Heylmann, Alexandra Stephanie; Gomes Wessler, Patrícia; da Rosa Silveira, Flávia; Damázio, Louyse S; Mastella, Gustavo Antunes; Kist, Luiza W; Bogo, Maurício R; Quevedo, João; Gama, Clarissa S

    2015-01-15

    Schizophrenia is a debilitating neurodevelopmental disorder that is associated with dysfunction in the cholinergic system. Early prevention is a target of treatment to improve long-term outcomes. Therefore, we evaluated the preventive effects of omega-3 fatty acids on AChE activity in the prefrontal cortex, hippocampus and striatum in an animal model of schizophrenia. Young Wistar rats (30 days old) were initially treated with omega-3 fatty acids or vehicle alone. Animals received ketamine to induce an animal model of schizophrenia or saline plus omega-3 fatty acids or vehicle alone for 7 consecutive days beginning on day 15. A total of 22 days elapsed between the treatment and intervention. Animals were sacrificed, and brain structures were dissected to evaluate AChE activity and gene expression. Our results demonstrate that ketamine increased AChE activity in these three structures, and omega-3 fatty acids plus ketamine showed lower values for the studied parameters, which indicate a partial preventive mechanism of omega-3 fatty acid supplementation. We observed no effect on AChE expression. Together, these results indicate that omega-3 fatty acid supplementation effectively reduced AChE activity in an animal model of schizophrenia in all studied structures. In conclusion, the present study provides evidence that ketamine and omega-3 fatty acids affect the cholinergic system, and this effect may be associated with the physiopathology of schizophrenia. Further studies are required to investigate the mechanisms that are associated with this effect. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Acid-sensitive channel inhibition prevents fetal alcohol spectrum disorders cerebellar Purkinje cell loss.

    PubMed

    Ramadoss, Jayanth; Lunde, Emilie R; Ouyang, Nengtai; Chen, Wei-Jung A; Cudd, Timothy A

    2008-08-01

    Ethanol is now considered the most common human teratogen. Educational campaigns have not reduced the incidence of ethanol-mediated teratogenesis, leading to a growing interest in the development of therapeutic prevention or mitigation strategies. On the basis of the observation that maternal ethanol consumption reduces maternal and fetal pH, we hypothesized that a pH-sensitive pathway involving the TWIK-related acid-sensitive potassium channels (TASKs) is implicated in ethanol-induced injury to the fetal cerebellum, one of the most sensitive targets of prenatal ethanol exposure. Pregnant ewes were intravenously infused with ethanol (258+/-10 mg/dl peak blood ethanol concentration) or saline in a "3 days/wk binge" pattern throughout the third trimester. Quantitative stereological analysis demonstrated that ethanol resulted in a 45% reduction in the total number of fetal cerebellar Purkinje cells, the cell type most sensitive to developmental ethanol exposure. Extracellular pH manipulation to create the same degree and pattern of pH fall caused by ethanol (manipulations large enough to inhibit TASK 1 channels), resulted in a 24% decrease in Purkinje cell number. We determined immunohistochemically that TASK 1 channels are expressed in Purkinje cells and that the TASK 3 isoform is expressed in granule cells of the ovine fetal cerebellum. Pharmacological blockade of both TASK 1 and TASK 3 channels simultaneous with ethanol effectively prevented any reduction in fetal cerebellar Purkinje cell number. These results demonstrate for the first time functional significance of fetal cerebellar two-pore domain pH-sensitive channels and establishes them as a potential therapeutic target for prevention of ethanol teratogenesis.

  12. Omega-3 polyunsaturated fatty acid supplementation in the prevention of cardiovascular disease

    PubMed Central

    Walz, Courtney P.; Barry, Arden R.; Koshman, Sheri L.

    2016-01-01

    Introduction: Omega-3 polyunsaturated fatty acids (PUFAs) have purported protective cardiovascular (CV) effects. We sought to assess the evidence available for the use of omega-3 PUFAs for the prevention of cardiovascular disease (CVD). Methods: A systematic literature search was conducted using MEDLINE and EMBASE from 1999 to 2015. Placebo-controlled, randomized controlled trials (RCTs) that enrolled over 1000 patients with follow-up greater than 1 year and meta-analyses of RCTs were included. Results: Eight RCTs and 2 meta-analyses were included. In patients with preexisting CVD, only 1 of 5 included RCTs demonstrated a reduction in CV events with omega-3 PUFAs; however, the effect size was minimal, and the study was limited by an open-label design and lack of placebo control. Two meta-analyses concluded omega-3 PUFAs do not reduce CV events in addition to standard, evidence-based therapy in patients after myocardial infarction. Of the 3 predominantly primary prevention RCTs, only 1 demonstrated a minor reduction in major coronary events; however, it was also an open-label study. Furthermore, the safety of omega-3 PUFAs should be considered. While data from RCTs have not demonstrated serious safety concerns, omega-3 PUFAs can increase the risk of bleeding and may interact with other medications that affect hemostasis, such as antiplatelet agents and warfarin. Discussion and Conclusion: There is currently a lack of evidence to support the routine use of omega-3 PUFAs in the primary and secondary prevention of CVD. Pharmacists are ideally situated to engage patients in the discussion of the lack of benefit and possible risk of omega-3 PUFA supplements. PMID:27212967

  13. Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid (TPOP): study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Preclinical and clinical studies suggest that supplementation with omega-3 fatty acids after trauma might reduce subsequent posttraumatic stress disorder (PTSD). To date, we have shown in an open trial that PTSD symptoms in critically injured patients can be reduced by taking omega-3 fatty acids, hypothesized to stimulate hippocampal neurogenesis. The primary aim of the present randomized controlled trial is to examine the efficacy of omega-3 fatty acid supplementation in the secondary prevention of PTSD following accidental injury, as compared with placebo. This paper describes the rationale and protocol of this trial. Methods/design The Tachikawa Project for Prevention of Posttraumatic Stress Disorder with Polyunsaturated Fatty Acid (TPOP) is a double-blinded, parallel group, randomized controlled trial to assess whether omega-3 fatty acid supplementation can prevent PTSD symptoms among accident-injured patients consecutively admitted to an intensive care unit. We plan to recruit accident-injured patients and follow them prospectively for 12 weeks. Enrolled patients will be randomized to either the omega-3 fatty acid supplement group (1,470 mg docosahexaenoic acid and 147 mg eicosapentaenoic acid daily) or placebo group. Primary outcome is score on the Clinician-Administered PTSD Scale (CAPS). We will need to randomize 140 injured patients to have 90% power to detect a 10-point difference in mean CAPS scores with omega-3 fatty acid supplementation compared with placebo. Secondary measures are diagnosis of PTSD and major depressive disorder, depressive symptoms, physiologic response in the experiment using script-driven imagery and acoustic stimulation, serum brain-derived neurotrophic factor, health-related quality of life, resilience, and aggression. Analyses will be by intent to treat. The trial was initiated on December 13 2008, with 104 subjects randomized by November 30 2012. Discussion This study promises to be the first trial to provide a novel

  14. Prevention of Alzheimer's disease: Omega-3 fatty acid and phenolic anti-oxidant interventions.

    PubMed

    Cole, Greg M; Lim, Giselle P; Yang, Fusheng; Teter, Bruce; Begum, Aynun; Ma, Qiulan; Harris-White, Marni E; Frautschy, Sally A

    2005-12-01

    Alzheimer's disease (AD) and cardiovascular disease (CVD) are syndromes of aging that share analogous lesions and risk factors, involving lipoproteins, oxidative damage and inflammation. Unlike in CVD, in AD, sensitive biomarkers are unknown, and high-risk groups are understudied. To identify potential prevention strategies in AD, we have focused on pre-clinical models (transgenic and amyloid infusion models), testing dietary/lifestyle factors strongly implicated in reducing risk in epidemiological studies. Initially, we reported the impact of non-steroidal anti-inflammatory drugs (NSAIDs), notably ibuprofen, which reduced amyloid accumulation, but suppressed few inflammatory markers and without reducing oxidative damage. Safety concerns with chronic NSAIDs led to a screen of alternative NSAIDs and identification of the phenolic anti-inflammatory/anti-oxidant compound curcumin, the yellow pigment in turmeric that we found targeted multiple AD pathogenic cascades. The dietary omega-3 fatty acid, docosahexaenoic acid (DHA), also limited amyloid, oxidative damage and synaptic and cognitive deficits in a transgenic mouse model. Both DHA and curcumin have favorable safety profiles, epidemiology and efficacy, and may exert general anti-aging benefits (anti-cancer and cardioprotective.).

  15. Tauroursodeoxycholic acid prevents hearing loss and hair cell death in Cdh23(erl/erl) mice.

    PubMed

    Hu, J; Xu, M; Yuan, J; Li, B; Entenman, S; Yu, H; Zheng, Q Y

    2016-03-01

    Sensorineural hearing loss has long been the subject of experimental and clinical research for many years. The recently identified novel mutation of the Cadherin23 (Cdh23) gene, Cdh23(erl/erl), was proven to be a mouse model of human autosomal recessive nonsyndromic deafness (DFNB12). Tauroursodeoxycholic acid (TUDCA), a taurine-conjugated bile acid, has been used in experimental research and clinical applications related to liver disease, diabetes, neurodegenerative diseases, and other diseases associated with apoptosis. Because hair cell apoptosis was implied to be the cellular mechanism leading to hearing loss in Cdh23(erl/erl) mice (erl mice), this study investigated TUDCA's otoprotective effects in erl mice: preventing hearing impairment and protecting against hair cell death. Our results showed that systemic treatment with TUDCA significantly alleviated hearing loss and suppressed hair cell death in erl mice. Additionally, TUDCA inhibited apoptotic genes and caspase-3 activation in erl mouse cochleae. The data suggest that TUDCA could be a potential therapeutic agent for human DFNB12. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. TAUROURSODEOXYCHOLIC ACID PREVENTS HEARING LOSS AND HAIR CELL DEATH IN Cdh23erl/erl MICE

    PubMed Central

    HU, J.; XU, M.; YUAN, J.; LI, B.; Entenman, S.; YU, H.; ZHENG, Q.Y.

    2016-01-01

    Sensorineural hearing loss has long been the subject of experimental and clinical research for many years. The recently identified novel mutation of the Cdh23 gene, Cdh23erl/erl, was proven to be a mouse model of human autosomal recessive nonsyndromic deafness (DFNB12). Tauroursodeoxycholic acid (TUDCA), a taurine-conjugated bile acid, has been used in experimental research and clinical applications related to liver disease, diabetes, neurodegenerative diseases, and other diseases associated with apoptosis. Because hair cell apoptosis was implied to be the cellular mechanism leading to hearing loss in Cdh23erl/erl mice (erl mice), this study investigated TUDCA’s otoprotective effects in erl mice: preventing hearing impairment and protecting against hair cell death. Our results showed that systemic treatment with TUDCA significantly alleviated hearing loss and suppressed hair cell death in erl mice. Additionally, TUDCA inhibited apoptotic genes and caspase-3 activation in erl mouse cochleae. The data suggest that TUDCA could be a potential therapeutic agent for human DFNB12. PMID:26748055

  17. Prevention of cardiovascular diseases and highly concentrated n-3 polyunsaturated fatty acids (PUFAs).

    PubMed

    Weber, Heinz S; Selimi, Dzevair; Huber, Gustav

    2006-12-01

    30 years ago the observation of a lower incidence of cardiovascular diseases in Inuits (Eskimos) was related to the higher fish consumption when compared to the residual Danish population. Clinical studies confirmed this finding. It was explained by the higher content of polyunsaturated fatty acids (PUFA) in fish, especially of omega-3 PUFAs. Experimental studies in cell cultures and also in animals with and without infarction models verified the anti-arrhythmic effect of omega-3 PUFAs among other possible contributing factors when compared to other fatty acids. In clinical studies a significant reduction (ca. 40%) of sudden cardiac deaths (SCD) could be found in patients after an acute myocardial infarction, if they were treated with at least 1 g omega-3 PUFAs daily, either by consumption of fish twice weekly or of a highly purified preparation omega-3 PUFAs in capsules. These findings led to recommendations of the American Heart Association and the European Society of Cardiology to a higher fish consumption and/or the daily intake of 1 g omega-3 PUFAs for primary and especially for secondary prevention of cardiovascular diseases. The much fewer side-effects, and the standardised dosage on one hand and the negative effect of the sometimes higher mercury content of fish make the intake of omega-3 PUFAs as capsules the better choice.

  18. [Effect of kanggusong in prevention and treatment of retinoic acid induced osteoporosis in rats].

    PubMed

    Wu, B; Xu, B; Huang, T Y

    1996-01-01

    Retinoic acid 70 mg/kg.d was given by gastrogavage to Wistar rat for 14 days to induce osteoporosis. Kanggusong (KGS), a mixture of extracts from 8 traditional Chinese drugs, was given to 3 test groups of rats simultaneously in various dosage. Results showed that the KGS displayed obvious action in preventing osteoporosis, the trabecular loss of tibiae and bone loss of compact bone were lowered markedly in KGS groups with high (3.0 g/kg.d) or middle (1.0 g/kg.d) dosage in comparing with control model group, the trabecular area percentage and compact bone area percentage were increased significantly (P < 0.05) which approached to the level of normal control group. KGS could also improve the pathological changes in microstructure of bone, increase the thickness of trabecula and cortex (P < 0.05), reduce the trabecular gap and bone marrow cavity (P < 0.05). The mechanism of KGS might be relevant with its action of suppressing the osteoclast activity and activating osteoblast, resulting a positive balance of bone metabolism, increasing the blood concentration of calcium and estrogen as well as its antagonistic action against the injury of sex glands by retinoic acid.

  19. Chlorogenic Acid Prevents Osteoporosis by Shp2/PI3K/Akt Pathway in Ovariectomized Rats

    PubMed Central

    Zuo, Hui Ling; Yao, Fen Fen; Ruan, Hui Bing; Xu, Jin; Song, Wei; Zhou, Yi Cheng; Wen, Shi Yao; Dai, Jiang Hua; Zhu, Mei Lan; Luo, Jun

    2016-01-01

    Cortex Eucommiae is used worldwide in traditional medicine, various constituents of Cortex Eucommiae, such as chlorogenic acid (CGA), has been reported to exert anti-osteoporosis activity in China, but the mechanism about their contribution to the overall activity is limited. The aims of this study were to determine whether chlorogenic acid can prevent estrogen deficiency-induced osteoporosis and to analyze the mechanism of CGA bioactivity. The effect of CGA on estrogen deficiency-induced osteoporosis was performed in vivo. Sixty female Sprague-Dawley rats were divided randomly among a sham-operated group and five ovariectomy (OVX) plus treatment subgroups: saline vehicle, 17α-ethinylestradiol (E2), or CGA at 9, 27, or 45 mg/kg/d. The rats’ femoral metaphyses were evaluated by micro-computed tomography (μCT). The mechanism of CGA bioactivity was investigated in vitro. Bone mesenchymal stem cells (BMSCs) were treated with CGA, with or without phosphoinositide 3-kinase (PI3K) inhibitor LY294002. BMSCs proliferation and osteoblast differentiation were assessed with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and alkaline phosphatase, with or without Shp2 interfering RNA (RNAi). The results display that CGA at 27 and 45 mg/kg/day inhibited the decrease of bone mineral density (BMD) that induced by OVX in femur (p< 0.01), significantly promoted the levels of bone turnover markers, and prevented bone volume fraction (BV/TV), connectivity density (CoonD), trabecular number (Tb.N), trabecular thickness (Tb.Th) (all p< 0.01) to decrease and prevented the trabecular separation (Tb.Sp), structure model index (SMI)(both p< 0.01) to increase. CGA at 1 or 10 μM enhanced BMSC proliferation in a dose-dependent manner. CGA at 0.1 to 10 μM increased phosphorylated Akt (p-Akt) and cyclin D1. These effects were reversed by LY294002. CGA at 1 or 10 μM increased BMSC differentiation to osteoblasts (p< 0.01), Shp2 RNAi suppressed CGA-induced osteoblast

  20. Vitamin U, a novel free radical scavenger, prevents lens injury in rats administered with valproic acid.

    PubMed

    Tunali, S; Kahraman, S; Yanardag, R

    2015-09-01

    Valproic acid (2-propyl-pentanoic acid, VPA) is the most widely prescribed antiepileptic drug due to its ability to treat a broad spectrum of seizure types. VPA exhibits various side effects such as organ toxicity, teratogenicity, and visual disturbances. S-Methylmethioninesulfonium is a derivative of the amino acid methionine and it is widely referred to as vitamin U (Vit U). This study was aimed to investigate the effects of Vit U on lens damage parameters of rats exposed to VPA. Female Sprague Dawley rats were divided into four groups. Group I comprised control animals. Group II included control rats supplemented with Vit U (50 mg/kg/day) for 15 days. Group III was given only VPA (500 mg/kg/day) for 15 days. Group IV was given VPA + Vit U (in same dose and time). Vit U was given to rats by gavage and VPA was given intraperitoneally. On the 16th day of experiment, all the animals which were fasted overnight were killed. Lens was taken from animals, homogenized in 0.9% saline to make up to 10% (w/v) homogenate. The homogenates were used for protein, glutathione, lipid peroxidation levels, and antioxidant enzymes activities. Lens lipid peroxidation levels and aldose reductase and sorbitol dehydrogenase activities were increased in VPA group. On the other hand, glutathione levels, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and paraoxonase activities were decreased in VPA groups. Treatment with Vit U reversed these effects. This study showed that Vit U exerted antioxidant properties and may prevent lens damage caused by VPA.

  1. Omega 6 fatty acids for the primary prevention of cardiovascular disease.

    PubMed

    Al-Khudairy, Lena; Hartley, Louise; Clar, Christine; Flowers, Nadine; Hooper, Lee; Rees, Karen

    2015-11-16

    Omega 6 plays a vital role in many physiological functions but there is controversy concerning its effect on cardiovascular disease (CVD) risk. There is conflicting evidence whether increasing or decreasing omega 6 intake results in beneficial effects. The two primary objectives of this Cochrane review were to determine the effectiveness of:1. Increasing omega 6 (Linoleic acid (LA), Gamma-linolenic acid (GLA), Dihomo-gamma-linolenic acid (DGLA), Arachidonic acid (AA), or any combination) intake in place of saturated or monounsaturated fats or carbohydrates for the primary prevention of CVD.2. Decreasing omega 6 (LA, GLA, DGLA, AA, or any combination) intake in place of carbohydrates or protein (or both) for the primary prevention of CVD. We searched the following electronic databases up to 23 September 2014: the Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library (Issue 8 of 12, 2014); MEDLINE (Ovid) (1946 to September week 2, 2014); EMBASE Classic and EMBASE (Ovid) (1947 to September 2014); Web of Science Core Collection (Thomson Reuters) (1990 to September 2014); Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment Database, and Health Economics Evaluations Database on the Cochrane Library (Issue 3 of 4, 2014). We searched trial registers and reference lists of reviews for further studies. We applied no language restrictions. Randomised controlled trials (RCTs) of interventions stating an intention to increase or decrease omega 6 fatty acids, lasting at least six months, and including healthy adults or adults at high risk of CVD. The comparison group was given no advice, no supplementation, a placebo, a control diet, or continued with their usual diet. The outcomes of interest were CVD clinical events (all-cause mortality, cardiovascular mortality, non-fatal end points) and CVD risk factors (changes in blood pressure, changes in blood lipids, occurrence of type 2 diabetes). We excluded trials involving

  2. Ascorbic acid supplementation partially prevents the delayed reproductive development in juvenile male rats exposed to rosuvastatin since prepuberty.

    PubMed

    Leite, Gabriel Adan Araújo; Figueiredo, Thamiris Moreira; Sanabria, Marciana; Dias, Ana Flávia Mota Gonçalves; Silva, Patrícia Villela E; Martins Junior, Airton da Cunha; Barbosa Junior, Fernando; Kempinas, Wilma De Grava

    2017-07-18

    Dyslipidemias are occurring earlier in the population due to the increase of obesity and bad eating habits. Rosuvastatin inhibits the enzyme HMG-CoA reductase, decreasing total cholesterol. Ascorbic acid is an important antioxidant compound for male reproductive system. This study aimed to evaluate whether ascorbic acid supplementation may prevent the reproductive damage provoked by rosuvastatin administration at prepuberty. Male pups were distributed into six experimental groups that received saline solution 0.9%, 3 or 10mg/kg/day of rosuvastatin, 150mg/day of ascorbic acid, or 150mg/day of ascorbic acid associated with 3 or 10mg/kg/day of rosuvastatin from post-natal day (PND) 23 until PND53. Rosuvastatin-treated groups showed delayed puberty installation, androgen depletion and impairment on testicular and epididymal morphology. Ascorbic acid partially prevented these reproductive damages. In conclusion, rosuvastatin exposure is a probable risk to reproductive development and ascorbic acid supplementation may be useful to prevent the reproductive impairment of rosuvastatin exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

    USDA-ARS?s Scientific Manuscript database

    Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

  4. Folic Acid Protected Neural Cells Against Aluminum-Maltolate-Induced Apoptosis by Preventing miR-19 Downregulation.

    PubMed

    Zhu, Mingming; Li, Bingfei; Ma, Xiao; Huang, Cong; Wu, Rui; Zhu, Weiwei; Li, Xiaoting; Liang, Zhaofeng; Deng, Feifei; Zhu, Jianyun; Xie, Wei; Yang, Xue; Jiang, Ye; Wang, Shijia; Wu, Jieshu; Geng, Shanshan; Xie, Chunfeng; Zhong, Caiyun; Liu, Haiyan

    2016-08-01

    Aluminum (Al)-induced apoptosis is considered as the major cause of its neurotoxicity. Folic acid possesses neuroprotective function by preventing neural cell apoptosis. microRNAs (miRNAs) are important regulators of gene expression participating in cellular processes. As a key component of the miR-17-92 cluster, miR-19 is implicated in regulating apoptotic process, while its role in the neuroprotective effect of folic acid has not been investigated. The present study aimed to investigate the potential involvement and function of miR-19 in the protective action of folic acid against Al-induced neural cell apoptosis. Human SH-SY5Y cells were treated with Al-maltolate (Al-malt) in the presence or absence of folic acid. Results showed that Al-malt-induced apoptosis of SH-SY5Y cells was effectively prevented by folic acid. Al-malt suppressed the expression of miR-19a/19b, along with alterations of miR-19 related apoptotic proteins including PTEN, p-AKT, p53, Bax, Bcl-2, caspase 9 and caspase 3; and these effects were ameliorated by folic acid. miR-19 inhibitor alone induced apoptosis of SH-SY5Y cells. Combination treatment of folic acid and miR-19 inhibitor diminished the neuroprotective effect of folic acid. These findings demonstrated that folic acid protected neuronal cells against Al-malt-induced apoptosis by preventing the downregulation of miR-19 and modulation of miR-19 related downstream PTEN/AKT/p53 pathway.

  5. [Attitudes of pregnant Japanese women and folic acid intake for the prevention of neural tube defects: a nationwide Internet survey].

    PubMed

    Sato, Yoko; Nakanishi, Tomoko; Chiba, Tsuyoshi; Umegaki, Keizo

    2014-01-01

    Folic acid intake is recommended for pregnant women because it significantly reduces the risk of neural tube defects (NTD) in the fetus. However, the risk of NTD remains medium in Japan. In this study, the attitudes of pregnant Japanese women and factors related to folic acid intake for the prevention of NTD were evaluated using a nationwide survey. An Internet-based questionnaire was conducted on 2,367 pregnant Japanese women who were registrants of a Japanese social research company in January 2012; 1,236 of these women responded. In the questionnaires, the knowledge regarding the folate intake (i.e., name of folic acid, the risk of NTD, recommended doses, and timing), actual intake of folic acid, demographic factors (i.e., age, geographical area, gestational age, and birth order), and intake of dietary supplements were surveyed. Eighty-five percent of respondents consumed folate, which was mostly obtained through dietary folic acid supplements during the first month of pregnancy or after. Factors associated with loss of folic acid intake until 3 months of pregnancy included lack of knowledge, failure to consume dietary supplements, younger age, and multigravida. Many pregnant women in Japan consumed folic acid. However, most of them started supplementation after pregnancy recognition, which is too late to reduce the risk of NTD. Alternative strategies to increase the efficacy of folic acid intake, such as recommending folic acid-enriched foods, promoting folic acid fortification efforts, and providing access to practical information, are necessary.

  6. Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro.

    PubMed

    Elbaz, Alexandre; Wu, Xiying; Rivas, Daniel; Gimble, Jeffrey M; Duque, Gustavo

    2010-04-01

    Although increased bone marrow fat in age-related bone loss has been associated with lower trabecular mass, the underlying mechanism responsible remains unknown. We hypothesized that marrow adipocytes exert a lipotoxic effect on osteoblast function and survival through the reversible biosynthesis of fatty acids (FA) into the bone marrow microenvironment. We have used a two-chamber system to co-culture normal human osteoblasts (NHOst) with differentiating pre-adipocytes in the absence or presence of an inhibitor of FA synthase (cerulenin) and separated by an insert that allowed unidirectional trafficking of soluble factors only and prevented direct cell-cell contact. Supernatants were assayed for the presence of FA using mass spectophotometry. After 3 weeks in co-culture, NHOst showed significantly lower levels of differentiation and function based on lower mineralization and expression of alkaline phosphatase, osterix, osteocalcin and Runx2. In addition, NHOst survival was affected by the presence of adipocytes as determined by MTS-formazan and TUNEL assays as well as higher activation of caspases 3/7. These toxic effects were inhibited by addition of cerulenin. Furthermore, culture of NHOst with either adipocyte-conditioned media alone in the absence of adipocytes themselves or with the addition of the most predominant FA (stearate or palmitate) produced similar toxic results. Finally, Runx2 nuclear binding was affected by addition of either adipocyte conditioned media or FA into the osteogenic media. We conclude that the presence of FA within the marrow milieu can contribute to the age-related changes in bone mass and can be prevented by the inhibition of FA synthase.

  7. Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro

    PubMed Central

    Elbaz, Alexandre; Wu, Xiying; Rivas, Daniel; Gimble, Jeffrey M; Duque, Gustavo

    2010-01-01

    Abstract Although increased bone marrow fat in age-related bone loss has been associated with lower trabecular mass, the underlying mechanism responsible remains unknown. We hypothesized that marrow adipocytes exert a lipotoxic effect on osteoblast function and survival through the reversible biosynthesis of fatty acids (FA) into the bone marrow microenvironment. We have used a two-chamber system to co-culture normal human osteoblasts (NHOst) with differentiating pre-adipocytes in the absence or presence of an inhibitor of FA synthase (cerulenin) and separated by an insert that allowed unidirectional trafficking of soluble factors only and prevented direct cell–cell contact. Supernatants were assayed for the presence of FA using mass spectophotometry. After 3 weeks in co-culture, NHOst showed significantly lower levels of differentiation and function based on lower mineralization and expression of alkaline phosphatase, osterix, osteocalcin and Runx2. In addition, NHOst survival was affected by the presence of adipocytes as determined by MTS-formazan and TUNEL assays as well as higher activation of caspases 3/7. These toxic effects were inhibited by addition of cerulenin. Furthermore, culture of NHOst with either adipocyte-conditioned media alone in the absence of adipocytes themselves or with the addition of the most predominant FA (stearate or palmitate) produced similar toxic results. Finally, Runx2 nuclear binding was affected by addition of either adipocyte conditioned media or FA into the osteogenic media. We conclude that the presence of FA within the marrow milieu can contribute to the age-related changes in bone mass and can be prevented by the inhibition of FA synthase. PMID:19382912

  8. Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?

    PubMed

    Obeid, Rima; Holzgreve, Wolfgang; Pietrzik, Klaus

    2013-09-01

    Women have higher requirements for folate during pregnancy. An optimal folate status must be achieved before conception and in the first trimester when the neural tube closes. Low maternal folate status is causally related to neural tube defects (NTDs). Many NTDs can be prevented by increasing maternal folate intake in the preconceptional period. Dietary folate is protective, but recommending increasing folate intake is ineffective on a population level particularly during periods of high demands. This is because the recommendations are often not followed or because the bioavailability of food folate is variable. Supplemental folate [folic acid (FA) or 5-methyltetrahydrofolate (5-methylTHF)] can effectively increase folate concentrations to the level that is considered to be protective. FA is a synthetic compound that has no biological functions unless it is reduced to dihydrofolate and tetrahydrofolate. Unmetabolized FA appears in the circulation at doses of >200 μg. Individuals show wide variations in their ability to reduce FA. Carriers of certain polymorphisms in genes related to folate metabolism or absorption can better benefit from 5-methylTHF instead of FA. 5-MethylTHF [also known as (6S)-5-methylTHF] is the predominant natural form that is readily available for transport and metabolism. In contrast to FA, 5-methylTHF has no tolerable upper intake level and does not mask vitamin B12 deficiency. Supplementation of the natural form, 5-methylTHF, is a better alternative to supplementation of FA, especially in countries not applying a fortification program. Supplemental 5-methylTHF can effectively improve folate biomarkers in young women in early pregnancy in order to prevent NTDs.

  9. Prevention of amino acid conversion in SILAC experiments with embryonic stem cells.

    PubMed

    Bendall, Sean C; Hughes, Chris; Stewart, Morag H; Doble, Brad; Bhatia, Mickie; Lajoie, Gilles A

    2008-09-01

    Recent studies using stable isotope labeling with amino acids in culture (SILAC) in quantitative proteomics have made mention of the problematic conversion of isotope-coded arginine to proline in cells. The resulting converted proline peptide divides the heavy peptide ion signal causing inaccuracy when compared with the light peptide ion signal. This is of particular concern as it can effect up to half of all peptides in a proteomic experiment. Strategies to both compensate for and limit the inadvertent conversion have been demonstrated, but none have been shown to prevent it. Additionally, these methods combined with SILAC labeling in general have proven problematic in their large scale application to sensitive cell types including embryonic stem cells (ESCs) from the mouse and human. Here, we show that by providing as little as 200 mg/liter L-proline in SILAC media, the conversion of arginine to proline can be rendered completely undetectable. At the same time, there was no compromise in labeling with isotope-coded arginine, indicating there is no observable back conversion from the proline supplement. As a result, when supplemented with proline, correct interpretation of "light" and "heavy" peptide ratios could be achieved even in the worst cases of conversion. By extending these principles to ESC culture protocols and reagents we were able to routinely SILAC label both mouse and human ESCs in the absence of feeder cells and without compromising the pluripotent phenotype. This study provides the simplest protocol to prevent proline artifacts in SILAC labeling experiments with arginine. Moreover, it presents a robust, feeder cell-free, protocol for performing SILAC experiments on ESCs from both the mouse and the human.

  10. Comparison of 4 % icodextrin and omega 3 Fatty acids in prevention of peritoneal adhesions.

    PubMed

    Karakas, Dursun Ozgur; Yigitler, Cengizhan; Gulec, Bulent; Kucukodaci, Zafer; Ipcioglu, Osman Metin; Akin, Mehmet Levhi

    2014-06-01

    Postoperative peritoneal adhesions are major concerns in abdominal surgery. In this experimental study, the effects of 4 % icodextrin and omega-3 fatty acids (ω-3 FA) on prevention of postoperative peritoneal adhesions were evaluated. Twenty-four Wistar albino rats were divided into three groups. After laparotomy, serosal abrasion was carried out by cecal brushing. Intraperitoneally 3 cm(3) 0.9 % NaCl, 3 cm(3) 4 % icodextrin, and 200 mg/kg ω-3 FAs for each group were applied, and then the abdomen was closed. All subjects sacrificed 10 days postoperatively. Macroscopic and histopathological cellular reactions as a function of giant cell, lymphocyte/plasmocyte, neutrophil, histiocyte, intracellular adhesion molecule-1 (ICAM-1), and platelet endothelial cell adhesion molecule-1 (PECAM-1) were assessed and hydroxyproline levels were measured in all three groups and compared using Kruskal-Wallis and ANOVA tests when appropriate. Macroscopically, both ω-3 FAs and 4 % icodextrin reduced adhesion formation but the difference was not statistically significant (P = 0.253). Histopathological examination revealed that there was no statistical significance in terms of giant cell, lymphocyte/plasmocyte, neutrophil, ICAM-1, and PECAM-1 scores; however, both ω-3 FAs and 4 % icodextrin were found to be prone to reduce fibrosis (P = 0.047), whereas in the ω-3 FA group, histiocytic reaction was significantly increased (P = 0.001), and hydroxyproline levels were significantly lower than other groups (P = 0.044). In this study, ω-3 FAs were found to be superior to 4 % icodextrin with the lower hydroxyproline level and greater histiocytic reaction. Considering these results, ω-3 FAs can be a promising agent in the prevention of adhesion formation.

  11. Chlorhexidine prevents hypochlorous acid-induced inactivation of alpha1-antitrypsin.

    PubMed

    Montecucco, Fabrizio; Bertolotto, M; Ottonello, L; Pende, A; Dapino, P; Quercioli, A; Mach, F; Dallegri, F

    2009-11-01

    1. Chlorhexidine digluconate has been used as a topical antiseptic in the treatment of acne vulgaris and periodontitis. The acute phase of these diseases involves neutrophilic infiltration. Neutrophil activation and recruitment to inflammatory sites are crucial in both protection against bacterial infection and the induction of hystotoxic damage. Activated neutrophils release several enzymes, including elastase and myeloperoxidase (MPO), which contribute to tissue injury via direct toxic actions, the generation of oxidants and inactivation of protective factors, such as alpha1-antitrypsin (alpha1-AT). In the present study, we investigated whether chlorhexidine can modulate neutrophil-mediated histotoxicity. 2. Human primary neutrophils were isolated from healthy donors. Inactivation of alpha1-AT by neutrophils or hypochlorous acid (HOCl) was evaluated by spectrophotometry and sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis of its capacity to complex with porcine pancreatic elastase (PPE). Neutrophil generation of HOCl, superoxide anion and MPO release were assessed spectrophometrically. 3. Chlorhexidine (0, 0.5, 1, 5 and 10 micromol/L) dose-dependently prevented HOCl-induced inactivation of alpha1-AT and reduced HOCl recovery from phorbol myristate acetate (PMA)-treated human neutrophils, but did not inhibit superoxide anion and MPO release. Chlorhexidine directly inhibited HOCl recovery from neutrophils and HOCl-induced inactivation of alpha1-AT in a cell-free assay. Accordingly, chlorhexidine reversed HOCl-mediated inhibition of alpha1-AT capacity to complex with PPE. 4. These data suggest that chlorhexidine prevents neutrophil-induced alpha1-AT inactivation via a direct inhibitory action on HOCl. Although highly speculative, the present study indicates that chlorhexidine may protect inflamed tissues not only through its antimicrobial properties, but also via a direct anti-inflammatory effect on neutrophil toxic products.

  12. Berries and Ellagic Acid Prevent Estrogen-Induced Mammary Tumorigenesis by Modulating Enzymes of Estrogen Metabolism

    PubMed Central

    Aiyer, Harini S.; Gupta, Ramesh C.

    2010-01-01

    In order to determine whether dietary berries and ellagic acid prevent 17β estradiol (E2) -induced mammary tumors by altering estrogen metabolism, we randomized ACI rats (n=6/group) into 5 groups − sham implant + control diet (SH-CD), E2 − implant + control diet (E2-CD), E2+2.5% black raspberry (E2-BRB); E2+2.5% blueberry (E2-BB) and E2+ 400ppm ellagic acid (E2-EA). Animals were euthanized at early (6wk), intermediate (18wk) and late (24wk) phases of E2-carcinogenesis and the mammary tissue analyzed for gene-expression changes using quantitative real-time PCR. At 6 weeks, E2-treatment caused 48-fold increase in cytochrome P4501A1(CYP1A1) (p<0.0001), which was attenuated by both BRB and BB diets to 12- and 21-fold, respectively (p<0.001). E2 did not alter CYP1B1 levels, but both berry and EA diets significantly suppressed it by 11- and 3.5-fold, respectively from baseline (p<0.05). There was a 5-fold increase in 17β-Hydroxysteroid dehyrdogenase(17βHSD7) and this was moderately abrogated to about 2-fold by all supplementation (p<0.05). At 18 weeks, CYP1A1 was elevated by 15-fold in E2-CD and only E2-BB reduced this increase to 7-fold (p<0.05). Catechol-O-methyl transferase(COMT) expression was elevated 2-fold by E2-treatment (p<0.05) and all supplementation reversed this. At 24 weeks, CYP1A1 expression was less pronounced, but still high (8-fold) in E2-treated rats. This increase was reduced to 3.2 and 4.6-fold, by E2-BRB and E2-EA, respectively (p<0.05), but not by E2-BB. Supplementation did not alter the effect of E2 on steroid receptors. The diets also significantly suppressed mammary tumor incidence (10–30%), volume (41–67%) and multiplicity (38 to 51%) (p<0.05). Berries may prevent mammary tumors by suppressing the levels of E2-metabolizing enzymes during the early phase of E2-carcinogenesis. PMID:20501861

  13. Hyaluronic acid and oxidized regenerated cellulose prevent adhesion reformation after adhesiolysis in rat models

    PubMed Central

    Zhang, Yan; Liu, Qin; Yang, Ning; Zhang, Xuegang

    2016-01-01

    Postsurgical adhesion formation is the most common complication in abdominal and pelvic surgery. Adhesiolysis is the most commonly applied treatment for adhesion formation but is often followed by adhesion reformation. Therefore, an efficient strategy should be adopted to solve these problems. This study aimed to explore whether hyaluronic acid and oxidized regenerated cellulose (ORC) could prevent adhesion formation and reformation. Thirty female Sprague Dawley rats were randomly divided into three groups (n=10 each) and subjected to different treatments during the first and second surgery. The control group was treated with isotonic sodium chloride, the ORC group was treated with ORC (1.5×1 cm), and the medical sodium hyaluronate (MSH) group was treated with 1% MSH (0.5 mL). At 2 weeks after the first surgery, adhesion scores in the MSH group (1.90±0.99) and the ORC group (1.40±0.97) were significantly lower than those in the control group (3.00±0.82) (P=0.005). Similarly, 2 weeks after the second surgery, adhesion scores in the MSH group (2.00±0.82) and the ORC group (1.50±1.27) were significantly lower than those in the control group (3.50±0.53) (P=0.001). In addition, body weights in the MSH group and the ORC group did not change significantly, whereas the control group showed a consistent decrease in body weight during the experiment. Histological examination revealed that inflammatory infiltration was involved in both adhesion formation and reformation. In conclusion, hyaluronic acid and ORC were both efficient in reducing adhesion formation and reformation in the rat model. PMID:27822014

  14. Hyaluronic acid and oxidized regenerated cellulose prevent adhesion reformation after adhesiolysis in rat models.

    PubMed

    Zhang, Yan; Liu, Qin; Yang, Ning; Zhang, Xuegang

    2016-01-01

    Postsurgical adhesion formation is the most common complication in abdominal and pelvic surgery. Adhesiolysis is the most commonly applied treatment for adhesion formation but is often followed by adhesion reformation. Therefore, an efficient strategy should be adopted to solve these problems. This study aimed to explore whether hyaluronic acid and oxidized regenerated cellulose (ORC) could prevent adhesion formation and reformation. Thirty female Sprague Dawley rats were randomly divided into three groups (n=10 each) and subjected to different treatments during the first and second surgery. The control group was treated with isotonic sodium chloride, the ORC group was treated with ORC (1.5×1 cm), and the medical sodium hyaluronate (MSH) group was treated with 1% MSH (0.5 mL). At 2 weeks after the first surgery, adhesion scores in the MSH group (1.90±0.99) and the ORC group (1.40±0.97) were significantly lower than those in the control group (3.00±0.82) (P=0.005). Similarly, 2 weeks after the second surgery, adhesion scores in the MSH group (2.00±0.82) and the ORC group (1.50±1.27) were significantly lower than those in the control group (3.50±0.53) (P=0.001). In addition, body weights in the MSH group and the ORC group did not change significantly, whereas the control group showed a consistent decrease in body weight during the experiment. Histological examination revealed that inflammatory infiltration was involved in both adhesion formation and reformation. In conclusion, hyaluronic acid and ORC were both efficient in reducing adhesion formation and reformation in the rat model.

  15. Knowledge and practice of urban Iranian pregnant women towards folic acid intake for neural tube defect prevention.

    PubMed

    Nosrat, Sepideh Bakhshande; Sedehi, Maliheh; Golalipour, Mohammad Jafar

    2012-08-01

    To assess the knowledge and practice of urban Iranian pregnant women regarding periconceptional folic acid intake for neural tube defect (NTD) prevention. The population-based study was done on 676 primiparous women in an urban area in Golestan province in northern Iran from June to November, 2008. A questionnaire was completed by the subjects regarding their knowledge of folic acid. Questionnaires were administered to women who were seeking routine antenatal care at health centres, private gynaecological clinic and the Dezyani Gynaecologic and Obstetric Hospital. Questions covered knowledge and use of folic acid supplements and demographic and socioeconomic characteristics. Out of the 676 women surveyed, 96.2% reported that they heard of folate. Of these, only 27.6% knew that folate was something important in the prevention of neural tube defects. Overall, 20.12% of the total women took folic acid during periconceptional period. The most common information sources on folate were healthcare service (54.5%). Besides, 37.6% of the subjects who heard about folate were aware that green leafy vegetables were fortified with folic acid. In univariate analysis, knowledge and intake of folic acid was not associated with education and the age of women. A healthcare plan for intervention to increase the knowledge and intake of folic acid by pregnant women during the protective period is required.

  16. Eicosapentaenoic acid prevents high fat diet-induced metabolic disorders: Genomic and metabolomic analyses of underlying mechanism

    USDA-ARS?s Scientific Manuscript database

    Previously our lab demonstrated eicosapenaenoic acid (EPA)'s ability to prevent high-fat (HF) diet-induced obesity by decreasing insulin resistance, glucose intolerance and inflammation. In the current study, we used genomic and metabolomic approaches to further investigate the molecular basis for t...

  17. Valproic acid prevents penile fibrosis and erectile dysfunction in cavernous nerve-injured rats.

    PubMed

    Hannan, Johanna L; Kutlu, Omer; Stopak, Bernard L; Liu, Xiaopu; Castiglione, Fabio; Hedlund, Petter; Burnett, Arthur L; Bivalacqua, Trinity J

    2014-06-01

    Bilateral cavernous nerve injury (BCNI) causes profound penile changes such as apoptosis and fibrosis leading to erectile dysfunction (ED). Histone deacetylase (HDAC) has been implicated in chronic fibrotic diseases. This study will characterize the molecular changes in penile HDAC after BCNI and determine if HDAC inhibition can prevent BCNI-induced ED and penile fibrosis. Five groups of rats (8-10 weeks, n = 10/group) were utilized: (i) sham; (ii and iii) BCNI 14 and 30 days following injury; and (iv and v) BCNI treated with HDAC inhibitor valproic acid (VPA 250 mg/kg; 14 and 30 days). All groups underwent cavernous nerve stimulation (CNS) to determine intracavernosal pressure (ICP). Penile HDAC3, HDAC4, fibronectin, and transforming growth factor-β1 (TGF-β1) protein expression (Western blot) were assessed. Trichrome staining and the fractional area of fibrosis were determined in penes from each group. Cavernous smooth muscle content was assessed by immunofluorescence to alpha smooth muscle actin (α-SMA) antibodies. We measured ICP; HDAC3, HDAC4, fibronectin, and TGF-β1 protein expression; penile fibrosis; penile α-SMA content. There was a voltage-dependent decline (P < 0.05) in ICP to CNS 14 and 30 days after BCNI. Penile HDAC3, HDAC4, and fibronectin were significantly increased (P < 0.05) 14 days after BCNI. There was a slight increase in TGF-β1 protein expression after BCNI. Histological analysis showed increased (P < 0.05) corporal fibrosis after BCNI at both time points. VPA treatment decreased (P < 0.05) penile HDAC3, HDAC4, and fibronectin protein expression as well as corporal fibrosis. There was no change in penile α-SMA between all groups. Furthermore, VPA-treated BCNI rats had improved erectile responses to CNS (P < 0.05). HDAC-induced pathological signaling in response to BCNI contributes to penile vascular dysfunction. Pharmacological inhibition of HDAC prevents penile fibrosis, normalizes fibronectin expression, and

  18. Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease

    USDA-ARS?s Scientific Manuscript database

    Multiple randomized controlled trials (RCTs) have assessed the effects of supplementation with eicosapentaenoic acid plus docosahexaenoic acid (omega-3 polyunsaturated fatty acids, commonly called fish oils) on the occurrence of clinical cardiovascular diseases. Although the effects of supplementati...

  19. Preventive effects of p-coumaric acid on lysosomal dysfunction and myocardial infarct size in experimentally induced myocardial infarction.

    PubMed

    Jyoti Roy, Abhro; Stanely Mainzen Prince, P

    2013-01-15

    The present study was designed to evaluate the preventive effects of p-coumaric acid on lysosomal dysfunction and myocardial infarct size in isoproterenol induced myocardial infarcted rats. Male albino Wistar rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days after which isoproterenol (100mg/kg body weight) was injected subcutaneously into rats twice at an interval of 24h (8th and 9th day).The activity/levels of serum cardiac diagnostic markers, heart lysosomal lipid peroxidation products and the activities of lysosomal enzymes (β-glucuronidase, β-galactosidase, cathepsin-B and cathepsin-D) were significantly (P<0.05) increased in the serum and heart of isoproterenol induced myocardial infarcted rats. Isoproterenol also lowered the activities of β-glucuronidase and cathepsin-D in the lysosomal fraction. The pretreatment with p-coumaric acid significantly (P<0.05) prevented the changes in the levels of lysosomal lipid peroxidation products and the activities of lysosomal enzymes. In addition, p-coumaric acid greatly reduced myocardial infarct size. p-Coumaric acid pretreatment (8 mg/kg body weight) to normal rats did not show any significant effect. Thus, this study showed that p-coumaric acid prevents lysosomal dysfunction against cardiac damage induced by isoproterenol and brings back the levels of lipid peroxidation products and activities of lysosomal enzymes to near normal levels. The in vitro study also revealed the free radical scavenging activity of p-coumaric acid. Thus, the observed effects are due to p-coumaric acid's free radical scavenging and membrane stabilizing properties.

  20. Activation of Retinold X Receptors by Phytanic acid and Docohexaenoic Acid: Role in the Prevention and Therapy of Prostate Cancer

    DTIC Science & Technology

    2006-01-01

    group of natural and synthetic small, lipophilic molecules which are vitamin A (retinol) derivatives, regulate cell proliferation and differentiation...oxidation of the phytol side chain of chlorophyll in mammals (Jansen et al., 1996). All phytanic acid in the human body comes from dairy products and...ruminant fats in the diet (Baxter, 1968). Docosahexaenoic acid (DHA) is a long chain, ω-3 polyunsaturated fatty acid that is present at high levels

  1. Citrulline and Nonessential Amino Acids Prevent Fructose-Induced Nonalcoholic Fatty Liver Disease in Rats.

    PubMed

    Jegatheesan, Prasanthi; Beutheu, Stéphanie; Ventura, Gabrielle; Nubret, Esther; Sarfati, Gilles; Bergheim, Ina; De Bandt, Jean-Pascal

    2015-10-01

    Fructose induces nonalcoholic fatty liver disease (NAFLD). Citrulline (Cit) may exert a beneficial effect on steatosis. We compared the effects of Cit and an isonitrogenous mixture of nonessential amino acids (NEAAs) on fructose-induced NAFLD. Twenty-two male Sprague Dawley rats were randomly assigned into 4 groups (n = 4-6) to receive for 8 wk a 60% fructose diet, either alone or supplemented with Cit (1 g · kg(-1) · d(-1)), or an isonitrogenous amount of NEAAs, or the same NEAA-supplemented diet with starch and maltodextrin instead of fructose (controls). Nutritional and metabolic status, liver function, and expression of genes of hepatic lipid metabolism were determined. Compared with controls, fructose led to NAFLD with significantly higher visceral fat mass (128%), lower lean body mass (-7%), insulin resistance (135%), increased plasma triglycerides (TGs; 67%), and altered plasma amino acid concentrations with decreased Arg bioavailability (-27%). This was corrected by both NEAA and Cit supplementation. Fructose caused a 2-fold increase in the gene expression of fatty acid synthase (Fas) and 70% and 90% decreases in that of carnitine palmitoyl-transferase 1a and microsomal TG transfer protein via a nearly 10-fold higher gene expression of sterol regulatory element-binding protein-1c (Srebp1c) and carbohydrate-responsive element-binding protein (Chrebp), and a 90% lower gene expression of peroxisome proliferator-activated receptor α (Ppara). NEAA or Cit supplementation led to a Ppara gene expression similar to controls and decreased those of Srebp1c and Chrebp in the liver by 50-60%. Only Cit led to Fas gene expression and Arg bioavailability similar to controls. In our rat model, Cit and NEAAs effectively prevented fructose-induced NAFLD. On the basis of literature data and our findings, we propose that NEAAs may exert their effects specifically on the liver, whereas Cit presumably acts at both the hepatic and whole-body level, in part via improved

  2. Flufenamic acid prevents behavioral manifestations of salicylate-induced tinnitus in the rat

    PubMed Central

    Ustundag, Yasemin; Bulut, Funda; Demir, Caner Feyzi; Bal, Ali

    2016-01-01

    Introduction Tinnitus is defined as a phantom auditory sensation, the perception of sound in the absence of external acoustic stimulation. Given that flufenamic acid (FFA) blocks TRPM2 cation channels, resulting in reduced neuronal excitability, we aimed to investigate whether FFA suppresses the behavioral manifestation of sodium salicylate (SSA)-induced tinnitus in rats. Material and methods Tinnitus was evaluated using a conditioned lick suppression model of behavioral testing. Thirty-one Wistar rats, randomly divided into four treatment groups, were trained and tested in the behavioral experiment: (1) control group: DMSO + saline (n = 6), (2) SSA group: DMSO + SSA (n = 6), (3) FFA group: FFA (66 mg/kg bw) + saline (n = 9), (4) FFA + SSA group: FFA (66 mg/kg bw) + SSA (400 mg/kg bw) (n = 10). Localization of TRPM2 to the plasma membrane of cochlear nucleus neurons was demonstrated by confocal microscopy. Results Pavlovian training resulted in strong suppression of licking, having a mean value of 0.05 ±0.03 on extinction day 1, which is below the suppression training criterion level of 0.20 in control tinnitus animals. The suppression rate for rats having both FFA (66 mg/kg bw) and SSA (400 mg/kg bw) injections was significantly lower than that for the rats having SSA injections (p < 0.01). Conclusions We suggest that SSA-induced tinnitus could possibly be prevented by administration of a TRPM2 ion channel antagonist, FFA at 66 mg/kg bw. PMID:26925138

  3. Betulinic acid prevents alcohol-induced liver damage by improving the antioxidant system in mice

    PubMed Central

    Xia, Wei; Wu, Jianping; Yuan, Liyun; Wu, Jing; Tu, Di; Fang, Jun

    2014-01-01

    Betulinic acid (BA), a pentacyclic lupane-type triterpene, has a wide range of bioactivities. The main objective of this work was to evaluate the hepatoprotective activity of BA and the potential mechanism underlying the ability of this compound to prevent liver damage induced by alcohol in vivo. Mice were given oral doses of BA (0.25, 0.5, and 1.0 mg/kg) daily for 14 days, and induced liver injury by feeding 50% alcohol orally at the dosage of 10 ml/kg after 1 h last administration of BA. BA pretreatment significantly reduced the serum levels of alanine transaminase, aspartate transaminase, total cholesterol, and triacylglycerides in a dose-dependent manner in the mice administered alcohol. Hepatic levels of glutathione, superoxide dismutase, glutathione peroxidase, and catalase were remarkably increased, while malondialdehyde contents and microvesicular steatosis in the liver were decreased by BA in a dose-dependent manner after alcohol-induced liver injury. These findings suggest that the mechanism underlying the hepatoprotective effects of BA might be due to increased antioxidant capacity, mainly through improvement of the tissue redox system, maintenance of the antioxidant system, and decreased lipid peroxidation in the liver. PMID:24378582

  4. Prevention of Polyglycolic Acid-Induced Peritoneal Adhesions Using Alginate in a Rat Model

    PubMed Central

    Matoba, Mari; Hashimoto, Ayumi; Tanzawa, Ayumi; Orikasa, Taichi; Ikeda, Junki; Iwame, Yoshizumi; Ozamoto, Yuki; Miyamoto, Hiroe; Yoshida, Chiko; Hashimoto, Toru; Torii, Hiroko; Takamori, Hideki; Morita, Shinichiro; Tsujimoto, Hiroyuki; Hagiwara, Akeo

    2015-01-01

    Postoperative intra-abdominal or intrathoracic adhesions sometimes cause significant morbidity. We have designed three types of alginate-based treatments using strongly cross-linked (SL), weakly cross-linked (WL), and non-cross-linked (NL) alginate with calcium gluconate. In rat experiments, we compared the antiadhesive effects of the three types of alginate-based treatments, fibrin glue treatment (a standard treatment), and no treatment against adhesions caused by polyglycolic acid (PGA) mesh (PGA-induced adhesions). The antiadhesive materials were set on the PGA sheet fixed on the parietal peritoneum of the abdomen. Fifty-six days later, the adhesions were evaluated macroscopically by the adhesion scores and microscopically by hematoxylin-eosin staining and immunostaining. We also tested the fibroblast growth on the surface of the antiadhesive materials in vitro. The antiadhesive effects of WL and NL were superior to the no treatment and fibrin glue treatment. A microscopic evaluation confirmed that the PGA sheet was covered by a peritoneal layer constructed of well-differentiated mesothelial cells, and the inflammation was most improved in the NL and WL. The fibroblast growth was inhibited most on the surfaces of the NL and WL. These results suggest that either the WL or NL treatments are suitable for preventing PGA-induced adhesions compared to SL or the conventional treatment. PMID:26078949

  5. Salicylic acid prevents Trichoderma harzianum from entering the vascular system of roots.

    PubMed

    Alonso-Ramírez, Ana; Poveda, Jorge; Martín, Ignacio; Hermosa, Rosa; Monte, Enrique; Nicolás, Carlos

    2014-10-01

    Trichoderma is a soil-borne fungal genus that includes species with a significant impact on agriculture and industrial processes. Some Trichoderma strains exert beneficial effects in plants through root colonization, although little is known about how this interaction takes place. To better understand this process, the root colonization of wild-type Arabidopsis and the salicylic acid (SA)-impaired mutant sid2 by a green fluorescent protein (GFP)-marked Trichoderma harzianum strain was followed under confocal microscopy. Trichoderma harzianum GFP22 was able to penetrate the vascular tissue of the sid2 mutant because of the absence of callose deposition in the cell wall of root cells. In addition, a higher colonization of sid2 roots by GFP22 compared with that in Arabidopsis wild-type roots was detected by real-time polymerase chain reaction. These results, together with differences in the expression levels of plant defence genes in the roots of both interactions, support a key role for SA in Trichoderma early root colonization stages. We observed that, without the support of SA, plants were unable to prevent the arrival of the fungus in the vascular system and its spread into aerial parts, leading to later collapse.

  6. Syringic Acid Extracted from Herba dendrobii Prevents Diabetic Cataract Pathogenesis by Inhibiting Aldose Reductase Activity

    PubMed Central

    Wei, Xiaoyong; Chen, Dan; Yi, Yanchun; Qi, Hui; Gao, Xinxin; Fang, Hua; Gu, Qiong; Wang, Ling; Gu, Lianquan

    2012-01-01

    Objective. Effects of Syringic acid (SA) extracted from dendrobii on diabetic cataract (DC) pathogenesis were explored. Methods. Both in vitro and in vivo DC lens models were established using D-gal, and proliferation of HLEC exposed to SA was determined by MMT assay. After 60-day treatment with SA, rat lens transparency was observed by anatomical microscopy using a slit lamp. SA protein targets were extracted and isolated using 2-DE and MALDI TOF/TOF. AR gene expression was investigated using qRT-PCR. Interaction sites and binding characteristics were determined by molecule-docking techniques and dynamic models. Results. Targeting AR, SA provided protection from D-gal-induced damage by consistently maintaining lens transparency and delaying lens turbidity development. Inhibition of AR gene expression by SA was confirmed by qRT-PCR. IC50 of SA for inhibition of AR activity was 213.17 μg/mL. AR-SA binding sites were Trp111, His110, Tyr48, Trp20, Trp79, Leu300, and Phe122. The main binding modes involved hydrophobic interactions and hydrogen bonding. The stoichiometric ratio of non-covalent bonding between SA and AR was 1.0 to 13.3. Conclusion. SA acts to prevent DC in rat lenses by inhibiting AR activity and gene expression, which has potential to be developed into a novel drug for therapeutic management of DC. PMID:23365598

  7. {alpha}-Lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice

    SciTech Connect

    Lee, Young; Naseem, R. Haris; Park, Byung-Hyun; Garry, Daniel J.; Richardson, James A.; Schaffer, Jean E.; Unger, Roger H. . E-mail: roger.unger@utsouthwestern.edu

    2006-05-26

    {alpha}-Lipoic acid ({alpha}-LA) mimics the hypothalamic actions of leptin on food intake, energy expenditure, and activation of AMP-activated protein kinase (AMPK). To determine if, like leptin, {alpha}-LA protects against cardiac lipotoxicity, {alpha}-LA was fed to transgenic mice with cardiomyocyte-specific overexpression of the acyl CoA synthase (ACS) gene. Untreated ACS-transgenic mice died prematurely with increased triacylglycerol content and dilated cardiomyopathy, impaired systolic function and myofiber disorganization, apoptosis, and interstitial fibrosis on microscopy. In {alpha}-LA-treated ACS-transgenic mice heart size, echocardiogram and TG content were normal. Plasma TG fell 50%, hepatic-activated phospho-AMPK rose 6-fold, sterol regulatory element-binding protein-1c declined 50%, and peroxisome proliferator-activated receptor-{gamma} cofactor-1{alpha} mRNA rose 4-fold. Since food restriction did not prevent lipotoxicity, we conclude that {alpha}-LA treatment, like hyperleptinemia, protects the heart of ACS-transgenic mice from lipotoxicity.

  8. Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load

    PubMed Central

    Walsh, Lauren K.; Restaino, Robert M.; Neuringer, Martha; Manrique, Camila; Padilla, Jaume

    2017-01-01

    Postprandial hyperglycemia leads to a transient impairment in endothelial function; however, the mechanisms remain largely unknown. Previous work in cell culture models demonstrate that high glucose results in endoplasmic reticulum (ER) stress and, in animal studies, ER stress has been implicated as a cause of endothelial dysfunction. Herein we tested the hypothesis that acute oral administration of tauroursodeoxycholic acid (TUDCA, 1500mg), a chemical chaperone known to alleviate ER stress, would prevent hyperglycemia-induced endothelial dysfunction. In 12 young healthy subjects (seven men, five women), brachial artery flow-mediated dilation (FMD) was assessed at baseline, 1 hour, and 2 hours post an oral glucose challenge. Subjects were tested on two separate visits in a single-blind randomized crossover design: after oral ingestion of TUDCA or placebo capsules. FMD was reduced from baseline during hyperglycemia under the placebo condition (−32% at 1 hr and −28% at 2 hr post oral glucose load; p<0.05 from baseline) but not under the TUDCA condition (−4% at 1 hr and +0.3% at 2 hr post oral glucose load; p>0.05 from baseline). Postprandial plasma glucose and insulin were not altered by TUDCA ingestion. Plasma oxidative stress markers 3-nitrotyrosine and TBARs remained unaltered throughout the oral glucose challenge in both conditions. These results suggest that hyperglycemia-induced endothelial dysfunction can be mitigated by oral administration of TUDCA, thus supporting the hypothesis that ER stress may contribute to endothelial dysfunction during postprandial hyperglycemia. PMID:27503949

  9. Conjugated linoleic acid (CLA) prevents body fat accumulation and weight gain in an animal model.

    PubMed

    Park, Y; Albright, K J; Storkson, J M; Liu, W; Pariza, M W

    2007-10-01

    Conjugated linoleic acid (CLA) has been shown to reduce body fat and increase lean body mass in mice, rats, and pigs. A recent human trial indicated that CLA may work more effectively if used for prevention of body fat deposition and weight gain. To test this hypothesis, we conducted 2 experiments using relatively old mice (older than 6 mo): experiment 1, supplementation of CLA during dietary restriction and experiment 2, supplementation during ad libitum feeding followed by restriction. In experiment 1, there were significant effects of diet restriction and CLA supplementation on body composition, while CLA decreased body fat content in ad libitum diet but not significantly during diet restriction. In experiment 2, CLA fed animals had body weights similar to restricted animals and CLA significantly reduced body fat (significantly lower than prior to and post restriction, or pair fed). This suggests that CLA exerted modulation of body fat independent of reduced food intake. Based on these results, we concluded that CLA may be more effective at protecting against fat mass regain following weight loss than as a weight loss treatment.

  10. Oleanolic acid prevents cartilage degeneration in diabetic mice via PPARγ associated mitochondrial stabilization.

    PubMed

    Kang, Xia; Yang, Zhikui; Sheng, Jun; Liu, Jin-Biao; Xie, Qing-Yun; Zheng, Wei; Chen, Ken

    2017-08-26

    Hyperglycemia-induced cartilage degeneration induces osteoarthritis (OA). Since oleanolic acid (OLA) have several pharmacological effects such as anti-inflammatory, anti-oxidant, we hypothesized it possesses protection against high glucose injured cartilage. We now report that OLA decreased type X collagen and reversed the cartilage degeneration in growth plate from db/db mice. OLA increased type Ⅱ collagen expression in a concentration-dependent manner (10-50 μΜ) in high glucose-treated chondrocytes. OLA prevented the high glucose induced cell injury and decreased the level of MMP-13, PGE2 and IL-6 due to decreasing mitochondrial membrane potential and stimulated the ATP production. Moreover, OLA treatment inhibited apoptosis. And the reversed SOD2 expression and activity may be ascribed to decreased SOD2 protein degradation by OLA treatment, via PPPAγ. In conclusion, OLA protected against the high-glucose-induced cartilage injury via PPARγ/SOD2 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Resveratrol prevents social deficits in animal model of autism induced by valproic acid.

    PubMed

    Bambini-Junior, Victorio; Zanatta, Geancarlo; Della Flora Nunes, Gustavo; Mueller de Melo, Gabriela; Michels, Marcus; Fontes-Dutra, Mellanie; Nogueira Freire, Valder; Riesgo, Rudimar; Gottfried, Carmem

    2014-11-07

    Autism spectrum disorders (ASD) involve a complex interplay of both genetic and environmental risk factors, such as prenatal exposure to valproic acid (VPA). Considering the neuroprotective, antioxidant and anti-inflammatory effects of resveratrol (RSV), we investigated the influence of prenatal RSV treatment on social behaviors of a rodent model of autism induced by prenatal exposure to VPA. In the three-chambered apparatus test, the VPA group showed a reduced place preference conditioned by conspecific and no preference between exploring a wire-cage or a rat enclosed inside a wire cage, revealing sociability impairments. Prenatal administration of RSV prevented the VPA-induced social impairments evaluated in this study. A bioinformatics analysis was used to discard possible molecular interactions between VPA and RSV during administration. The interaction energy between RSV and VPA is weak and highly unstable, suggesting cellular effects instead of a single chemical process. In summary, the present study highlights a promising experimental strategy to evaluate new molecular targets possibly involved in the etiology of autism and developmental alterations implicated in neural and behavioral impairments in ASD.

  12. Awareness and intake of folic acid for the prevention of neural tube defects among Lebanese women of childbearing age.

    PubMed

    Nasr Hage, Claudine; Jalloul, Maya; Sabbah, Mohamad; Adib, Salim M

    2012-01-01

    Since the early 1990s, international recommendations have promoted folic acid supplementation during the periconception period as an effective way of preventing neural tube defects (NTDs). However, the adoption of this recommendation remains insufficient. To assess the awareness and actual intake of folic acid among married Lebanese women aged 18-45 years, a cross-sectional study was conducted among 600 women selected from all five administrative districts in Lebanon, using a multistage cluster sampling procedure. An anonymous questionnaire was completed which covered measures of knowledge and use of folate supplements, as well as demographic, socioeconomic and obstetrical factors. Sixty percent of surveyed women (60%; n = 360) had heard about folic acid. Doctors were the most frequent source of information (61.1%) but only 24.7% of women have been told of the correct period during which folic acid supplementation was useful. Overall, only 6.2% had taken folic acid tablets during the adequate period. Younger age, higher education level and stability/sufficiency of income appeared to be significant predictors of awareness among Lebanese women. Actual folic acid intake was significantly associated with younger age, higher number of pregnancies, planning the last pregnancy and having had that last one after 1990. In Lebanon, the level of folic acid awareness and adequate intake remain relatively low. Several approaches should be used to promote folic acid intake including awareness campaigns, and routine counseling by primary health care physicians on folic acid during preconception visits.

  13. Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid.

    PubMed

    Heseker, Helmut B; Mason, Joel B; Selhub, Jacob; Rosenberg, Irwin H; Jacques, Paul F

    2009-07-01

    Some countries have introduced mandatory folic acid fortification, whereas others support periconceptional supplementation of women in childbearing age. Several European countries are considering whether to adopt a fortification policy. Projections of the possible beneficial effects of increased folic acid intake assume that the measure will result in a considerable reduction in neural-tube defects (NTD) in the target population. Therefore, the objective of the present study is to evaluate the beneficial effects of different levels of folic acid administration on the prevalence of NTD. Countries with mandatory fortification achieved a significant increase in folate intake and a significant decline in the prevalence of NTD. This was also true for supplementation trials. However, the prevalence of NTD at birth declined to approximately five cases at birth per 10 000 births and seven to eight cases at birth or abortion per 10 000 births. This decline was independent of the amount of folic acid administered and apparently reveals a 'floor effect' for folic acid-preventable NTD. This clearly shows that not all cases of NTD are preventable by increasing the folate intake. The relative decline depends on the initial NTD rate. Countries with NTD prevalence close to the observed floor may have much smaller reductions in NTD rates with folic acid fortification. Additionally, potential adverse effects of fortification on other vulnerable population groups have to be seriously considered. Policy decisions concerning national mandatory fortification programmes must take into account realistically projected benefits as well as the evidence of risks to all vulnerable groups.

  14. Folic acid and polyunsaturated fatty acids improve cognitive function and prevent depression, dementia, and Alzheimer's disease--but how and why?

    PubMed

    Das, Undurti N

    2008-01-01

    Low blood folate and raised homocysteine concentrations are associated with poor cognitive function. Folic acid supplementation improves cognitive function. Folic acid enhances the plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). EPA, DHA, and arachidonic acid (AA) are of benefit in dementia and Alzheimer's disease by up-regulating gene expression concerned with neurogenesis, neurotransmission and connectivity, improving endothelial nitric oxide (eNO) generation, enhancing brain acetylcholine levels, and suppressing the production of pro-inflammatory cytokines. EPA, DHA, and AA also form precursors to anti-inflammatory compounds such as lipoxins, resolvins, and neuroprotectin D1 (NPD1) that protect neurons from the cytotoxic action of various noxious stimuli. Furthermore, various neurotrophins and statins enhance the formation of NPD1 and thus, protect neurons from oxidative stress and prevent neuronal apoptosis Folic acid improves eNO generation, enhances plasma levels of EPA/DHA and thus, could augment the formation of NPD1. These results suggest that a combination of EPA, DHA, AA and folic acid could be of significant benefit in dementia, depression, and Alzheimer's disease and improve cognitive function.

  15. Ellagic acid peracetate is superior to ellagic acid in the prevention of genotoxicity due to aflatoxin B1 in bone marrow and lung cells.

    PubMed

    Kumar, Ajit; Tyagi, Yogesh K; Ponnan, Prija; Rohil, Vishwajeet; Prasad, Ashok K; Dwarkanath, Bilekere S; Parmar, Virinder S; Raj, Hanumantharao G

    2007-01-01

    Earlier observations carried out in our laboratory highlighted the mode of action of acetoxy 4-methylcoumarins and quercetin pentaacetate in preventing the genotoxicity of aflatoxin B1 (AFB1). We have extended the observation to an acetoxy biscoumarin i.e. ellagic acid peracetate (EAPA), which unlike ellagic acid (EA) has demonstrated time-dependent inhibition of liver microsomes catalysed AFB1-epoxidation as measured by AFB1 binding to DNA. EAPA was more potent than EA in preventing bone marrow and lung cells from AFB1-induced genotoxicity. EAPA was acted upon by microsomal acetoxy drug:protein transacetylase (TAase) leading to modulation of the catalytic activity of certain functional proteins (cytochrome P450, NADPH cytochrome c reductase and glutathione S-transferase), possibly by way of protein acetylation.

  16. Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment.

    PubMed

    Connolly, Roisin M; Nguyen, Nguyen K; Sukumar, Saraswati

    2013-04-01

    Retinoids and their naturally metabolized and synthetic products (e.g., all-trans retinoic acid, 13-cis retinoic acid, bexarotene) induce differentiation in various cell types. Retinoids exert their actions mainly through binding to the nuclear retinoic acid receptors (α, β, γ), which are transcriptional and homeostatic regulators with functions that are often compromised early in neoplastic transformation. The retinoids have been investigated extensively for their use in cancer prevention and treatment. Success has been achieved with their use in the treatment of subtypes of leukemia harboring chromosomal translocations. Promising results have been observed in the breast cancer prevention setting, where fenretinide prevention trials have provided a strong rationale for further investigation in young women at high risk for breast cancer. Ongoing phase III randomized trials investigating retinoids in combination with chemotherapy in non-small cell lung cancer aim to definitively characterize the role of retinoids in this tumor type. The limited treatment success observed to date in the prevention and treatment of solid tumors may relate to the frequent epigenetic silencing of RARβ. Robust evaluation of RARβ and downstream genes may permit optimized use of retinoids in the solid tumor arena.

  17. Insights into prevention of human neural tube defects by folic acid arising from consideration of mouse mutants.

    PubMed

    Harris, Muriel J

    2009-04-01

    Almost 30 years after the initial study by Richard W. Smithells and coworkers, it is still unknown how maternal periconceptional folic acid supplementation prevents human neural tube defects (NTDs). In this article, questions about human NTD prevention are considered in relation to three groups of mouse models: NTD mutants that respond to folate, NTD mutants and strains that do not respond to folate, and mutants involving folate-pathway genes. Of the 200 mouse NTD mutants, only a few have been tested with folate; half respond and half do not. Among responsive mutants, folic acid supplementation reduces exencephaly and/or spina bifida aperta frequency in the Sp(2H), Sp, Cd, Cited2, Cart1, and Gcn5 mutants. Prevention ranges from 35 to 85%. The responsive Sp(2H) (Pax3) mutant has abnormal folate metabolism, but the responsive Cited2 mutant does not. Neither folic nor folinic acid reduces NTD frequency in Axd, Grhl3, Fkbp8, Map3k4, or Nog mutants or in the curly tail or SELH/Bc strains. Spina bifida frequency is reduced in Axd by methionine and in curly tail by inositol. Exencephaly frequency is reduced in SELH/Bc by an alternative commercial ration. Mutations in folate-pathway genes do not cause NTDs, except for 30% exencephaly in folate-treated Folr1. Among folate-pathway mutants, neural tube closure is normal in Cbs, Folr2, Mthfd1, Mthfd2, Mthfr, and Shmt1 mutants. Embryos die by midgestation in Folr1, Mtr, Mtrr, and RFC1 mutants. The mouse models point to genetic heterogeneity in the ability to respond to folic acid and also to heterogeneity in genetic cause of NTDs that can be prevented by folic acid.

  18. Comparison between conjugated linoleic acid and essential fatty acids in preventing oxidative stress in bovine mammary epithelial cells.

    PubMed

    Basiricò, L; Morera, P; Dipasquale, D; Tröscher, A; Bernabucci, U

    2017-03-01

    Some in vitro and in vivo studies have demonstrated protective effects of conjugated linoleic acid (CLA) isomers against oxidative stress and lipid peroxidation. However, only a few and conflicting studies have been conducted showing the antioxidant potential of essential fatty acids. The objectives of the study were to compare the effects of CLA to other essential fatty acids on the thiol redox status of bovine mammary epithelia cells (BME-UV1) and their protective role against oxidative damage on the mammary gland by an in vitro study. The BME-UV1 cells were treated with complete medium containing 50 μM of cis-9,trans-11 CLA, trans-10,cis-12 CLA, α-linolenic acid, γ-linolenic acid, and linoleic acid. To assess the cellular antioxidant response, glutathione, NADPH, and γ-glutamyl-cysteine ligase activity were measured 48 h after addition of fatty acids (FA). Intracellular reactive oxygen species and malondialdehyde production were also assessed in cells supplemented with FA. Reactive oxygen species production after 3 h of H2O2 exposure was assessed to evaluate and to compare the potential protection of different FA against H2O2-induced oxidative stress. All FA treatments induced an intracellular GSH increase, matched by high concentrations of NADPH and an increase of γ-glutamyl-cysteine ligase activity. Cells supplemented with FA showed a reduction in intracellular malondialdehyde levels. In particular, CLA isomers and linoleic acid supplementation showed a better antioxidant cellular response against oxidative damage induced by H2O2 compared with other FA. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

  19. Intermittent zoledronic Acid prevents bone loss in adults after allogeneic hematopoietic cell transplantation.

    PubMed

    Hari, Parameswaran; DeFor, Todd E; Vesole, David H; Bredeson, Christopher N; Burns, Linda J

    2013-09-01

    Bone mineral density (BMD) loss is common in survivors of allogeneic hematopoietic cell transplantation (alloHCT). We performed a multicenter, phase II, randomized open-label trial of intravenous zoledronic acid (ZA) to prevent BMD loss in adult recipients of alloHCT with osteopenia before HCT. The treatment group received ZA 4 mg intravenously within 28 days pre-HCT and at 3 and 6 months after HCT. Both treatment and control groups received calcium carbonate and vitamin D supplements. Of 61 patients, 32 were randomized to the ZA cohort and 29 to the control cohorts. More patients in the ZA group had an HCT comorbidity index high-risk score of ≥3 (50% versus 21%, P < .01). Baseline BMD, T-scores, serum osteocalcin, bone alkaline phosphatase, and urine N-telopeptide (UNTX) levels were similar in both cohorts. Thirty patients were evaluable for outcomes (11 from the treatment and 19 from the control group). At 12 months, subjects in the treatment group had an improvement in BMD at the femoral neck (mean change, .018 for ZA group versus -.054 for controls; P = .04) and a significant decline in levels of UNTX (-56 for ZA group versus -9 for control; P = .04) compared with baseline. ZA was well tolerated and not associated with any cases of osteonecrosis of jaw or renal impairment. Lower survival observed in the ZA cohort was likely related to baseline imbalance in HCT-CI scores. Intermittent ZA is effective in preserving long-term bone health in adult alloHCT recipients at risk for osteoporosis. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  20. Conjugation of Hyaluronic Acid onto Surfaces via the Interfacial Polymerization of Dopamine to Prevent Protein Adsorption.

    PubMed

    Huang, Renliang; Liu, Xia; Ye, Huijun; Su, Rongxin; Qi, Wei; Wang, Libing; He, Zhimin

    2015-11-10

    A versatile, convenient, and cost-effective method that can be used for grafting antifouling materials onto different surfaces is highly desirable in many applications. Here, we report the one-step fabrication of antifouling surfaces via the polymerization of dopamine and the simultaneous deposition of anionic hyaluronic acid (HA) on Au substrates. The water contact angle of the Au surfaces decreased from 84.9° to 24.8° after the attachment of a highly uniform polydopamine (PDA)/HA hybrid film. The results of surface plasmon resonance analysis showed that the Au-PDA/HA surfaces adsorbed proteins from solutions of bovine serum albumin, lysozyme, β-lactoglobulin, fibrinogen, and soybean milk in ultralow or low amounts (4.8-31.7 ng/cm(2)). The hydrophilicity and good antifouling performance of the PDA/HA surfaces is attributable to the HA chains that probably attached onto their upper surface via hydrogen bonding between PDA and HA. At the same time, the electrostatic repulsion between PDA and HA probably prevents the aggregation of PDA, resulting in the formation of a highly uniform PDA/HA hybrid film with the HA chains (with a stretched structure) on the upper surface. We also developed a simple method for removing this PDA/HA film and recycling the Au substrates by using an aqueous solution of NaOH as the hydrolyzing agent. The Au surface remained undamaged, and a PDA/HA film could be redeposited on the surface, with the surface exhibiting good antifouling performance even after 10 such cycles. Finally, it was found that this grafting method is applicable to other substrates, including epoxy resins, polystyrene, glass, and steel, owing to the strong adhesion of PDA with these substrates.

  1. Structured triacylglycerol containing behenic and oleic acids suppresses triacylglycerol absorption and prevents obesity in rats

    PubMed Central

    2010-01-01

    Background Dietary 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol (BOO) has been reported to inhibit pancreatic lipase activity in vitro and suppress postprandial hypertriacylglycerolemia in humans. In the present study, the anti-obesity activities of BOO and its inhibitory effects on lymphatic triacylglycerol (TAG) absorption were investigated in rats. Methods In Experiment 1, rats were fed either BOO or soybean oil (SO) diet for 6 weeks. In the BOO diet, 20% of SO was replaced with an experimental oil rich in BOO. In Experiments 2 and 3, rats cannulated in the thoracic duct were administered an emulsions containing trioleoylglycerol (OOO) or an oil mixture (OOO:BOO, 9:1). Tri[1-14C]oleoylglycerol (14C-OOO) was added to the emulsions administered in Experiment 3. Results No observable differences were detected in food intake or body weight gain between the BOO and SO groups in Experiment 1. Plasma and liver TAG concentrations and visceral fat weights were significantly lower in the BOO group than in the SO group. The apparent absorption rate of fat was significantly lower in the BOO group than in the SO group. In Experiment 2, the lymphatic recovery of oleic and behenic acids was significantly lower at 5 and 6 h after BOO administration than after OOO administration. In Experiment 3, the lymphatic recovery of 14C-OOO was significantly lower at 5 and 6 h after BOO administration than after OOO administration. Conclusions These results suggest that BOO prevents deposition of visceral fat and hepatic TAG by lowering and delaying intestinal absorption of TAG. PMID:20653972

  2. D-amino acid-based peptide inhibitors as early or preventative therapy in Alzheimer disease.

    PubMed

    Kumar, Jitendra; Sim, Valerie

    2014-01-01

    Beta amyloid (Aβ) accumulation is recognized as a hallmark of Alzheimer disease (AD) pathology and the aggregation of Aβ peptide is hypothesized to drive pathogenesis. As such, Aβ is a logical target for therapeutic intervention and there have been many studies looking at diverse classes of drugs that target Aβ. Of concern is the recent failure of several clinical trials, highlighting the need for earlier, possibly preventative intervention, and raising the question of what form of Aβ is the best target. The Aβ oligomers are considered to be the toxic species, but many therapies, such as antibody therapies, target monomers, removing them as substrates for aggregation. Peptide inhibitors, in contrast, are able to interfere with the aggregation process itself. Designing peptide inhibitors requires some knowledge of Aβ structure; while there is structural information about the amyloid core of Aβ fibrils, the transient nature of oligomers makes them difficult to characterize. Fortunately, some interaction sites have been identified between monomers and oligomers of Aβ and these, plus known aggregation-prone sequences in Aβ, can serve as a basis for inhibitor design. In this mini-review we focus on D-amino acid based peptide inhibitors and discuss how their non-toxic and stable nature can be beneficial, while they specifically target aggregation-prone sequences within the Aβ peptide. Many peptide inhibitors have been designed using the LVFFA domain within Aβ to disrupt the self-assembly of Aβ peptide. While this may be sufficient to stop aggregation in vitro, other aggregation sites at the C-terminus may promote aggregation independently and the flexible N terminus may be a good target to induce clearance of aggregates. Ultimately, it may be a combination of targets that provides the best therapeutic strategy.

  3. Palmitoleic acid prevents palmitic acid-induced macrophage activation and consequent p38 MAPK-mediated skeletal muscle insulin resistance.

    PubMed

    Talbot, Nicola A; Wheeler-Jones, Caroline P; Cleasby, Mark E

    2014-08-05

    Obesity and saturated fatty acid (SFA) treatment are both associated with skeletal muscle insulin resistance (IR) and increased macrophage infiltration. However, the relative effects of SFA and unsaturated fatty acid (UFA)-activated macrophages on muscle are unknown. Here, macrophages were treated with palmitic acid, palmitoleic acid or both and the effects of the conditioned medium (CM) on C2C12 myotubes investigated. CM from palmitic acid-treated J774s (palm-mac-CM) impaired insulin signalling and insulin-stimulated glycogen synthesis, reduced Inhibitor κBα and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase in myotubes. p38 MAPK inhibition or siRNA partially ameliorated these defects, as did addition of tumour necrosis factor-α blocking antibody to the CM. Macrophages incubated with both FAs generated CM that did not induce IR, while palmitoleic acid-mac-CM alone was insulin sensitising. Thus UFAs may improve muscle insulin sensitivity and counteract SFA-mediated IR through an effect on macrophage activation.

  4. All-trans retinoic acid stealth liposomes prevent the relapse of breast cancer arising from the cancer stem cells.

    PubMed

    Li, Ruo-Jing; Ying, Xue; Zhang, Yan; Ju, Rui-Jun; Wang, Xiao-Xing; Yao, Hong-Juan; Men, Ying; Tian, Wei; Yu, Yang; Zhang, Liang; Huang, Ren-Jie; Lu, Wan-Liang

    2011-02-10

    The relapse of cancer is mostly due to the proliferation of cancer stem cells which could not be eliminated by a standard chemotherapy. A new kind of all-trans retinoic acid stealth liposomes was developed for preventing the relapse of breast cancer and for treating the cancer in combination with a cytotoxic agent, vinorelbine stealth liposomes. In vitro studies were performed on the human breast cancer MCF-7 and MDA-MB-231 cells. In vivo evaluations were performed on the newly established relapse model with breast cancer stem cells. Results showed that the particle size of all-trans retinoic acid stealth liposomes was approximately 80nm, and the encapsulation efficiency was >90%. Breast cancer stem cells were identified with the CD44(+)/CD24(-) phenotype and characterized with properties: resistant to cytotoxic agent, stronger capability of proliferation, and stronger capability of differentiation. Inhibitory effect of all-trans retinoic acid stealth liposomes was more potent in cancer stem cells than in cancer cells. The mechanisms were defined to be two aspects: arresting breast cancer stem cells at the G(0)/G(1) phase in mitosis, and inducing the differentiation of breast cancer stem cells. The cancer relapse model was successfully established by xenografting breast cancer stem cells into NOD/SCID mice, and the formation and growth of the xenografted tumors were significantly inhibited by all-trans retinoic acid stealth liposomes. The combination therapy of all-trans retinoic acid stealth liposomes with vinorelbine stealth liposomes produced the strongest inhibitory effect to the relapse tumor model. It could be concluded that all-trans retinoic acid stealth liposomes could be used for preventing the relapse of breast cancer by differentiating cancer stem cells and arresting the cell-cycle, and for treating breast cancer as a co-therapy, thus providing a novel strategy for treating breast cancer and preventing relapse derived from breast cancer stem cells.

  5. Oral co-administration of α-lipoic acid, quercetin and captopril prevents gallium arsenide toxicity in rats.

    PubMed

    Bhatt, Kapil; Flora, S J S

    2009-07-01

    Gallium arsenide (GaAs), an inter-metallic semiconductor, known to exhibit superior optical and electronic properties compared to silicon, promotes its use in semiconductor industries. Extensive use of GaAs will inevitably lead to an increase in the exposure of workers manufacturing these products. Antioxidants are exogenous or endogenous compounds acting in several ways, including scavenging reactive oxygen species (ROS) or their precursors, inhibiting ROS formation, and binding metal ions needed for the catalysis of ROS generation. In the present study we investigated the protective efficacy of α-lipoic acid, quercetin and captopril individually against gallium arsenide exposure. Co-administration of α-lipoic acid with GaAs was most effective in reducing GaAs induced inhibition of blood δ-aminolevulinic acid dehydratase (ALAD) activity, liver, kidney and brain reduced glutathione (GSH) level and elevation of oxidized glutathione (GSSG). Captopril, on the other hand was effective in reducing thiobarbituric acid reactive substance (TBARS) levels, while quercetin reduced ROS in liver and kidney. The results suggest comparatively better preventive efficacy of concomitant α-lipoic acid administration during Gallium arsenide exposure compared to quercetin and captopril in preventing GaAs induced oxidative stress.

  6. Effect of processing on folic acid fortified Baladi bread and its possible effect on the prevention of colon cancer.

    PubMed

    Omar, Rasha M; Ismail, Hanaa M; El-Lateef, Bothyna M Abd; Yousef, Mokhtar I; Gomaa, Naglaa F; Sheta, Manal

    2009-07-01

    This paper studied the possible effect of folic acid in fortified Baladi bread on the prevention of colon cancer development in rats. Wheat flour samples (82% extraction rate) and soy bean flour were analyzed to determine their folic acid contents using the High Performance Liquid Chromatography (HPLC). Unfortified and folic acid fortified Baladi breads were prepared. Samples from each step of bread preparation were analyzed for folic acid concentration. Protein, fat, ash, fibers and carbohydrates percentages were also determined. Rats were divided into five groups, four of them were injected subcutaneously with dimethylhydrazine (DMH). After 15 weeks, the rats were sacrificed for pathological examination. Results showed that the folic acid content in wheat flour (82% extraction rate) was found to be highly significantly lower than that in soybean flour. After baking, folic acid content in all breads was found to decrease significantly. The highest protein and fat contents were found in soybean flour fortified Baladi bread. The colons of rats of groups 3 (fed 5% soy flour fortified Baladi bread) and 5 (fed Baladi bread fortified with 5% soy flour+8 mg folic acid/kg wheat flour) were the mostly affected by DMH injection as premalignant changes were observed.

  7. Inhibition of sterile danger signals, uric acid and ATP, prevents inflammasome activation and protects from alcoholic steatohepatitis in mice

    PubMed Central

    Iracheta-Vellve, Arvin; Petrasek, Jan; Satishchandran, Abhishek; Gyongyosi, Benedek; Saha, Banishree; Kodys, Karen; Fitzgerald, Katherine A.; Kurt-Jones, Evelyn A.; Szabo, Gyongyi

    2015-01-01

    Background & Aims The inflammasome is a well-characterized inducer of inflammation in ASH. Inflammasome activation requires two signals for mature interleukin (IL)-1β production. Here we asked whether metabolic danger signals trigger inflammasome activation in ASH. Methods Wild-type mice, ATP receptor 2×7 (P2rx7)-KO mice, or mice overexpressing uricase were fed Lieber-DeCarli ethanol or control diet. We also implemented a pharmacological approach in which mice were treated with probenecid or allopurinol. Results The sterile danger signals, ATP and uric acid, were increased in the serum and liver of alcohol-fed mice. Depletion of uric acid or ATP, or lack of ATP signaling attenuated ASH and prevented inflammasome activation and its major downstream cytokine, IL-1β. Pharmacological depletion of uric acid with allopurinol provided significant protection from alcohol-induced inflammatory response, steatosis and liver damage, and additional protection was achieved in mice treated with probenecid, which depletes uric acid and blocks ATP-induced P2rx7 signaling. We found that alcohol-damaged hepatocytes released uric acid and ATP in vivo and in vitro and that these sterile danger signals activated the inflammasome in LPS-exposed liver mononuclear cells. Conclusions Our data indicate that the second signal in inflammasome activation and IL-1β production in ASH results from the endogenous danger signals, uric acid and ATP. Inhibition of signaling triggered by uric acid and ATP may have therapeutic implications in ASH. PMID:26100496

  8. Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects.

    PubMed

    Czeizel, Andrew E; Dudás, Istvan; Vereczkey, Attila; Bánhidy, Ferenc

    2013-11-21

    Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD) as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled) trials indicated that periconceptional folic acid (FA)-containing multivitamin supplementation prevented the major proportion (about 90%) of neural-tube defects (NTD) as well as a certain proportion (about 40%) of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional supplementation; and (iii) flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin's statement: "An ounce of prevention is better than a pound of care".

  9. Ferulic acid prevents methylglyoxal-induced protein glycation, DNA damage, and apoptosis in pancreatic β-cells.

    PubMed

    Sompong, Weerachat; Cheng, Henrique; Adisakwattana, Sirichai

    2017-02-01

    Methylglyoxal (MG) can react with amino acids of proteins to induce protein glycation and consequently the formation of advanced glycation end-products (AGEs). Previous studies reported that ferulic acid (FA) prevented glucose-, fructose-, and ribose-induced protein glycation. In this study, FA (0.1-1 mM) inhibited MG-induced protein glycation and oxidative protein damage in bovine serum albumin (BSA). Furthermore, FA (0.0125-0.2 mM) protected against lysine/MG-mediated oxidative DNA damage, thereby inhibiting superoxide anion and hydroxyl radical generation during lysine and MG reaction. In addition, FA did not have the ability to trap MG. Finally, FA (0.1 mM) pretreatment attenuated MG-induced decrease in cell viability and prevented MG-induced cell apoptosis in pancreatic β-cells. The results suggest that FA is capable of protecting β-cells from MG-induced cell damage during diabetes.

  10. Folate Deficiency and Folic Acid Supplementation: The Prevention of Neural-Tube Defects and Congenital Heart Defects

    PubMed Central

    Czeizel, Andrew E.; Dudás, Istvan; Vereczkey, Attila; Bánhidy, Ferenc

    2013-01-01

    Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD) as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled) trials indicated that periconceptional folic acid (FA)-containing multivitamin supplementation prevented the major proportion (about 90%) of neural-tube defects (NTD) as well as a certain proportion (about 40%) of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional supplementation; and (iii) flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin’s statement: “An ounce of prevention is better than a pound of care”. PMID:24284617

  11. Folic acid therapy reduces serum uric acid in hypertensive patients: a substudy of the China Stroke Primary Prevention Trial (CSPPT).

    PubMed

    Qin, Xianhui; Li, Youbao; He, Mingli; Tang, Genfu; Yin, Delu; Liang, Min; Wang, Binyan; Nie, Jing; Huo, Yong; Xu, Xin; Hou, Fan Fan

    2017-04-01

    Background: The effect of folic acid supplementation on uric acid (UA) concentrations is still inconclusive.Objective: We aimed to test the efficacy of folic acid therapy in reducing serum UA in hypertensive patients.Design: A total of 15,364 hypertensive patients were randomly assigned to a double-blind daily treatment with a single tablet that contained 10 mg enalapril and 0.8 mg folic acid (n = 7685) or 10 mg enalapril alone (n = 7679). The main outcome was the change in serum UA, which was defined as UA at the exit visit minus that at baseline. Secondary outcomes were as follows: 1) controlled hyperuricemia (UA concentration <357 μmol/L after treatment) and 2) new-onset hyperuricemia in participants with normal UA concentrations (<357 μmol/L).Results: After a median of 4.4 y of treatment, the mean ± SD UA concentration increased by 34.7 ± 72.5 μmol/L in the enalapril-alone group and by 30.7 ± 71.8 μmol/L in the enalapril-folic acid group, which resulted in a mean group difference of -4.0 μmol/L (95% CI: -6.5, -1.6 μmol/L; P = 0.001). Furthermore, compared with enalapril alone, enalapril-folic acid treatment showed an increase in controlled hyperuricemia (30.3% compared with 25.6%; OR: 1.31; 95% CI: 1.01, 1.70) and a decrease in new-onset hyperuricemia (15.0% compared with 16.3%; OR: 0.89; 95% CI: 0.79, 0.99). A greater beneficial effect was observed in subjects with hyperuricemia (P-interaction = 0.07) or higher concentrations of total homocysteine (tHcy) (P-interaction = 0.02) at baseline. Furthermore, there was a significant inverse relation (P < 0.001) between the reduction of tHcy and the change in UA concentrations.Conclusions: Enalapril-folic acid therapy, compared with enalapril alone, can significantly reduce the magnitude of the increase of UA concentrations in hypertensive adults. This trial was registered at clinicaltrials.gov as NCT00794885. © 2017 American Society for Nutrition.

  12. Phytic acid prevents oxidative stress in seeds: evidence from a maize (Zea mays L.) low phytic acid mutant.

    PubMed

    Doria, Enrico; Galleschi, Luciano; Calucci, Lucia; Pinzino, Calogero; Pilu, Roberto; Cassani, Elena; Nielsen, Erik

    2009-01-01

    A maize mutant defective in the synthesis of phytic acid during seed maturation was used as a tool to study the consequences of the lack of this important reserve substance on seed survival. Data on germinability, free iron level, free radical relative abundance, protein carbonylation level, damage to DNA, degree of lipid peroxidation, alpha- and gamma-tocopherol amount and antioxidant capacity were recorded on seeds of maize B73 and of an isogenic low phytic acid mutant (lpa1-241), either unaged or incubated for 7 d in accelerated ageing conditions (46 degrees C and 100% relative humidity). The lpa1-241 mutant, compared to wild type (wt), showed a lower germination capacity, which decreased further after accelerated ageing. Whole lpa1-241 mutant kernels contained about 50% more free or weakly bound iron than wt ones and showed a higher content of free radicals, mainly concentrated in embryos; in addition, upon accelerated ageing, lpa1-241 seed proteins were more carbonylated and DNA was more damaged, whereas lipids did not appear to be more peroxidated, but the gamma-tocopherol content was decreased by about 50%. These findings can be interpreted in terms of previously reported but never proven antioxidant activity of phytic acid through iron complexation. Therefore, a novel role in plant seed physiology can be assigned to phytic acid, that is, protection against oxidative stress during the seed's life span. As in maize kernels the greater part of phytic acid (and thus of metal ions) is concentrated in the embryo, its antioxidant action may be of particular relevance in this crop.

  13. Glycyrrhizic acid prevents enteritis through reduction of NF‑κB p65 and p38MAPK expression in rat.

    PubMed

    Wang, Yi-Ming; Du, Guo-Qiang

    2016-04-01

    Glycyrrhizic acid has a variety of biological properties, including a protective function in the liver, and anti‑inflammatory, anti‑ulcer, anti‑anaphylaxis, anti‑oxidant, immunoregulatory, antiviral and anticancer activities. The efficacy of glycyrrhizic acid can be increased when combined with other medicines. In the present study, the potential protective effects of glycyrrhizic acid against enteritis in rats, and its role in regulating anti‑inflammation, anti‑oxidation, angiogenic and apoptotic mechanisms were investigated using enzyme‑linked immunosorbent and bicinchoninic acid assays, and reverse transcription‑quantitative polymerase chain reaction and western blotting analyses. Adult male Sprague‑Dawley rats were injected with 20 mg/kg methotrexate (MTX) to establish enteritis. Additionally, rats with MTX‑induced enteritis were peritoneally injected with 200 mg glycyrrhizic acid for 9 weeks. The current study demonstrated that glycyrrhizic acid could alleviate MTX‑induced increases of tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6 levels, and raise IL‑10 levels, in rats with enteritis. Treatment with glycyrrhizic acid significantly reduced D‑lactate and intercellular adhesion molecule‑1 gene expression (P<0.01), but did not inhibit diamine oxidase activity in MTX‑induced enteritis. Pretreatment with glycyrrhizic acid significantly suppressed the promotion of p38 mitogen‑activated protein kinase (p38MAPK), nuclear factor‑κB p65 (NF‑κB p65) protein expression, interferon‑γ protein concentration, and caspase‑3 and cycloxygenase‑2 activity in MTX‑induced enteritis (P<0.01). The findings of the current study suggest that glycyrrhizic acid may prevent enteritis by reducing NF‑κB p65 and p38MAPK expression levels, which may inform future therapeutic strategies for the treatment of enteritis.

  14. Folic Acid Supplementation for the Prevention of Neural Tube Defects: An Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

    PubMed

    Viswanathan, Meera; Treiman, Katherine A; Kish-Doto, Julia; Middleton, Jennifer C; Coker-Schwimmer, Emmanuel J L; Nicholson, Wanda K

    2017-01-10

    Neural tube defects are among the most common congenital anomalies in the United States. Periconceptional folic acid supplementation is a primary care-relevant preventive intervention. To review the evidence on folic acid supplementation for preventing neural tube defects to inform the US Preventive Services Task Force for an updated Recommendation Statement. MEDLINE, Cochrane Library, EMBASE, and trial registries through January 28, 2016, with ongoing surveillance through November 11, 2016; references; experts. English-language studies of folic acid supplementation in women. Excluded were poor-quality studies; studies of prepubertal girls, men, women without the potential for childbearing, and neural tube defect recurrence; and studies conducted in developing countries. Two investigators independently reviewed abstracts, full-text articles, and risk of bias of included studies. One investigator extracted data and a second checked accuracy. Because of heterogeneity, data were not pooled. Neural tube defects, harms of treatment (twinning, respiratory outcomes). A total of 24 studies (N > 58 860) were included. In 1 randomized clinical trial from Hungary initiated in 1984, incidence of neural tube defects for folic acid supplementation compared with trace element supplementation was 0% vs 0.25% (Peto odds ratio [OR], 0.13 [95% CI, 0.03-0.65]; n = 4862). Odds ratios from cohort studies recruiting participants between 1984 and 1996 demonstrated beneficial associations and ranged from 0.11 to 0.27 (n = 19 982). Three of 4 case-control studies with data from 1976 through 1998 reported ORs ranging from 0.6 to 0.7 (n > 7121). Evidence of benefit led to food fortification in the United States beginning in 1998, after which no new prospective studies have been conducted. More recent case-control studies drawing from data collected after 1998 have not demonstrated a protective association consistently with folic acid supplementation, with ORs ranging from

  15. Potential preventive role of lactic acid bacteria against aflatoxin M₁ immunotoxicity and genotoxicity in mice.

    PubMed

    Ben Salah-Abbès, Jalila; Abbès, Samir; Jebali, Rania; Haous, Zohra; Oueslati, Ridha

    2015-01-01

    Aflatoxin M1 (AFM1) is a mycotoxin produced by numerous Aspergillus species in pre- or post-harvest cereals and milk. Exposure to AFM1 imparts potent economic losses in the livestock industry. Toxicologically, it also causes severe immune system problems. The aims of this study were to evaluate a new AFM1-binding/degrading microorganism for biologic detoxification, to examine its ability to degrade AFM1 in liquid medium, and to evaluate its potential for in vivo preventative effects against AFM1-induced immunotoxicity and genotoxicity in mice. Lactobacillus plantarum MON03 (LP) isolated from Tunisian artisanal butter was found to display significant binding ability to AFM1 in PBS (93%) within 24 h of incubation. Further, the LP was able to tolerate gastric acidity, bile salts, and adhere efficiently to Caco-3 cells in vitro. The in vivo study used Balb/c mice that received either vehicle (control), LP only (at 1 × 10(9)CFU/L, ∼1 mg/kg bw), AFM1 (100 mg/kg bw), or AFM1 + LP daily for 15 days (by gavage); two other groups received a single dose of colchicine (4 mg/kg) or mitomycin C (1 mg/kg) as positive controls for induction of micronuclei and chromosomal aberrations, respectively. The results showed that, compared to in control mice, AFM1 treatment led to significantly decreased body weight gains, and caused cytotoxic/genotoxic effects as indicated by increases in frequencies of polychromatic erythrocytes, as well as those with micronucleation (PCEMN) and chromosomal aberrations, among bone marrow cells. The concurrent administration of LP with AFM1 strongly reduced the adverse effects of AFM1 on each parameter. Mice receiving AFM1 + LP co-treatment displayed no significant differences in the assayed parameters as compared to the control mice. By itself, the bacteria caused no adverse effects. Based on the data, it is concluded that the test bacteria could potentially be beneficial in the detoxification of AFM1-contaminated foods and feeds

  16. Combined application of acellular bovine pericardium and hyaluronic acid in prevention of postoperative pericardial adhesion.

    PubMed

    Shen, Jia; Xu, Zhi Wei

    2014-03-01

    An experiment was designed to find the suitable acellular bovine pericardium (ABP) patch in pericardial cavity reconstruction and to evaluate the effect of sodium hyaluronic acid (NaHA) on inflammatory reaction in prevention of pericardial adhesions. The pericardial adhesion model was established in 20 rabbits, weighing from 3.2 to 3.6 kg. Groups were classified as follows: Group A (n = 5), the control group, the pericardium was directly closed; Group B (n = 5), 0.15% glutaraldehyde-treated ABP (low cross-link degree); Group C, 0.3% glutaraldehyde-treated ABP (middle cross-link degree); Group D, 0.15% glutaraldehyde-treated ABP + NaHA solution. Blood samples were collected at 6 h, 24 h, 3 days, and 5 days, to assay postoperative inflammatory reaction. The tenacity and severity of adhesions were evaluated 2 months after operation, by macroscopic and microscopic examinations, and Q-PCR (real-time quantitative polymerase chain reaction) test was used to quantitatively analyze the associated genes with adhesion. Pericardium regeneration was demonstrated by immunohistochemical technique to identify mesothelial cells. In Group D, the serum concentration of tumor necrosis factor-α (TNF-α) was significantly lower in the early postoperative period, and the mean adhesion score (adhesion between the epicardium and ABP) was significantly lower compared with the control group (Groups D vs. A: 0.20 ± 0.45 vs. 2.00 ± 0.71, P = 0.009*). The signs of degradation of the ABPs were observed 2 months postoperation in Groups D and B. Immunohistochemically, the positive cytokeratin AE1 staining results demonstrated the relatively total regeneration of the pericardium in Group D. Signs of regeneration were observed in Group D. Compared with the control group, the level of TGF-β2 in Group D was significantly lower (0.00132 ± 0.00114, P = 0.022*). The TGF-β3 level was statistically significant, being highest in Group D (0.00805 ± 0.00136, P = 0.029*). The mean quantity of Smad6 in

  17. Acanthoic Acid Can Partially Prevent Alcohol Exposure-Induced Liver Lipid Deposition and Inflammation.

    PubMed

    Yao, You-Li; Han, Xin; Li, Zhi-Man; Lian, Li-Hua; Nan, Ji-Xing; Wu, Yan-Ling

    2017-01-01

    droplets, and SREBP-1 and CYP2E1 expressions, compared with EtOH/LPS treatment. AA also significantly increased protein expressions of Sirt1, p-LKB1, p-ACC, PPARα, and decreased protein expression of PPARγ, compared with EtOH/LPS treatment. Conclusion: Acanthoic acid can partially prevent alcohol exposure-induced liver lipid deposition and inflammation via regulation of LKB1/Sirt1/AMPK/ACC and LXRs pathways.

  18. Acanthoic Acid Can Partially Prevent Alcohol Exposure-Induced Liver Lipid Deposition and Inflammation

    PubMed Central

    Yao, You-Li; Han, Xin; Li, Zhi-Man; Lian, Li-Hua; Nan, Ji-Xing; Wu, Yan-Ling

    2017-01-01

    droplets, and SREBP-1 and CYP2E1 expressions, compared with EtOH/LPS treatment. AA also significantly increased protein expressions of Sirt1, p-LKB1, p-ACC, PPARα, and decreased protein expression of PPARγ, compared with EtOH/LPS treatment. Conclusion: Acanthoic acid can partially prevent alcohol exposure-induced liver lipid deposition and inflammation via regulation of LKB1/Sirt1/AMPK/ACC and LXRs pathways. PMID:28360860

  19. Long-term effectiveness of dietary iron and ascorbic acid in the prevention and cure of cadmium toxicity in rats.

    PubMed

    Suzuki, T; Yoshida, A

    1978-09-01

    The protective and curative effects of dietary iron and ascorbic acid on chronic (180 days) cadmium toxicity in rats were examined. Growth retardation and anemia were observed in rats fed a diet containing 50 ppm of cadmium for 180 days; during this period the contents of iron in the liver, kidney, spleen, testis, intestine, and tibia decreased and the zinc contents of the liver and kidney increased, but the calcium content of bone did not change. Addition of 400 ppm of iron and 1% of ascorbic acid to the cadmium-containing diet overcame the growth retardation and anemia due to cadmium toxicity and reduced the tissue levels of cadmium; however, it did not restore the zinc contents in the liver, kidney, and bone to normal. Similar effects were observed when these compounds were added to cadmium containing diet for 90 days after feeding the cadmium diet alone for 90 days. The glutamic-pyruvic transminase and glutamic-oxaloacetic transminase activities in the plasma of rats fed the cadmium diet increased significantly and these increases were prevented by supplementing the diet with iron and ascorbic acid. Glucose, urea, and alkaline phosphatase in the plasma and glycogen in the liver were not changed by feeding the cadmium diet for 180 days. These results indicate the long-term effectiveness of supplementing the diet with iron and ascorbic-acid for preventing and curing dietary cadmium toxicity in rats.

  20. Linolenic acid prevents early and advanced glycation end-products (AGEs) modification of albumin.

    PubMed

    Prasanna, Govindarajan; Saraswathi, N T

    2017-02-01

    In this study, we report the protective effects of linolenic acid towards the formation of early (HbA1c) and advanced glycation end-products (AGEs) based on fluorescence, circular dichroism, confocal microscopy and molecular interaction studies. Linolenic acid was found to be a potent inhibitor of AGEs formed by both glucose and fructose. The HbA1c (early glycation product) level was found to be reduced to 7.4% when compared to glycated control (8.4%). Similarly, linolenic acid also inhibited the methylglyoxal mediated AGEs formation. Circular dichroism spectroscopy studies suggested that the protective effect of linolenic acid for the helical structure of albumin. The molecular interaction studies showed that linolenic acid interacts with arginine residues of albumin with high affinity. Results suggested linolenic acid to be a potent antiglycation compound and also it could be a better lead compound for AGE inhibition.

  1. Preventive effect of phytic acid on lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats.

    PubMed

    Brindha, E; Rajasekapandiyan, M

    2015-02-01

    This study was aimed to evaluate the preventive role of phytic acid on lysosomal enzymes in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats subcutaneously injected with ISO (85 mg/kg) at an interval of 24 h for two days showed a significant increase in the activities of lysosomal enzymes (glucuronidase, N-acetyl glucosaminidase, galactosidase, cathepsin-B and cathepsin-D) were increased significantly in serum and the heart of ISO-induced rats, but the activities of glucuronidase and cathepsin-D were decreased significantly in the lysosomal fraction of the heart. Pretreatment with phytic acid (25 and 50 mg/kg) daily for a period of 56 d positively altered activities of lysosomal hydrolases in ISO-induced rats. Thus, phytic acid possesses a cardioprotective effect in ISO-induced MI in rats.

  2. [Conjugated linoleic acid as a potential protective factor in prevention of breast cancer].

    PubMed

    Białek, Agnieszka; Tokarz, Andrzej

    2013-01-11

    Cancers are the second leading cause of deaths in Poland, among both women and men. Breast cancer is the malignancy most frequently diagnosed in women. In 2008 mammary cancer was diagnosed in up to 14 500 patients. It is also the second most common cause of cancer deaths among women in our country. Although the etiology of most cases of this disease is not known, risk factors include a variety of nutritional factors. The amount of fat consumed in the diet and the quantity and quality of fatty acids are especially crucial. Among fatty acids to which great importance in modification of cancer risk is attributed are conjugated linoleic acid. Conjugated linoleic acids (CLA) are a group of positional and geometric isomers of linoleic acid, with a conjugated double bond system in the carbon chain. The main natural source of them is milk and dairy products and meat of different species of ruminants, in which cis-9, trans-11 octadecadienoic acid (rumenic acid) occurs in the largest quantities, constituting over 90% of the total pool of CLA. Another important isomer is trans-10, cis-12 octadecadienoic acid, which occurs with rumenic acid in dietary supplements, usually in the ratio 1:1. Surveys conducted show their possible health promoting effects in obesity, atherosclerosis, cardiovascular diseases, osteoporosis, diabetes, insulin resistance, inflammation, and various types of cancer, especially breast cancer. 

  3. Iron prevents ascorbic acid (vitamin C) induced hydrogen peroxide accumulation in copper contaminated drinking water.

    PubMed

    Jansson, Patric J; Lindqvist, Christer; Nordström, Tommy

    2005-11-01

    Ascorbic acid (vitamin C) induced hydrogen peroxide (H(2)O(2)) formation was measured in household drinking water and metal supplemented Milli-Q water by using the FOX assay. Here we show that ascorbic acid readily induces H(2)O(2) formation in Cu(II) supplemented Milli-Q water and poorly buffered household drinking water. In contrast to Cu(II), iron was not capable to support ascorbic acid induced H(2)O(2) formation during acidic conditions (pH: 3.5-5). In 12 out of the 48 drinking water samples incubated with 2 mM ascorbic acid, the H(2)O(2) concentration exceeded 400 microM. However, when trace amounts of Fe(III) (0.2 mg/l) was present during incubation, the ascorbic acid/Cu(II)-induced H(2)O(2) accumulation was totally blocked. Of the other common divalent or trivalent metal ions tested, that are normally present in drinking water (calcium, magnesium, zinc, cobalt, manganese or aluminum), only calcium and magnesium displayed a modest inhibitory activity on the ascorbic acid/Cu(II)-induced H(2)O(2) formation. Oxalic acid, one of the degradation products from ascorbic acid, was confirmed to actively participate in the iron induced degradation of H(2)O(2). Ascorbic acid/Cu(II)-induced H(2)O(2) formation during acidic conditions, as demonstrated here in poorly buffered drinking water, could be of importance in host defense against bacterial infections. In addition, our findings might explain the mechanism for the protective effect of iron against vitamin C induced cell toxicity.

  4. Cyclin A2 and CDK2 as Novel Targets of Aspirin and Salicylic acid: a Potential Role in Cancer Prevention

    PubMed Central

    Dachineni, Rakesh; Ai, Guoqiang; Kumar, D. Ramesh; Sadhu, Satya S.; Tummala, Hemachand; Bhat, G. Jayarama

    2015-01-01

    Data emerging from the past 10 years have consolidated the rationale for investigating the use of aspirin as a chemopreventive agent; however, the mechanisms leading to its anti-cancer effects are still being elucidated. We hypothesized that aspirin’s chemopreventive actions may involve cell cycle regulation through modulation of the levels or activity of cyclin A2/cyclin dependent kinase-2 (CDK2). In this study, HT-29 and other diverse panel of cancer cells were used to demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2 (CCNA2) and CDK2 protein and mRNA levels. The down regulatory effect of either drugs on cyclin A2 levels was prevented by pretreatment with lactacystin, an inhibitor of proteasomes, suggesting the involvement of 26S proteasomes. In-vitro kinase assays showed that lysates from cells treated with salicylic acid had lower levels of CDK2 activity. Importantly, three independent experiments revealed that salicylic acid directly binds to CDK2. Firstly, inclusion of salicylic acid in naïve cell lysates, or in recombinant CDK2 preparations, increased the ability of the anti-CDK2 antibody to immunoprecipitate CDK2, suggesting that salicylic acid may directly bind and alter its conformation. Secondly, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, pre-incubation of CDK2 with salicylic acid, dose-dependently quenched the fluorescence due to ANS. Thirdly, computational analysis using molecular docking studies identified Asp145 and Lys33 as the potential sites of salicylic acid interactions with CDK2. These results demonstrate that aspirin and salicylic acid down-regulate cyclin A2/CDK2 proteins in multiple cancer cell lines, suggesting a novel target and mechanism of action in chemoprevention. Implications Biochemical and structural studies indicate that the anti-proliferative actions of aspirin are mediated through cyclin A2/CDK2. PMID:26685215

  5. Cyclin A2 and CDK2 as Novel Targets of Aspirin and Salicylic Acid: A Potential Role in Cancer Prevention.

    PubMed

    Dachineni, Rakesh; Ai, Guoqiang; Kumar, D Ramesh; Sadhu, Satya S; Tummala, Hemachand; Bhat, G Jayarama

    2016-03-01

    Data emerging from the past 10 years have consolidated the rationale for investigating the use of aspirin as a chemopreventive agent; however, the mechanisms leading to its anticancer effects are still being elucidated. We hypothesized that aspirin's chemopreventive actions may involve cell-cycle regulation through modulation of the levels or activity of cyclin A2/cyclin-dependent kinase-2 (CDK2). In this study, HT-29 and other diverse panel of cancer cells were used to demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2 (CCNA2) and CDK2 protein and mRNA levels. The downregulatory effect of either drugs on cyclin A2 levels was prevented by pretreatment with lactacystin, an inhibitor of proteasomes, suggesting the involvement of 26S proteasomes. In-vitro kinase assays showed that lysates from cells treated with salicylic acid had lower levels of CDK2 activity. Importantly, three independent experiments revealed that salicylic acid directly binds to CDK2. First, inclusion of salicylic acid in naïve cell lysates, or in recombinant CDK2 preparations, increased the ability of the anti-CDK2 antibody to immunoprecipitate CDK2, suggesting that salicylic acid may directly bind and alter its conformation. Second, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, preincubation of CDK2 with salicylic acid dose-dependently quenched the fluorescence due to ANS. Third, computational analysis using molecular docking studies identified Asp145 and Lys33 as the potential sites of salicylic acid interactions with CDK2. These results demonstrate that aspirin and salicylic acid downregulate cyclin A2/CDK2 proteins in multiple cancer cell lines, suggesting a novel target and mechanism of action in chemoprevention. Biochemical and structural studies indicate that the antiproliferative actions of aspirin are mediated through cyclin A2/CDK2. ©2015 American Association for Cancer Research.

  6. Carnosic acid promotes myocardial antioxidant response and prevents isoproterenol-induced myocardial oxidative stress and apoptosis in mice.

    PubMed

    Sahu, Bidya Dhar; Putcha, Uday Kumar; Kuncha, Madhusudana; Rachamalla, Shyam Sunder; Sistla, Ramakrishna

    2014-09-01

    Carnosic acid is a well-known antioxidant. Recently, it has been identified as modulator of nuclear factor erythroid 2-related factor 2 (Nrf2). The effect of carnosic acid in the context of cardiovascular disorders has not been studied. In the present study, we investigated the beneficial effect and the underlying cardioprotective mechanism of carnosic acid by using mouse model of isoproterenol (ISO)-induced myocardial stress. Elevated serum levels of Troponin I, CK-MB, LDH, SGOT and SGPT, and myofibrillar degeneration with necrotic damage, and the presence of epicardial inflammatory infiltrate (H & E staining) confirmed the ISO-induced myocardial stress. Myocardial content of vitamin C, reduced glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, quinine oxidoreductase 1, superoxide dismutase, catalase, nuclear translocation of Nrf2 and protein expression heme oxygenase-1 were evaluated. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and myocardial expression of cleaved caspase-3, caspase-9, p53, Bax, and Bcl-2 were investigated to assess the apoptotic cell death. Pretreatment with carnosic acid attenuated ISO-induced elevated serum levels of Troponin I, CK-MB, LDH, SGOT and SGPT, and histopathological alterations in heart. Moreover, carnosic acid enhanced the nuclear translocation of Nrf2 and up-regulated the phase II/antioxidant enzyme activities. Furthermore, TUNEL assay and apoptosis-related protein analysis indicated that carnosic acid prevented ISO-induced cardiomyocyte apoptosis. Isoproterenol-induced myocardial lipid peroxidation and protein oxidation were also significantly decreased by carnosic acid pretreatment. The overall results clearly indicate that therapeutic application of carnosic acid might be beneficial in treating cardiovascular disorders.

  7. Targeting arachidonic acid pathway to prevent programmed hypertension in maternal fructose-fed male adult rat offspring.

    PubMed

    Tain, You-Lin; Lee, Wei-Chia; Wu, Kay L H; Leu, Steve; Chan, Julie Y H

    2016-12-01

    Hypertension can be programmed in response to nutritional insults in early life. Maternal high-fructose (HF) intake induced programmed hypertension in adult male offspring, which is associated with renal programming and arachidonic acid metabolism pathway. We examined whether early treatment with a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-Deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) can prevent HF-induced programmed hypertension. Pregnant Sprague Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) during the whole period of pregnancy and lactation. Four groups of male offspring were studied: control, HF, HF+AUDA and HF+15dPGJ2. In HF+AUDA group, mother rats received AUDA 25 mg/L in drinking water during lactation. In the HF+15dPGJ2 group, male offspring received 15dPGJ2 1.5 mg/kg body weight by subcutaneous injection once daily for 1 week after birth. Rats were sacrificed at 12 weeks of age. Maternal HF-induced programmed hypertension is associated with increased renal protein level of SEH and oxidative stress, which early AUDA therapy prevents. Comparison of AUDA and 15dPGJ2 treatments demonstrated that AUDA was more effective in preventing HF-induced programmed hypertension. AUDA therapy increases angiotensin converting enzyme-2 (ACE2) protein levels and PGE2 levels in adult offspring kidney exposed to maternal HF. 15dPGJ2 therapy increases plasma asymmetric dimethylarginine (ADMA) levels and decreases L-arginine-to-ADMA ratio. Better understanding of the impact of arachidonic acid pathway, especially inhibition of SEH, on renal programming may aid in developing reprogramming strategy to prevent programmed hypertension in children exposed to antenatal HF intake.

  8. Treatment and prevention systems for acid mine drainage and halogenated contaminants

    DOEpatents

    Jin, Song [Fort Collins, CO; Fallgren, Paul H [Laramie, WY; Morris, Jeffrey M [Laramie, WY

    2012-01-31

    Embodiments include treatments for acid mine drainage generation sources (10 perhaps by injection of at least one substrate (11) and biologically constructing a protective biofilm (13) on acid mine drainage generation source materials (14). Further embodiments include treatments for degradation of contaminated water environments (17) with substrates such as returned milk and the like.

  9. Prevention of small black spots on sugar-coated tablets containing aluminum acetylsalicylic acid.

    PubMed

    Tomida, Y; Makino, T

    1999-04-01

    Sugar-coated tablets containing aluminum acetylsalicylate gradually developed black spots on their surface. A factorial experiment was performed based on an L32 orthogonal array table in an attempt to halt this phenomenon. The factor responsible proved to be talc used to formulate the smooth coating layer over the subcoating layer containing aluminum acetylsalicylate. When HCl-treated talc was used as a filler for the smoothing layer, the black spots were markedly decreased. The spotting mechanism was considered to be due to hydrolysis of aluminum acetylsalicylate in the subcoating layer to salicylic acid and acetic acid, which sublimated into the pores of the smoothing layer. Then, ferrous ion substituted from magnesium ion in the talc molecule center was extracted by salicylic acid, acetic acid, and moisture. Finally, the ferrous ion was oxidized to ferric ion, and this produced an Fe3+ chelate compound together with salicylic acid.

  10. Docosahexaenoic acid prevents trans-10, cis-12-conjugated linoleic acid-induced nonalcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation.

    PubMed

    Fedor, Dawn M; Adkins, Yuriko; Mackey, Bruce E; Kelley, Darshan S

    2012-06-01

    Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented trans-10, cis-12-conjugated linoleic acid (CLA)-induced nonalcoholic fatty liver disease (NAFLD) and insulin resistance. The effective dose of DHA and mechanisms involved are poorly understood. We examined the ability of DHA (0.5% and 1.5%) to prevent increases in NAFLD and homeostatic model assessment of insulin resistance (HOMA-IR) induced by CLA (0.5%) when fed concomitantly for 4 weeks to C57BL/6N female mice. We also examined changes in expression of hepatic genes involved in fatty acid synthesis and oxidation. CLA supplementation increased liver triglycerides (TG) and HOMA-IR by 221% and 547%, respectively, and decreased mass of different adipose depots by 65%-90% when compared to those in the control group. When fed concomitantly, DHA prevented CLA-induced increases in liver TG and circulating insulin with varying efficiency, but it did not prevent loss in adipose tissue mass. In the CLA+0.5% DHA group, the liver TG did not differ from those in the control group, but circulating insulin and HOMA-IR were 285% and 264%, respectively. In the CLA+1.5% DHA group, liver TG were 54% lower than those in the control group, but circulating insulin concentration and HOMA-IR did not differ between these two groups. CLA increased the expression of hepatic genes involved in fatty acid synthesis and decreased the expression of genes involved in fatty acid oxidation, and 1.5% DHA prevented changes in the expression of hepatic genes caused by CLA. Response of different tissues to CLA and DHA varied; CLA was more potent than DHA in altering depot fat and insulin concentrations.

  11. Clomipramine causes osteoporosis by promoting osteoclastogenesis via E3 ligase Itch, which is prevented by Zoledronic acid

    PubMed Central

    Li, Xing; Sun, Wen; Li, Jinbo; Wang, Mengmeng; Zhang, Hengwei; Pei, Lingpeng; Boyce, Brendan F.; Wang, Zhiyu; Xing, Lianping

    2017-01-01

    Patients taking antidepressants, including Clomipramine (CLP), have an increased risk of osteoporotic fracture. However, the effects of CLP on bone metabolism are unknown. Here, we demonstrate that WT mice treated with CLP for 2 weeks had significantly reduced trabecular bone volume and cortical bone thickness, associated with increased osteoclast (OC) numbers, but had no change in osteoblast numbers or bone formation rate. Bone marrow cells from CLP-treated mice had normal OC precursor frequency, but formed significantly more OCs when they were cultured with RANKL and M-CSF. CLP promoted OC formation and bone resorption and expression of OC-associated genes. CLP-induced bone loss was prevented by Zoledronic acid. At the molecular level, CLP inhibited the activity of the ubiquitin E3 ligase Itch. CLP did not promote OC formation from bone marrow cells of Itch−/− mice in vitro nor induce bone loss in Itch−/− mice. Our findings indicate that CLP causes bone loss by enhancing Itch-mediated osteoclastogenesis, which was prevented by Zoledronic acid. Thus, anti-resorptive therapy could be used to prevent bone loss in patients taking antidepressants, such as CLP. PMID:28145497

  12. Prophylactic Valproic Acid Treatment Prevents Schizophrenia-Related Behaviour in Disc1-L100P Mutant Mice

    PubMed Central

    Lipina, Tatiana V.; Haque, Fahmida Nipa; McGirr, Alexander; Boutros, Paul C.; Berger, Thorsten; Mak, Tak W.; Roder, John C.; Wong, Albert H. C.

    2012-01-01

    Background Schizophrenia is a neurodevelopmental disorder with onset early in adulthood. Disrupted-In-Schizophrenia-1 (DISC1) is a susceptibility gene for schizophrenia and other psychiatric disorders. Disc1-L100P mutant mice show behaviors relevant to schizophrenia at 12 weeks, but not at 8 weeks of age, and may be useful for investigating the onset of schizophrenia in early adulthood. Methods We investigated whether early valproic acid treatment would prevent behavioral, cellular and gene expression abnormalities in Disc1-L100P mutants. Results Valproic acid prevented hyperactivity and deficits in prepulse inhibition and latent inhibition in Disc1-L100P mice. Genome-wide transcription profiling identified Lcn2 (lipocalin2) transcripts as being elevated by the Disc1 mutation and corrected by valproate. Disc1-L100P mice also had increased glial cell numbers in the subventricular zone, which was normalized by valproate. Genetic deletion of Lcn2 normalized glial cell numbers and behavior in Disc1-L100P mutants. Conclusions Pharmacological treatments are a feasible way of preventing abnormal behaviour in a genetic model of schizophrenia. Lcn2 is a potential novel drug target for early intervention in schizophrenia. PMID:23272119

  13. Parenteral safflower oil emulsion (Liposyn 10%): safety and effectiveness in treating or preventing essential fatty acid deficiency in surgical patients.

    PubMed Central

    Bivins, B A; Rapp, R P; Record, K; Meng, H C; Griffen, W O

    1980-01-01

    The safety and effectiveness of a 10% safflower oil emulsion in treating or preventing essential fatty acid deficiency was tested in a prospective study of 15 surgical patients requiring total parenteral nutrition for two to four weeks. Three dosage regimens were evaluated including: Group I: 4% of calories as linoleate daily (five patients), Group II: 4% of calories as linoleate every other day (two patients), and Group III: 8% of calories every other day (eight patients). Patients were monitored for laboratory changes from baseline specifically in those areas where previous fat emulsions have caused serious deviations. No significant changes were noted in hematologic parameters, coagulation studies, cholesterol and triglyceride serum levels. Although there were sporadic mild deviations in liver function changes in several patients, no clinically significant adverse effects could be directly attributed to infusion of the fat emulsion. Three patients had baseline triene/tetraene ratios of 0.4 or greater, indicative of essential fatty/acid deficiency, and these ratios dropped to less than 0.4 within eight days of beginning therapy with the parenteral fat emulsion. The remaining 12 patients maintained a normal triene/tetraene ratio of less than 0.4 throughout the 28 day study period. All three dosage regimens were considered effective for treatment and prevention of essential fatty acid deficiency. Images Fig. 1. Fig. 2. Fig. 3. PMID:6767452

  14. Rapid effects of environmental disturbance on rat plasma unesterified fatty acid and tryptophan concentrations and their prevention by antilopolytic drugs.

    PubMed Central

    Curzon, G; Knott, P J

    1975-01-01

    1 Changes of plasma unesterified fatty acid (UFA) and tryptophan concentration in group-housed rats following removal of their cage-mates and the effects of antilipolytic drugs on these changes were investigated. 2 Removal of group-housed 24 h fasted rats but not fed rats from cages resulted in increased plasma UFA concentration in the remaining rats which was associated with significant increases of the proportion of free tryptophan but significant falls of total tryptophan concentration. These rapid changes were not associated with brain tryptophan changes. Plasma tyrosine concentration was unaffected. 3 The fall of plasma tryptophan did not appear to be due to passage into red cells as erythrocyte tryptophan concentration remained unchanged. 4 Plasma UFA concentrations correlated positively and significantly with corticosterone concentrations which were also increased following removal of cage-mates. 5 Plasma UFA increases and tryptophan changes in the fasting rats were both prevented by nicotinic acid or propranolol. Corticosterone concentration was increased by nicotinic acid but unaffected by propranolol. 6 The possible importance of these rapid changes of plasma tryptophan and of their prevention by antilipolytic drugs is discussed. PMID:1164595

  15. Effects of folic acid supplementation during different pregnancy periods and relationship with the other primary prevention measures to neural tube defects.

    PubMed

    Gong, Rui; Wang, Zhi-Ping; Wang, Meng; Gao, Li-Jie; Zhao, Zhong-Tang

    2016-12-01

    To find out the prevention effects of folic acid supplements during different pregnancy periods on neural tube defects (NTDs) and the relationship of folic acid supplements with the other NTDs' primary preventive measures. A 1:1 case-control study was conducted. Four hundred and fifty-nine women who delivered or gestate infants/fetuses with NTDs in the last two years were randomly selected as cases and were matched with women who delivered babies without obvious birth defects as controls. For anencephaly, folic acid supplementation during the periconceptional period and preconceptional period has a 57-83% reduction in risk of NTDs(ORs ranged from 0.17 to 0.43). For spina bifida, folic acid supplementation during the periconceptional period has a 79% reduction in risk of NTDs (OR = 0.21). For encephalocele, folic acid supplementation during the periconceptional period has a 67% reduction in risk of NTDs (OR = 0.33). The prevention effects on NTDs were significant when these preventive measures combined with folic acid supplements during the periconceptional period, with OR 0.04, 0.07, 0.10 and 0.11. The specific effects of folic acid supplementation during different periods show the reduction in the risk of NTDs, anencephaly, spina bifida, encephalocele. During periconceptional period, folic acid supplements have preventive effects on all NTDs' subtypes.

  16. Once-yearly zoledronic acid in the prevention of osteoporotic bone fractures in postmenopausal women

    PubMed Central

    Lambrinoudaki, Irene; Vlachou, Sophia; Galapi, Fotini; Papadimitriou, Dimitra; Papadias, K

    2008-01-01

    Zoledronic acid is a nitrogen-containing, third-generation bisphosphonate that has recently been approved for the treatment of postmenopausal osteoporosis as an annual intravenous infusion. Zoledronic acid is an antiresorptive agent which has a high affinity for mineralized bone and especially for sites of high bone turnover. Zoledronic acid is excreted by the kidney without further metabolism. Zoledronic acid administered as a 5 mg intravenous infusion annually increases bone mineral density in the lumbar spine and femoral neck by 6.7% and 5.1% respectively and reduces the incidence of new vertebral and hip fractures by 70% and 41% respectively in postmenopausal women with osteoporosis. Most common side effects are post-dose fever, flu-like symptoms, myalgia, arthralgia, and headache which usually occur in the first 3 days after infusion and are self-limited. Rare adverse effects include renal dysfunction, hypocalcemia, atrial fibrillation, and osteonecrosis of the jaw. PMID:18982915

  17. [A two-faced vitamin : Folic acid - prevention or promotion of colon cancer?

    PubMed

    Weißenborn, Anke; Ehlers, Anke; Hirsch-Ernst, Karen-I; Lampen, Alfonso; Niemann, Birgit

    2017-03-01

    In the late 1930s, it was discovered that liver and yeast extracts can be used to correct certain cases of megaloblastic anemia in pregnancy. The factor responsible for this was isolated from spinach leaves in the 1940s, and referred to as folate, a term derived from the Latin word folium for leaf. Folate is considered an essential nutrient for human beings. Folic acid, the synthetic form of the vitamin, is used in dietary supplements, medicines and fortified foods. Since the 1980s, it has been recommended that women who plan to become pregnant and pregnant women during the first trimester of pregnancy take folic acid supplements. This recommendation was based on studies that revealed that periconceptional folic acid supplementation can reduce the risk for neural tube defects (NTDs). Many countries later implemented folic acid fortification programs. The resulting population-wide increase of folic acid intakes led to significant reductions in NTD rates. However, a temporarily increased colorectal cancer incidence has been reported to coincide with the fortification programs in the USA and Canada. On the basis of currently available data from experimental and human studies it can be concluded that the association between folate/folic acid and cancer is rather complex: Folate intake in the range of the dietary reference intake (DRI) is associated with a reduced risk for cancer in healthy populations, whereas high intakes of folic acid might result in an increased risk for cancer incidence or progression in persons with precancerous lesions and under certain conditions. Since no adverse effects have been observed in association with the intake of dietary folate, research activities that aim at investigating cause and effect relationships focus on folic acid.

  18. Chromosomal Integration of Retinoic Acid Response Elements Prevents Cooperative Transcriptional Activation by Retinoic Acid Receptor and Retinoid X Receptor

    PubMed Central

    Lefebvre, Bruno; Brand, Céline; Lefebvre, Philippe; Ozato, Keiko

    2002-01-01

    All-trans-retinoic acid receptors (RAR) and 9-cis-retinoic acid receptors (RXR) are nuclear receptors known to cooperatively activate transcription from retinoid-regulated promoters. By comparing the transactivating properties of RAR and RXR in P19 cells using either plasmid or chromosomal reporter genes containing the mRARβ2 gene promoter, we found contrasting patterns of transcriptional regulation in each setting. Cooperativity between RXR and RAR occurred at all times with transiently introduced promoters, but was restricted to a very early stage (<3 h) for chromosomal promoters. This time-dependent loss of cooperativity was specific for chromosomal templates containing two copies of a retinoid-responsive element (RARE) and was not influenced by the spacing between the two RAREs. This loss of cooperativity suggested a delayed acquisition of RAR full transcriptional competence because (i) cooperativity was maintained at RAR ligand subsaturating concentrations, (ii) overexpression of SRC-1 led to loss of cooperativity and even to strong repression of chromosomal templates activity, and (iii) loss of cooperativity was observed when additional cis-acting response elements were activated. Surprisingly, histone deacetylase inhibitors counteracted this loss of cooperativity by repressing partially RAR-mediated activation of chromosomal promoters. Loss of cooperativity was not correlated to local histone hyperacetylation or to alteration of constitutive RNA polymerase II (RNAP) loading at the promoter region. Unexpectedly, RNAP binding to transcribed regions was correlated to the RAR activation state as well as to acetylation levels of histones H3 and H4, suggesting that RAR acts at the mRARβ promoter by triggering the switch from an RNA elongation-incompetent RNAP form towards an RNA elongation-competent RNAP. PMID:11839811

  19. Natural xenobiotics to prevent cyanobacterial and algal growth in freshwater: contrasting efficacy of tannic acid, gallic acid, and gramine.

    PubMed

    Laue, Pauline; Bährs, Hanno; Chakrabarti, Shumon; Steinberg, Christian E W

    2014-06-01

    Allelochemical action against planktonic phototrophs is one central issue in freshwater ecology and quality management. To determine some basic mechanisms of this toxic action, we exposed the coccal green alga, Desmodesmus armatus, and the coccal cyanobacterium, Microcystis aeruginosa, in a batch culture well-supplied with carbon dioxide to increasing concentrations of the polyphenols tannic acid and gallic acid and the alkaloid gramine. The phototrophs were checked after 2d and at the end of the culture for biomass-based growth rates, cell volume, maximum quantum yield of photosystem II (ΦPSIImax), chlorophyll a content (chla) after 2d and at the end of the culture, and lipid peroxidation only at the end of the culture. During the culture, the pH rose from 7.64 to 10.95, a pH characteristic of eutrophic freshwater bodies during nuisance algal blooms. All xenobiotics reduced the growth rate, ΦPSIImax, and chla during the first 2d with M. aeruginosa being more sensitive to the polyphenols than D. armatus. The efficacy of the polyphenols declined with increasing pH, indicating potential polymerization and corresponding reduced bioavailability of the polyphenols. In contrast to the polyphenols, gramine increased its toxic action over time, independent of the prevailing pH. All exposures caused slight to severe lipid peroxidation (LPO) in the phototrophs. Hence, one mechanism of growth inhibition may be oxidative stress-mediated reduction in photosynthesis. The presented results suggest that in successful field trials with leachate, the prevailing environmental conditions may inactivate polyphenols and xenobiotics other than polyphenols may be more effective. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Acid Sphingomyelinase Deficiency Prevents Diet-induced Hepatic Triacylglycerol Accumulation and Hyperglycemia in Mice*

    PubMed Central

    Deevska, Gergana M.; Rozenova, Krassimira A.; Giltiay, Natalia V.; Chambers, Melissa A.; White, James; Boyanovsky, Boris B.; Wei, Jia; Daugherty, Alan; Smart, Eric J.; Reid, Michael B.; Merrill, Alfred H.; Nikolova-Karakashian, Mariana

    2009-01-01

    Acid sphingomyelinase plays important roles in ceramide homeostasis, which has been proposed to be linked to insulin resistance. To test this association in vivo, acid sphingomyelinase deletion (asm–/–) was transferred to mice lacking the low density lipoprotein receptor (ldlr–/–), and then offsprings were placed on control or modified (enriched in saturated fat and cholesterol) diets for 10 weeks. The modified diet caused hypercholesterolemia in all genotypes; however, in contrast to asm+/+/ldlr–/–, the acid sphingomyelinase-deficient littermates did not display hepatic triacylglyceride accumulation, although sphingomyelin and other sphingolipids were substantially elevated, and the liver was enlarged. asm–/–/ldlr–/– mice on a modified diet did not accumulate body fat and were protected against diet-induced hyperglycemia and insulin resistance. Experiments with hepatocytes revealed that acid sphingomyelinase regulates the partitioning of the major fatty acid in the modified diet, palmitate, into two competitive and inversely related pools, triacylglycerides and sphingolipids, apparently via modulation of serine palmitoyltransferase, a rate-limiting enzyme in de novo sphingolipid synthesis. These studies provide evidence that acid sphingomyelinase activity plays an essential role in the regulation of glucose metabolism by regulating the hepatic accumulation of triacylglycerides and sphingolipids during consumption of a diet rich in saturated fats. PMID:19074137

  1. Palatinose and oleic acid act together to prevent pancreatic islet disruption in nondiabetic obese Zucker rats.

    PubMed

    Sato, Kazusa; Arai, Hidekazu; Miyazawa, Yui; Fukaya, Makiko; Uebanso, Takashi; Koganei, Megumi; Sasaki, Hajime; Sato, Tadatoshi; Yamamoto, Hironori; Taketani, Yutaka; Takeda, Eiji

    2008-08-01

    We showed previously that 8-wk consumption of a diet containing palatinose (P, a slowly-absorbed sucrose analogue) and oleic acid (O) ameliorates but a diet containing sucrose (S) and linoleic acid (L) aggravates metabolic abnormalities in Zucker fatty (fa/fa) rats. In this study, we aimed to identify early changes in metabolism in rats induced by certain combinations of carbohydrates and fatty acids. Specifically, male Zucker fatty rats were fed an isocaloric diet containing various combinations of carbohydrates (P; S) and fatty acids (O; L). After 4 wk, no significant differences in body weight, visceral fat mass, plasma parameters (glucose, insulin, lipids, and adipokines), hepatic adiposity and gene expression, and adipose inflammation were observed between dietary groups. In contrast, pancreatic islets of palatinose-fed (PO and PL) rats were smaller and less fibrotic than sucrose-fed (SO and SL) rats. The abnormal alpha-cell distribution and sporadic staining of active caspase-3 common to islets of linoleic-acid-fed rats were not observed in oleic-acid-fed (PO and SO) rats. Accordingly, progressive beta-cell loss was seen in SL rats, but not in PO rats. These findings suggest that pancreatic islets may be initial sites that translate the effects of different combinations of dietary carbohydrates and fats into metabolic changes.

  2. Preventive effect of ferulic acid on bone loss in ovariectomized rats.

    PubMed

    Sassa, Shuji; Kikuchi, Takashi; Shinoda, Hisashi; Suzuki, Satoe; Kudo, Hideki; Sakamoto, Shinobu

    2003-01-01

    An extract from corn germ induced a positive response in the pigeon crop sack test, used for the detection of prolactin-like substances. One of the substances extracted was identified as ferulic acid, which was reported to affect serum gonadotropin levels in ovariectomized male rats. To evaluate the effects of ferulic acid on bone loss, ovariectomized female rats of the Sprague-Dawley strain at age 35 weeks were given ferulic acid and/or 17a-ethynylestradiol daily for 8 weeks, and serum hormone levels and tibial bone mineral density were measured. In metaphysis of the tibia, which was abundant in cancellous bone and more reflective of BMD than whole tibia, the BMD was markedly reduced by ovariectomy and enhanced by the treatment with estrogen or ferulic acid in the ovariectomized rats. The treatment slightly increased the serum levels of estrogen and progesterone and alkaline phosphatase activity, which was reduced by estrogentreatment, i.e. the mechanism of bone formation by ferulic acid was suggested to be different from that by estrogens. These results indicate that ferulic acid promotes bone remodeling, leading to a predominantly osteoblastic phase, besides bone resorption by osteoclasts.

  3. Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice

    PubMed Central

    Park, Han-Sol; Jang, Jung Eun; Ko, Myoung Seok; Woo, Sung Hoon; Kim, Bum Joong; Kim, Hyun Sik; Park, Hye Sun; Park, In-Sun; Koh, Eun Hee

    2016-01-01

    Background Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown. Methods Seven-week-old C57BL/6J mice were given normal chow or a methionine- and choline-deficient diet (MCDD) with or without various statins, fluvastatin, pravastatin, simvastatin, atorvastatin, and rosuvastatin (15 mg/kg/day), for 6 weeks. Histological lesions were analyzed by grading and staging systems of NASH. We also measured mitochondrial and peroxisomal FAO in the liver. Results Statin treatment prevented the development of MCDD-induced NASH. Both steatosis and inflammation or fibrosis grades were significantly improved by statins compared with MCDD-fed mice. Gene expression levels of peroxisomal proliferator-activated receptor α (PPARα) were decreased by MCDD and recovered by statin treatment. MCDD-induced suppression of mitochondrial and peroxisomal FAO was restored by statins. Each statin's effect on increasing FAO and improving NASH was independent on its effect of decreasing cholesterol levels. Conclusion Statins prevented NASH and increased mitochondrial and peroxisomal FAO via induction of PPARα. The ability to increase hepatic FAO is likely the major determinant of NASH prevention by statins. Improvement of peroxisomal function by statins may contribute to the prevention of NASH. PMID:27098507

  4. Melatonin Prevents Myeloperoxidase Heme Destruction and the Generation of Free Iron Mediated by Self-Generated Hypochlorous Acid

    PubMed Central

    Shaeib, Faten; Khan, Sana N.; Ali, Iyad; Najafi, Tohid; Maitra, Dhiman; Abdulhamid, Ibrahim; Saed, Ghassan M.; Pennathur, Subramaniam; Abu-Soud, Husam M.

    2015-01-01

    Myeloperoxidase (MPO) generated hypochlorous acid (HOCl) formed during catalysis is able to destroy the MPO heme moiety through a feedback mechanism, resulting in the accumulation of free iron. Here we show that the presence of melatonin (MLT) can prevent HOCl-mediated MPO heme destruction using a combination of UV-visible photometry, hydrogen peroxide (H2O2)-specific electrode, and ferrozine assay techniques. High performance liquid chromatography (HPLC) analysis showed that MPO heme protection was at the expense of MLT oxidation. The full protection of the MPO heme requires the presence of a 1:2 MLT to H2O2 ratio. Melatonin prevents HOCl–mediated MPO heme destruction through multiple pathways. These include competition with chloride, the natural co-substrate; switching the MPO activity from a two electron oxidation to a one electron pathway causing the buildup of the inactive Compound II, and its subsequent decay to MPO-Fe(III) instead of generating HOCl; binding to MPO above the heme iron, thereby preventing the access of H2O2 to the catalytic site of the enzyme; and direct scavenging of HOCl. Collectively, in addition to acting as an antioxidant and MPO inhibitor, MLT can exert its protective effect by preventing the release of free iron mediated by self-generated HOCl. Our work may establish a direct mechanistic link by which MLT exerts its antioxidant protective effect in chronic inflammatory diseases with MPO elevation. PMID:25835505

  5. Dietary Supplementation with Docosahexaenoic Acid, but Not Eicosapentanoic Acid, Dramatically Alters Cardiac Mitochondrial Phospholipid Fatty Acid Composition and Prevents Permeability Transition

    PubMed Central

    Khairallah, Ramzi J.; Sparagna, Genevieve C.; Khanna, Nishanth; O’Shea, Karen M.; Hecker, Peter A.; Kristian, Tibor; Fiskum, Gary; Rosiers, Christine Des; Polster, Brian M.; Stanley, William C.

    2010-01-01

    Treatment with the ω-3 polyunsaturated fatty acids (PUFAs) docosahexanoic acid (DHA) and eicosapentanoic acid (EPA) exerts cardioprotective effects, and suppresses Ca2+-induced opening of the mitochondrial permeability transition pore (MPTP). These effects are associated with increased DHA and EPA, and lower arachidonic acid (ARA) in cardiac phospholipids. While clinical studies suggest the triglyceride lowering effects of DHA and EPA are equivalent, little is known about the independent effects of DHA and EPA on mitochondria function. We compared the effects of dietary supplementation with the ω-3 PUFAs DHA and EPA on cardiac mitochondrial phospholipid fatty acid composition and Ca2+-induced MPTP opening. Rats were fed a standard lab diet with either normal low levels of ω-3 PUFA, or DHA or EPA at 2.5% of energy intake for 8 weeks, and cardiac mitochondria were isolated and analyzed for Ca2+-induced MPTP opening and phospholipid fatty acyl composition. DHA supplementation increased both DHA and EPA and decreased ARA in mitochondrial phospholipid, and significantly delayed MPTP opening as assessed by increased Ca2+ retention capacity and decreased Ca2+-induced mitochondria swelling. EPA supplementation increased EPA in mitochondrial phospholipids, but did not affect DHA, only modestly lowered ARA, and did not affect MPTP opening. In summary, dietary supplementation with DHA but not EPA, profoundly altered mitochondrial phospholipid fatty acid composition and delayed Ca2+-induced MPTP opening. PMID:20471951

  6. Chicoric acid supplementation prevents systemic inflammation-induced memory impairment and amyloidogenesis via inhibition of NF-κB.

    PubMed

    Liu, Qian; Chen, Yuwei; Shen, Chun; Xiao, Yating; Wang, Yutang; Liu, Zhigang; Liu, Xuebo

    2016-12-21

    Chicoric acid (CA), a natural phenolic acid extracted from chicory and the echinacea (purple coneflower) plant (Echinacea purpurea), has been regarded as a nutraceutical that has powerful antioxidant and antiobesity activities. We investigated the inhibitory effects of CA on systemic inflammation-induced neuroinflammation, amyloidogenesis, and cognitive impairment. C57BL/6J mice were treated with 0.05% CA in the drinking water for 45 d. The mice were then treated by intraperitoneal injection of LPS (lipopolysaccharide). It was found that CA prevented LPS-induced memory impairment and neuronal loss through behavioral tests and histological examination. Furthermore, amyloidogenesis in the CNS was detected. The results showed that CA prevented LPS-induced increases in β-amyloid (1-42 specific) (Aβ1-42) accumulation, levels of amyloid precursor protein, and neuronal β-secretase 1 (BACE1), as well as the equilibrium cholinergic system in mouse brain. Moreover, CA down-regulated LPS-induced glial overactivation by inhibiting the MAPK and NF-κB pathway. Consequently, CA reduced the levels of NF-κB transcriptionally regulated inflammatory mediators and cytokines such as iNOS, cyclooxygenase-2 (COX-2), IL-1β, and TNF-α in both mouse brain and BV2 microglial cells. These results demonstrated that CA alleviated memory impairment and amyloidogenesis triggered by LPS through suppressing NF-κB transcriptional pathway, suggesting that CA might be a plausible therapeutic intervention for neuroinflammation-related diseases such as Alzheimer disease.-Liu, Q., Chen, Y., Shen, C., Xiao, Y., Wang, Y., Liu, Z., Liu, X. Chicoric acid supplementation prevents systemic inflammation-induced memory impairment and amyloidogenesis via inhibition of NF-κB.

  7. Novel application of proton pump inhibitor for the prevention of colitis-induced colorectal carcinogenesis beyond acid suppression.

    PubMed

    Kim, Yoon Jae; Lee, Jeong Sang; Hong, Kyung Sook; Chung, Jun Won; Kim, Ju Hyun; Hahm, Ki Baik

    2010-08-01

    Colitis-associated cancers arise in the setting of chronic inflammation wherein an "inflammation-dysplasia-carcinoma" sequence prevails. Based on our previous findings in which the proton pump inhibitor could impose significant levels of anti-inflammatory, antiangiogenic, and selective apoptosis induction beyond gastric acid suppression, we investigated whether omeprazole could prevent the development of colitis-associated cancer in a mouse model induced by repeated bouts of colitis. Omeprazole, 10 mg/kg, was given i.p. all through the experimental periods for colitis-associated carcinogenesis. Molecular changes regarding inflammation and carcinogenesis were compared between control groups and colitis-associated cancer groups treated with omeprazole in addition to chemopreventive outcome. Nine of 12 (75.0%) mice in the control group developed multiple colorectal tumors, whereas tumors were noted in only 3 of 12 (25.0%) mice treated with daily injections of omeprazole. The cancer-preventive results of omeprazole treatment was based on significant decreases in the levels of nitric oxide, thiobarbituric acid-reactive substance, and interleukin-6 accompanied with attenuated expressions of tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2. The expressions of matrix metalloproteinase (MMP)-9, MMP-11, and MT1-MMMP were significantly decreased in mice treated with omeprazole in accordance with significant decreases in the number of beta-catenin-accumulated crypts. A significant induction of apoptosis was observed in tumor tissue treated with omeprazole. Omeprazole could block the trophic effect of gastrin in colon epithelial cells. The significant anti-inflammatory, antioxidative, and antimutagenic activities of omeprazole played a cancer-preventive role against colitis-induced carcinogenesis, and our novel in vivo evidence is suggestive of chemopreventive action independent of gastric acid suppression.

  8. Prevention of effects of ethanol on amino acid concentrations in plasma and tissues by hepatic lipotropic factors in rats.

    PubMed

    Stanko, R T; Morse, E L; Adibi, S A

    1979-01-01

    The authors' previous studies have shown that hepatic steatosis of chronic ethanol ingestion in rats can be prevented by adding pyruvate, dihydroxyacetone, and riboflavin to their diet. In this study, the authors investigated the effect of chronic ethanol ingestion, with or without addition of the above metabolites to the diet, on protein and amino acid concentrations in tissues. Rats (120 g) were divided into three groups and fed isocalorically one of the fellowing diets for 30 days: control diet (28% fat, 15% protein, and 57% carbohydrate), ethanol diet (28% fat, 15% protein, 23% carbohydrate, and 24% ethanol), and metabolite diet (ethanol diet plus pyruvate, dihydroxyacetone, and riboflavin). Chronic ethanol ingestion reduced growth of muscle and intestinal mucosa without affecting that of liver and kidney. Among the 15 amino acids measured, chronic ethanol ingestion had the most consistent effect on plasma and tissue concentrations of leucine, alanine and alpha-amino-n-butyrate. The concentration of leucine was increased in muscle, liver, and plasma; that of alpha-amino-n-butyrate was increased in muscle and plasma, whereas that of alanine was decreased in plasma and liver. Addition of pyruvate, dihydroxyacetone, and riboflavin to the ethanol diet either totally or partially prevented ethanol-induced changes in plasma and tissue concentrations of amino acids despite similarity in plasma ethanol levels. Although these metabolites prevented the inhibition of the growth of intestinal mucosa, they were ineffective in blunting the effect of ehtanol on the skeletal muscle. This latter observation suggests that the mechanism of ethanol-induced inhibition of tissue growth is not the same for these tissues.

  9. Does folic acid supplementation prevent or promote colorectal cancer? Results from model-based predictions.

    PubMed

    Luebeck, E Georg; Moolgavkar, Suresh H; Liu, Amy Y; Boynton, Alanna; Ulrich, Cornelia M

    2008-06-01

    Folate is essential for nucleotide synthesis, DNA replication, and methyl group supply. Low-folate status has been associated with increased risks of several cancer types, suggesting a chemopreventive role of folate. However, recent findings on giving folic acid to patients with a history of colorectal polyps raise concerns about the efficacy and safety of folate supplementation and the long-term health effects of folate fortification. Results suggest that undetected precursor lesions may progress under folic acid supplementation, consistent with the role of folate role in nucleotide synthesis and cell proliferation. To better understand the possible trade-offs between the protective effects due to decreased mutation rates and possibly concomitant detrimental effects due to increased cell proliferation of folic acid, we used a biologically based mathematical model of colorectal carcinogenesis. We predict changes in cancer risk based on timing of treatment start and the potential effect of folic acid on cell proliferation and mutation rates. Changes in colorectal cancer risk in response to folic acid supplementation are likely a complex function of treatment start, duration, and effect on cell proliferation and mutations rates. Predicted colorectal cancer incidence rates under supplementation are mostly higher than rates without folic acid supplementation unless supplementation is initiated early in life (before age 20 years). To the extent to which this model predicts reality, it indicates that the effect on cancer risk when starting folic acid supplementation late in life is small, yet mostly detrimental. Experimental studies are needed to provide direct evidence for this dual role of folate in colorectal cancer and to validate and improve the model predictions.

  10. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    SciTech Connect

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik; Jeong, Soyeon; Shin, Soyeon; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

    2015-01-30

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.

  11. Synthesis of the cancer preventive peptide lunasin by lactic acid bacteria during sourdough fermentation.

    PubMed

    Rizzello, Carlo G; Nionelli, Luana; Coda, Rossana; Gobbetti, Marco

    2012-01-01

    This study aimed to exploit the potential of sourdough lactic acid bacteria to release lunasin during fermentation of cereal and nonconventional flours. The peptidase activities of a large number of sourdough lactic acid bacteria were screened using synthetic substrates. Selected lactic acid bacteria were used as sourdough starters to ferment wholemeal wheat, soybean, barley, amaranth, and rye flours. Proteinase activity during fermentation was characterized by SDS-PAGE analysis of the water-soluble extracts. Albumins having molecular masses of 18 to 22 kDa, which included the size of lunasin precursors, were markedly affected by proteolysis of lactic acid bacteria. After fermentation, lunasin from the water-soluble extracts was quantified, purified, and identified through RP-HPLC and nano-LC-ESI-MS analyses. Compared to control doughs, the concentration of lunasin increased up to 2-4 times during fermentation. Lactobacillus curvatus SAL33 and Lactobacillus brevis AM7 synthesized the highest concentrations of lunasin in all the flours. Besides the presence of the entire lunasin sequence, fragments containing the immunoreactive epitope RGDDDDDDDDD were also found. This study shows that fermentation by lactic acid bacteria increased the concentration of lunasin to levels that would suggest new possibilities for the biological synthesis and for the formulation of functional foods.

  12. α-Linolenic Acid-Enriched Diet Prevents Myocardial Damage and Expands Longevity in Cardiomyopathic Hamsters

    PubMed Central

    Fiaccavento, Roberta; Carotenuto, Felicia; Minieri, Marilena; Masuelli, Laura; Vecchini, Alba; Bei, Roberto; Modesti, Andrea; Binaglia, Luciano; Fusco, Angelo; Bertoli, Aldo; Forte, Giancarlo; Carosella, Luciana; Di Nardo, Paolo

    2006-01-01

    Randomized clinical trials have demonstrated that the increased intake of ω-3 polyunsaturated fatty acids significantly reduces the risk of ischemic cardiovascular disease, but no investigations have been performed in hereditary cardiomyopathies with diffusely damaged myocardium. In the present study, δ-sarcoglycan-null cardiomyopathic hamsters were fed from weaning to death with an α-linolenic acid (ALA)-enriched versus standard diet. Results demonstrated a great accumulation of ALA and eicosapentaenoic acid and an increased eicosapentaenoic/arachidonic acid ratio in cardiomyopathic hamster hearts, correlating with the preservation of myocardial structure and function. In fact, ALA administration preserved plasmalemma and mitochondrial membrane integrity, thus maintaining proper cell/extracellular matrix contacts and signaling, as well as a normal gene expression profile (myosin heavy chain isoforms, atrial natriuretic peptide, transforming growth factor-β1) and a limited extension of fibrotic areas within ALA-fed cardiomyopathic hearts. Consequently, hemodynamic indexes were safeguarded, and more than 60% of ALA-fed animals were still alive (mean survival time, 293 ± 141.8 days) when all those fed with standard diet were deceased (mean survival time, 175.9 ± 56 days). Therefore, the clinically evident beneficial effects of ω-3 polyunsaturated fatty acids are mainly related to preservation of myocardium structure and function and the attenuation of myocardial fibrosis. PMID:17148657

  13. [Prevention of preeclampsia with low-dose acetyl salicylic acid: critical assessment].

    PubMed

    Verrotti, C; Fieni, S; Gualdi, M; Cavatorta, E

    1999-01-01

    The Authors present a critical review of the published literature about the effect of low dose of acido acetilsalicilico on prevention and treatment of preeclampic. Beginning from the effects of low daily dose of acido acetilsalicilico on the pregnancy, the Authors present the published datas from 1970 until today, and suggest the present directions for use of acido acetilsalicilico in pregnancy.

  14. On the Mechanism by which Alkaline pH Prevents Expression of an Acid-Expressed Gene

    PubMed Central

    Espeso, Eduardo A.; Arst, Herbert N.

    2000-01-01

    Previous work has shown that zinc finger transcription factor PacC mediates the regulation of gene expression by ambient pH in the fungus Aspergillus nidulans. This regulation ensures that the syntheses of molecules functioning in the external environment, such as permeases, secreted enzymes, and exported metabolites, are tailored to the pH of the growth environment. A direct role for PacC in activating the expression of an alkaline-expressed gene has previously been demonstrated, but the mechanism by which alkaline ambient pH prevents the expression of any eukaryotic acid-expressed gene has never been reported. Here we show that a double PacC binding site in the promoter of the acid-expressed gabA gene, encoding γ-aminobutyrate (GABA) permease, overlaps the binding site for the transcriptional activator IntA, which mediates ω-amino acid induction. Using bacterially expressed fusion proteins, we have shown that PacC competes with IntA for DNA binding in vitro at this site. Thus, PacC repression of GABA permease synthesis is direct and occurs by blocking induction. A swap of IntA sites between promoters for gabA and amdS, a gene not subject to pH regulation, makes gabA expression pH independent and amdS acid expressed. PMID:10779325

  15. Omega-3 polyunsaturated fatty acids for the prevention of cardiovascular disease: do formulation, dosage & comparator matter?

    PubMed

    DiNicolantonio, James J; Meier, Pascal; O'Keefe, James H

    2013-01-01

    Multiple trials over the past two decades testing omega-3 polyunsaturated fatty acids (PUFAs), containing eicosapentaenoic acid (EPA) and or docosahexaenoic acid (DHA), have shown substantial benefits for reducing major coronary heart disease (CHD) events, all-cause mortality, cardiovascular (CV) death, sudden cardiac death (SCD), and stroke. However, recent trials testing omega-3s have generally failed to confirm these benefits. While increased fish and fish oil intake among the general population, increased use of optimal medical therapy (including statins, aspirin, and modern antihypertensive medications) probably make it more challenging for fish oil supplementation to show additional benefits, there might be further explanations in the formulation, dosage, and comparator used in these recent omega-3 trials.

  16. [Management, prevention and control of megaloblastic anemia, secondary to folic acid deficiency].

    PubMed

    de Paz, R; Hernández-Navarro, F

    2006-01-01

    Folic acid deficiency is the second most common cause of anemia in our environment, after anemia secondary to iron deficiency. Folates are essential components of human and animal diet. Folic acid is mainly in poliglutamate form, and it is hydrolyzed in the proximal jejunum. It is important to identify adequately the exact vitamin deficiency that causes megaloblastic anemia, because vitamin B12 administration in folate deficiency may correct partially megaloblastic alterations, but administration of folic acid in cobalamin deficient patients improves haematological parameters but deteriorates the neurological syndrome. Main causes of anemia secondary to folate deficiency are inadequate dietetic administration, increased requirements, impaired absorption and pharmacologic interactions. Folates are altered by light, high temperature and by water affinity, which facilitates its elimination by washing or cooking.

  17. Prevention of Diet-Induced Metabolic Dysregulation, Inflammation, and Atherosclerosis in Ldlr(-/-) Mice by Treatment With the ATP-Citrate Lyase Inhibitor Bempedoic Acid.

    PubMed

    Samsoondar, Joshua P; Burke, Amy C; Sutherland, Brian G; Telford, Dawn E; Sawyez, Cynthia G; Edwards, Jane Y; Pinkosky, Stephen L; Newton, Roger S; Huff, Murray W

    2017-04-01

    Bempedoic acid (ETC-1002, 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) is a novel low-density lipoprotein cholesterol-lowering compound. In animals, bempedoic acid targets the liver where it inhibits cholesterol and fatty acid synthesis through inhibition of ATP-citrate lyase and through activation of AMP-activated protein kinase. In this study, we tested the hypothesis that bempedoic acid would prevent diet-induced metabolic dysregulation, inflammation, and atherosclerosis. APPROACH AND RESULTS: Ldlr(-/-) mice were fed a high-fat, high-cholesterol diet (42% kcal fat, 0.2% cholesterol) supplemented with bempedoic acid at 0, 3, 10 and 30 mg/kg body weight/day. Treatment for 12 weeks dose-dependently attenuated diet-induced hypercholesterolemia, hypertriglyceridemia, hyperglycemia, hyperinsulinemia, fatty liver and obesity. Compared to high-fat, high-cholesterol alone, the addition of bempedoic acid decreased plasma triglyceride (up to 64%) and cholesterol (up to 50%) concentrations, and improved glucose tolerance. Adiposity was significantly reduced with treatment. In liver, bempedoic acid prevented cholesterol and triglyceride accumulation, which was associated with increased fatty acid oxidation and reduced fatty acid synthesis. Hepatic gene expression analysis revealed that treatment significantly increased expression of genes involved in fatty acid oxidation while suppressing inflammatory gene expression. In full-length aorta, bempedoic acid markedly suppressed cholesteryl ester accumulation, attenuated the expression of proinflammatory M1 genes and attenuated the iNos/Arg1 ratio. Treatment robustly attenuated atherosclerotic lesion development in the aortic sinus by 44%, with beneficial changes in morphology, characteristic of earlier-stage lesions. Bempedoic acid effectively prevents plasma and tissue lipid elevations and attenuates the onset of inflammation, leading to the prevention of atherosclerotic lesion development in a mouse model of metabolic

  18. Combination of Antiestrogens and Omega-3 Fatty Acids for Breast Cancer Prevention

    PubMed Central

    Manni, Andrea; El-Bayoumy, Karam; Skibinski, Christine G.; Thompson, Henry J.; Santucci-Pereira, Julia; Bidinotto, Lucas Tadeu; Russo, Jose

    2015-01-01

    The molecular and biological heterogeneity of human breast cancer emphasizes the importance of a multitargeted approach for effective chemoprevention. Targeting the estrogen receptor pathway alone with the antiestrogens, Tamoxifen and Raloxifene reduces the incidence of estrogen receptor positive tumors but is ineffective against the development of hormone independent cancers. Our preclinical data indicate that the administration of omega-3 fatty acids potentiates the antitumor effects of Tamoxifen by inhibiting multiple proliferative and antiapoptotic pathways, several of which interact with estrogen receptor signaling. The complementarity in the mechanism of antitumor action of Tamoxifen and omega-3 fatty acids is well supported by our signaling, genomic, and proteomic studies. Furthermore, administration of omega-3 fatty acids allows the use of lower and, hence, likely less toxic doses of Tamoxifen. If these findings are supported in the clinical setting, the combination of omega-3 fatty acids and anteistrogens may emerge as a promising, effective, and safe chemopreventive strategy to be tested in a large multi-institutional trial using breast cancer incidence as the primary endpoint. PMID:26339626

  19. Combined metoprolol and ascorbic acid treatment prevents intrinsic damage to the heart during diabetic cardiomyopathy.

    PubMed

    Saran, Varun; Sharma, Vijay; Wambolt, Richard; Yuen, Violet G; Allard, Michael; McNeill, John Hugh

    2014-10-01

    Metabolic disturbances and oxidative stress have been highlighted as potential causative factors for the development of diabetic cardiomyopathy. The β-blocker metoprolol is known to improve function in the diabetic rat heart and ameliorates the sequelae associated with oxidative stress, without lowering oxidative stress. The antioxidant ascorbic acid is known to improve function in the diabetic rat heart. We tested whether a combination of ascorbic acid and metoprolol treatment would improve function further than each drug individually. Control and streptozotocin-induced diabetic Wistar rats were treated with metoprolol (15 mg·(kg body mass)(-1)·day(-1), via an osmotic pump) and (or) ascorbic acid (1000 mg·(kg body mass)(-1)·day(-1), via their drinking water). To study the effect of treatment on the development of dysfunction, we examined time points before (5 weeks diabetic) and after (7 weeks diabetic) development of overt systolic dysfunction. Echocardiography and working-heart-perfusion were used to assess cardiac function. Blood and tissue samples were collected to assess the severity of disease and oxidative stress. While both drugs improved function, only ascorbic acid had effects on oxidative damage. Combination treatment had a more pronounced improvement in function. Our β-blocker + antioxidant treatment strategy focused on oxidative stress, not diabetes specifically; therefore, it may prove useful in other diseases where oxidative stress contributes to the pathology.

  20. PREVENTION OF ACID MINE DRAINAGE GENERATION FROM OPEN-PIT MINE HIGHWALLS

    EPA Science Inventory



    Exposed, open pit mine highwalls contribute significantly to the production of acid mine

    drainage (AMD) thus causing environmental concerns upon closure of an operating mine. Available information on the generation of AMD from open-pit mine highwalls is very limit...

  1. Preventing acid phosphate attack in coordinated phosphate programs for high-pressure boilers

    SciTech Connect

    Hollander, O.

    1999-12-01

    Coordinated phosphate programs were introduced to maintain bulk water and underdeposit chemistries in a safe pH range. With the wide assortment of additives routinely employed in modern treatment programs, it is no longer a simple matter to control the treatment. The errors induced by the additives and impurities can lead to acid attack and boiler tube failure.

  2. PREVENTION OF ACID MINE DRAINAGE GENERATION FROM OPEN-PIT MINE HIGHWALLS

    EPA Science Inventory



    Exposed, open pit mine highwalls contribute significantly to the production of acid mine

    drainage (AMD) thus causing environmental concerns upon closure of an operating mine. Available information on the generation of AMD from open-pit mine highwalls is very limit...

  3. Knowledge and use of folic acid for prevention of birth defects amongst Honduran women.

    PubMed

    Wu, D Ying; Brat, Gabriel; Milla, Gayle; Kim, Jae

    2007-06-01

    To characterize determinants of folic acid (FA) use among women of reproductive age and patient education practices of health care professionals in one region of Honduras. 508 female outpatients and 128 health workers were interviewed in six primary care clinics in Honduras. Results were analyzed using univariate and multivariate regression models. The survey showed that 45% patients were familiar with FA. Of that number, 30% knew appropriate timing of consumption and 25% reported proper pre-natal supplementation. Increasing education was strongly correlated with knowledge of folic acid function (OR=252.52, P<0.0001) and actual use (OR=12.65, P<0.000). Age is associated with knowledge of proper timing of FA usage (OR=3.94, P<0.01). Most women learned about FA from medical professionals, but only half of providers educate their female patients about FA. Healthcare providers should remember to discuss the role of folic acid with their patients, particularly those of low education and at the extremes of reproductive age. While long-term efforts to develop fortification programs continue, interim Honduran health campaigns to increase proper consumption of folic acid should target these particularly vulnerable populations.

  4. Prevention of topical surfactant-induced itch-related responses by chlorogenic acid through the inhibition of increased histamine production in the epidermis.

    PubMed

    Inami, Yoshihiro; Andoh, Tsugunobu; Kuraishi, Yasushi

    2013-01-01

    Effects of chlorogenic acid on surfactant-induced itching were studied in mice. Topical application of sodium laurate increased hind-paw scratching, an itch-related response, 2 h after application, which was inhibited by topical post-treatment with chlorogenic acid. Sodium laurate increased the histamine content and 53-kDa L-histidine decarboxylase in the epidermis, which were also inhibited by post-treatment with chlorogenic acid. These results suggest that topical chlorogenic acid is effective in the prevention of itching induced by anionic surfactants. The inhibitory activity of chlorogenic acid may be due to the inhibition of an increase in histamine in the epidermis.

  5. Corrosion Prevention of Cold Rolled Steel Using Water Dispersible Lignosulfonic Acid Doped Polyaniline

    NASA Technical Reports Server (NTRS)

    Viswanathan, Tito (Inventor)

    2007-01-01

    The invention provides coatings useful for preventing corrosion of metals. The coatings comprise a film-forming resin and conductive polymers comprising linearly conjugated x-systems and residues of sulfonated lignin or a sulfonated polyflavonoid or derivatives of solfonated lignin or a sulfonated polyflavonoid. The invention also provides a latex formulation of the coatings, and articles of manufacture comprising a metal substrate and a coating in contact with the metal substrate.

  6. CORROSION PREVENTION OF COLD ROLLED STEEL USING WATER DISPERSIBLE LIGNOSULFONIC ACID DOPED POLYANILINE

    NASA Technical Reports Server (NTRS)

    Viswanathan, Tito (Inventor)

    2005-01-01

    The invention provides coatings useful for preventing corrosion of metals. The coatings comprise a film-forming resin and conductive polymers comprising linearly conjugated pi-systems and residues of sulfonated lignin or a sulfonated polyflavonoid or derivatives of sulfonated lignin or a sulfonated polyflavonoid. The invention also provides a latex formulation of the coatings, and articles of manufacture comprising a metal substrate and a coating in contact with the metal substrate.

  7. Corrosion prevention of cold rolled steel using water dispersible lignosulfonic acid doped polyaniline

    NASA Technical Reports Server (NTRS)

    Viswanathan, Tito (Inventor)

    2007-01-01

    The invention provides coatings useful for preventing corrosion of metals. The coatings comprise a film-forming resin and conductive polymers comprising linearly conjugated .pi.-systems and residues of sulfonated lignin or a sulfonated polyflavonoid or derivatives of solfonated lignin or a sulfonated polyflavonoid. The invention also provides a latex formulation of the coatings, and articles of manufacture comprising a metal substrate and a coating in contact with the metal substrate.

  8. Rapid development of glutathione-S-transferase-dependent drug resistance in vitro and its prevention by ethacrynic acid.

    PubMed

    Caffrey, P B; Zhu, M; Zhang, Y; Chinen, N; Frenkel, G D

    1999-02-08

    Exposure of A2780 human ovarian tumor cells to a low concentration of melphalan in vitro for 7 days resulted in the development of melphalan resistance. This resistance was not a stable characteristic of the cells since it was lost after 2 weeks in culture in the absence of drug. The melphalan-resistant cells exhibited significant cross-resistance to cisplatin but only minor cross-resistance to doxorubicin. The resistant cells had elevated levels of glutathione-S-transferase activity and mRNA. Exposure of the cells to the ethacrynic acid resulted in a decrease in enzyme activity as well as a reversal of their drug-resistant phenotype, indicating that the enzyme is involved in the resistance. When ethacrynic acid was present during the 7-day exposure of the cells to melphalan, the development of drug resistance was prevented. This system may serve as a useful preliminary step in screening for agents which can prevent the development of chemotherapy-induced drug resistance in human cancer.

  9. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis.

    PubMed

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik; Jeong, Soyeon; Shin, Soyeon; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

    2015-01-30

    Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson's disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson's disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.

  10. Biodegradable and injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for postoperative adhesion prevention.

    PubMed

    Li, Ling; Wang, Ning; Jin, Xun; Deng, Rui; Nie, Shihong; Sun, Lu; Wu, Qinjie; Wei, Yuquan; Gong, Changyang

    2014-04-01

    Postsurgical peritoneal adhesions are very common and serious complication after surgery. Biodegradable and injectable hydrogels derived from natural polysaccharides are ideal biomaterials for prevention of postoperative adhesion. In this work, we report a class of injectable, biodegradable, and non-toxic hydrogel derived from N, O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (A-HA), without requirement of any chemical linkers or radiant light sources. NOCC was prepared by introducing carboxymethyl groups to the N-position and the O-position of chitosan, and A-HA was prepared using periodate oxidation method. The gelation is attributed to the Schiff base between the amino groups of NOCC and aldehyde groups in A-HA, and the hydrogel precursors cross-linked to form a flexible hydrogel. NOCC, A-HA, and NOCC/A-HA hydrogel extract exhibited very low cytotoxicity and hemolysis, and the acute toxicity tests showed that the hydrogel was non-toxic. Besides, the highly porous three-dimensional hydrogel can supported the growth and proliferation of the cells encapsulated in the hydrogels, but was not favorable for the attachment of fibroblasts to the surface, suggesting that the NOCC/A-HA hydrogel can be developed for adhesion prevention. The hydrogel was susceptible to the lysozyme and can be degraded within 2 weeks in vivo. Furthermore, we employed a rat model of sidewall defect-cecum abrasion to investigate the efficacy of NOCC/A-HA hydrogel in preventing post-operative peritoneal adhesions. A significant reduction of peritoneal adhesion formation was found in the NOCC/A-HA-treated group, compared with commercial hyaluronic acid (HA) hydrogel group and normal saline group. In addition, the potential anti-adhesion mechanism of NOCC/A-HA hydrogel was discussed, which may attribute to the combination of barrier function and bioactivity of NOCC and A-HA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

    PubMed

    Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

    2013-12-05

    Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1β (10pg/ml) for 24h. IL-1β increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor β expression. Furthermore, IL-1β inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1β alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1β treatment. Moreover, IL-1β inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1β inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1β levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth.

  12. Metabolism, uptake, and excretion of a D-glucaric acid salt and its potential use in cancer prevention.

    PubMed

    Walaszek, Z; Szemraj, J; Narog, M; Adams, A K; Kilgore, J; Sherman, U; Hanausek, M

    1997-01-01

    D-Glucaric acid (GA) is a nontoxic, natural compound. One of its derivatives is the potent beta-glucuronidase inhibitor D-glucaro-1,4-lactone (1,4-GL). The goal of this study was to demonstrate the in vivo formation of 1,4-GL from a D-glucarate salt and determine its metabolism, uptake by selected organs, and excretion following oral administration of potassium hydrogen D-[14C]glucarate to male and female Sprague-Dawley rats. 1,4-GL increases detoxification of carcinogens and tumor promoters/progressors by inhibiting beta-glucuronidase and preventing hydrolysis of their glucuronides. 1,4-GL and its precursors, such as potassium hydrogen D-glucarate and calcium D-glucarate, may exert their anticancer action, in part, through alterations in steroidogenesis accompanied by changes in the hormonal environment and the proliferative status of the target organ. Thus, GA derivatives may be useful as new or adjuvant cancer preventive and therapeutic agents. In our study, 1,4-GL was found to be formed from the D-glucarate salt in the stomach of rats. It was apparently absorbed from the gastrointestinal tract, transported with the blood to different internal organs, and excreted in the urine and to a lesser extent in bile. There were no significant differences in the metabolism of PHG between male and female rats. Thus, formation of 1,4-GL from D-glucaric acid derivatives may be prerequisite for their inhibition of chemical carcinogenesis in rodents and prevention of breast, prostate, and colon cancer in humans.

  13. Hybrid therapy with locoregional steroid injection and polyglycolic acid sheets to prevent stricture after esophageal endoscopic submucosal dissection

    PubMed Central

    Nagami, Yasuaki; Shiba, Masatsugu; Tominaga, Kazunari; Ominami, Masaki; Fukunaga, Shusei; Sugimori, Satoshi; Tanaka, Fumio; Kamata, Noriko; Tanigawa, Tetsuya; Yamagami, Hirokazu; Watanabe, Toshio; Fujiwara, Yasuhiro; Arakawa, Tetsuo

    2016-01-01

    Background and study aim: The incidence of stricture formation caused by endoscopic submucosal dissection (ESD) for widespread lesions is high, and stricture formation can reduce quality of life. We evaluated the prophylactic efficacy of hybrid therapy using a locoregional steroid injection and polyglycolic acid (PGA) sheets with fibrin glue to prevent stricture formation after esophageal ESD in high risk patients in whom we predicted stricture formation would be difficult to prevent with a single prophylactic steroid injection. Methods: Ten patients who underwent esophageal ESD were enrolled (entire-circumference: n = 6; sub-circumference, more than 5/6 of the circumference: n = 4). A single locoregional steroid injection and PGA sheets with fibrin glue were used after ESD. We evaluated the incidence of stricture formation, the number of endoscopic balloon dilation (EBD) procedures needed to treat the stricture formation, and adverse events of the therapy. Results: Esophageal stricture formation occurred in 50.0 % of patients (5/10) (median EBD sessions 0.5, range 0 – 16). Subanalysis showed that stricture formation occurred in 37.5 % of patients (3/8) excluded the lesions located near a previous scar from ESD or surgical anastomosis site (median EBD sessions 0, range 0 – 4). Conclusion: Hybrid therapy using a locoregional steroid injection and PGA sheets with fibrin glue may have the potential to prevent esophageal stricture formation after esophageal ESD in high risk patients. PMID:27652294

  14. Long-term Administration of Nuclear Bile Acid Receptor FXR Agonist Prevents Spontaneous Hepatocarcinogenesis in Abcb4(-/-) Mice.

    PubMed

    Cariello, Marica; Peres, Claudia; Zerlotin, Roberta; Porru, Emanuele; Sabbà, Carlo; Roda, Aldo; Moschetta, Antonio

    2017-09-11

    Altered bile acid (BA) signaling is associated with hepatotoxicity. The farnesoid X receptor (FXR) is a nuclear receptor that transcriptionally regulates BA homeostasis. Mice with FXR ablation present hepatocarcinoma (HCC) due to high toxic BA levels. Mice with Abcb4 ablation accumulate toxic BA within the bile ducts and present HCC. We have previously shown that intestinal specific activation of FXR by transgenic VP16-FXR chimera is able to reduce BA pool size and prevent HCC. Here we tested chemical FXR activation by administering for 15 months the dual FXR/ membrane G protein-coupled receptor (TGR5) agonist INT-767 (6α-ethyl-3α,7α,23-trihydroxy-24-nor-5β-cholan-23-sulphate) to Fxr(-/-) and Abcb4(-/-) mice. HCC number and size were significantly reduced by INT-767 administration. In contrast, no changes in HCC tumor number and size were observed in Fxr(-/-) mice fed with or without INT-767. Notably, INT-767 preserved the hepatic parenchyma, improved hepatic function and down-regulated pro-inflammatory cytokines. Moreover, in Abcb4(-/-) mice INT-767 prevented fibrosis by reducing collagen expression and deposition. Thus, long term activation of FXR is able to reduce BA pool, reprogram BA metabolism and prevent HCC. These data provide the impetus to address the bona fide therapeutic potential of FXR activation in disease with BA-associated development of HCC.

  15. Nitro-Arachidonic Acid Prevents Angiotensin II-Induced Mitochondrial Dysfunction in a Cell Line of Kidney Proximal Tubular Cells.

    PubMed

    Sánchez-Calvo, Beatriz; Cassina, Adriana; Rios, Natalia; Peluffo, Gonzalo; Boggia, José; Radi, Rafael; Rubbo, Homero; Trostchansky, Andres

    2016-01-01

    Nitro-arachidonic acid (NO2-AA) is a cell signaling nitroalkene that exerts anti-inflammatory activities during macrophage activation. While angiotensin II (ANG II) produces an increase in reactive oxygen species (ROS) production and mitochondrial dysfunction in renal tubular cells, little is known regarding the potential protective effects of NO2-AA in ANG II-mediated kidney injury. As such, this study examines the impact of NO2-AA on ANG II-induced mitochondrial dysfunction in an immortalized renal proximal tubule cell line (HK-2 cells). Treatment of HK-2 cells with ANG II increases the production of superoxide (O2●-), nitric oxide (●NO), inducible nitric oxide synthase (NOS2) expression, peroxynitrite (ONOO-) and mitochondrial dysfunction. Using high-resolution respirometry, it was observed that the presence of NO2-AA prevented ANG II-mediated mitochondrial dysfunction. Attempting to address mechanism, we treated isolated rat kidney mitochondria with ONOO-, a key mediator of ANG II-induced mitochondrial damage, in the presence or absence of NO2-AA. Whereas the activity of succinate dehydrogenase (SDH) and ATP synthase (ATPase) were diminished upon exposure to ONOO-, they were restored by pre-incubating the mitochondria with NO2-AA. Moreover, NO2-AA prevents oxidation and nitration of mitochondrial proteins. Combined, these data demonstrate that ANG II-mediated oxidative damage and mitochondrial dysfunction is abrogated by NO2-AA, identifying this compound as a promising pharmacological tool to prevent ANG II-induced renal disease.

  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. Possible role of Epoxyeicosatrienoic acid in prevention of oxidative stress mediated neuroinflammation in Parkinson disorders.

    PubMed

    Lakkappa, Navya; Krishnamurthy, Praveen T; Hammock, Bruce D; Velmurugan, D; Bharath, M M Srinivas

    2016-08-01

    Parkinson's disease (PD) is a multifactorial neurodegenerative disease involving oxidative stress, neuroinflammation and apoptosis. Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites and they play a role in cytoprotection by modulating various cell signaling pathways. This cytoprotective role of EETs are well established in cerebral stroke, cardiac failure, and hypertension, and it is due to their ability to attenuate oxidative stress, endoplasmic reticulum stress, inflammation, caspase activation and apoptosis. The actions of EETs in brain closely parallel the effects which is observed in the peripheral tissues. Since many of these effects could potentially contribute to neuroprotection, EETs are, therefore, one of the potential therapeutic candidates in PD. Therefore, by increasing the half life of endogenous EETs in vivo via inhibition of sEH, its metabolizing enzyme can, therefore, constitutes an important therapeutic strategy in PD.

  18. Folic acid fortification prevents neural tube defects and may also reduce cancer risks.

    PubMed

    Jägerstad, Margaretha

    2012-10-01

    The prevalence of neural tube defect (NTD)-affected pregnancies ranges between 0.4 and 2/1000 pregnancies in EU. NTDs result in severe malformations and sometimes miscarriages. Children born with NTD suffer for the rest of their life of disability and chronic healthcare issues, and many women therefore choose termination of pregnancy if NTD is diagnosed prenatally. Women planning for pregnancy are recommended to eat 400 μg folic acid/d, whereas average figures across Europe indicate intakes of ∼250 μg/d for women of fertile age, a gap that could be bridged by implementation of folic acid fortification. The results of mandatory folic acid fortifications introduced in USA and Canada are a decrease between 25 and 45% of NTD pregnancies.   Evidence-based NTD prophylaxis is now practised in more than 60 countries worldwide. EU countries worry over possible cancer risks, but ignore a wealth of studies reporting decreasing cancer risks with folate intakes at recommended levels. Currently, there are indications of a U-shaped relationship, that is, higher cancer risks at low folate intakes (<150 μg/day) and highly elevated folate intakes (>1 mg/day), respectively. However neither the global World Cancer Research review nor EU's European Food Safety Authority report present data on increased cancer risk at physiological folate intake levels. Therefore, EU should act to implement folic acid fortification as NTD prophylaxis as soon as possible. © 2012 The Author/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

  19. 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.

  20. A full-scale porous reactive wall for prevention of acid mine drainage

    SciTech Connect

    Benner, S.G.; Blowes, D.W.; Ptacek, C.J.

    1997-12-31

    The generation and release of acidic drainage containing high concentrations of dissolved metals from decommissioned mine wastes is an environmental problem of international scale. A potential solution to many acid drainage problems is the installation of permeable reactive walls into aquifers affected by drainage water derived from mine waste materials. A permeable reactive wall installed into an aquifer impacted by low-quality mine drainage waters was installed in August 1995 at the Nickel Rim mine site near Sudbury, Ontario. The reactive mixture, containing organic matter, was designed to promote bacterially mediated sulfate reduction and subsequent metal sulfide precipitation. The reactive wall is installed to an average depth of 12 feet (3.6 m) and is 49 feet (15 m) long perpendicular to ground water flow. The wall thickness (flow path length) is 13 feet (4 m). Initial results, collected nine months after installation, indicate that sulfate reduction and metal sulfide precipitation is occurring. The reactive wall has effectively removed the capacity of the ground water to generate acidity on discharge to the surface. Calculations based on comparison to previously run laboratory column experiments indicate that the reactive wall has potential to remain effective for at least 15 years.

  1. Docosahexaenoic acid promotes oligodendrocyte differentiation via PPAR-γ signalling and prevents tumor necrosis factor-α-dependent maturational arrest.

    PubMed

    Bernardo, A; Giammarco, M L; De Nuccio, C; Ajmone-Cat, M A; Visentin, S; De Simone, R; Minghetti, L

    2017-09-01

    Docosahexaenoic acid (DHA) is an essential omega-3 fatty acid known to be neuroprotective in several models of human diseases, including multiple sclerosis. The protective effects of DHA are largely attributed to its ability to interfere with the activity of transcription factors controlling immune and inflammatory responses, including the agonist-dependent transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ). In this study, we used primary oligodendrocyte progenitor (OP) cultures from neonatal rat brain to investigate whether DHA could influence OP maturation and directly promote myelination, as previously reported for selective PPAR-γ agonists. We show that, similarly to the selective PPAR-γ agonist pioglitazone (PGZ), DHA promotes OP maturation and counteracts the maturational arrest induced by TNF-α, used to mimic inflammatory conditions. The PPAR-γ antagonist GW9662 prevented both DHA-induced OP maturation and PPAR-γ nuclear translocation, supporting the hypothesis that DHA acts through the activation of PPAR-γ. In addition, both PGZ and DHA induced the phosphorylation of extracellular signal-regulated-kinase 1-2 (ERK1/2), in a PPAR-γ-dependent manner. ERK1/2 activity is known to regulate the transition from OPs to immature oligodendrocytes and the presence of specific inhibitors of ERK1/2 phosphorylation (U0126 or PD98059) prevented the differentiating effects of both DHA and PGZ. These results indicate that DHA might influence the process of OP maturation through its PPAR-γ agonistic activity and provide novel molecular mechanisms for the action of this dietary fatty acid, further supporting the nutritional intervention in demyelinating diseases such as multiple sclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Innovative Approach to Prevent Acid Drainage from Uranium Mill Tailings Based on the Application of Na-Ferrate (VI)

    SciTech Connect

    Fernandes, H.M.; Reinhart, D.; Lettie, L.; Franklin, M.R.; Fernandes, H.M.; Franklin, M.R.; Daly, L.J.

    2006-07-01

    The operation of uranium mining and milling plants gives rise to huge amounts of wastes from both mining and milling operations. When pyrite is present in these materials, the generation of acid drainage can take place and result in the contamination of underground and surface waters through the leaching of heavy metals and radionuclides. To solve this problem, many studies have been conducted to find cost-effective solutions to manage acid mine drainage; however, no adequate strategy to deal with sulfide-ric h wastes is currently available. Ferrate (VI) is a powerful oxidizing agent in aqueous media. Under acidic conditions, the redox potential of the Ferrate (VI) ion is the highest of any other oxidant used in wastewater treatment processes. The standard half cell reduction potential of ferrate (VI) has been determined as +2.20 V to + 0.72 V in acidic and basic solutions, respectively. Ferrate (VI) exhibits a multitude of advantageous properties, including higher reactivity and selectivity than traditional oxidant alternatives, as well as disinfectant, flocculating, and coagulant properties. Despite numerous beneficial properties in environmental applications, ferrate (VI) has remained commercially unavailable. Starting in 1953, different methods for producing a high purity, powdered ferrate (VI) product were developed. However, producing this dry, stabilized ferrate (VI) product required numerous process steps which led to excessive synthesis costs (over $20/lb) thereby preventing bulk industrial use. Recently a novel synthesis method for the production of a liquid ferrate (VI) based on hypochlorite oxidation of ferric ion in strongly alkaline solutions has been discovered (USPTO 6,790,428; September 14, 2004). This on-site synthesis process dramatically reduces manufacturing cost for the production of ferrate (VI) by utilizing common commodity feedstocks. This breakthrough means that for the first time ferrate (VI) can be an economical alternative to treating

  3. Knowledge and use of folic acid for birth defect prevention among women of childbearing age in Shanghai, China: a prospective cross-sectional study.

    PubMed

    Lian, Huan; Ma, Duan; Zhou, Shu-Feng; Li, Xiaotian

    2011-12-01

    This study aimed to assess the knowledge, attitude, and practice of folic acid intake for prevention of birth defects in Chinese women of child-bearing age. In this prospective cross-sectional study, a total of 1,338 women aged 20-45 years were randomly selected for interview. Data on folic acid knowledge and information on folic acid intake in the subjects were collected. Age, education, contraception, and status of family planning were used as the independent variables in multivariate logistic regression. 55.6% of the subjects took contraception at all times, and 33.9% had pregnancy planning in the next six months. 49.7% of the interviewed women knew the benefits of folic acid and 34.6% realized the correct time of folic acid intake; and 14.9% of these women actually took folic acid daily. Planning to be pregnant in the next six months was associated with knowledge of folic acid benefits, correct time of folic acid intake and actual intake. A higher education level was correlated with the knowledge of folic acid benefits and correct time of folic acid intake, but was not linked to actual intake of folic acid. The knowledge and use of folic acid were at low to moderate levels in women at childbearing age in Shanghai, China, and general knowledge of folic acid benefits and correct time of folic acid intake should be conveyed to these women.

  4. Administration of ascorbic acid to prevent bleaching-induced tooth sensitivity: a randomized triple-blind clinical trial.

    PubMed

    de Paula, E A; Kossatz, S; Fernandes, D; Loguercio, A D; Reis, A

    2014-01-01

    This study evaluated the effect of ascorbic acid, 500 mg every eight hours, on bleaching-induced tooth sensitivity. A triple-blind, parallel design, and placebo-controlled randomized clinical trial was conducted on 39 adults. The pills (placebo or ascorbic acid) were administered three times per day for 48 hours; the first dose was given one hour prior to each bleaching session. Two bleaching sessions with 35% hydrogen peroxide gel were performed with a one-week interval. Tooth sensitivity was recorded up to 48 hours after bleaching. The color evaluation was performed before and 30 days after bleaching. The absolute risk and intensity of tooth sensitivity were evaluated by Fisher exact and Mann-Whitney U-tests, respectively. Color changes were evaluated by unpaired t-test (α=0.05). There were no significant differences in the absolute risk and intensity of tooth sensitivity and color change between the groups. Both groups showed a similar risk of tooth sensitivity (p>0.05). The perioperative use of an antioxidant, such as ascorbic acid (500 mg, three times daily) perorally, was not able to prevent bleaching-induced tooth sensitivity or reduce its intensity.

  5. Prevention of diabetes in the BB rat by essential fatty acid deficiency. Relationship between physiological and biochemical changes

    PubMed Central

    1990-01-01

    Essential fatty acid (EFA) deficiency exerts a striking protective effect in several animal models of autoimmune disease. We now report that EFA deprivation prevents diabetes in the BB rat, an animal model of human insulin-dependent diabetes mellitus. In diabetes-prone (DP)-BB rats, the incidences of spontaneous diabetes and insulitis (the pathological substrate of autoimmune diabetes) were greatly reduced by EFA deficiency. This beneficial effect of the deficiency state was also seen in diabetes-resistant (DR)-BB rats that, after treatment with antibody to eliminate RT6+ T cells, would otherwise have become diabetic. The susceptibility of EFA-deprived DP-BB rats to spontaneous diabetes was restored when they were given dietary supplements of linoleate at 70 d of age (during the usual period of susceptibility), but not when they were repleted beginning at 120 d (after the peak incidence of diabetes). EFA deficiency did lead to growth retardation, but calorically restricted control rats demonstrated that the protective effect of the deficiency state was not a function of decreased weight. To examine the relationship between the biochemical changes of EFA deficiency and its physiological effects in this system, we compared the fatty acid changes that occurred in EFA-deficient animals that did and did not develop diabetes. Nondiabetic animals had significantly lower levels of (n-6) fatty acids (i.e., linoleate and arachidonate) and higher levels of oleate, an (n-9) fatty acid, than did diabetic animals. Levels of 20:3(n-9), the fatty acid that uniquely characterizes EFA deficiency, were similar in both groups, however. Among diabetic EFA-deficient rats, the age at onset of diabetes was found to correlate inversely with the level of (n-6) fatty acids, the least depleted animals becoming diabetic earliest, whereas there was no correlation with levels of 20:3(n-9). Among animals repleted with linoleate beginning at 70 d, restoration of susceptibility to diabetes

  6. Ursolic acid protects monocytes against metabolic stress-induced priming and dysfunction by preventing the induction of Nox4☆

    PubMed Central

    Ullevig, Sarah L.; Kim, Hong Seok; Nguyen, Huynh Nga; Hambright, William S.; Robles, Andrew J.; Tavakoli, Sina; Asmis, Reto

    2014-01-01

    Aims Dietary supplementation with ursolic acid (UA) prevents monocyte dysfunction in diabetic mice and protects mice against atherosclerosis and loss of renal function. The goal of this study was to determine the molecular mechanism by which UA prevents monocyte dysfunction induced by metabolic stress. Methods and results Metabolic stress sensitizes or “primes” human THP-1 monocytes and murine peritoneal macrophages to the chemoattractant MCP-1, converting these cells into a hyper-chemotactic phenotype. UA protected THP-1 monocytes and peritoneal macrophages against metabolic priming and prevented their hyper-reactivity to MCP-1. UA blocked the metabolic stress-induced increase in global protein-S-glutathionylation, a measure of cellular thiol oxidative stress, and normalized actin-S-glutathionylation. UA also restored MAPK phosphatase-1 (MKP1) protein expression and phosphatase activity, decreased by metabolic priming, and normalized p38 MAPK activation. Neither metabolic stress nor UA supplementation altered mRNA or protein levels of glutaredoxin-1, the principal enzyme responsible for the reduction of mixed disulfides between glutathione and protein thiols in these cells. However, the induction of Nox4 by metabolic stress, required for metabolic priming, was inhibited by UA in both THP-1 monocytes and peritoneal macrophages. Conclusion UA protects THP-1 monocytes against dysfunction by suppressing metabolic stress-induced Nox4 expression, thereby preventing the Nox4-dependent dysregulation of redox-sensitive processes, including actin turnover and MAPK-signaling, two key processes that control monocyte migration and adhesion. This study provides a novel mechanism for the anti-inflammatory and athero- and renoprotective properties of UA and suggests that dysfunctional blood monocytes may be primary targets of UA and related compounds. PMID:24494201

  7. Conjugated linoleic acid (CLA) prevents age-associated skeletal muscle loss.

    PubMed

    Rahman, M; Halade, Ganesh V; El Jamali, Amina; Fernandes, Gabriel

    2009-06-12

    In this study, we examined the effect of CLA isomers in preventing age-associated muscle loss and the mechanisms underlying this effect, using 12-months-old C57BL/6 mice fed 10% corn oil (CO) or a diet supplemented with 0.5% c9t11-CLA, t10c12-CLA, or c9t11-CLA+t10c12-CLA (CLA-mix) for 6months. Both t10c12-CLA and CLA-mix groups showed significantly higher muscle mass, as compared to CO and c9t11-CLA groups, measured by dual-energy X-ray absorptiometry and muscle wet weight. Enhanced mitochondrial ATP production, with higher membrane potential, and elevated muscle antioxidant enzymes (catalase and glutathione peroxidase) production, accompanied by slight increase in H(2)O(2) production was noted in t10c12-CLA and CLA-mix groups, as compared to that of CO and c9t11-CLA groups. Oxidative stress, as measured by serum malondialdehyde and inflammation, as measured by LPS-treated splenocyte IL-6 and TNF-alpha, were significantly less in CLA isomers groups. Thus, CLA may be a novel dietary supplement that will prevent sarcopenia by maintaining redox balance during aging.

  8. Methamphetamine-induced dopaminergic toxicity prevented owing to the neuroprotective effects of salicylic acid.

    PubMed

    Thrash-Williams, Bessy; Karuppagounder, Senthilkumar S; Bhattacharya, Dwipayan; Ahuja, Manuj; Suppiramaniam, Vishnu; Dhanasekaran, Muralikrishnan

    2016-06-01

    Methamphetamine (Schedule-II drug, U.S. Drug Enforcement Administration) is one of the most abused illicit drug following cocaine, marijuana, and heroin in the USA. There are numerous health impairments and substantial economic burden caused by methamphetamine abuse. Salicylic acid, potent anti-inflammatory drug and a known neuroprotectant has shown to protect against toxicity-induced by other dopaminergic neurotoxins. Hence, in this study we investigated the neuroprotective effects of salicylic acid against methamphetamine-induced toxicity in mice. The current study investigated the effects of sodium salicylate and/or methamphetamine on oxidative stress, monoamine oxidase, mitochondrial complex I & IV activities using spectrophotometric and fluorimetric methods. Behavioral analysis evaluated the effect on movement disorders-induced by methamphetamine. Monoaminergic neurotransmitter levels were evaluated using high pressure liquid chromatography-electrochemical detection. Methamphetamine caused significant generation of reactive oxygen species and decreased complex-I activity leading to dopamine depletion. Striatal dopamine depletion led to significant behavioral changes associated with movement disorders. Sodium salicylate (50 & 100mg/kg) significantly scavenged reactive oxygen species, blocked mitochondrial dysfunction and exhibited neuroprotection against methamphetamine-induced neurotoxicity. In addition, sodium salicylate significantly blocked methamphetamine-induced behavioral changes related to movement abnormalities. One of the leading causative theories in nigral degeneration associated with movement disorders such as Parkinson's disease is exposure to stimulants, drugs of abuse, insecticide and pesticides. These neurotoxic substances can induce dopaminergic neuronal insult by oxidative stress, apoptosis, mitochondrial dysfunction and inflammation. Salicylic acid due to its antioxidant and anti-inflammatory effects could provide neuroprotection against the

  9. Folic acid in the prevention of neural tube defect--a programme for Malaysia?

    PubMed

    Ho, J J

    2004-03-01

    There is good evidence that folic acid is safe and efficacious for reducing neural tube defect (NTD). All women capable of becoming pregnant should take 400 microgram daily. This can be given in the form of a daily vitamin supplement, by food fortification, or by increasing natural dietary folates. Compulsory grain fortification has been shown to reduce NTD in a population but supplementation and dietary advice have not. Malaysia should work towards a programme of grain fortification and use alternative strategies to reach sections of the population that would not be covered but several research questions need to be answered before a programme could be implemented in Malaysia.

  10. Neonatal striatal grafts prevent lethal syndrome produced by bilateral intrastriatal injection of kainic acid.

    PubMed

    Tulipan, N; Huang, S; Whetsell, W O; Allen, G S

    1986-07-02

    It is reported that unilateral grafts of neonatal striatal tissue protect the recipient from the lethal aphagia and adipsia produced by bilateral intrastriatal injection of 10 nmol of kainic acid in rats. It is shown that neither adult striatum nor neonatal tissue from other sites have the same lifesaving effect and that the salutary effect of the graft is dependent upon graft survival. Grafts from a histoincompatible donor are apparently rejected, leading to the death of the recipient. Cyclosporine inhibits rejection thereby enabling recipient survival. It is postulated that the graft exerts a neurohumoral influence that protects the striatum from the toxic effect of kainate.

  11. Primary prevention of neural-tube defects and some other congenital abnormalities by folic acid and multivitamins: history, missed opportunity and tasks.

    PubMed

    Czeizel, Andrew E; Bártfai, Zoltán; Bánhidy, Ferenc

    2011-08-01

    The history of intervention trials of periconception folic acid with multivitamin and folic acid supplementation in women has shown a recent breakthrough in the primary prevention of structural birth defects, namely neural-tube defects and some other congenital abnormalities. Recently, some studies have demonstrated the efficacy of this new method in reducing congenital abnormalities with specific origin; for example, in the offspring of diabetic and epileptic mothers, and in pregnancy with high fever. The benefits and drawbacks of four possible uses of periconception folate/folic acid and multivitamin supplementation are discussed: we believe there has been a missed opportunity to implement this preventive approach in medical practice. The four methods are as follows: (i) dietary intake of folate and other vitamins, (ii) periconception folic acid/multivitamin supplementation, (iii) food fortification with folic acid, and (iv) the combination of oral contraceptives with 6S-5-methytetrahydrofolate ('folate').

  12. Primary prevention of neural-tube defects and some other congenital abnormalities by folic acid and multivitamins: history, missed opportunity and tasks

    PubMed Central

    Bártfai, Zoltán; Bánhidy, Ferenc

    2011-01-01

    The history of intervention trials of periconception folic acid with multivitamin and folic acid supplementation in women has shown a recent breakthrough in the primary prevention of structural birth defects, namely neural-tube defects and some other congenital abnormalities. Recently, some studies have demonstrated the efficacy of this new method in reducing congenital abnormalities with specific origin; for example, in the offspring of diabetic and epileptic mothers, and in pregnancy with high fever. The benefits and drawbacks of four possible uses of periconception folate/folic acid and multivitamin supplementation are discussed: we believe there has been a missed opportunity to implement this preventive approach in medical practice. The four methods are as follows: (i) dietary intake of folate and other vitamins, (ii) periconception folic acid/multivitamin supplementation, (iii) food fortification with folic acid, and (iv) the combination of oral contraceptives with 6S-5-methytetrahydrofolate (‘folate’). PMID:25083211

  13. [Awareness and knowledge of the use of folic acid in the prevention of neural tube defects: a survey of women living in Santiago, Chile].

    PubMed

    Pardo V, Rosa A; Lay-Son R, Guillermo; Aranda Ch, Waldo; Dib M, Martín; Espina M, Pablo; Muñoz K, María J; Muñoz B, Pilar; Navarrete C, María F; Ojeda M, Natalia V; Parra, Jorge; Rebolledo D, Cristian A; Recabal G, Pedro; Tenhamm T, Tamara

    2007-12-01

    Wheat flour in Chile is fortified with folie acid and pregnant women are also supplemented with the vitamin, but the population level of knowledge or awareness about this vitamin and its use by pregnant women is unknown. To assess the level of knowledge that postpartum women from Santiago de Chile have about folic acid. A questionnaire about folic acid and its effects on the prevention of neural tube defects was developed adapting questionnaires designed abroad. It was applied by medical students to puerperal women, hospitalized in public hospitals. The questionnaire was applied to 342 women aged 26 +/- 7 years. Sixty one percent were housewives and 55% completed high school education. Forty seven percent of these women had heard about folic acid, 9.6% knew that it was able to prevent congenital defects and only one received an adequate supplementation during pregnancy. Women aged 25 to 34 years and those with an adequate medical care during pregnancy had a significantly better knowledge about folic acid and its role in the prevention of congenital anomalies. The more common means to receive information about folic acid were midwives (34%), mass media (28%) and doctors (20%). Two hundred eleven women (62%) agreed to take folic acid in a future gestation and 58% preferred to do so using fortified foods. Post partum women from Santiago have a poor knowledge about the relevance of folic acid supplementation.

  14. Arundic Acid Prevents Developmental Upregulation of S100B Expression and Inhibits Enteric Glial Development

    PubMed Central

    Hao, Marlene M.; Capoccia, Elena; Cirillo, Carla; Boesmans, Werend; Vanden Berghe, Pieter

    2017-01-01

    S100B is expressed in various types of glial cells and is involved in regulating many aspects of their function. However, little is known about its role during nervous system development. In this study, we investigated the effect of inhibiting the onset of S100B synthesis in the development of the enteric nervous system, a network of neurons and glia located in the wall of the gut that is vital for control of gastrointestinal function. Intact gut explants were taken from embryonic day (E)13.5 mice, the day before the first immunohistochemical detection of S100B, and cultured in the presence of arundic acid, an inhibitor of S100B synthesis, for 48 h. The effects on Sox10-immunoreactive enteric neural crest progenitors and Hu-immunoreactive enteric neurons were then analyzed. Culture in arundic acid reduced the proportion of Sox10+ cells and decreased cell proliferation. There was no change in the density of Hu+ enteric neurons, however, a small population of cells exhibited atypical co-expression of both Sox10 and Hu, which was not observed in control cultures. Addition of exogenous S100B to the cultures did not change Sox10+ cell numbers. Overall, our data suggest that cell-intrinsic intracellular S100B is important for maintaining Sox10 and proliferation of the developing enteric glial lineage. PMID:28280459

  15. Monounsaturated fatty acids prevent the aversive effects of obesity on locomotion, brain activity, and sleep behavior.

    PubMed

    Sartorius, Tina; Ketterer, Caroline; Kullmann, Stephanie; Balzer, Michelle; Rotermund, Carola; Binder, Sonja; Hallschmid, Manfred; Machann, Jürgen; Schick, Fritz; Somoza, Veronika; Preissl, Hubert; Fritsche, Andreas; Häring, Hans-Ulrich; Hennige, Anita M

    2012-07-01

    Fat and physical inactivity are the most evident factors in the pathogenesis of obesity, and fat quality seems to play a crucial role for measures of glucose homeostasis. However, the impact of dietary fat quality on brain function, behavior, and sleep is basically unknown. In this study, mice were fed a diet supplemented with either monounsaturated fatty acids (MUFAs) or saturated fatty acids (SFAs) and their impact on glucose homeostasis, locomotion, brain activity, and sleep behavior was evaluated. MUFAs and SFAs led to a significant increase in fat mass but only feeding of SFAs was accompanied by glucose intolerance in mice. Radiotelemetry revealed a significant decrease in cortical activity in SFA-mice whereas MUFAs even improved activity. SFAs decreased wakefulness and increased non-rapid eye movement sleep. An intracerebroventricular application of insulin promoted locomotor activity in MUFA-fed mice, whereas SFA-mice were resistant. In humans, SFA-enriched diet led to a decrease in hippocampal and cortical activity determined by functional magnetic resonance imaging techniques. Together, dietary intake of MUFAs promoted insulin action in the brain with its beneficial effects for cortical activity, locomotion, and sleep, whereas a comparable intake of SFAs acted as a negative modulator of brain activity in mice and humans.

  16. Arundic Acid Prevents Developmental Upregulation of S100B Expression and Inhibits Enteric Glial Development.

    PubMed

    Hao, Marlene M; Capoccia, Elena; Cirillo, Carla; Boesmans, Werend; Vanden Berghe, Pieter

    2017-01-01

    S100B is expressed in various types of glial cells and is involved in regulating many aspects of their function. However, little is known about its role during nervous system development. In this study, we investigated the effect of inhibiting the onset of S100B synthesis in the development of the enteric nervous system, a network of neurons and glia located in the wall of the gut that is vital for control of gastrointestinal function. Intact gut explants were taken from embryonic day (E)13.5 mice, the day before the first immunohistochemical detection of S100B, and cultured in the presence of arundic acid, an inhibitor of S100B synthesis, for 48 h. The effects on Sox10-immunoreactive enteric neural crest progenitors and Hu-immunoreactive enteric neurons were then analyzed. Culture in arundic acid reduced the proportion of Sox10+ cells and decreased cell proliferation. There was no change in the density of Hu+ enteric neurons, however, a small population of cells exhibited atypical co-expression of both Sox10 and Hu, which was not observed in control cultures. Addition of exogenous S100B to the cultures did not change Sox10+ cell numbers. Overall, our data suggest that cell-intrinsic intracellular S100B is important for maintaining Sox10 and proliferation of the developing enteric glial lineage.

  17. Ascorbic acid prevents acetaminophen-induced hepatotoxicity in mice by ameliorating glutathione recovery and autophagy.

    PubMed

    Kurahashi, Toshihiro; Lee, Jaeyong; Nabeshima, Atsunori; Homma, Takujiro; Kang, Eun Sil; Saito, Yuka; Yamada, Sohsuke; Nakayama, Toshiyuki; Yamada, Ken-Ichi; Miyata, Satoshi; Fujii, Junichi

    2016-08-15

    Aldehyde reductase (AKR1A) plays a role in the biosynthesis of ascorbic acid (AsA), and AKR1A-deficient mice produce about 10-15% of the AsA that is produced by wild-type mice. We found that acetaminophen (AAP) hepatotoxicity was aggravated in AKR1A-deficient mice. The pre-administration of AsA in the drinking water markedly ameliorated the AAP hepatotoxicity in the AKR1A-deficient mice. Treatment of the mice with AAP decreased both glutathione and AsA levels in the liver in the early phase after AAP administration, and an AsA deficiency delayed the recovery of the glutathione content in the healing phase. While in cysteine supply systems; a neutral amino acid transporter ASCT1, a cystine transporter xCT, enzymes for the transsulfuration pathway, and autophagy markers, were all elevated in the liver as the result of the AAP treatment, the AsA deficiency suppressed their induction. Thus, AsA appeared to exert a protective effect against AAP hepatotoxicity by ameliorating the supply of cysteine that is available for glutathione synthesis as a whole. Because some drugs produce reactive oxygen species, resulting in the consumption of glutathione during the metabolic process, the intake of sufficient amounts of AsA would be beneficial for protecting against the hepatic damage caused by such drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Docosahexaenoic acid supplementation during pregnancy: a potential tool to prevent membrane rupture and preterm labor.

    PubMed

    Pietrantoni, Emanuela; Del Chierico, Federica; Rigon, Giuliano; Vernocchi, Pamela; Salvatori, Guglielmo; Manco, Melania; Signore, Fabrizio; Putignani, Lorenza

    2014-05-07

    Polyunsaturated fatty acids (PUFAs) are required to maintain the fluidity, permeability and integrity of cell membranes. Maternal dietary supplementation with ω-3 PUFAs during pregnancy has beneficial effects, including increased gestational length and reduced risk of pregnancy complications. Significant amounts of ω-3 docosahexaenoic acid (DHA) are transferred from maternal to fetal blood, hence ensuring high levels of DHA in the placenta and fetal bloodstream and tissues. Fetal DHA demand increases exponentially with gestational age, especially in the third trimester, due to fetal development. According to the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO), a daily intake of DHA is recommended during pregnancy. Omega-3 PUFAs are involved in several anti-inflammatory, pro-resolving and anti-oxidative pathways. Several placental disorders, such as intrauterine growth restriction, premature rupture of membranes (PROM) and preterm-PROM (pPROM), are associated with placental inflammation and oxidative stress. This pilot study reports on a preliminary evaluation of the significance of the daily DHA administration on PROM and pPROM events in healthy pregnant women. Further extensive clinical trials will be necessary to fully elucidate the correlation between DHA administration during pregnancy and PROM/pPROM occurrence, which is related in turn to gestational duration and overall fetal health.

  19. A Wood-Waste Cover Prevents Sulphide Oxidation and Treats Acid Effluents at the East-Sullivan Mine Site

    NASA Astrophysics Data System (ADS)

    Germain, D.; Tassé, N.; Cyr, J.

    2004-05-01

    At the East Sullivan site, wood wastes covering the abandoned mine tailings impoundment prevent sulphide oxidation by creating an anoxic environment. The addition of coarse ligneous wastes favours infiltration, resulting in a water table rise. This maintains most tailings saturated and thus provides an additional protection against sulphide oxidation. Moreover, high infiltration allows a more rapid flushing of acid prone groundwater generated prior to the cover placement. Finally, the pore-waters under the cover are characterized by a strong reducing potential and high alkalinity. These conditions favour sulphate reduction and base metal precipitation as sulphides and carbonates. The restoration strategy capitalized on the alkaline and reductive properties of the waters underlying the wood-waste cover. An original treatment of acid effluents, based on the recirculation of water discharging around the impoundment through the organic cover, was implemented in 1998. In 2003, the total volume of water treated was 725 000 m3. Data gathered near the dispersal zone show that despite dispersing acid water, the groundwater pH decreases by only one unit from 7 to 6, during the recirculation period: May to October. However, alkalinity decreases from 800 to 100 mg/L-CaCO3. But it is back up to 800 mg/L the following spring, thanks to sulphate reduction. Fe2+ concentrations near the dispersal zone are maintained below 2 mg/L. Evolution of the iron mass in the surface waters suggests that the contaminated groundwater flush is completed in the north and west sectors of the impoundment; the east and south ones are expected to be recovered within 3 to 4 years. A wood-waste cover, besides limiting sulphide oxidation, can fill the role of alkaline reducing barrier for the treatment of these acidogenic waters, until a balance between acidity and alkalinity in the effluent is reached.

  20. A combination of methotrexate and zoledronic acid prevents bone erosions and systemic bone mass loss in collagen induced arthritis

    PubMed Central

    2009-01-01

    Introduction Osteoclasts play a key role in the pathogenesis of bone erosion and systemic bone mass loss during rheumatoid arthritis (RA). In this study, we aimed to determine the effect of methotrexate (MTX) and zoledronic acid (ZA), used alone or in combination, on osteoclast-mediated bone erosions and systemic bone mass loss in a rat model of collagen induced arthritis (CIA). We hypothesized that MTX and ZA could have an additive effect to prevent both bone erosion and systemic bone loss. Methods Arthritis was induced in 64 female Sprague-Dawley rats. After the clinical onset of CIA, rats were assigned to treatment with MTX (1 mg/kg/week), ZA (100 μg/kg twice weekly), both treatments at the same regimens, or vehicle. Arthritis score and paw thickness were recorded twice weekly. The rats were sacrificed on D28 and hind paws were removed for radiographic, histological and immunohistochemical analysis. The effects of treatments on osteoclastogenesis were determined by Tartrate resistant acid phosphatase (TRAP) staining. Micro-CT of the tibia was carried out for histomorphometric analysis. Bone mass density was evaluated by densitometry. Results MTX significantly decreased the severity of CIA, whereas ZA slightly exacerbated it. When these two drugs were used in combination, MTX prevented the pro-inflammatory effect of ZA. The combination of ZA with MTX was more effective than MTX alone for reducing structural joint damage with a dramatic decrease of osteoclasts' number in the eroded joints. However, MTX alone also significantly reduced the number of osteoclasts and the number of CD68+ mononuclear cells. ZA alone, or ZA with MTX, significantly increased the systemic bone mass density measured by densitometry and bone volume on histomorphometric analysis. Conclusions A combination of MTX and ZA prevented both bone erosion and systemic bone loss in a rat model of arthritis. Both treatments independently decreased the number of osteoclasts in the eroded joint. However

  1. Knowledge and periconceptional use of folic acid for the prevention of neural tube defects in ethnic communities in the United Kingdom: systematic review and meta-analysis.

    PubMed

    Peake, Jordana N; Copp, Andrew J; Shawe, Jill

    2013-07-01

    It is widely accepted that periconceptional supplementation with folic acid can prevent a significant proportion of neural tube defects (NTDs). The present study evaluated how folic acid knowledge and periconceptional use for NTD prevention varies by ethnicity in the United Kingdom (U.K.). A literature search was conducted to identify studies that included assessment of folic acid knowledge or use in U.K. women of different ethnicities. Only research and referenced sources published after 1991, the year of the landmark Medical Research Council's Vitamin Study, were included. A meta-analysis was performed of studies that assessed preconceptional folic acid use in Caucasians and non-Caucasians. Five studies met the inclusion criteria for assessment of knowledge and/or use of folic acid supplements in U.K. women including non-Caucasians. The available evidence indicates that South Asians specifically have less knowledge and lower periconceptional use of folic acid than Caucasians; one study found that West Indian and African women also had lower folic acid uptake. A synthesis of results from three of the studies, in a meta-analysis, shows that Caucasians are almost three times more likely to take folic acid before conception than non-Caucasians. From the limited evidence available, U.K. women of non-Caucasian ethnicity appear to have less knowledge and a lower uptake of folic acid supplementation than Caucasians during the periconceptional period. Implementing targeted, innovative education campaigns together with a mandatory fortification policy, including the fortification of ethnic minority foods, will be required for maximum prevention of folic acid-preventable NTDs across different ethnic groups. Copyright © 2013 Wiley Periodicals, Inc.

  2. Preventive effect of zoledronic acid on aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole

    PubMed Central

    Sun, Shengliang; Wang, Fuchao; Dou, Honglei; Zhang, Longqiang; Li, Jiwen

    2016-01-01

    Background This study aims to compare the efficacy and safety between zoledronic acid combined with calcium and calcium alone to prevent aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole. Methods One hundred twenty patients were randomly divided into two groups, A and B. Patients in group A (n=60) received modified radical mastectomy or breast-conserving surgery + four cycles of AC followed by T regimen (optional) + radiotherapy (optional) + letrozole 2.5 mg daily + calcium 500 mg twice daily + vitamin D 400 international units daily +4 mg of zoledronic acid every 6 months, while patients in group B (n=60) were not given zoledronic acid and the rest of the treatments of group B were the same as group A. All the patients were followed up for 1 year. The primary endpoint was the intrapatient percentage change in lumbar spine (LS) bone mineral density (BMD) from baseline to month 12. Secondary endpoints included the percentage change in total hip (TH) and femoral neck (FN) BMD, the incidence of osteoporosis, the incidence of a clinically meaningful 5% decline in BMD at 1 year, change of serum N-telopeptide of type 1 collagen (NTX) and bone-specific alkaline phosphatase (BSAP) concentrations. Results Patients in group A had a statistically significant higher average change and average percent change in LS, FN, and TH than group B. Group A had a statistically significant lower incidence of a clinically meaningful loss of bone density at the LS, FN, or TH than Group B. The incidence of osteoporosis in group A was significantly lower than group B. The decreases in NTX and BSAP concentrations from baseline to month 12 in patients of group A were significant; in contrast, patients in group B were found to have increases in NTX and BSAP concentrations from baseline. The most common adverse reactions in patients are flu-like symptoms (38%), bone pain (28%), and joint pain (20%). Conclusion AI-associated bone loss

  3. Cost-Effectiveness of Zoledronic Acid to Prevent and Treat Postmenopausal Osteoporosis in Comparison with Routine Medical Treatment

    PubMed Central

    Golmohamdi, Fateme Rostami; Abbasi, Mahnaz; Karyani, Ali Kazemi; Sari, Ali Akbari

    2016-01-01

    Introduction Fractures caused by osteoporosis are prevalent among elderly females, which reduce quality of life significantly. This study aimed at comparing cost-effectiveness of Zoledronic acid in preventing and treating post-menopause osteoporosis as compared with routine medical treatment. Methods This cost-effectiveness study was carried out retrospectively from the Ministry of Health and insurance organizations perspective. Costs were evaluated based on the cost estimation of a sample of patients. Outcomes were obtained from a systematic review. The Cost-Effectiveness Ratio (CER) and incremental cost-effectiveness ratio (ICER) for outcome of femoral neck Bone Mineral Density (BMD), hip trochanter BMD, total hip BMD and lumbar spine BMD and cost-benefit of consuming Zoledronic Acid were calculated for fracture outcome obtained from reviewing hospital records. Results The results and the ICER calculated for study outcomes indicated that one percent increase of BMD on femoral neck BMD requires further cost of $386. One percent increase of BMD on hip trochanter BMD requires further cost of $264. One percent increase of BMD on total hip BMD requires further cost of $388, one percent increase of BMD on lumbar spine BMD requires further cost of $347. The Cost Benefit Analysis (CBA) calculated for vertebral and hip fracture, non-vertebral fracture, any clinical fracture, and morphometric fracture for a 36-month period were about 0.82, 0.57, and 1.06, respectively. Vertebral and hip fractures, and non-vertebral fractures or any clinical fracture for a 12-month period were calculated as 1.14 and 0.64, respectively. In other words, Zoledronic acid consumption approach is a cheaper and better approach based on an economic assessment, and it can be considered as a dominant approach. Conclusion According to the cost-effectiveness of zoledronic acid in the prevention and treatment of osteoporosis in women, despite the costs, it is recommended that insurance coverage for the

  4. Chlorogenic acid prevents isoproterenol-induced DNA damage in vascular smooth muscle cells

    PubMed Central

    Wang, Jingshuai; Li, Jiyang; Liu, Jie; Xu, Mengjiao; Tong, Xiaowen; Wang, Jianjun

    2016-01-01

    Numerous clinical therapeutic agents have been identified as DNA damaging. The present study revealed that isoproterenol (Iso) resulted in DNA damage in vascular smooth muscle cells (VSMCs) and increased the levels of intracellular oxygen free radicals. Administration of chlorogenic acid (CGA) inhibited this effect. Pretreatment with CGA abrogated the increase in protein expression levels of γ-H2A histone family member X, phosphorylated ataxia telangiectasia mutated, phosphorylated Rad3-related protein, breast cancer 1 and C-terminal Src homologous kinase induced by Iso. In addition, the increase in levels of intracellular reactive oxygen species (ROS) induced by Iso was inhibited by CGA pretreatment in a dose-dependent manner. The results of the present study suggest that CGA may inhibit Iso-induced VSMC damage via the suppression of ROS generation. Therefore, CGA may be a novel agent for the treatment of vascular diseases. PMID:27634104

  5. Role of zoledronic acid in the prevention and treatment of osteoporosis

    PubMed Central

    Räkel, Agnès; Boucher, Andrée; Ste-Marie, Louis-Georges

    2011-01-01

    Taken once a year, intravenous zoledronic acid (Zol) (Reclast® or Aclasta®) is a third-generation nitrogen-containing bisphosphonate that is effective compared with placebo in reducing the risk of fractures in patients with postmenopausal osteoporosis and recent low-trauma hip fracture. In glucocorticoid-induced osteoporosis, there is no significant difference between Zol and risedronate for new fractures. Improvements in bone mineral density and early reduction of bone remodeling markers are observed in postmenopausal osteoporosis, recent low-trauma hip fracture, and glucocorticoid-induced osteoporosis. Given that Zol is generally well tolerated and very convenient, it is an interesting therapeutic option for aging patients who take multiple oral drugs, who have adherence or gastrointestinal tolerance issues, and who have an indication for oral bisphosphonates. Zol is not recommended for patients with severe renal impairment. Vitamin D deficiency should be corrected before the administration of Zol. PMID:21594000

  6. Future opportunities in preventing ototoxicity: Caffeic acid phenethyl ester may be a candidate (Review).

    PubMed

    Akyol, Sumeyya; Isik, Bunyamin; Altuntas, Aynur; Erden, Gonul; Cakmak, Ozlem; Kurşunlu, S Fatih; Adam, Bahattin; Akyol, Omer

    2015-09-01

    Caffeic acid phenethyl ester (CAPE) is an important active component of propolis, which is derived from honeybee hives. It has received increasing attention in a variety of medical and pharmaceutical research, due to its anti‑oxidant, antiproliferative, anti‑inflammatory, antiviral and antifungal activity, in addition to its antineoplastic properties. Besides the use of CAPE as an antioxidant and anti‑inflammatory agent in a number of in vivo studies of ear disease, its beneficial effects have been reported in the treatment of cancer, arthritis, allergies, heart disease, diabetes, kidney disease, liver disease and neurological disease. CAPE influences a number of biochemical pathways, as well as several targets involved in ear diseases, in particular, in ototoxicity. The protective effects of CAPE in ototoxicity, which may be induced by a number factors, including lipopolysaccharides, hydrogen peroxide and streptomycin, are evaluated and discussed in the present review.

  7. Preventing disease transmission by deceased tissue donors by testing blood for viral nucleic acid.

    PubMed

    Strong, D Michael; Nelson, Karen; Pierce, Marge; Stramer, Susan L

    2005-01-01

    Nucleic acid testing (NAT) has reduced the risk of transmitting infectious disease through blood transfusion. Currently NAT for HIV-1 and HCV are FDA licensed and performed by nearly all blood collection facilities, but HBV NAT is performed under an investigational study protocol. Residual risk estimates indicate that NAT could potentially reduce disease transmission through transplanted tissue. However, tissue donor samples obtained post-mortem have the potential to produce an invalid NAT result due to inhibition of amplification reactions by hemolysis and other factors. The studies reported here summarize the development of protocols to allow NAT of deceased donor samples with reduced rates of invalid results. Using these protocols, inventories from two tissue centers were tested with greater than 99% of samples producing a valid test result.

  8. Saturated fatty acid diet prevents radiation-associated decline in intestinal uptake

    SciTech Connect

    Thomson, A.B.; Keelan, M.; Lam, T.; Cheeseman, C.I.; Walker, K.; Clandinin, M.T.

    1989-01-01

    Adult female Sprague-Dawley rats were fed isocaloric semipurified diets containing a high content of either polyunsaturated (P) or saturated (S) fatty acids; these diets were nutritionally adequate, providing for all known essential nutrient requirements. On day 3 after beginning S or P, one group of animals was exposed to a single 6-Gy dose of abdominal radiation, and the other half was sham irradiated. S or P diets were continued for a further 14 days. Brush-border membrane purification and sucrase-specific activities were unaffected by diet or by abdominal irradiation. In rats fed P, irradiation was associated with an increase in jejunal brush-border membrane total phospholipid and the ratio of phospholipid to cholesterol; these changes were not observed in animals fed S. In irradiated rats, ileal brush-border membrane phospholipid per cholesterol was high in animals fed S compared with P. In irradiated animals fed P, there was reduced jejunal and ileal uptake of several medium- and long-chain saturated and unsaturated fatty acids and cholesterol, and the ileal uptake of higher concentrations of glucose was reduced in irradiated animals fed P. In contrast, lipid uptake was similar in control and irradiated animals fed S except for cholesterol uptake, which was reduced. Ileal uptake of higher concentrations of glucose was increased in irradiated animals fed S. Quantitative autoradiography failed to demonstrate any change in the distribution of leucine or lysine transport sites along the villus 1 or 2 wk after abdominal irradiation or in response to feeding S or P. Also, these differences in transport achieved by feeding S to radiated animals were not explained by variations in the animals' food consumption or intestinal mucosal surface area.

  9. Sinapic Acid Prevents Hypertension and Cardiovascular Remodeling in Pharmacological Model of Nitric Oxide Inhibited Rats

    PubMed Central

    Silambarasan, Thangarasu; Manivannan, Jeganathan; Krishna Priya, Mani; Suganya, Natarajan; Chatterjee, Suvro; Raja, Boobalan

    2014-01-01

    Objectives Hypertensive heart disease is a constellation of abnormalities that includes cardiac fibrosis in response to elevated blood pressure, systolic and diastolic dysfunction. The present study was undertaken to examine the effect of sinapic acid on high blood pressure and cardiovascular remodeling. Methods An experimental hypertensive animal model was induced by L-NAME intake on rats. Sinapic acid (SA) was orally administered at a dose of 10, 20 and 40 mg/kg body weight (b.w.). Blood pressure was measured by tail cuff plethysmography system. Cardiac and vascular function was evaluated by Langendorff isolated heart system and organ bath studies, respectively. Fibrotic remodeling of heart and aorta was assessed by histopathologic analyses. Oxidative stress was measured by biochemical assays. mRNA and protein expressions were assessed by RT-qPCR and western blot, respectively. In order to confirm the protective role of SA on endothelial cells through its antioxidant property, we have utilized the in vitro model of H2O2-induced oxidative stress in EA.hy926 endothelial cells. Results Rats with hypertension showed elevated blood pressure, declined myocardial performance associated with myocardial hypertrophy and fibrosis, diminished vascular response, nitric oxide (NO) metabolites level, elevated markers of oxidative stress (TBARS, LOOH), ACE activity, depleted antioxidant system (SOD, CAT, GPx, reduced GSH), aberrant expression of TGF-β, β-MHC, eNOS mRNAs and eNOS protein. Remarkably, SA attenuated high blood pressure, myocardial, vascular dysfunction, cardiac fibrosis, oxidative stress and ACE activity. Level of NO metabolites, antioxidant system, and altered gene expression were also repaired by SA treatment. Results of in vitro study showed that, SA protects endothelial cells from oxidative stress and enhance the production of NO in a concentration dependent manner. Conclusions Taken together, these results suggest that SA may have beneficial role in the

  10. Salvianolic Acid A, a Novel Matrix Metalloproteinase-9 Inhibitor, Prevents Cardiac Remodeling in Spontaneously Hypertensive Rats

    PubMed Central

    Deng, Yanping; Teng, Fukang; Chen, Jing; Xue, Song; Kong, Xiangqian; Luo, Cheng; Shen, Xu; Jiang, Hualiang; Xu, Feng; Yang, Wengang; Yin, Jun; Wang, Yanhui; Chen, Hui; Wu, Wanying; Liu, Xuan; Guo, De-an

    2013-01-01

    Cardiac fibrosis is a deleterious consequence of hypertension which may further advance to heart failure and increased matrix metalloproteinase-9 (MMP-9) contributes to the underlying mechanism. Therefore, new therapeutic strategies to attenuate the effects of MMP-9 are urgently needed. In the present study, we characterize salvianolic acid A (SalA) as a novel MMP-9 inhibitor at molecular, cellular and animal level. We expressed a truncated form of MMP-9 which contains only the catalytic domain (MMP-9 CD), and used this active protein for enzymatic kinetic analysis and Biacore detection. Data generated from these assays indicated that SalA functioned as the strongest competitive inhibitor of MMP-9 among 7 phenolic acids from Salvia miltiorrhiza. In neonatal cardiac fibroblast, SalA inhibited fibroblast migration, blocked myofibroblast transformation, inhibited secretion of intercellular adhesion molecule (ICAM), interleukin-6 (IL-6) and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as collagen induced by MMP-9 CD. Functional effects of SalA inhibition on MMP-9 was further confirmed in cultured cardiac H9c2 cell overexpressing MMP-9 in vitro and in heart of spontaneously hypertensive rats (SHR) in vivo. Moreover, SalA treatment in SHR resulted in decreased heart fibrosis and attenuated heart hypertrophy. These results indicated that SalA is a novel inhibitor of MMP-9, thus playing an inhibitory role in hypertensive fibrosis. Further studies to develop SalA and its analogues for their potential clinical application of cardioprotection are warranted. PMID:23533637

  11. A newborn lethal defect due to inactivation of retinaldehyde dehydrogenase type 3 is prevented by maternal retinoic acid treatment

    PubMed Central

    Dupé, Valérie; Matt, Nicolas; Garnier, Jean-Marie; Chambon, Pierre; Mark, Manuel; Ghyselinck, Norbert B.

    2003-01-01

    The retinoic acid (RA) signal, produced locally from vitamin A by retinaldehyde dehydrogenase (Raldh) and transduced by the nuclear receptors for retinoids (RA receptor and 9-cis-RA receptor), is indispensable for ontogenesis and homeostasis of numerous tissues. We demonstrate that Raldh3 knockout in mouse suppresses RA synthesis and causes malformations restricted to ocular and nasal regions, which are similar to those observed in vitamin A-deficient fetuses and/or in retinoid receptor mutants. Raldh3 knockout notably causes choanal atresia (CA), which is responsible for respiratory distress and death of Raldh3-null mutants at birth. CA is due to persistence of nasal fins, whose rupture normally allows the communication between nasal and oral cavities. This malformation, which is similar to isolated congenital CA in humans and may result from impaired RA-controlled down-regulation of Fgf8 expression in nasal fins, can be prevented by a simple maternal treatment with RA. PMID:14623956

  12. Implementing preventive iron-folic acid supplementation among women of reproductive age in some Western Pacific countries: possibilities and challenges.

    PubMed

    Smitasiri, Suttilak; Solon, Florentino S

    2005-12-01

    Lack of effective implementation mechanisms is identified as a major obstacle in the prevention and control of iron-deficiency anemia. This paper discusses experiences gained from implementing iron-folic acid supplementation in the Philippines, Vietnam, and Cambodia. The understanding of contextual elements is proposed as a foundation for planning interventions. Moreover, it is suggested that a social marketing framework should provide a way of thinking about how to influence related behaviors. The application of a social marketing framework applied using a "5 P's" approach: public relations and collaboration, product, price, place, and promotion, is described, as well as enabling factors (possibilities) and inhibiting factors (challenges) of this approach. Although a program to improve iron nutrition among women of reproductive age may not be simple to implement, it is essential to enhancing health, human development, and economic advancement in developing countries.

  13. Prevention of human fascioliasis: a study on the role of acids detergents and potassium permenganate in clearing salads from metacercariae.

    PubMed

    el-Sayad, M H; Allam, A F; Osman, M M

    1997-04-01

    Prevention of human fascioliasis could depend on clearing of the leafy salads from the metacercariae. The present work evaluated the role of some chemicals in detaching and killing this infective stage. It was observed that washing in running water for 10 minutes detached only 50% of the metacercariae. Citric acid in the concentration of (10 ml/L) commercial vinegar (120 ml/L), liquid soap (12 ml/L) and KMnO4 (24 mg/L) detached all metacercariae after 10 minutes exposure. The use of vinegar and KMnO4 is recommended: the first is lethal to other parasites in the vegetables, the second destroyed the metacercariae. Vegetable leaves were not softened and remained fresh.

  14. Cost analysis of use of tranexamic Acid to prevent major bleeding complications in hip and knee arthroplasty surgery.

    PubMed

    Slover, James; Bosco, Joseph

    2014-10-01

    We used decision analysis to assess the cost profile associated with preoperative use of tranexamic acid (TXA) to prevent major bleeding complications associated with hip and knee arthroplasty surgery. We defined major bleeding complications as blood loss sufficient to require transfusion or surgical evacuation of a postoperative hematoma. In the absence of a reduction in revision rates, using current cost data, TXA use is not cost-saving for institutions with baseline blood transfusion rates under 25%. For centers with baseline transfusion rates above 25%, however, TXA becomes increasingly cost-saving as the reduction in transfusion rates seen with use of the drug increases, but a minimum 12% reduction in transfusion rates is needed, even if the expected baseline transfusion rate is 100%. Nevertheless, TXA use is much more likely to be cost-saving, regardless of transfusion rates, if it leads to a reduction in need for revision surgery.

  15. Prevention of alcoholic fatty liver and mitochondrial dysfunction in the rat by long-chain polyunsaturated fatty acids

    PubMed Central

    Song, Byoung-Joon; Moon, Kwan-Hoon; Olsson, Nils U.; Salem, Norman

    2008-01-01

    Background/Aims We reported that reduced dietary intake of polyunsaturated fatty acids (PUFA) such as arachidonic (AA,20:4n6, omega-6) and docosahexaenoic (DHA,22:6n3, omega-3) acids led to alcohol-induced fatty liver and fibrosis. This study was aimed at studying the mechanisms by which a DHA/AA-supplemented diet prevents alcohol-induced fatty liver. Methods Male Long-Evans rats were fed an ethanol or control liquid-diet with or without DHA/AA for 9 weeks. Plasma transaminase levels, liver histology, oxidative/nitrosative stress markers, and activities of oxidatively-modified mitochondrial proteins were evaluated. Results Chronic alcohol administration increased the degree of fatty liver but fatty liver decreased significantly in rats fed the alcohol-DHA/AA-supplemented diet. Alcohol exposure increased oxidative/nitrosative stress with elevated levels of ethanol-inducible CYP2E1, nitric oxide synthase, nitrite and mitochondrial hydrogen peroxide. However, these increments were normalized in rats fed the alcohol-DHA/AA-supplemented diet. The number of oxidatively-modified mitochondrial proteins was markedly increased following alcohol exposure but significantly reduced in rats fed the alcohol-DHA/AA-supplemented diet. The suppressed activities of mitochondrial aldehyde dehydrogenase, ATP synthase, and 3-ketoacyl-CoA thiolase in ethanol-exposed rats were also recovered in animals fed the ethanol-DHA/AA-supplemented diet. Conclusions Addition of DHA/AA prevents alcohol-induced fatty liver and mitochondrial dysfunction in an animal model by protecting various mitochondrial enzymes most likely through reducing oxidative/nitrosative stress. PMID:18571270

  16. Salicylic acid improves the salinity tolerance of Medicago sativa in symbiosis with Sinorhizobium meliloti by preventing nitrogen fixation inhibition.

    PubMed

    Palma, F; López-Gómez, M; Tejera, N A; Lluch, C

    2013-07-01

    In this work we have investigated the contribution of pretreatment with 0.1 and 0.5mM salicylic acid (SA) to the protection against salt stress in root nodules of Medicago sativa in symbiosis with Sinorhizobium meliloti. SA alleviated the inhibition induced by salinity in the plant growth and photosynthetic capacity of M. sativa-S. meliloti symbiosis. In addition, SA prevented the inhibition of the nitrogen fixation capacity under salt stress since nodule biomass was not affected by salinity in SA pretreated plants. Antioxidant enzymes peroxidase (POX), superoxide dismutase (SOD), ascorbate peroxidase (APX), dehidroascorbate reductase (DHAR) and glutathione reductase (GR), key in the main pathway that scavenges H2O2 in plants, were induced by SA pretreatments which suggest that SA may participate in the redox balance in root nodules under salt stress. Catalase activity (CAT) was inhibited around 40% by SA which could be behind the increase of H2O2 detected in nodules of plants pretreated with SA. The accumulation of polyamines (PAs) synthesized in response to salinity was prevented by SA which together with the induction of 1-aminocyclopropane-l-carboxylic acid (ACC) content suggest the prevalence of the ethylene signaling pathway induced by SA in detriment of the synthesis of PAs. In conclusion, SA alleviated the negative effect of salt stress in the M. sativa-S. meliloti symbiosis through the increased level of nodule biomass and the induction of the nodular antioxidant metabolism under salt stress. The H2O2 accumulation and the PAs inhibition induced by SA in nodules of M. sativa suggest that SA activates a hypersensitive response dependent on ethylene.

  17. The retinaldehyde reductase DHRS3 is essential for preventing the formation of excess retinoic acid during embryonic development

    PubMed Central

    Billings, Sara E.; Pierzchalski, Keely; Butler Tjaden, Naomi E.; Pang, Xiao-Yan; Trainor, Paul A.; Kane, Maureen A.; Moise, Alexander R.

    2013-01-01

    Oxidation of retinol via retinaldehyde results in the formation of the essential morphogen all-trans-retinoic acid (ATRA). Previous studies have identified critical roles in the regulation of embryonic ATRA levels for retinol, retinaldehyde, and ATRA-oxidizing enzymes; however, the contribution of retinaldehyde reductases to ATRA metabolism is not completely understood. Herein, we investigate the role of the retinaldehyde reductase Dhrs3 in embryonic retinoid metabolism using a Dhrs3-deficient mouse. Lack of DHRS3 leads to a 40% increase in the levels of ATRA and a 60% and 55% decrease in the levels of retinol and retinyl esters, respectively, in Dhrs3−/− embryos compared to wild-type littermates. Furthermore, accumulation of excess ATRA is accompanied by a compensatory 30–50% reduction in the expression of ATRA synthetic genes and a 120% increase in the expression of the ATRA catabolic enzyme Cyp26a1 in Dhrs3−/− embryos vs. controls. Excess ATRA also leads to alterations (40–80%) in the expression of several developmentally important ATRA target genes. Consequently, Dhrs3−/− embryos die late in gestation and display defects in cardiac outflow tract formation, atrial and ventricular septation, skeletal development, and palatogenesis. These data demonstrate that the reduction of retinaldehyde by DHRS3 is critical for preventing formation of excess ATRA during embryonic development.—Billings, S. E., Pierzchalski, K., Butler Tjaden, N. E., Pang, X.-Y., Trainor, P. A., Kane, M. A., Moise, A. R. The retinaldehyde reductase DHRS3 is essential for preventing the formation of excess retinoic acid during embryonic development. PMID:24005908

  18. A Malaria Transmission-Blocking (+)-Usnic Acid Derivative Prevents Plasmodium Zygote-to-Ookinete Maturation in the Mosquito Midgut.

    PubMed

    Pastrana-Mena, Rebecca; Mathias, Derrick K; Delves, Michael; Rajaram, Krithika; King, Jonas G; Yee, Rebecca; Trucchi, Beatrice; Verotta, Luisella; Dinglasan, Rhoel R

    2016-12-16

    The evolution of drug resistance is a recurrent problem that has plagued efforts to treat and control malaria. Recent emergence of artemisinin resistance in Southeast Asia underscores the need to develop novel antimalarials and identify new targetable pathways in Plasmodium parasites. Transmission-blocking approaches, which typically target gametocytes in the host bloodstream or parasite stages in the mosquito gut, are recognized collectively as a strategy that when used in combination with antimalarials that target erythrocytic stages will not only cure malaria but will also prevent subsequent transmission. We tested four derivatives of (+)-usnic acid, a metabolite isolated from lichens, for transmission-blocking activity against Plasmodium falciparum using the standard membrane feeding assay. For two of the derivatives, BT37 and BT122, we observed a consistent dose-response relationship between concentration in the blood meal and oocyst intensity in the midgut. To explore their mechanism of action, we used the murine model Plasmodium berghei and found that both derivatives prevent ookinete maturation. Using fluorescence microscopy, we demonstrated that in the presence of each compound zygote vitality was severely affected, and those that did survive failed to elongate and mature into ookinetes. The observed phenotypes were similar to those described for mutants of specific kinases (NEK2/NEK4) and of inner membrane complex 1 (IMC1) proteins, which are all vital to the zygote-to-ookinete transition. We discuss the implications of our findings and our high-throughput screening approach to identifying next generation, transmission-blocking antimalarials based on the scaffolds of these (+)-usnic acid derivatives.

  19. Salvianolic acid B prevents steroid-induced osteonecrosis of the femoral head via PPARγ expression in rats

    PubMed Central

    Li, Shuangqing; Wang, Juan

    2017-01-01

    Salvianolic acid B (Sal B) is a water-soluble phenolic compound derived from Salvia Miltiorrhiza. Recent studies show Sal B has a clear function of anti-cerebral ischemia injury, which is closely related to antioxidation, free radical scavenging, neuroprotection and the blood brain barrier. The aim of the present study was to verify whether Sal B prevents steroid-induced osteonecrosis of the femoral head and to investigate its underlying pharmacological mechanisms. Steroid-induced osteonecrosis rat models were established to evaluate the effects of Sal B on osteonecrotic changes and repair processes. The use of Sal B improved steroid-induced histopathological scores and inhibited osteoclast differentiation in rats. Notably, Sal B induced bone marrow-derived mesenchymal stem cells into osteogenesis. Moreover, Sal B treatment suppressed peroxisome proliferator-activated receptor (PPAR)γ and AP2 protein expression levels and increased runt-related transcription factor 2 and Collagen I protein expression levels in steroid-induced rats. osteocalcin and alkaline phosphatase content in steroid-induced rats was enhanced by treatment with Sal B. These results suggest that Sal B prevents steroid-induced osteonecrosis of the femoral head via PPARγ expression in rats. The present pilot study provides a brief insight into the effect of Sal B on steroid-induced osteonecrosis. PMID:28352346

  20. Is intravesical instillation of hyaluronic acid and chondroitin sulfate useful in preventing recurrent bacterial cystitis? A multicenter case control analysis.

    PubMed

    Gugliotta, Giorgio; Calagna, Gloria; Adile, Giorgio; Polito, Salvatore; Saitta, Salvatore; Speciale, Patrizia; Palomba, Stefano; Perino, Antonino; Granese, Roberta; Adile, Biagio

    2015-10-01

    Urinary tract infections (UTIs) are common in the female population and, over a lifetime, about half of women have at least one episode of UTI requiring antibiotic therapy. The aim of the current study was to compare two different strategies for preventing recurrent bacterial cystitis: intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS), and antibiotic prophylaxis with sulfamethoxazole plus trimethoprim. This was a retrospective review of two different cohorts of women affected by recurrent bacterial cystitis. Cases (experimental group) were women who received intravesical instillations of a sterile solution of high concentration of HA + CS in 50 mL water with calcium chloride every week during the 1(st) month and then once monthly for 4 months. The control group included women who received traditional therapy for recurrent cystitis based on daily antibiotic prophylaxis using sulfamethoxazole 200 mg plus trimethoprim 40 mg for 6 weeks. Ninety-eight and 76 patients were treated with experimental and control treatments, respectively. At 12 months after treatment, 69 and 109 UTIs were detected in the experimental and control groups, respectively. The proportion of patients free from UTIs was significantly higher in the experimental than in the control group (36.7% vs. 21.0%; p = 0.03). Experimental treatment was well tolerated and none of the patients stopped it. The intravesical instillation of HA + CS is more effective than long-term antibiotic prophylaxis for preventing recurrent bacterial cystitis. Copyright © 2015. Published by Elsevier B.V.

  1. Probiotic mixture supplementation in the preventive management of trinitrobenzenesulfonic acid-induced inflammation in a murine model.

    PubMed

    Traina, G; Menchetti, L; Rappa, F; Casagrande-Proietti, P; Barbato, O; Leonardi, L; Carini, F; Piro, F; Brecchia, G

    2016-01-01

    Inflammatory bowel diseases (IBD) are characterized by inflammatory conditions of the intestine. Probiotic bacteria (PB) can have beneficial effects in several gastrointestinal disorders. The objectives of this study were: (i) to provide an acute experimental IBD model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in CD-1 mice, and (ii) to assess the preventive effects of Citogenex (Lactobacillus casei and Bifidobacterum lactis) supplementation on intestinal tissues and microbiota. Mice were inoculated intrarectally with saline, ethanol or different TNBS solutions. 1%TNBS induced clinical signs of colitis (P less than 0.01) and histological damage (P less than 0.01). Based on these results, mice were pre-treated with Citogenex or saline for 1, 2 or 3 weeks before 1%TNBS treatment. Probiotic pre-treatment determined a reduction of clinical signs (P less than 0.05), histological alterations of colitis (P less than 0.05) and increased beneficial bacteria (P less than 0.05). This study confirms that TNBS-induced colitis in CD-1 mice is useful for studying the mechanisms involved in IBD pathogenesis, and pre-treatment with Citogenex prevents the intestinal damage induced by TNBS.

  2. Ferulic acid promotes survival and differentiation of neural stem cells to prevent gentamicin-induced neuronal hearing loss.

    PubMed

    Gu, Lintao; Cui, Xinhua; Wei, Wei; Yang, Jia; Li, Xuezhong

    2017-09-12

    Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed. Gentamicin was used to induce neuronal hearing loss in mice, in the presence and absence of FA, followed by assessments of auditory brainstem response (ABR) and distortion product optoacoustic emissions (DPOAE) amplitude. FA promoted survival, neurosphere formation and differentiation of NSCs, as well as neurite outgrowth and excitability of in vitro neuronal network. Furthermore, FA restored ABR threshold shifts and DPOAE in gentamicin-induced neuronal hearing loss mouse model in vivo. Our data, for the first time, support potential therapeutic efficacy of FA in promoting survival and differentiation of NSCs to prevent gentamicin-induced neuronal hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Periconceptional use of folic acid and risk of miscarriage - findings of the Oral Cleft Prevention Program in Brazil.

    PubMed

    Vila-Nova, Camila; Wehby, George L; Queirós, Fernanda C; Chakraborty, Hrishkesh; Félix, Temis M; Goco, Norman; Moore, Janet; Gewehr, Eduardo V; Lins, Lorene; Affonso, Carla M C; Murray, Jeffrey C

    2013-07-01

    We report on the risk of miscarriage with high- and low-dosage periconceptional folic acid (FA) supplementation from a double-blind randomized clinical trial for prevention of orofacial cleft recurrence in Brazil. Women at risk of recurrence of orofacial clefts in their offspring were randomized into high (4 mg/day) and low (0.4 mg/day) doses of FA supplementation. The women received the study pills before pregnancy, and supplementation continued throughout the first trimester. Miscarriage rates were compared between the two FA groups and with the population rate. A total of 268 pregnancies completed the study protocol, with 141 in the 4.0-mg group and 127 in the 0.4-mg group. The miscarriage rate was 14.2% in the low-dose FA group (0.4 mg/day) and 11.3% for the high-dose group (4 mg/day) (P=0.4877). These miscarriage rates are not significantly different from the miscarriage rate in the Brazilian population, estimated to be around 14% (P=0.311). These results indicate that high-dose FA does not increase miscarriage risk in this population and add further information to the literature on the safety of high FA supplementation for prevention of birth defect recurrence.

  4. Estimate of the potential impact of folic acid fortification of corn masa flour on the prevention of neural tube defects.

    PubMed

    Tinker, Sarah C; Devine, Owen; Mai, Cara; Hamner, Heather C; Reefhuis, Jennita; Gilboa, Suzanne M; Dowling, Nicole F; Honein, Margaret A

    2013-10-01

    Hispanics in the US have a higher prevalence of neural tube defect (NTD) -affected pregnancies than non-Hispanic whites, and lower median total folic acid (FA) intake. FA fortification of corn masa flour (CMF) is a policy-level intervention for NTD prevention; however, the impact on NTD prevalence has not been estimated. We developed a model to estimate the percentage reduction in prevalence of spina bifida and anencephaly (NTDs) that could occur with FA fortification of CMF. Model inputs included estimates of the percentage reduction in United States NTD prevalence attributed to FA fortification of enriched cereal grain products (1995-1996 vs. 1998-2002), the increase in median FA intake after enriched cereal grain product fortification, and the estimated increase in median FA intake that could occur with CMF fortification at the same level as enriched cereal grain products (140 μg/100 g). We used Monte Carlo simulation to quantify uncertainty. We stratified analyses by racial/ethnic group and rounded results to the nearest 10. We estimated CMF fortification could prevent 30 Hispanic infants from having spina bifida (95% uncertainty interval: 0, 80) and 10 infants from having anencephaly (95% uncertainty interval: 0, 40) annually. The estimated impact among non-Hispanic whites and blacks was smaller. CMF fortification with FA could prevent from 0 to 120 infants, with the most likely value of approximately 40, from having spina bifida or anencephaly among Hispanics, the population most likely to benefit from the proposed intervention. While this estimated reduction is unlikely to be discernible using current birth defect surveillance methods, it still suggests an important benefit to the target population. Copyright © 2013 Wiley Periodicals, Inc.

  5. Melatonin prevents hypochlorous acid-induced alterations in microtubule and chromosomal structure in metaphase-II mouse oocytes.

    PubMed

    Banerjee, Jashoman; Maitra, Dhiman; Diamond, Michael P; Abu-Soud, Husam M

    2012-09-01

    Hypochlorous acid (HOCl) is generated by myeloperoxidase, using chloride and hydrogen peroxide as substrates. Here we demonstrate that HOCl alters metaphase-II mouse oocyte microtubules and chromosomal (CH) alignment which can be prevented by melatonin. Metaphase-II mouse oocytes, obtained commercially, were grouped as: control, melatonin (150, 200nmol/mL), HOCl (10, 20, 50, and 100nmol/mL), and HOCl (50nmol/mL) pretreated with 150 and 200 nmol/mL of melatonin. Microtubule and CH alignment was studied utilizing an indirect immunofluorescence technique and scored by two observers. Pearson chi-square test and Fisher's exact test were used to compare outcomes between controls and treated groups and also among each group. Poor scores for the spindle and chromosomes increased significantly at 50nmol/mL of HOCl (P<0.001). Oocytes treated with melatonin only at 150 and 200 nmol/mL showed no changes; significant differences (P<0.001) were observed when oocytes exposed to 50nmol/mL of HOCl were compared to oocytes pretreated with 200 nmol/mL melatonin. Fifty percent of the oocytes demonstrated good scores, both in microtubule and CH alterations, when pretreated with melatonin at 150 nmol/mL compared to 0% in the HOCl-only group. HOCl alters the metaphase-II mouse oocyte spindle and CH alignment in a dose-dependant manner, which might be a potential cause of poor oocyte quality (e.g., in patients with endometriosis). Melatonin prevented the HOCl-mediated spindle and CH damage, and therefore, may be an attractive therapeutic option to prevent oocyte damage in endometriosis or inflammatory diseases where HOCl levels are known to be elevated. © 2012 John Wiley & Sons A/S.

  6. ALA, fatty fish or marine n-3 fatty acids for preventing DM?: a systematic review and meta-analysis.

    PubMed

    Muley, Arti; Muley, Prasad; Shah, Monali

    2014-05-01

    Diabetes mellitus (T2DM) has become a global problem. Role of n-3 FA in its prevention is still not completely understood. We carried out this systematic review and meta-analysis to assess the relation of dietary intake of fish and n-3PUFA with risk of diabetes. We searched PUBMED, EMBASE and GOOGLE with cross references to identify relevant articles. Since no RCTs were available, we searched for prospective cohort studies. Sixteen studies with 6,79,763 participants which assessed the association of dietary intake of fish and n-3 PUFA (marine or alpha-linolenic acid) with incidence of T2DM in > 18 years population and provided relative risk (RR) or hazard ratio (HR) with the corresponding 95% confidence interval (CI) of T2DM for each category of fish or n-3 PUFA intake were included. Three independent reviewers reviewed all eligible studies and abstracted the relevant information from individual studies. Meta-analysis confirmed the previous finding that marine n-3 FA increased risk of T2DM in Americans but reduced the same in Asians. We observed that two and seven times increased intake of ALA and fatty fish respectively reduced the risk of T2DM significantly and ALA did not increase the risk in Americans. We concluded that ALA may have some role in preventing T2DM, but is not studied widely. Hence, it should be studied in greater details (with higher degrees of intake; more than two times) to aid in developing effective preventive strategies against diabetes.

  7. Knowledge and periconceptional use of folic acid for the prevention of neural tube defects in ethnic communities in the United Kingdom: Systematic review and meta-analysis

    PubMed Central

    Peake, Jordana N; Copp, Andrew J; Shawe, Jill

    2013-01-01

    BACKGROUND: It is widely accepted that periconceptional supplementation with folic acid can prevent a significant proportion of neural tube defects (NTDs). The present study evaluated how folic acid knowledge and periconceptional use for NTD prevention varies by ethnicity in the United Kingdom (U.K.). METHODS: A literature search was conducted to identify studies that included assessment of folic acid knowledge or use in U.K. women of different ethnicities. Only research and referenced sources published after 1991, the year of the landmark Medical Research Council’s Vitamin Study, were included. A meta-analysis was performed of studies that assessed preconceptional folic acid use in Caucasians and non-Caucasians. RESULTS: Five studies met the inclusion criteria for assessment of knowledge and/or use of folic acid supplements in U.K. women including non-Caucasians. The available evidence indicates that South Asians specifically have less knowledge and lower periconceptional use of folic acid than Caucasians; one study found that West Indian and African women also had lower folic acid uptake. A synthesis of results from three of the studies, in a meta-analysis, shows that Caucasians are almost three times more likely to take folic acid before conception than non-Caucasians. CONCLUSION: From the limited evidence available, U.K. women of non-Caucasian ethnicity appear to have less knowledge and a lower uptake of folic acid supplementation than Caucasians during the periconceptional period. Implementing targeted, innovative education campaigns together with a mandatory fortification policy, including the fortification of ethnic minority foods, will be required for maximum prevention of folic acid–preventable NTDs across different ethnic groups. Birth Defects Research (Part A) 97:444–451, 2013. © 2013 Wiley Periodicals, Inc. PMID:23873812

  8. The Effect of Omega-3 Fatty Acids on Psychophysiological Assessment for the Secondary Prevention of Posttraumatic Stress Disorder: An Open-Label Pilot Study

    PubMed Central

    Matsumura, Kenta; Noguchi, Hiroko; Nishi, Daisuke; Matsuoka, Yutaka

    2012-01-01

    Our recent pilot study has shown that the supplementation of omega-3 fatty acids (fish oil) immediately after a traumatic event may be effective toward the secondary prevention of post-traumatic disorder (PTSD). To lay the groundwork for addressing the mechanism by which omega-3 fatty acids can prevent PTSD, we analyzed its psychophysiological data. The psychophysiological data included heart rate, skin conductance, and continuous blood pressure during patient subjection to startling tones and idiographic trauma-related cues. Of the 8 patients, 1 met the diagnostic criteria for PTSD. Compared to the seven patients without PTSD, one patient with PTSD showed relatively large reactivity to the startle tones. In contrast, this patient did not show large reactivity to the trauma-related cue during script-driven imagery. The combination of psychophysiological measurements in our randomized control trial should shed light on the underlying mechanisms by which omega-3 fatty acids can prevent PTSD. PMID:22980098

  9. Effective prevention of chill-haze in beer using an acid proline-specific endoprotease from Aspergillus niger.

    PubMed

    Lopez, Michel; Edens, Luppo

    2005-10-05

    Chill-haze formation during beer production is known to involve polyphenols that interact with proline-rich proteins. We hypothesized that incubating beer wort with a proline-specific protease would extensively hydrolyze these proline-rich proteins, yielding a peptide fraction that is unable to form a haze. Predigestion of the proline-rich wheat gliadin with different proteases pointed toward a strong haze-suppressing effect by a proline-specific enzyme. This finding was confirmed in small-scale brewing experiments using a recently identified proline-specific protease with an acidic pH optimum. Subsequent pilot plant trials demonstrated that, upon its addition during the fermentation phase of beer brewing, even low levels of this acidic enzyme effectively prevented chill-haze formation in bottled beer. Results of beer foam stability measurements indicated that the enzyme treatment leaves the beer foam almost unaffected. In combination with the enzyme's cost-effectiveness and regulatory status, these preliminary test results seem to favor further industrial development of this enzymatic beer stabilization method.

  10. A Prevention of Pre-eclampsia with the Use of Acetylsalicylic Acid and Low-molecular Weight Heparin - Molecular Mechanisms.

    PubMed

    Darmochwal-Kolarz, Dorota; Kolarz, Bogdan; Korzeniewski, Michal; Kimber-Trojnar, Zaneta; Patro-Malysza, Jolanta; Mierzynski, Radzisław; Przegalinska-Kałamucka, Monika; Oleszczuk, Jan

    Pre-eclampsia appears to be the main cause for the maternal and fetal morbidity and mortality. Pregnant women with pre-eclampsia are more likely to be threatened with conditions which potentially may be lethal, such as: disseminated intravascular coagulation, cerebral hemorrhage, liver and renal failure. Pregnancy complicated with pre-eclampsia is also associated with a greater risk for iatrogenic prematurity, intrauterine growth retardation, premature abruption of placenta, and even intrauterine fetal death. In the majority of cases the reasons for arterial hypertension among pregnant women remain obscure. For the past decades, there were many abortive attempts in the use of some microelements, vitamins or specific diets, such as polyunsaturated fatty acids, for the prophylaxis of pre-eclampsia. Recently, it has been shown that a prevention of pre-eclampsia with the use of a lowmolecular- weight heparins (LMWHs) and acetylsalicylic acid (ASA) could considerably reduce the frequency of preeclampsia. In this review, we present the studies concerning the applications of LMWHs and aspirin in the prophylaxis of pre-eclampsia and some important data about the mechanisms of anti-inflammatory actions of LMWHs and ASA.

  11. Omega-3 fatty acids and HDL. How do they work in the prevention of cardiovascular disease?

    PubMed

    Burillo, Elena; Martín-Fuentes, Paula; Mateo-Gallego, Rocío; Baila-Rueda, Lucía; Cenarro, Ana; Ros, Emilio; Civeira, Fernando

    2012-07-01

    Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) from marine origin have been strongly associated with cardiovascular protection, even at low doses ( < 1g/d). Despite the research performed in this promising area, basic aspects, such as the ideal doses and the mechanisms by which ω-3 PUFAs act, are not precisely defined. The best known biological property of ω-3 PUFAs is their hypotriglyceridemic effect, but other cardioprotective actions, such as reduction of arrhythmia susceptibility, antithrombotic, antiinflammatory and antioxidant effects, improvement of endothelial function, and delayed atherosclerosis development have received an increased interest in recent years. Some of these actions are also ascribable to high-density lipoproteins (HDL). Abundant epidemiological evidence links increasing HDL-cholesterol concentrations to cardiovascular protection. Recently, the protein cargo (proteome) of HDL particles has been attributed a key role in their functionality. In this review, we summarize the main effects of ω-3 PUFAs on HDL-cholesterol, HDL subfractions, and its main proteins, apolipoproteins (apo) AI and AII. The shared cardioprotective actions of ω-3 PUFAs and HDL are reviewed as well.

  12. Valproic Acid Limits Pancreatic Recovery after Pancreatitis by Inhibiting Histone Deacetylases and Preventing Acinar Redifferentiation Programs

    PubMed Central

    Eisses, John F.; Criscimanna, Angela; Dionise, Zachary R.; Orabi, Abrahim I.; Javed, Tanveer A.; Sarwar, Sheharyar; Jin, Shunqian; Zhou, Lili; Singh, Sucha; Poddar, Minakshi; Davis, Amy W.; Tosun, Akif Burak; Ozolek, John A.; Lowe, Mark E.; Monga, Satdarshan P.; Rohde, Gustavo K.; Esni, Farzad; Husain, Sohail Z.

    2016-01-01

    The mechanisms by which drugs induce pancreatitis are unknown. A definite cause of pancreatitis is due to the antiepileptic drug valproic acid (VPA). On the basis of three crucial observations—that VPA inhibits histone deacetylases (HDACs), HDACs mediate pancreas development, and aspects of pancreas development are recapitulated during recovery of the pancreas after injury—we hypothesized that VPA does not cause injury on its own, but it predisposes patients to pancreatitis by inhibiting HDACs and provoking an imbalance in pancreatic recovery. In an experimental model of pancreatic injury, we found that VPA delayed recovery of the pancreas and reduced acinar cell proliferation. In addition, pancreatic expression of class I HDACs (which are the primary VPA targets) increased in the midphase of pancreatic recovery. VPA administration inhibited pancreatic HDAC activity and led to the persistence of acinar-to-ductal metaplastic complexes, with prolonged Sox9 expression and sustained β-catenin nuclear activation, findings that characterize a delay in regenerative reprogramming. These effects were not observed with valpromide, an analog of VPA that lacks HDAC inhibition. This is the first report, to our knowledge, that VPA shifts the balance toward pancreatic injury and pancreatitis through HDAC inhibition. The work also identifies a new paradigm for therapies that could exploit epigenetic reprogramming to enhance pancreatic recovery and disorders of pancreatic injury. PMID:26476347

  13. Enzyme responsive hyaluronic acid nanocapsules containing polyhexanide and their exposure to bacteria to prevent infection.

    PubMed

    Baier, Grit; Cavallaro, Alex; Vasilev, Krasimir; Mailänder, Volker; Musyanovych, Anna; Landfester, Katharina

    2013-04-08

    Antibacterial nanodevices could bring coatings of plastic materials and wound dressings a big step forward if the release of the antibacterial agents could be triggered by the presence of the bacteria themselves. Here, we show that novel hyaluronic acid (HA)-based nanocapsules containing the antimicrobial agent polyhexanide are specifically cleaved in the presence of hyaluronidase, a factor of pathogenicity and invasion for bacteria like Staphylococcus aureus and Escherichia coli. This resulted in an efficient killing of the pathogenic bacteria by the antimicrobial agent. The formation of different polymeric nanocapsules was achieved through a polyaddition reaction in inverse miniemulsion. After the synthesis, the nanocapsules were transferred to an aqueous medium and investigated in terms of size, size distribution, functionality, and morphology using dynamic light scattering, zeta potential measurements and scanning electron microscopy. The enzyme triggered release of a model dye and the antimicrobial polyhexanide was monitored using fluorescence and UV spectroscopy. The stability of the nanocapsules in several biological media was tested and the interaction of nanocapsules with human serum protein was studied using isothermal titration calorimetry. The antibacterial effectiveness is demonstrated by determination of the antibacterial activity and determination of the minimal bactericidal concentration (MBC).

  14. Tauroursodeoxycholic acid prevents E22Q Alzheimer’s Aβ toxicity in human cerebral endothelial cells

    PubMed Central

    Viana, R. J. S.; Nunes, A. F.; Castro, R. E.; Ramalho, R. M.; Meyerson, J.; Fossati, S.; Ghiso, J.; Rostagno, A.

    2009-01-01

    The vasculotropic E22Q mutant of the amyloid-β (Aβ) peptide is associated with hereditary cerebral hemorrhage with amyloidosis Dutch type. The cellular mechanism(s) of toxicity and nature of the AβE22Q toxic assemblies are not completely understood. Comparative assessment of structural parameters and cell death mechanisms elicited in primary human cerebral endothelial cells by AβE22Q and wild-type Aβ revealed that only AβE22Q triggered the Bax mitochondrial pathway of apoptosis. AβE22Q neither matched the fast oligomerization kinetics of Aβ42 nor reached its predominant β-sheet structure, achieving a modest degree of oligomerization with a secondary structure that remained a mixture of β and random conformations. The endogenous molecule tauroursodeoxycholic acid (TUDCA) was a strong modulator of AβE22Q-triggered apoptosis but did not significantly change the secondary structures and fibrillogenic propensities of Aβ peptides. These data dissociate the pro-apoptotic properties of Aβ peptides from their distinct mechanisms of aggregation/fibrillization in vitro, providing new perspectives for modulation of amyloid toxicity. PMID:19189048

  15. Prevention of valproic acid-induced neural tube defects by sildenafil citrate.

    PubMed

    Tiboni, Gian Mario; Ponzano, Adalisa

    2015-08-15

    This study was undertaken to test the effects of sildenafil citrate (SC), a type 5 phosphodiesterase inhibitor, on valproic acid (VPA)-induced teratogenesis. On gestation day (GD) 8, ICR (CD-1) mice were treated by gastric intubation with SC at 0 (vehicle), 1.0, 2.5, 5.0 or 10mg/kg. One hour later, animals received a teratogenic dose of VPA (600mg/kg) or vehicle. Developmental endpoints were evaluated near the end of gestation. Twenty-eighth percent of fetuses exposed to VPA had neural tube defects (exencephaly). Pretreatment with SC at 2.5, 5.0 or 10mg/kg significantly reduced the rate of VPA-induced exencephaly to 15.9%, 13.7%, and 10.0%, respectively. Axial skeletal defects were observed in 75.8% of VPA-exposed fetuses. Pre-treatment with SC at 10mg/kg, but not at lower doses, significantly decreased the rate of skeletally affected fetuses to 61.6%. These results show that SC, which prolongs nitric oxide (NO) signaling action protects from VPA-induced teratogenesis.

  16. Intraperitoneal administration of butyrate prevents the severity of acetic acid colitis in rats

    PubMed Central

    Malago, Joshua J.; Sangu, Catherine L.

    2015-01-01

    Intrarectal infusion of butyrate improves colorectal disorders including ulcerative colitis (UC). However, it is not established whether systemically administered butyrate benefits such patients. The current study aimed at exploring and comparing the potential of intraperitoneally, intrarectally, and orally administered butyrate against acetic acid (AA)-induced UC in rats. Intrarectal administration of 2 ml of 50% AA was done after or without prior treatment of rats for 7 consecutive days with 100 mg/kg sodium butyrate (SB) intraperitoneally, intrarectally, or orally. Rats were sacrificed after 48 h of AA-treatment. Subsequently, colon sections were processed routinely for histopathological examination. We clinically observed diarrhea, loose stools, and hemoccult-positive stools, and histologically, epithelial loss and ulceration, crypt damage, goblet cell depletion, hemorrhage, and mucosal infiltration of inflammatory cells. The changes were significantly reduced by intraperitoneal, intrarectal, or oral butyrate, with intraperitoneal butyrate exhibiting the highest potency. It is concluded that intraperitoneal administration of butyrate abrogates the lesions of AA-induced UC and its potency surpasses that of intrarectal or oral butyrate. PMID:25743124

  17. Glycyrrhizic Acid Prevents Sepsis-Induced Acute Lung Injury and Mortality in Rats

    PubMed Central

    Zhao, Hongyu; Zhao, Min; Wang, Yu; Li, Fengchun; Zhang, Zhigang

    2015-01-01

    Glycyrrhizic acid (GA), an active ingredient in licorice, has multiple pharmacological activities. However, the effects of GA on sepsis-induced acute lung injury (ALI) have not been determined. Tthe aim of this study was to investigate the molecular mechanism involved in the effects of GA against sepsis-induced ALI in rats. We found that GA alleviated sepsis-induced ALI through improvements in various pathological changes, as well as decreases in the lung wet/dry weight ratio and total protein content in bronchoalveolar lavage fluid, and a significant increase in the survival rate of treated rats. Additionally, GA markedly inhibited sepsis-induced pulmonary inflammatory responses. Moreover, we found that treatment with GA inhibited oxidative stress damage and apoptosis in lung tissue induced by ALI. Finally, GA treatment significantly inhibited NF-κ B, JNK and P38 MAPK activation. Our data indicate that GA has a protective effect against sepsis-induced ALI by inhibiting the inflammatory response, damage from oxidative stress, and apoptosis via inactivation of NF-κB and MAPK signaling pathways, providing a molecular basis for a new medical treatment for sepsis-induced ALI. PMID:26385569

  18. Common congenital anomalies: Environmental causes and prevention with folic acid containing multivitamins.

    PubMed

    Sarmah, Swapnalee; Muralidharan, Pooja; Marrs, James A

    2016-09-01

    Congenital anomalies, congenital defects, or birth defects are significant causes of death in infants. The most common congenital defects are congenital heart defects (CHDs) and neural tube defects (NTDs). Defects induced by genetic mutations, environmental exposure to toxins, or a combination of these effects can result in congenital malformations, leading to infant death or long-term disabilities. These defects produce significant mortality and morbidity in the affected individuals, and families are affected emotional and financially. Also, society is impacted on many levels. Congenital anomalies may be reduced by dietary supplements of folic acid and other vitamins. Here, we review the evidence for specific roles of toxins (alcohol, cigarette smoke) in causing common severe congenital anomalies like CHDs, NTDs, and ocular defects. We also review the evidence for beneficial effects for dietary supplementation, and highlight gaps in our knowledge, where research may contribute to additional benefits of intervention that can reduce birth defects. Extensive discussion of common severe congenital anomalies (CHDs, NTDs, and ocular defects) illustrates the effects of diet on the frequency and severity of these defects. Birth Defects Research (Part C) 108:274-286, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Valproic Acid Limits Pancreatic Recovery after Pancreatitis by Inhibiting Histone Deacetylases and Preventing Acinar Redifferentiation Programs.

    PubMed

    Eisses, John F; Criscimanna, Angela; Dionise, Zachary R; Orabi, Abrahim I; Javed, Tanveer A; Sarwar, Sheharyar; Jin, Shunqian; Zhou, Lili; Singh, Sucha; Poddar, Minakshi; Davis, Amy W; Tosun, Akif Burak; Ozolek, John A; Lowe, Mark E; Monga, Satdarshan P; Rohde, Gustavo K; Esni, Farzad; Husain, Sohail Z

    2015-12-01

    The mechanisms by which drugs induce pancreatitis are unknown. A definite cause of pancreatitis is due to the antiepileptic drug valproic acid (VPA). On the basis of three crucial observations-that VPA inhibits histone deacetylases (HDACs), HDACs mediate pancreas development, and aspects of pancreas development are recapitulated during recovery of the pancreas after injury-we hypothesized that VPA does not cause injury on its own, but it predisposes patients to pancreatitis by inhibiting HDACs and provoking an imbalance in pancreatic recovery. In an experimental model of pancreatic injury, we found that VPA delayed recovery of the pancreas and reduced acinar cell proliferation. In addition, pancreatic expression of class I HDACs (which are the primary VPA targets) increased in the midphase of pancreatic recovery. VPA administration inhibited pancreatic HDAC activity and led to the persistence of acinar-to-ductal metaplastic complexes, with prolonged Sox9 expression and sustained β-catenin nuclear activation, findings that characterize a delay in regenerative reprogramming. These effects were not observed with valpromide, an analog of VPA that lacks HDAC inhibition. This is the first report, to our knowledge, that VPA shifts the balance toward pancreatic injury and pancreatitis through HDAC inhibition. The work also identifies a new paradigm for therapies that could exploit epigenetic reprogramming to enhance pancreatic recovery and disorders of pancreatic injury.

  20. Glycyrrhizic Acid Prevents Sepsis-Induced Acute Lung Injury and Mortality in Rats.

    PubMed

    Zhao, Hongyu; Zhao, Min; Wang, Yu; Li, Fengchun; Zhang, Zhigang

    2016-02-01

    Glycyrrhizic acid (GA), an active ingredient in licorice, has multiple pharmacological activities. However, the effects of GA on sepsis-induced acute lung injury (ALI) have not been determined. Tthe aim of this study was to investigate the molecular mechanism involved in the effects of GA against sepsis-induced ALI in rats. We found that GA alleviated sepsis-induced ALI through improvements in various pathological changes, as well as decreases in the lung wet/dry weight ratio and total protein content in bronchoalveolar lavage fluid, and a significant increase in the survival rate of treated rats. Additionally, GA markedly inhibited sepsis-induced pulmonary inflammatory responses. Moreover, we found that treatment with GA inhibited oxidative stress damage and apoptosis in lung tissue induced by ALI. Finally, GA treatment significantly inhibited NF-κ B, JNK and P38 MAPK activation. Our data indicate that GA has a protective effect against sepsis-induced ALI by inhibiting the inflammatory response, damage from oxidative stress, and apoptosis via inactivation of NF-κB and MAPK signaling pathways, providing a molecular basis for a new medical treatment for sepsis-induced ALI.

  1. Fusarium Head Blight Control and Prevention of Mycotoxin Contamination in Wheat with Botanicals and Tannic Acid

    PubMed Central

    Forrer, Hans-Rudolf; Musa, Tomke; Schwab, Fabienne; Jenny, Eveline; Bucheli, Thomas D.; Wettstein, Felix E.; Vogelgsang, Susanne

    2014-01-01

    Suspensions or solutions with 1% of Chinese galls (Galla chinensis, GC) or 1% of tannic acid (TA), inhibited germination of conidia or mycelium growth of Fusarium graminearum (FG) by 98%–100% or by 75%–80%, respectively, whereas dried bark from buckthorn (Frangula alnus, FA) showed no effect at this concentration. In climate chamber experiments where the wheat variety “Apogee” was artificially inoculated with FG and F. crookwellense (FCr) and treated with 5% suspensions of TA, GC and FA, the deoxynivalenol (DON) content in grains was reduced by 81%, 67% and 33%, respectively. In field experiments with two commercial wheat varieties and artificial or semi-natural inoculations, mean DON reductions of 66% (TA) and 58% (FA), respectively, were obtained. Antifungal toxicity can explain the high efficacies of TA and GC but not those of FA. The Fusarium head blight (FHB) and mycotoxin reducing effect of FA is probably due to elicitation of resistance in wheat plants. With semi-natural inoculation, a single FA application in the first half of the flowering period performed best. However, we assume that applications of FA at the end of ear emergence and a treatment, triggered by an infection period, with TA or GC during flowering, might perform better than synthetic fungicides. PMID:24577585

  2. Fusarium head blight control and prevention of mycotoxin contamination in wheat with botanicals and tannic acid.

    PubMed

    Forrer, Hans-Rudolf; Musa, Tomke; Schwab, Fabienne; Jenny, Eveline; Bucheli, Thomas D; Wettstein, Felix E; Vogelgsang, Susanne

    2014-02-26

    Suspensions or solutions with 1% of Chinese galls (Galla chinensis, GC) or 1% of tannic acid (TA), inhibited germination of conidia or mycelium growth of Fusarium graminearum (FG) by 98%-100% or by 75%-80%, respectively, whereas dried bark from buckthorn (Frangula alnus, FA) showed no effect at this concentration. In climate chamber experiments where the wheat variety "Apogee" was artificially inoculated with FG and F. crookwellense (FCr) and treated with 5% suspensions of TA, GC and FA, the deoxynivalenol (DON) content in grains was reduced by 81%, 67% and 33%, respectively. In field experiments with two commercial wheat varieties and artificial or semi-natural inoculations, mean DON reductions of 66% (TA) and 58% (FA), respectively, were obtained. Antifungal toxicity can explain the high efficacies of TA and GC but not those of FA. The Fusarium head blight (FHB) and mycotoxin reducing effect of FA is probably due to elicitation of resistance in wheat plants. With semi-natural inoculation, a single FA application in the first half of the flowering period performed best. However, we assume that applications of FA at the end of ear emergence and a treatment, triggered by an infection period, with TA or GC during flowering, might perform better than synthetic fungicides.

  3. Should acetylsalicylic acid (ASA) therapy for prevention of thromboembolic events be stopped prior to surgical extractions?

    PubMed

    Dodson, Tom

    2012-01-01

    Randomised controlled trial. Patients with coronary artery disease who were receiving 100 mg/day of ASA for the prevention of thromboembolic events, and requiring at least one molar tooth extracted were randomised to either having their ASA therapy suspended for seven days before tooth extraction and restarted the day following the surgical procedure or not having their ASA therapy suspended at any point before or after the procedure. A single dentist who was unaware of the patients' ASA therapy status performed all the extractions. Outcomes were a platelet aggregation test carried out on the day of the operation and the amount of bleeding measured during the intra-operative period. Bleeding was controlled with local haemostatic methods and there were no reported episodes of haemorrhaging during the intra- and post-operative periods. The mean (±SD) volume of bleeding was 12.10 ±9.37 mL for patients who underwent ASA therapy suspension and 16.38±13.54 mL for those patients whose treatments were unaltered (P= .151). The platelet reactivity index values exhibited statistically significant differences between the two investigated groups (P= .004). The platelet reactivity index values for the group with ASA therapy suspended was 242.58 ± 71.26 compared with 192.09 ± 60.54 in the group that continued with ASA. There was no difference in the amount of bleeding that occurred during tooth extraction between patients who continued ASA therapy and patients who suspended their ASA therapy. The platelet reactivity test demonstrated a reduction in platelet aggregation in the ASA therapy group, but this was without clinical consequence.

  4. [Cost-effectiveness analysis of prevention of reinfarction using low-dose acetylsalicylic acid; model calculation].

    PubMed

    Schädlich, P K; Brecht, J G

    1997-01-01

    The purpose of this study is to estimate the potential of savings which can be achieved by prophylaxis of myocardial reinfarction with low-dose acetylsalicylic acid (ASA) at 75 mg per day over a treatment period of two years. After secondary analysis of published data, the effectiveness of low-dose ASA is compared to placebo by a model calculation. The difference in the effectiveness between the prophylaxis with ASA and placebo is taken from an international meta-analysis. The economic valuation of this difference is carried out by a cost-effectiveness analysis applying disease costs per case. According to the model calculation, 5535 DM can be saved per patient with a history of myocardial infarction with 75 mg ASA a day over a treatment period of two years. In 1991 there were around 740,000 patients with a history of myocardial infarction in the age group of 25-64 in the Old Bundesländer of the Federal Republic of Germany. The application of the results of the model calculation would lead to considerable savings. Even in the sensitivity analysis with different assumptions regarding costs incurred by hospital treatment and costs incurred by premature retirement, the cost advantage of the ASA-prophylaxis remains. Due to the cautious and conservative assumptions in the model calculation the potential of savings is likely underestimated. Nevertheless, there is a distinct advantage for the prophylaxis with low-dose ASA which already occurs in direct costs thus leading to advantages also for cost carriers.

  5. Preventive effect of ursodeoxycholic acid on parenteral nutrition-associated liver disease in infants.

    PubMed

    Simić, Dusica; Milojević, Irina; Bogićević, Dragana; Milenović, Miodrag; Radlović, Vladimir; Drasković, Biljana; Benka, Anna Uram; Sindjić, Sanja; Maksimović, Ruzica

    2014-01-01

    Parenteral nutrition-associated cholestasis is well recognized phenomenon in the term and preterm infant receiving long-term parenteral nutrition. The aim of this study was to evaluate the effect of ursodeoxycholic acid (UDCA) use on cholestasis in newborns on prolonged TPN. A total of 56 infants were enrolled in this retrospective study: control group consisted of lower (1500 g) birth weight infants (n = 30), as well as the group of pediatric (n = 11) and surgical patients (n = 15) treated with UDCA. Blood chemistries were obtained two times weekly. All of 56 newborns developed cholestasis but duration of parenteral nutrition (PN) before onset of cholestasis was significantly longer in UDCA treated patients. Average duration of PN before the onset of cholestasis in control group of patients was 25 days in distinction from treated pediatric and surgical patients (39 and 34 days, respectively).The peak serum conjugated bilirubin (CB), AST, ALT and alkaline phosphatase (AP) levels were significantly lower in the treated groups.There was no significant difference among treated pediatric and surgical patients and between lower and higher birth weight infants considering the CB, ALT, AST and AP peak. Duration of cholestasis was significantly decreased in all treated groups.There was a significant difference in time needed to achieve complete enteral intake between pediatric and surgical patient group. Cholestasis developed significantly later in treated groups than in the controls. UDCA appears to be very successful in reducing the symptoms of cholestasis. The difference in efficacy of UDCA treatment between lower and higher birth weight infants could not be proven.

  6. Stearidonic acid: is there a role in the prevention and management of type 2 diabetes mellitus?

    PubMed

    Banz, William J; Davis, Jeremy E; Clough, Richard W; Cheatwood, Joseph L

    2012-03-01

    Obesity and its related comorbidities are major public health concerns in the United States with over two-thirds of adults and one-third of children classified as overweight or obese. The prevalence of type 2 diabetes mellitus (T2DM) has similarly risen to an estimated 25.8 million, which accounts for a staggering $174 billion in annual healthcare costs. Identification of dietary interventions that protect against the development of T2DM would markedly reduce the medical and economic consequences of the disease. Hence, we review current evidence supporting a role of (n-3) PUFA in T2DM and explore potential therapeutic implications of stearidonic acid (SDA). The low consumption of fish in the US along with a reduced efficiency to interconvert most plant (n-3) PUFA highlights a need to find alternative sources of (n-3) PUFA. The efficient biological conversion of SDA to EPA underscores the potential implications of SDA as a source of (n-3) PUFA. The full therapeutic efficacy of SDA remains to be further determined. However, recent data have suggested a protective role of SDA consumption on markers of dyslipidemia and inflammation. The AHA recommends that healthy individuals consume oily fish at least twice per week and individuals with a history of cardiovascular disease consume 1 g of EPA+DHA/d. These goals will likely not be met by the typical American diet. Therefore, SDA may represent a sustainable alternative to marine-based (n-3) PUFA and may have novel therapeutic efficacy regarding the development of T2DM.

  7. Pseudolaric acid B activates autophagy in MCF-7 human breast cancer cells to prevent cell death

    PubMed Central

    YU, JINGHUA; CHEN, CHUNHAI; XU, TIANYANG; YAN, MINGHUI; XUE, BIANBIAN; WANG, YING; LIU, CHUNYU; ZHONG, TING; WANG, ZENGYAN; MENG, XIANYING; HU, DONGHUA; YU, XIAOFANG

    2016-01-01

    Pseudolaric acid B (PAB) has been demonstrated to exert antitumor effects in MCF-7 human breast cancer cells. The present study aimed to investigate the mechanism of resistance to PAB-induced cell death. Following incubation with 4 µM of PAB for 3 days, the majority of MCF-7 cells became senescent, while some retained the same morphology as control cells, as assessed using a senescence detection kit. Additionally, 36 h of treatment with 4 µM of PAB increased the positive staining of autophagy markers, as shown by monodansylcadaverine and acridine orange staining. Western blot analysis indicated that this treatment also increased expression of the autophagy-related proteins Beclin-1 and microtubule-associated protein 1 light chain 3. Furthermore, treatment with PAB and the autophagy inhibitor 3-methyl adenine significantly decreased the ratio of autophagy, as assessed by flow cytometric analysis of monodansylcadaverine staining density (P<0.001), and increased the ratio of cell death, as assessed by MTT analysis (P<0.001). This indicated that autophagy promotes cell survival as a resistance mechanism to PAB treatment. Additionally, the present study demonstrated that PAB treatment did not affect the mitochondrial membrane potential, which may be related to autophagy. Increased Bcl-2 expression may explain why PAB did not affect the mitochondrial membrane potential. A Bcl-2 binding test demonstrated that PAB treatment inhibits the binding of Bcl-2 and Beclin-1, which may free Beclin-1 to participate in autophagy. Therefore, the present study demonstrated that autophagy may be activated by PAB treatment in human breast cancer MCF-7 cells, contributing to resistance to cell death. PMID:26998069

  8. Pseudolaric acid B activates autophagy in MCF-7 human breast cancer cells to prevent cell death.

    PubMed

    Yu, Jinghua; Chen, Chunhai; Xu, Tianyang; Yan, Minghui; Xue, Bianbian; Wang, Ying; Liu, Chunyu; Zhong, Ting; Wang, Zengyan; Meng, Xianying; Hu, Donghua; Yu, Xiaofang

    2016-03-01

    Pseudolaric acid B (PAB) has been demonstrated to exert antitumor effects in MCF-7 human breast cancer cells. The present study aimed to investigate the mechanism of resistance to PAB-induced cell death. Following incubation with 4 µM of PAB for 3 days, the majority of MCF-7 cells became senescent, while some retained the same morphology as control cells, as assessed using a senescence detection kit. Additionally, 36 h of treatment with 4 µM of PAB increased the positive staining of autophagy markers, as shown by monodansylcadaverine and acridine orange staining. Western blot analysis indicated that this treatment also increased expression of the autophagy-related proteins Beclin-1 and microtubule-associated protein 1 light chain 3. Furthermore, treatment with PAB and the autophagy inhibitor 3-methyl adenine significantly decreased the ratio of autophagy, as assessed by flow cytometric analysis of monodansylcadaverine staining density (P<0.001), and increased the ratio of cell death, as assessed by MTT analysis (P<0.001). This indicated that autophagy promotes cell survival as a resistance mechanism to PAB treatment. Additionally, the present study demonstrated that PAB treatment did not affect the mitochondrial membrane potential, which may be related to autophagy. Increased Bcl-2 expression may explain why PAB did not affect the mitochondrial membrane potential. A Bcl-2 binding test demonstrated that PAB treatment inhibits the binding of Bcl-2 and Beclin-1, which may free Beclin-1 to participate in autophagy. Therefore, the present study demonstrated that autophagy may be activated by PAB treatment in human breast cancer MCF-7 cells, contributing to resistance to cell death.

  9. Role of hepatic transporters in prevention of bile acid toxicity after partial hepatectomy in mice

    PubMed Central

    Csanaky, Iván L.; Aleksunes, Lauren M.; Tanaka, Yuji; Klaassen, Curtis D.

    2009-01-01

    The enterohepatic recirculation of bile acids (BAs) is important in several physiological processes. Although there has been considerable research on liver regeneration after two-thirds partial hepatectomy (PHx), little is known about how the liver protects itself against BA toxicity during regeneration. In this study, various BAs in plasma and liver, the composition of micelle-forming bile constituents, as well as gene expression of the main hepatobiliary transporters were quantified in sham-operated and PHx mice 24 and 48 h after surgery. PHx did not influence the hepatic concentrations of taurine-conjugated BAs (T-BA) but increased the concentration of glycine-conjugated (G-BA) and unconjugated BAs. Total BA excretion (μg·min−1·g liver wt−1) increased 2.4-fold and was accompanied by a 55% increase in bile flow after PHx. The plasma concentrations of T-BAs (402-fold), G-BAs (17-fold), and unconjugated BAs (500-fold) increased. The mRNA and protein levels of the BA uptake transporter Ntcp were unchanged after PHx, whereas the canalicular Bsep protein increased twofold at 48 h. The basolateral efflux transporter Mrp3 was induced at the mRNA (2.6-fold) and protein (3.1-fold) levels after PHx, which may contribute to elevated plasma BA and bilirubin levels. Biliary phospholipid excretion was nearly doubled in PHx mice, most likely owing to increased mRNA expression of the phospholipid transporter, Mdr2. In conclusion, the remnant liver after PHx excretes 2.5-fold more BAs and three times more phospholipids per gram liver than the sham-operated mouse liver. Upregulation of phospholipid transport may be important in protecting the biliary tract from BA toxicity during PHx. PMID:19497955

  10. Dietary Conjugated Linoleic Acid-c9t11 Prevents Collagen-Induced Arthritis, Whereas Conjugated Linoleic Acid-t10c12 Increases Arthritic Severity.

    PubMed

    Muhlenbeck, Jessica A; Butz, Daniel E; Olson, Jake M; Uribe-Cano, Daniela; Cook, Mark E

    2017-04-01

    Two conjugated linoleic acid (CLA) isomers, cis-9, trans-11 (CLAc9t11) and trans-10, cis-12 (CLAt10c12), reduce inflammation in a number of animal models, including collagen-induced arthritis (CA). However, little is known about the ability of individual CLA isomers to prevent autoimmune disease onset. Evidence that mixed isomer CLA drives T helper cell (Th) 1 responses suggests that CLA, or a specific isomer, exacerbates onset of Th1 autoimmune diseases. In two experiments, we examined if prior dietary exposure to CLAt10c12 (experiment 1) or CLAc9t11 (experiment 2) affected the incidence or severity of CA. DBA/1 mice were fed a semi purified diet with either 6% corn oil (CO, w/w), 5.75% CO plus 0.25% CLAt10c12, or 5.5% CO plus 0.5% CLAc9t11 prior to arthritis development. Arthritis incidence and severity, anti-collagen antibodies, paw cytokines, and hepatic fatty acids were measured. CLAt10c12 had no effect on arthritis incidence but increased arthritic severity (42%, P = 0.02); however, CLAc9t11 decreased arthritis incidence 39% compared to CO fed mice (P = 0.01), but had no effect on disease severity. CLAt10c12-induced increase in anti-collagen type II IgG antibodies may be a mechanism by which this isomer increased arthritic severity, and CLAc9t11-induced increase in Th2 paw cytokines (IL-4 and IL-10, P ≤ 0.04) may explain how CLAc9t11 reduced the arthritis incidence. While both isomers are well known to reduce inflammation in arthritic mice, these new data suggest isomer differences when fed prior to autoimmune disease.

  11. Minodronic acid (ONO-5920/YM529) prevents decrease in bone mineral density and bone strength, and improves bone microarchitecture in ovariectomized cynomolgus monkeys.

    PubMed

    Mori, Hiroshi; Tanaka, Makoto; Kayasuga, Ryoji; Masuda, Taisei; Ochi, Yasuo; Yamada, Hiroyuki; Kishikawa, Katsuya; Ito, Masako; Nakamura, Toshitaka

    2008-11-01

    This study examined the effect of the highly potent nitrogen-containing bisphosphonate, minodronic acid (ONO-5920/YM529), on bone mineral density (BMD), bone turnover, bone microarchitecture and bone strength in ovariectomized (OVX) cynomolgus monkeys. Skeletally mature female cynomolgus monkeys, aged 9-17 years, were ovariectomized or sham-operated. Minodronic acid was administered orally once a day in doses of 0, 0.015, and 0.15 mg/kg from the day after surgery for 17 months. Bone resorption markers (urinary N-terminal cross-linking telopeptide of type I collagen and deoxypyridinoline), bone formation markers (serum osteocalcin and bone alkaline phosphatase) and lumbar vertebral BMD were measured at baseline and at 4, 8, 12 and 16 months after surgery. Treatment with minodronic acid dose-dependently inhibited OVX-induced increase in bone turnover markers and decrease in lumbar vertebral BMD, and minodronic acid at 0.15 mg/kg completely prevented these changes. At 17 months after surgery, minodronic acid also suppressed bone resorption (Oc.S/BS and N.Oc/BS) and bone formation (OS/BS, MS/BS, MAR, BFR/BS, and BFR/BV) in the lumbar vertebral bodies and tibia. In the mechanical tests, ultimate load on lumbar vertebral bodies and femoral neck of the OVX-control animals were significantly reduced compared to the sham animals. Minodronic acid prevented these reductions in bone strength at 0.15 mg/kg. There was significant correlation between BMD and bone strength, suggesting that the increase in bone strength was associated with the increase in BMD produced by minodronic acid. In micro-CT analysis of the lumbar vertebral bodies, minodronic acid improved trabecular architecture, converting rod structures into plate structures, and preventing the increase in trabecular disconnectivity at 0.15 mg/kg. In conclusion, similar to patients with postmenopausal osteoporosis, reduction in bone strength of lumbar vertebral bodies and femoral neck was clearly demonstrated in OVX

  12. [Prevention of neural tube defects: prevalence of folic acid supplementation during pregnancy and associated factors in Pelotas, Rio Grande do Sul State, Brazil].

    PubMed

    Mezzomo, Cíntia Leal Sclowitz; Garcias, Gilberto de Lima; Sclowitz, Marcelo Leal; Sclowitz, Iandora Timm; Brum, Clarice Brinck; Fontana, Tiago; Unfried, Ricardo Issler

    2007-11-01

    To determine folic acid use and associated factors, a cross-sectional population-based study was conducted in all five maternity hospitals in Pelotas, Rio Grande do Sul State, Brazil. Data were collected from April 1 to August 15, 2006 (n = 1,450 women). A standard questionnaire was applied in the hospitals. Statistical analysis used Poisson regression. Prevalence of folic acid consumption during pregnancy was 31.8%, and periconceptional use was 4.3%. The following were associated with folic acid use: white skin color, schooling > 9 years, family income > R$600, age > 30 years, planned pregnancy, > or =7 prenatal visits, knowledge on folic acid, and prenatal care in the private health system. In order to prevent neural tube defects, it is important to promote folic acid use among childbearing-age women and to supply folic acid to poor women.

  13. Omega 3 fatty acids for prevention and treatment of cardiovascular disease

    PubMed Central

    Hooper, Lee; Harrison, Roger A; Summerbell, Carolyn D; Moore, Helen; Worthington, Helen V; Ness, Andrew; Capps, Nigel; Smith, George Davey; Riemersma, Rudolph; Ebrahim, Shah

    2014-01-01

    Background It has been suggested that omega 3 (W3, n-3 or omega-3) fats from oily fish and plants are beneficial to health. Objectives To assess whether dietary or supplemental omega 3 fatty acids alter total mortality, cardiovascular events or cancers using both RCT and cohort studies. Search methods Five databases including CENTRAL, MEDLINE and EMBASE were searched to February 2002. No language restrictions were applied. Bibliographies were checked and authors contacted. Selection criteria RCTs were included where omega 3 intake or advice was randomly allocated and unconfounded, and study duration was at least six months. Cohorts were included where a cohort was followed up for at least six months and omega 3 intake estimated. Data collection and analysis Studies were assessed for inclusion, data extracted and quality assessed independently in duplicate. Random effects meta-analysis was performed separately for RCT and cohort data. Main results Forty eight randomised controlled trials (36,913 participants) and 41 cohort analyses were included. Pooled trial results did not show a reduction in the risk of total mortality or combined cardiovascular events in those taking additional omega 3 fats (with significant statistical heterogeneity). Sensitivity analysis, retaining only studies at low risk of bias, reduced heterogeneity and again suggested no significant effect of omega 3 fats. Restricting analysis to trials increasing fish-based omega 3 fats, or those increasing short chain omega 3s, did not suggest significant effects on mortality or cardiovascular events in either group. Subgroup analysis by dietary advice or supplementation, baseline risk of CVD or omega 3 dose suggested no clear effects of these factors on primary outcomes. Neither RCTs nor cohorts suggested increased relative risk of cancers with higher omega 3 intake but estimates were imprecise so a clinically important effect could not be excluded. Authors’ conclusions It is not clear that dietary

  14. Is prophylactic tranexamic acid administration effective and safe for postpartum hemorrhage prevention?

    PubMed Central

    Li, Chunbo; Gong, Yuping; Dong, Lingling; Xie, Bingying; Dai, Zhiyuan

    2017-01-01

    Abstract Background: To assess the efficacy and safety of tranexamic acid (TA) in reducing blood loss and lowering transfusion needs for patients undergoing caesarean section (CS) or vaginal delivery (VD). Methods: An electronic literature search of PubMed, EMBASE, OVID, Cochrane library, Scopus, Central, and Clinical trials.gov was performed to identify studies that evaluating the usage of TA in CS or VD. The methodological quality of included trials was assessed and data extraction was performed. Results: Finally, 25 articles with 4747 participants were included. Our findings indicated TA resulted in a reduced intra-, postoperative, and total blood loss by a mean volume of 141.25 mL (95% confidence interval [CI] −186.72 to −95.79, P < 0.00001), 36.42 mL (95% CI −46.50 to −26.34, P < 0.00001), and 154.25 mL (95% CI −182.04 to −126.47, P < 0.00001) in CS. TA administration in VD was associated with a reduced intra-, postoperative, and total blood loss by a mean volume of 22.88 mL (95% CI −50.54 to 4.77, P = 0.10), 41.24 mL (95% CI −55.50 to −26.98, P < 0.00001), and 84.79 mL (95% CI −109.93 to −59.65, P < 0.00001). In addition, TA could lower the occurrence rate of postpartum hemorrhage (PPH) and severe PPH, and reduce the risk of blood transfusions. No increased risk of deep vein thrombosis (DVT) after CS or VD was associated with TA usage, while the minor side effects were more common. Conclusions: Our findings indicated that intravenous TA for patients undergoing CS was effective and safe. Although prophylactic TA administration is associated with reduced PPH, current existing data are insufficient to draw definitive recommendations about its clinical significance due to the poor to moderate quality of the included literatures. Thus, high-quality randomized controlled trials with larger samples are needed to validate our findings. PMID:28072700

  15. Folic acid usage and associated factors in the prevention of neural tube defects among pregnant women in Ethiopia: cross-sectional study.

    PubMed

    Dessie, Meselech Ambaw; Zeleke, Ejigu Gebeye; Workie, Shimelash Bitew; Berihun, Ayanaw Worku

    2017-09-21

    Neural tube defects are among the most common birth defects, contributing to miscarriage, infant mortality, severe congenital abnormalities and serious disabilities. It is burdensome to patients, caregivers, healthcare systems and society. It could be reduced if women consume a folic acid supplement before and during the early weeks of pregnancy. This study assesses folic acid usage and associated factors for the prevention of neural tube defects among pregnant women in Ethiopia. Institution based cross-sectional study was conducted on 417 systematically sampled, consented pregnant women that visited Adama hospital medical college for antenatal care during August to November 2014. Pretested interviewer administered questionnaire was used to collect socio-demographic, obstetric characteristics and folic acid usage of women. About 48.4% of women took a folic acid supplement at different period of pregnancy; but, only 1.92% of women took the supplement at a protective period against neural tube defects. Age, the early timing of antenatal registration, was a preconception consulted, previous unsuccessful pregnancies and level of folic acid awareness were significantly associated with folic acid usage for prevention of neural tube defects. Folic acid usage during the protective period against neural tube defects among women in Ethiopia is very low, so healthcare plan to improve intake of folic acid is required.

  16. Colanic Acid Intermediates Prevent De Novo Shape Recovery of Escherichia coli Spheroplasts, Calling into Question Biological Roles Previously Attributed to Colanic Acid

    PubMed Central

    Ranjit, Dev K.

    2016-01-01

    ABSTRACT After losing their protective peptidoglycan, bacterial spheroplasts can resynthesize a cell wall to recreate their normal shape. In Escherichia coli, this process requires the Rcs response. In its absence, spheroplasts do not revert to rod shapes but instead form enlarged spheroids and lyse. Here, we investigated the reason for this Rcs requirement. Rcs-deficient spheroids exhibited breaks and bulges in their periplasmic spaces and failed to synthesize a complete peptidoglycan cell wall, indicating that the bacterial envelope was defective. To determine the Rcs-dependent gene(s) required for shape recovery, we tested spheroplasts lacking selected RcsB-regulated genes and found that colanic acid (CA) biosynthesis appeared to be involved. Surprisingly, though, extracellular CA was not required for recovery. Instead, lysis was caused by mutations that interrupted CA biosynthesis downstream of the initial glycosyl transferase, WcaJ. Deleting wcaJ prevented lysis of spheroplasts lacking ensuing steps in the pathway, and providing WcaJ in trans to a mutant lacking the entire CA operon triggered spheroplast enlargement and lysis. Thus, CA is not required for spheroplast recovery. Instead, CA intermediates accumulate as dead-end products which inhibit recovery of wall-less cells. The results strongly imply that CA may not be required for the survival E. coli L-forms. More broadly, these findings mandate that previous conclusions about the role of colanic acid in biofilm formation or virulence must be reevaluated. IMPORTANCE Wall-less bacteria can resynthesize their walls and recreate a normal shape, which in Escherichia coli requires the Rcs response. While attempting to identify the Rcs-dependent gene required for shape recovery, we found that colanic acid (CA) biosynthesis appeared to be involved. Surprisingly, though, cell death was caused by mutations that interrupted CA biosynthesis downstream of the initial step in the pathway, creating dead-end compounds

  17. Glycyrrhizic acid, active component from Glycyrrhizae radix, prevents toxicity of graphene oxide by influencing functions of microRNAs in nematode Caenorhabditis elegans.

    PubMed

    Zhao, Yunli; Jia, Ruhan; Qiao, Yan; Wang, Dayong

    2016-04-01

    We investigated effects of pretreatment with Glycyrrhizae radix (GR) or its specific components on toxicity of graphene oxide (GO) in Caenorhabditis elegans. GR pretreatment prevented GO toxicity on function of both primary and secondary targeted organs. Among active components in GR, the beneficial effects of GR were attributable to presence of glycyrrhizic acid. Glycyrrhizic acid pretreatment suppressed translocation of GO into secondary targeted organs through intestinal barrier. Glycyrrhizic acid pretreatment recovered expression patterns of dysregulated microRNAs (miRNAs) induced by GO, and genes required for oxidative stress control acted as targeted genes for some of these miRNAs. Among these miRNAs, mir-360 mutation enhanced beneficial effects of glycyrrhizic acid. We hypothesize that glycyrrhizic acid may prevent GO toxicity and translocation by influencing functions of miRNAs which upstream regulate functions of their targeted genes. Furthermore, glycyrrhizic acid had potential to extend lifespan, and to suppress accelerated aging process induced by GO. Exposure to graphene oxide may pose toxic effects to health, as suggested in animal studies. In this article, the authors showed that the use of glycyrrhizae radix (GR) prevented toxicity of graphene oxide in Caenorhabditis elegans. These results may provide novel strategies in the reducing potential side effects of nanoparticles. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

    PubMed

    Roy, Abhro Jyoti; Stanely Mainzen Prince, P

    2013-10-01

    The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats.

  19. Prevention of Acid Mine Drainage Through Complexation of Ferric Iron by Soluble Microbial Growth Products

    NASA Astrophysics Data System (ADS)

    Pandey, S.; Yacob, T. W.; Silverstein, J.; Rajaram, H.; Minchow, K.; Basta, J.

    2011-12-01

    Acid mine drainage (AMD) is a widespread environmental problem with deleterious impacts on water quality in streams and watersheds. AMD is generated largely by the oxidation of metal sulfides (i.e. pyrite) by ferric iron. This abiotic reaction is catalyzed by conversion of ferrous to ferric iron by iron and sulfur oxidizing microorganisms. Biostimulation is currently being investigated as an attempt to inhibit the oxidation of pyrite and growth of iron oxidizing bacteria through addition of organic carbon. This may stimulate growth of indigenous communities of acidophilic heterotrophic bacteria to compete for oxygen. The goal of this research is to investigate a secondary mechanism associated with carbon addition: complexation of free Fe(III) by soluble microbial growth products (SMPs) produced by microorganisms growing in waste rock. Exploratory research at the laboratory scale examined the effect of soluble microbial products (SMPs) on the kinetics of oxidation of pure pyrite during shaker flask experiments. The results confirmed a decrease in the rate of pyrite oxidation that was dependent upon the concentration of SMPs in solution. We are using these data to verify results from a pyrite oxidation model that accounts for SMPs. This reactor model involves differential-algebraic equations incorporating total component mass balances and mass action laws for equilibrium reactions. Species concentrations determined in each time step are applied to abiotic pyrite oxidation rate expressions from the literature to determine the evolution of total component concentrations. The model was embedded in a parameter estimation algorithm to determine the reactive surface area of pyrite in an abiotic control experiment, yielding an optimized value of 0.0037 m2. The optimized model exhibited similar behavior to the experiment for this case; the root mean squared of residuals for Fe(III) was calculated to be 7.58 x 10-4 M, which is several orders of magnitude less than the actual

  20. Effects of folic acid awareness on knowledge and consumption for the prevention of birth defects among Hispanic women in several U.S. Communities.

    PubMed

    Prue, Christine E; Hamner, Heather C; Flores, Alina L

    2010-04-01

    The neural tube defects (NTDs) anencephaly and spina bifida, are serious birth defects of the brain and spine that affect about 3000 pregnancies per year in the United States. Research has found a strong link between periconceptional folic acid consumption and NTD prevention. Because Hispanic women have higher rates of NTD-affected births, targeted folic acid promotion efforts were conducted in several major cities from 1999 to 2002. Efforts included paid and unpaid placements of Spanish language public service announcements (PSAs) and community-level education through the use of promotoras. Analyses focused on whether or not women's reported awareness of folic acid, regardless of promotion type, impacted their knowledge or behavior. Women who reported awareness of folic acid had greater folic acid knowledge and use of vitamins containing folic acid than those not aware. Analyses also examined the use of vitamins containing folic acid by pregnancy intention among women who reported awareness of folic acid. The results were varied. Pregnancy wanters were most likely to use vitamins containing folic acid daily. For this group, however, awareness did not play as large a role in whether they reported consuming a vitamin containing folic acid or not, as it did for pregnancy waiters and avoiders.

  1. Alteration in inflammatory/apoptotic pathway and histone modifications by nordihydroguaiaretic acid prevents acute pancreatitis in swiss albino mice.

    PubMed

    Mahajan, Ujwal Mukund; Gupta, Chanchal; Wagh, Preshit Ravindra; Karpe, Pinakin Arun; Tikoo, Kulbhushan

    2011-11-01

    Reactive oxygen radicals, pro-inflammatory mediators and cytokines have been implicated in caerulein induced acute pancreatitis. Nordihydroguaiaretic acid (NDGA), a plant lignin, has marked anti-inflammatory properties. The present study aimed to investigate the possible protective effect of NDGA against caerulein induced pancreatitis. Acute pancreatitis was induced by intraperitoneal administration of eight doses of caerulein in male swiss albino mice. NDGA was administered after 9 h of acute pancreatitis induction. Pancreatic damage and the protective effect of NDGA were assessed by oxidative stress parameters and histopathology of pancreas. The mRNA expression of heat shock proteins (DNAJ C15 and HSPD1) was examined by real-time RT-PCR analysis. Expression of HSP 27, NF-κB, TNF-α, p-p38, Bcl-2, p-PP2A, procaspase-3, caspase-3 and histone modifications were examined by western blotting. NDGA attenuated the oxidative stress, led to increased plasma α-amylase and decreased IGF-1 in AP mice. It modulated the mRNA and protein levels of heat shock proteins and reduced the expression of NF-κB, TNF-α and p-p38. It increased the number of TUNEL positive apoptotic cells in the pancreas of AP mice. In addition, NDGA prevented the changes in modifications of histone H3 in acute pancreatitis. To best of our knowledge, this is the first report which suggests that NDGA prevents the progression of acute pancreatitis by involving alteration of histone H3 modifications and modulating the expression of genes involved in inflammatory/apoptotic cascade, which may be responsible for decreased necrosis and increased apoptosis in this model of acute pancreatitis.

  2. [Therapeutic evaluation of the polylactic acid gel (PLA-G) used for preventing skin flap adhesion in modified radical mastectomy].

    PubMed

    Chen, Guojing; Liu, Tao

    2013-12-01

    The present preliminary study was to observe the feasibility of the use of polylactic acid gel (PLA-G) in modified radical mastectomy and the ability of the PLA-G in the prevention of flap adhesion after operation. Sixty-eight patients were diagnosed with breast cancer, and received modified radical mastectomy from Jan. 2004 to Dec. 2006. The patients were divided randomly into a treatment group and a control group (with 34 cases each). The PLA-G was used under the surface of the auxiliary operative wound in the treatment group, and nothing was used in the control group. The wound healing, the wound complication, the amount of drainage solution, the indwelling time of the drainage tube and the auxiliary skin adhesion were evaluated after operation in both groups. There were no statistical difference on wound healing between the first intension (29:27) and the second intention (5:7), and the wound dehiscence after taking the stitches out (0:0) between the two intensions, the hematoma (0:1) and the effusion of the wound (5:6), and the flap necrosis (1:2) between two groups. There were also no statistical difference on the amount of drainage solution per day (6 +/- 3) and indwelling time of the drainage tube (6 +/- 4) after operation between the two groups (P > 0.5). After the operation, the case load with no flap adhesion in the treatment group was significant higher compared with the control group (22:8). The case load with complete acquired skin flap adhesion in the treatment group was visibly lower than in the control group (3:19), which proved that there was a significant statistical difference between the two groups (P < 0.05). This study suggested that the using of PLA-G in the breast cancer modified radical mastectomy could prevent skin flap adhesion without any harmful effects in the wound healing.

  3. Nutritional parameters modify muricidal behavior of male Wistar rats: preventive effects of amino acids and 4' Cl diazepam.

    PubMed

    Miachon, S; Augier, S; Jouvenet, M; Boucher, P; Vallon, J J

    2001-10-26

    In male Wistar rats fed a diet enriched in polyunsaturated fatty acids and starch (PUFA+S), the percentage of muricidal (Mu) rats increased to 82% within 60 days. Mu rats had higher serum triglyceride levels and lower cholesterol levels than non-Mu rats. Water intake decreased in all rats on the PUFA+S diet concurrently with the increase in the proportion of Mu rats; protracted water restriction in rats fed standard diet also increased the percentage of Mu rats. In the offspring of two Wistar females fed the PUFA+S diet, the proportion of young Mu rats was 67%. When the PUFA+S diet was replaced with standard diet, the induced Mu behavior was not reversed. PK11195 (6 mg/kg i.p.), clonazepam (0.2 mg/kg i.p.), and flumazenil (15 mg/kg i.p.) were ineffective in reversing the induced Mu behavior, whereas 4'-chlorodiazepam (5 mg/kg i.p.) or muscimol (0.5 mg/kg i.p.) caused reversals of 63% or 50%, respectively. A 5-hydroxytryptophan overload (60 mg/kg i.p.) also reversed Mu behavior by 71%. All reversal effects were temporary. Pretreatment with yeast for 7 days before the PUFA+S diet was given prevented induction for more than 90 days on the PUFA+S diet, while similar pretreatment 4'Cl-diazepam resulted in 71% prevention of induction. The results are analyzed in terms of the involvement of endozepin, vasopressin, and serotonin receptors, and of possible genetic parameters.

  4. α-Lipoic acid prevents the intestinal epithelial monolayer damage under heat stress conditions: model experiments in Caco-2 cells.

    PubMed

    Varasteh, Soheil; Fink-Gremmels, Johanna; Garssen, Johan; Braber, Saskia

    2017-03-27

    Under conditions of high ambient temperatures and/or strenuous exercise, humans and animals experience considerable heat stress (HS) leading among others to intestinal epithelial damage through induction of cellular oxidative stress. The aim of this study was to characterize the effects of α-Lipoic Acid (ALA) on HS-induced intestinal epithelial injury using an in vitro Caco-2 cell model. A confluent monolayer of Caco-2 cells was pre-incubated with ALA (24 h) prior to control (37 °C) or HS conditions (42 °C) for 6 or 24 h and the expression of heat shock protein 70 (HSP70), heat shock factor-1 (HSF1), and the antioxidant Nrf2 were investigated. Intestinal integrity was determined by measuring transepithelial resistance, paracellular permeability, junctional complex reassembly, and E-cadherin expression and localization. Furthermore, cell proliferation was measured in an epithelial wound healing assay and the expression of the inflammatory markers cyclooxygenase-2 (COX-2) and transforming growth Factor-β (TGF-β) was evaluated. ALA pretreatment increased the HSP70 mRNA and protein expression under HS conditions, but did not significantly modulate the HS-induced activation of HSF1. The HS-induced increase in Nrf2 gene expression as well as the Nrf2 nuclear translocation was impeded by ALA. Moreover, ALA prevented the HS-induced impairment of intestinal integrity. Cell proliferation under HS conditions was improved by ALA supplementation as demonstrated in an epithelial wound healing assay and ALA was able to affect the HS-induced inflammatory response by decreasing the COX-2 and TGF-β mRNA expression. ALA supplementation could prevent the disruption of intestinal epithelial integrity by enhancing epithelial cell proliferation, and reducing the inflammatory response under HS conditions in an in vitro Caco-2 cell model.

  5. [Prevention of intrauterine adhesion with auto-crosslinked hyaluronic acid gel: a prospective, randomized, controlled clinical study].

    PubMed

    Xiao, Songshu; Wan, Yajun; Zou, Fangjun; Ye, Mingzhu; Deng, Henan; Ma, Jiezhi; Wei, Yingying; Tan, Chen; Xue, Min

    2015-01-01

    To evaluate the efficacy and safety of auto-crosslinked hyaluronic acid (HA) gel for preventing intrauterine adhesion (IUA) after hysteroscopic adhesiolysis. A prospective, randomized, double blinded and controlled clinical trial (level I) was performed. According to American Fertility Society (AFS) scoring system, 120 patients (treatment group: 60 cases, control group: 60 cases) with moderate to severe IUA were enrolled. Upon completion of adhesiolysis, a Foley balloon catheter was first introduced into the uterine cavity and then 3 ml of auto-crosslinked HA gel for patients in the treatment group; patients in the control group, however, only received Foley balloon catheter. Second-look hysteroscopic examination was performed to all patients at 3 months postoperatively for evaluation of IUA. Primary endpoint was the reduction rate of IUA at 3 months after surgery. The secondary endpoints include total AFS score, score of each individual AFS category. At 3 months after surgery, auto-crosslinked HA gel resulted in significantly higher effective rate for reduction of adhesion, the effective rate were 76% (42/55) and 48% (27/56) respectively (P = 0.000 9); the total AFS score of treatment group was 2.1 ± 1.1, and significantly lower than that of control group (3.7 ± 2.5, P = 0.000 8). Application of auto-crosslinked HA gel after surgery significantly enhanced the improvement for each individual patient with regard to their adhesive type and menstrual pattern (P = 0.037 8, P = 0.000 4). The treatment group had significantly lower proportion of patients with moderate to severe adhesive stages than that of control group [13% (7/55) versus 38% (21/56), P = 0.000 6]. No adverse events and complications were observed. Auto-crosslinked HA gel coule be able to reduce IUA, decrease adhesion severity, and improve menopause postoperatively. This absorbable auto-crosslinked HA gel is proposed as a barrier for preventing IUA after intrauterine procedures.

  6. Polylactic acid nanosheets in prevention of postoperative intestinal adhesion and their effects on bacterial propagation in an experimental model.

    PubMed

    Hinoki, A; Saito, A; Kinoshita, M; Yamamoto, J; Saitoh, D; Takeoka, S

    2016-05-01

    Ultrathin films (nanosheets) adhere tightly to organ surfaces but prevent adhesion to other organs. The antiadhesive effect of nanosheets and their effect on bacterial propagation were investigated in a murine intestinal adhesion model. Polylactic acid nanosheets (approximately 80 nm thick) were produced. Serosal defects were created by peeling off the intestinal serosa; these were left open or covered with nanosheets or Seprafilm® and the formation of intestinal adhesions was analysed. To examine bacterial propagation, a nanosheet or Seprafilm® was placed on intact murine jejunum followed by Escherichia coli inoculation at the site. Treatment both with nanosheets and with Seprafilm® reduced postoperative intestinal adhesion (mean adhesion score 0·67 for nanosheets, 0·43 for Seprafilm® and 2·87 for no antiadhesive treatment; P < 0·001 for nanosheets or Seprafilm® versus no adhesive treatment). Nanosheet treatment did not affect bacterial propagation in the peritoneal cavity, whereas Seprafilm®-treated mice showed bacterial propagation, leading to increased mortality. Nanosheets may be effective novel antiadhesive agents even in the presence of bacterial contamination. Surgical relevance Intra-abdominal adhesions following surgical contamination can trigger postoperative complications and lead to deterioration in long-term quality of life. However, currently there are no effective antiadhesion materials to prevent the formation of adhesions. Treatment with ultrathin nanosheets effectively reduced postoperative intestinal adhesion in an experimental mouse model, and did not affect bacterial propagation in the peritoneal cavity. These nanosheets are potent novel antiadhesive materials that potentially can be applied even in contaminated conditions. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  7. Prevention of perceptual-motor decline by branched-chain amino acids, arginine, citrulline after tennis match.

    PubMed

    Yang, C-C; Wu, C-L; Chen, I-F; Chang, C-K

    2017-09-01

    Perceptual-motor performance in prolonged tennis matches may be affected by central fatigue. The purpose of this study was to investigate the supplementation of branched-chain amino acids (BCAA), arginine, and citrulline on tennis-specific perceptual-motor performance after a simulated match. Nine male tennis players consumed 0.17 g/kg BCAA, 0.05 g/kg arginine, and 0.05 g/kg citrulline (AA trial), or placebo (PB trial) 1 h before the match. In the perceptual-motor performance test before and after the match, the subjects hit balls to the opposite direction of the examiner's movement. The AA trial showed significantly higher rate of correct direction than the PB trial after the match (AA trial: 93.63 ± 1.28%, PB trial: 69.09 ± 2.40%). The AA trial also demonstrated significantly higher post-match accuracy and consistency than the PB trial. The AA trial showed significantly lower heart rate and ratings of perceive exertion during the match, concurrently with a significantly lower plasma total tryptophan/BCAA ratio. Similar post-match plasma NH3 concentrations were found in both trials while the AA trial was significantly higher in NOx concentration. This study suggested that the supplementation could prevent the decline in perceptual-motor performance through alleviation of central fatigue by BCAA and prevention of excess hyperammonemia by arginine and citrulline. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Association between inhibition of arachidonic acid release and prevention of calcium loading during ATP depletion in cultured rat cardiac myocytes.

    PubMed Central

    Jones, R. L.; Miller, J. C.; Hagler, H. K.; Chien, K. R.; Willerson, J. T.; Buja, L. M.

    1989-01-01

    -fold increase in cellular Ca, a four fold increase in cellular Na, and a seven fold decrease in cellular K, and associated changes in cytoplasm and mitochondria. U26,384 treatment markedly reduced these electrolyte abnormalities, and maintained normal Ca levels in some protocols. Mepacrine treatment was less effective, but did produce normal Ca levels in 50% of myocytes. Prevention of IAA-induced cellular hypercontraction and blebbing also was observed. These data support the hypothesis that reduction of free fatty acid accumulation by inhibition of accelerated phospholipid degradation is associated with protection of myocytes from calcium loading and morphologic damage during inhibition of ene Images Figure 2 Figure 3 Figure 4 PMID:2506756

  9. The tumor-educated-macrophage increase of malignancy of human pancreatic cancer is prevented by zoledronic acid.

    PubMed

    Hiroshima, Yukihiko; Maawy, Ali; Hassanein, Mohamed K; Menen, Rhiana; Momiyama, Masashi; Murakami, Takashi; Miwa, Shinji; Yamamoto, Mako; Uehara, Fuminari; Yano, Shuya; Mori, Ryutaro; Matsuyama, Ryusei; Chishima, Takashi; Tanaka, Kuniya; Ichikawa, Yasushi; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2014-01-01

    We previously defined macrophages harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors as "tumor-educated-macrophages" (Edu) and macrophages harvested from mice without tumors as "naïve-macrophages" (Naïve), and demonstrated that Edu-macrophages promoted tumor growth and metastasis. In this study, Edu- and Naïve-macrophages were compared for their ability to enhance pancreatic cancer malignancy at the cellular level in vitro and in vivo. The inhibitory efficacy of Zoledronic acid (ZA) on Edu-macrophage-enhanced metastasis was also determined. XPA1 human pancreatic cancer cells in Gelfoam co-cultured with Edu-macrophages proliferated to a greater extent compared to XPA1 cells cultured with Naïve-macrophages (P = 0.014). XPA1 cells exposed to conditioned medium harvested from Edu culture significantly increased proliferation (P = 0.016) and had more migration stimulation capability (P<0.001) compared to cultured cancer cells treated with the conditioned medium from Naïve. The mitotic index of the XPA1 cells, expressing GFP in the nucleus and RFP in the cytoplasm, significantly increased in vivo in the presence of Edu- compared to Naïve-macrophages (P = 0.001). Zoledronic acid (ZA) killed both Edu and Naïve in vitro. Edu promoted tumor growth and metastasis in an orthotopic mouse model of the XPA1 human pancreatic cancer cell line. ZA reduced primary tumor growth (P = 0.006) and prevented metastasis (P = 0.025) promoted by Edu-macrophages. These results indicate that ZA inhibits enhanced primary tumor growth and metastasis of human pancreatic cancer induced by Edu-macrophages.

  10. trans-10,cis-12 conjugated linoleic acid prevents adiposity but not insulin resistance induced by an atherogenic diet in hamsters.

    PubMed

    Simón, Edurne; Macarulla, M Teresa; Churruca, Itziar; Fernández-Quintela, Alfredo; Portillo, María P

    2006-02-01

    While conjugated linoleic acid (CLA) has received a great deal of attention as a supplement that can favourably modify body composition, its potential impact on insulin sensitivity has not received equal attention. The aim of the present work was to analyse the effects of trans-10,cis-12 CLA isomer on insulin sensitivity in hamsters fed an atherogenic diet. Hamsters were divided into three groups: one group was fed a chow diet (control) and the other two a semipurified atherogenic diet supplemented with 0.5% linoleic acid (LA) or trans-10,cis-12 CLA, respectively. Serum glucose, FFAs, insulin, leptin and adiponectin were measured using commercial kits. HOMA-IR was calculated using the formula of Matthews et al. PPARgamma mRNA was assessed in epididymal adipose tissue by reverse transcription-polymerase chain reaction (RT-PCR). After 6 weeks, atherogenic feeding produced an increase in body fat accumulation as compared with control feeding. The addition of trans-10,cis-12 CLA to the atherogenic diet avoided this feature. Atherogenic feeding also led to significantly higher serum concentrations of glucose, insulin, FFAs, as well as greater HOMA-IR values. trans-10,cis-12 CLA did not prevent these effects. No significant differences were found among experimental groups in serum leptin and adiponectin concentrations, nor in PPARgamma expression. In summary, although the addition of trans-10,cis-12 CLA to an atherogenic diet reduces fat accumulation, it does not improve the impairment of insulin action associated with this feeding. The maintenance of insulin resistance in hamsters fed the atherogenic CLA-enriched diet is probably due to the high serum FFA concentration observed in these animals.

  11. Preventing lipid oxidation during recovery of functional proteins from herring (Clupea harengus) fillets by an acid solubilization process.

    PubMed

    Undeland, Ingrid; Hall, Gunnar; Wendin, Karin; Gangby, Ingela; Rutgersson, Annika

    2005-07-13

    It has previously been found that a process based on solubilization at pH 2.7 gives high yields of herring muscle proteins with good functionality. In this study, the development of lipid oxidation during acid processing of herring mince was studied. It was tested how modifications of the process conditions and/or additions of antioxidants could prevent lipid oxidation during the actual process and then during ice storage of the protein isolates. Processing parameters evaluated were prewash of the mince, exposure time to pH 2.7, inclusion or exclusion of a high-speed centrifugation, and addition of antioxidants. Antioxidants tested were erythorbate (0.2%, 9.3 mM), sodium tripolyphosphate (STPP; 0.2%, 5.4 mM), ethylenediaminetetraacetic acid (EDTA; 0.044%, 1.5 mM), and milk proteins (4%). The first three antioxidants were added in the prewash or during the homogenization step, whereas milk proteins were added to the final precipitate. At time 0, all isolates were analyzed for pH, moisture content, and thiobarbituric reactive substances (TBARS). Selected isolates were also analyzed for lipid and protein content. Stability during ice storage was followed in terms of odor, TBARS, and color (a/b values). Extensive lipid oxidation took place using the "control" process without high-speed centrifugation. This was not significantly (p < or = 0.05) affected by a prewash or varied exposure time to pH 2.7. Including high-speed centrifugation (20 min, 10,000g) significantly (p < or = 0.05) reduced TBARS values, total lipids, a values and b values. Erythorbate alone, or in combination with STPP/EDTA, significantly (p < or = 0.05) reduced lipid oxidation during processing if added in the prewash or homogenization step. During ice storage, better stability was gained when antioxidants were added in both of these steps and when EDTA was used instead of STPP.

  12. Bile acid binding resin prevents fat accumulation through intestinal microbiota in high-fat diet-induced obesity in mice.

    PubMed

    Kusumoto, Yukie; Irie, Junichiro; Iwabu, Kaho; Tagawa, Hirotsune; Itoh, Arata; Kato, Mari; Kobayashi, Nana; Tanaka, Kumiko; Kikuchi, Rieko; Fujita, Masataka; Nakajima, Yuya; Morimoto, Kohkichi; Sugizaki, Taichi; Yamada, Satoru; Kawai, Toshihide; Watanabe, Mitsuhiro; Oike, Yuichi; Itoh, Hiroshi

    2017-06-01

    Bile acid binding resin (BAR) absorbs intestinal bile acids, and improves obesity and metabolic disorders, but the precise mechanism remains to be clarified. Recent findings reveal that obesity is associated with skewed intestinal microbiota. Thus, we investigated the effect of BAR on intestinal microbiota and the role of microbiota in the prevention of obesity in high-fat diet-induced obesity in mice. Male Balb/c mice were fed a low-fat diet (LFD), high-fat diet (HFD), or HFD with BAR (HFD+BAR), and then metabolic parameters, caecal microbiota, and metabolites were investigated. The same interventions were conducted in germ-free and antibiotic-treated mice. The frequency of Clostridium leptum subgroup was higher in both HFD-fed and HFD+BAR-fed mice than in LFD-fed mice. The frequency of Bacteroides-Prevotella group was lower in HFD-fed mice than in LFD-fed mice, but the frequency was higher in HFD+BAR-fed mice than in HFD-fed mice. Caecal propionate was lower in HFD-fed mice than in LFD-fed mice, and higher in HFD+BAR-fed mice than in HFD-fed mice. HFD+BAR-fed mice showed lower adiposity than HFD-fed mice, and the reduction was not observed in germ-free or antibiotic-treated mice. Colonized germ-free mice showed a reduction in adiposity by BAR administration. Energy expenditure was lower in HFD-fed mice and higher in HFD+BAR-fed mice, but the increments induced by administration of BAR were not observed in antibiotic-treated mice. Modulation of intestinal microbiota by BAR could be a novel therapeutic approach for obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. [Neural tube defects in Austria: Assumption and calculations on the prevention potential through folic acid enrichment and supplementation].

    PubMed

    Schiller-Frühwirth, I; Mittermayr, T; Wild, C

    2010-12-01

    Countries with obligatory fortification of food (USA, Canada) document a significant decrease of neural tube defects in newborns. In this study the Daly or, respectively, the Wald method was employed for calculating the potential of fortification/and supplementation for prevention in Austria. According to the EUROCAT study, in Austria the overall prevalence of neural tube defects (live birth, still births and induced abortions due to neural defect) is assumed to be 7.95 per 10,000 live and still births, and the prevalence of 3.9 per 10,000 live births - that is 62 or, respectively, 30 in absolute numbers per 78,000 births per year. In 2006, 26 live-born children with neural tube defects were actually reported in Austria by Statistik Austria. Different folic acid fortification and supplementation strategies can avoid 1.2-1.4 per 10,000 (9-11 cases) of neural tube defects (live and still births). Folic acid supplements are effective to decrease the amount of neural tube defects, however, only when pregnancies are planned. Thus, evidence-based neural tube defects are more common among lower social groups. An obligatory fortification of food could therefore reach unplanned pregnancies and women facing social problems. A reason to justify this population-based intervention where people need not decide for themselves could be the reduction of social imbalances. There are, of course, advantages and disadvantages of obligatory fortification of food and, therefore, all circumstances have to be taken into consideration. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Omega-3 fatty acids and cardiovascular disease.

    PubMed

    Jain, A P; Aggarwal, K K; Zhang, P-Y

    2015-01-01

    Cardioceuticals are nutritional supplements that contain all the essential nutrients including vitamins, minerals, omega-3-fatty acids and other antioxidants like a-lipoic acid and coenzyme Q10 in the right proportion that provide all round protection to the heart by reducing the most common risks associated with the cardiovascular disease including high low-density lipoprotein cholesterol and triglyceride levels and factors that contribute to coagulation of blood. Omega-3 fatty acids have been shown to significantly reduce the risk for sudden death caused by cardiac arrhythmias and all-cause mortality in patients with known coronary heart disease. Omega-3 fatty acids are also used to treat hyperlipidemia and hypertension. There are no significant drug interactions with omega-3 fatty acids. The American Heart Association recommends consumption of two servings of fish per week for persons with no history of coronary heart disease and at least one serving of fish daily for those with known coronary heart disease. Approximately 1 g/day of eicosapentaenoic acid plus docosahexaenoic acid is recommended for cardio protection. Higher dosages of omega-3 fatty acids are required to reduce elevated triglyceride levels (2-4 g/day). Modest decreases in blood pressure occur with significantly higher dosages of omega-3 fatty acids.

  15. Inhibition of c-Jun-N-terminal Kinase Increases Cardiac Peroxisome Proliferator-activated Receptor α Expression and Fatty Acid Oxidation and Prevents Lipopolysaccharide-induced Heart Dysfunction*

    PubMed Central

    Drosatos, Konstantinos; Drosatos-Tampakaki, Zoi; Khan, Raffay; Homma, Shunichi; Schulze, P. Christian; Zannis, Vassilis I.; Goldberg, Ira J.

    2011-01-01

    Septic shock results from bacterial infection and is associated with multi-organ failure, high mortality, and cardiac dysfunction. Sepsis causes both myocardial inflammation and energy depletion. We hypothesized that reduced cardiac energy production is a primary cause of ventricular dysfunction in sepsis. The JNK pathway is activated in sepsis and has also been implicated in impaired fatty acid oxidation in several tissues. Therefore, we tested whether JNK activation inhibits cardiac fatty acid oxidation and whether blocking JNK would restore fatty acid oxidation during LPS treatment. LPS treatment of C57BL/6 mice and adenovirus-mediated activation of the JNK pathway in cardiomyocytes inhibited peroxisome proliferator-activated receptor α expression and fatty acid oxidation. Surprisingly, none of the adaptive responses that have been described in other types of heart failure, such as increased glucose utilization, reduced αMHC:βMHC ratio or induction of certain microRNAs, occurred in LPS-treated mice. Treatment of C57BL/6 mice with a general JNK inhibitor (SP600125) increased fatty acid oxidation in mice and a cardiomyocyte-derived cell line. JNK inhibition also prevented LPS-mediated reduction in fatty acid oxidation and cardiac dysfunction. Inflammation was not alleviated in LPS-treated mice that received the JNK inhibitor. We conclude that activation of JNK signaling reduces fatty acid oxidation and prevents the peroxisome proliferator-activated receptor α down-regulation that occurs with LPS. PMID:21873422

  16. Salvianolic acid B prevents bone loss in prednisone-treated rats through stimulation of osteogenesis and bone marrow angiogenesis.

    PubMed

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S S; Wu, Tie

    2012-01-01

    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10(-6) mol/L to 10(-7) mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  17. Salvianolic Acid B Prevents Bone Loss in Prednisone-Treated Rats through Stimulation of Osteogenesis and Bone Marrow Angiogenesis

    PubMed Central

    Cui, Liao; Li, Ting; Liu, Yuyu; Zhou, Le; Li, Pinghua; Xu, Bilian; Huang, Lianfang; Chen, Yan; Liu, Yanzhi; Tian, Xiaoyan; Jee, Webster S. S.; Wu, Tie

    2012-01-01

    Glucocorticoid (GC) induced osteoporosis (GIO) is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B) is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1) In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d) for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d) not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2) In vitro study: In concentration from 10−6 mol/L to 10−7 mol/L, Sal B stimulated bone marrow stromal cell (MSC) differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with

  18. Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association.

    PubMed

    Siscovick, David S; Barringer, Thomas A; Fretts, Amanda M; Wu, Jason H Y; Lichtenstein, Alice H; Costello, Rebecca B; Kris-Etherton, Penny M; Jacobson, Terry A; Engler, Mary B; Alger, Heather M; Appel, Lawrence J; Mozaffarian, Dariush

    2017-03-13

    Multiple randomized controlled trials (RCTs) have assessed the effects of supplementation with eicosapentaenoic acid plus docosahexaenoic acid (omega-3 polyunsaturated fatty acids, commonly called fish oils) on the occurrence of clinical cardiovascular diseases. Although the effects of supplementation for the primary prevention of clinical cardiovascular events in the general population have not been examined, RCTs have assessed the role of supplementation in secondary prevention among patients with diabetes mellitus and prediabetes, patients at high risk of cardiovascular disease, and those with prevalent coronary heart disease. In this scientific advisory, we take a clinical approach and focus on common indications for omega-3 polyunsaturated fatty acid supplements related to the prevention of clinical cardiovascular events. We limited the scope of our review to large RCTs of supplementation with major clinical cardiovascular disease end points; meta-analyses were considered secondarily. We discuss the features of available RCTs and provide the rationale for our recommendations. We then use existing American Heart Association criteria to assess the strength of the recommendation and the level of evidence. On the basis of our review of the cumulative evidence from RCTs designed to assess the effect of omega-3 polyunsaturated fatty acid supplementation on clinical cardiovascular events, we update prior recommendations for patients with prevalent coronary heart disease, and we offer recommendations, when data are available, for patients with other clinical indications, including patients with diabetes mellitus and prediabetes and those with high risk of cardiovascular disease, stroke, heart failure, and atrial fibrillation.

  19. Current Review of Genetically Modified Lactic Acid Bacteria for the Prevention and Treatment of Colitis Using Murine Models

    PubMed Central

    de Moreno de LeBlanc, Alejandra; Chatel, Jean-Marc; Miyoshi, Anderson; Langella, Philippe; Bermúdez-Humarán, Luis G.

    2015-01-01

    Inflammatory Bowel Diseases (IBD) are disorders of the gastrointestinal tract characterized by recurrent inflammation that requires lifelong treatments. Probiotic microorganisms appear as an alternative for these patients; however, probiotic characteristics are strain dependent and each probiotic needs to be tested to understand the underlining mechanisms involved in their beneficial properties. Genetic modification of lactic acid bacteria (LAB) was also described as a tool for new IBD treatments. The first part of this review shows different genetically modified LAB (GM-LAB) described for IBD treatment since 2000. Then, the two principally studied strategies are discussed (i) GM-LAB producing antioxidant enzymes and (ii) GM-LAB producing the anti-inflammatory cytokine IL-10. Different delivery systems, including protein delivery and DNA delivery, will also be discussed. Studies show the efficacy of GM-LAB (using different expression systems) for the prevention and treatment of IBD, highlighting the importance of the bacterial strain selection (with anti-inflammatory innate properties) as a promising alternative. These microorganisms could be used in the near future for the development of therapeutic products with anti-inflammatory properties that can improve the quality of life of IBD patients. PMID:26064086

  20. Omega-3 fatty acids regulate NLRP3 inflammasome activation and prevent behavior deficits after traumatic brain injury.

    PubMed

    Lin, Chao; Chao, Honglu; Li, Zheng; Xu, Xiupeng; Liu, Yinlong; Bao, Zhongyuan; Hou, Lijun; Liu, Yan; Wang, Xiaoming; You, Yongping; Liu, Ning; Ji, Jing

    2017-04-01

    Omega-3 fatty acids (ω-3 FAs) attenuate inflammation and improve neurological outcome in response to traumatic brain injury (TBI), but the specific anti-inflammatory mechanisms remain to be elucidated. Here we found that NLRP3 inflammasome and subsequent pro-inflammatory cytokines were activated in human brains after TBI. Rats treated with ω-3 FAs had significantly less TBI-induced caspase-1 cleavage and IL-1β secretion than those with vehicle. G protein-coupled receptor 40 (GPR40) was observed to be involved in this anti-inflammation. GW1100, a GPR40 inhibitor, eliminated the anti-inflammatory effect of ω-3 FAs after TBI. β-Arrestin-2 (ARRB2), a downstream scaffold protein of GPR40, was activated to inhibit inflammation via directly binding with NLRP3 in the ω-3 FAs treatment group. Interestingly, we also observed that ω-3 FAs prevented NLRP3 mitochondrial localization, which was reversed by GW1100. Furthermore, ω-3 FAs markedly ameliorated neuronal death and behavioral deficits after TBI, while GW1100 significantly suppressed this effect. Collectively, these data indicate that the GPR40-mediated pathway is involved in the inhibitory effects of ω-3 FAs on TBI-induced inflammation and ARRB2 is activated to interact with NLRP3.

  1. The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spinal cord ischemia in the rat

    SciTech Connect

    Hao, J.X.; Xu, X.J.; Aldskogius, H.; Seiger, A.; Wiesenfeld-Hallin, Z. )

    1991-08-01

    Protection by the NMDA receptor antagonist MK-801 against transient spinal cord ischemia-induced hypersensitivity was studied in rats. The spinal ischemia was initiated by vascular occlusion resulting from the interaction between the photosensitizing dye Erythrosin B and an argon laser beam. The hypersensitivity, termed allodynia, where the animals reacted by vocalization to nonnoxious mechanical stimuli in the flank area, was consistently observed during several days after induction of the ischemia. Pretreatment with MK-801 (0.1-0.5 mg/kg, iv) 10 min before laser irradiation dose dependently prevented the occurrence of allodynia. The neuroprotective effect of MK-801 was not reduced by maintaining normal body temperature during and after irradiation. There was a significant negative correlation between the delay in the administration of MK-801 after irradiation and the protective effect of the drug. Histological examination revealed slight morphological damage in the spinal cord in 38% of control rats after 1 min of laser irradiation without pretreatment with MK-801. No morphological abnormalities were observed in rats after pretreatment with MK-801 (0.5 mg/kg). The present results provide further evidence for the involvement of excitatory amino acids, through activation of the NMDA receptor, in the development of dysfunction following ischemic trauma to the spinal cord.

  2. Oral administration of poly-γ-glutamic acid prevents the development of atopic dermatitis in NC/Nga mice.

    PubMed

    Lee, Sung Won; Park, Hyun Jung; Park, Se-Ho; Hong, Seokmann

    2013-08-01

    Bacillus subtilis-derived poly-γ-glutamic acid (γPGA) has demonstrated adjuvant activity in promoting Th1/Th17 cell differentiation. Here, the NC/Nga (NC) mouse model was used to determine whether γPGA modulates the outcome of atopic dermatitis (AD), which is known to be a Th2-biased immune disease. We found that oral administration of γPGA dramatically reduced the development of AD in NC mice. Antigen-presenting cells activated with γPGA produced pro-inflammatory cytokines, such as IL12/23 and IFNγ, which, in turn, induced the differentiation of Th1 and Th17 cells. Concomitantly, Th2 responses, such as high levels of serum IgE, were dramatically decreased. Furthermore, in vivo γPGA treatment altered several cellular components of allergic reactions, such as mast cells and eosinophils. Taken together, our results strongly demonstrate that in vivo treatment with γPGA at early time points can prevent the development of AD in NC mice and suggest that γPGA may have therapeutic applications for human AD. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Ammonia-induced oxidative damage in neurons is prevented by resveratrol and lipoic acid with participation of heme oxygenase 1.

    PubMed

    Bobermin, Larissa Daniele; Wartchow, Krista Minéia; Flores, Marianne Pires; Leite, Marina Concli; Quincozes-Santos, André; Gonçalves, Carlos-Alberto

    2015-07-01

    Ammonia is a metabolite that, at high concentrations, is implicated in neurological disorders, such as hepatic encephalopathy (HE), which is associated with acute or chronic liver failure. Astrocytes are considered the primary target of ammonia toxicity in the central nervous system (CNS) because glutamine synthetase (GS), responsible for ammonia metabolism in CNS, is an astrocytic enzyme. Thus, neuronal dysfunction has been associated as secondary to astrocytic impairment. However, we demonstrated that ammonia can induce direct effects on neuronal cells. The cell viability was decreased by ammonia in SH-SY5Y cells and cerebellar granule neurons. In addition, ammonia induced increased reactive oxygen species (ROS) production and decreased GSH intracellular content, the main antioxidant in CNS. As ammonia neurotoxicity is strongly associated with oxidative stress, we also investigated the potential neuroprotective roles of the antioxidants, resveratrol (RSV) and lipoic acid (LA), against ammonia toxicity in cerebellar granule neurons. RSV and LA were able to prevent the oxidative damage induced by ammonia, maintaining the levels of ROS production and GSH close to basal values. Both antioxidants also decreased ROS production and increased GSH content under basal conditions (in the absence of ammonia). Moreover, we showed that heme oxygenase 1 (HO1), a protein associated with protection against stress conditions, is involved in the beneficial effects of RSV and LA in cerebellar granule neurons. Thus, this study reinforces the neuroprotective effects of RSV and LA. Although more studies in vivo are required, RSV and LA could represent interesting therapeutic strategies for the management of HE.

  4. The retinaldehyde reductase DHRS3 is essential for preventing the formation of excess retinoic acid during embryonic development.

    PubMed

    Billings, Sara E; Pierzchalski, Keely; Butler Tjaden, Naomi E; Pang, Xiao-Yan; Trainor, Paul A; Kane, Maureen A; Moise, Alexander R

    2013-12-01

    Oxidation of retinol via retinaldehyde results in the formation of the essential morphogen all-trans-retinoic acid (ATRA). Previous studies have identified critical roles in the regulation of embryonic ATRA levels for retinol, retinaldehyde, and ATRA-oxidizing enzymes; however, the contribution of retinaldehyde reductases to ATRA metabolism is not completely understood. Herein, we investigate the role of the retinaldehyde reductase Dhrs3 in embryonic retinoid metabolism using a Dhrs3-deficient mouse. Lack of DHRS3 leads to a 40% increase in the levels of ATRA and a 60% and 55% decrease in the levels of retinol and retinyl esters, respectively, in Dhrs3(-/-) embryos compared to wild-type littermates. Furthermore, accumulation of excess ATRA is accompanied by a compensatory 30-50% reduction in the expression of ATRA synthetic genes and a 120% increase in the expression of the ATRA catabolic enzyme Cyp26a1 in Dhrs3(-/-) embryos vs. controls. Excess ATRA also leads to alterations (40-80%) in the expression of several developmentally important ATRA target genes. Consequently, Dhrs3(-/-) embryos die late in gestation and display defects in cardiac outflow tract formation, atrial and ventricular septation, skeletal development, and palatogenesis. These data demonstrate that the reduction of retinaldehyde by DHRS3 is critical for preventing formation of excess ATRA during embryonic development.

  5. Protocatechuic Acid Prevents oxLDL-Induced Apoptosis by Activating JNK/Nrf2 Survival Signals in Macrophages

    PubMed Central

    Varì, Rosaria; Scazzocchio, Beatrice; Santangelo, Carmela; Filesi, Carmelina; Galvano, Fabio; D'Archivio, Massimo; Masella, Roberta; Giovannini, Claudio

    2015-01-01

    Protocatechuic acid (PCA), one of the main metabolites of complex polyphenols, exerts numerous biological activities including antiapoptotic, anti-inflammatory, and antiatherosclerotic effects. Oxidised LDL have atherogenic properties by damaging arterial wall cells and inducing p53-dependent apoptosis in macrophages. This study was aimed at defining the molecular mechanism responsible for the protective effects of PCA against oxidative and proapoptotic damage exerted by oxLDL in J774 A.1 macrophages. We found that the presence of PCA in cells treated with oxLDL completely inhibited the p53-dependent apoptosis induced by oxLDL. PCA decreased oxLDL-induced ROS overproduction and in particular prevented the early increase of ROS. This decrease seemed to be the main signal responsible for maintaining the intracellular redox homeostasis hindering the activation of p53 induced by ROS, p38MAPK, and PKCδ. Consequently the overexpression of the proapoptotic p53-target genes such as p66Shc protein did not occur. Finally, we demonstrated that PCA induced the activation of JNK, which, in turn, determined the increase of nuclear Nrf2, leading to inhibition of the early ROS overproduction. We concluded that the antiapoptotic mechanism of PCA was most likely related to the activation of the JNK-mediated survival signals that strengthen the cellular antioxidant defences rather than to the PCA antioxidant power. PMID:26180584

  6. Application of hyaluronic acid/sodium alginate-based microparticles to prevent tissue adhesion in a rabbit model.

    PubMed

    Back, Ja Hoon; Cho, Wan Jin; Kim, Jun Ho; Park, Il Kyu; Kwon, Sung Won

    2016-04-01

    Postsurgical adhesion formation is a concern in every field of surgery. We evaluated the efficacy of hyaluronic acid/sodium alginate-based microparticle anti-adhesive agents (MP) for the prevention of postsurgical adhesion formation in a standardized rabbit model. To evaluate the anti-adhesion effect, a uterus-abdominal wall abrasion model was created in rabbits. On the surface of the injured uterus, an anti-adhesive agent, Interceed(®) or MP, was applied (positive control and study groups, respectively; n = 10 each). In another group of 10 animals, neither agent was applied (negative control group). The adhesion levels were graded 3 weeks after surgery. Acute and chronic toxicity was also evaluated. The grade of adhesion was significantly lower in the MP group than in the negative control and positive control groups. No evidence of acute or chronic toxicity induced by this material was found in blood and tissue analysis. MP shows potential as an effective novel type of resorbable biomaterial to reduce postoperative adhesion. The easy placement and handling of this material make the MP powder attractive as a tissue adhesion barrier.

  7. A study on the prevention of salmonella infection by using the aggregation characteristics of lactic Acid bacteria.

    PubMed

    Kim, Min-Soo; Yoon, Yeo-Sang; Seo, Jae-Gu; Lee, Hyun-Gi; Chung, Myung-Jun; Yum, Do-Young

    2013-06-01

    Salmonella is one of the major pathogenic bacteria that cause food poisoning. This study investigated whether heat-killed as well as live Lactobacillus protects host animal against Salmonella infection. Live and heat-killed Lactobacillusacidophilus was administered orally to Sprague-Dawley rats for 2 weeks before the rats were inoculated with Salmonella. Rise in body temperature was moderate in the group that was treated with heat-killed bacteria as compared to the Salmonella control group. The mean amount of feed intake and water consumption of each rat in the heat-killed bacteria group were nearly normal. The number of fecal Salmonellae was comparable between the live and the heat-killed L. acidophilus groups. This finding shows that L. acidophilus facilitates the excretion of Salmonella. Moreover, the levels of pro inflammatory cytokines, including tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta, in the heat-killed L. acidophilus group were significantly lower when compared to the levels in the Salmonella control group. These results indicate that nonviable lactic acid bacteria also could play an important role in preventing infections by enteric pathogens such as Salmonella.

  8. All-Trans Retinoic Acid Prevents Osteosarcoma Metastasis by Inhibiting M2 Polarization of Tumor-Associated Macrophages.

    PubMed

    Zhou, Qian; Xian, Miao; Xiang, Senfeng; Xiang, Danyan; Shao, Xuejing; Wang, Jincheng; Cao, Ji; Yang, Xiaochun; Yang, Bo; Ying, Meidan; He, Qiaojun

    2017-07-01

    M2-polarized tumor-associated macrophages (TAM) play a critical role in cancer invasion and metastasis. Here, we report that M2 macrophages enhanced metastasis of K7M2 WT osteosarcoma cells to the lungs in mice, thus establishing M2 TAMs as a therapeutic target for blocking osteosarcoma metastasis. We found that all-trans retinoic acid (ATRA) inhibited osteosarcoma metastasis via inhibiting the M2 polarization of TAMs. ATRA suppressed IL13- or IL4-induced M2-type macrophages, and then inhibited migration of osteosarcoma cells as promoted by M2-type macrophages in vitro ATRA reduced the number of pulmonary metastatic nodes of osteosarcoma and decreased expression of M2-type macrophages in metastatic nodes both in intravenous injection and orthotopic transplantation models. ATRA's effect was independent of conventional STAT3/6 or C/EBPβ signaling, which regulate M2-like polarization of macrophages. Quantitative genomic and functional analyses revealed that MMP12, a macrophage-secreted elastase, was elevated in IL13-skewed TAM polarization, whereas ATRA treatment downregulated IL13-induced secretion of MMP12. This downregulation correlates with the antimetastasis effect of ATRA. Our results show the role of TAM polarization in osteosarcoma metastasis, identify a therapeutic opportunity for antimetastasis treatment, and indicate ATRA treatment as an approach for preventing osteosarcoma metastasis via M2-type polarization intervention. Cancer Immunol Res; 5(7); 547-59. ©2017 AACR. ©2017 American Association for Cancer Research.

  9. Moderate water stress prevents the postharvest decline of ascorbic acid in spinach (Spinacia oleracea L.) but not in spinach beet (Beta vulgaris L.).

    PubMed

    Mogren, Lars M; Beacham, Andrew M; Reade, John P H; Monaghan, James M

    2016-07-01

    Babyleaf salads such as spinach (Spinacia oleracea L.) and spinach beet (Beta vulgaris L. subsp. cicla var. cicla) are an important dietary source of antioxidants such as ascorbic acid (vitamin C). Such compounds may be important in disease prevention in consumers but the level of these compounds in leaves frequently declines after harvest. As such, methods to maintain antioxidant levels in fresh produce are being sought. Irrigation deficits were used to apply water stress to S. oleracea and B. vulgaris plants. This treatment prevented postharvest decline of leaf ascorbic acid content in S. oleracea but not in B. vulgaris. Ascorbic acid levels in leaves at harvest were unaffected by the treatment in both species compared to well-watered controls. We have shown that restricted irrigation provides a viable means to maintain leaf vitamin content after harvest in S. oleracea, an important finding for producers, retailers and consumers alike. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  10. Folic Acid

    MedlinePlus

    Folic acid is used to treat or prevent folic acid deficiency. It is a B-complex vitamin needed by ... Folic acid comes in tablets. It usually is taken once a day. Follow the directions on your prescription label ...

  11. Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity

    PubMed Central

    Ryu, Yuhee; Jin, Li; Kee, Hae Jin; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Lin, Ming Quan; Jeong, Myung Ho

    2016-01-01

    Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro. Moreover, it prevented interstitial collagen deposition and expression of fibrosis-associated genes. Upregulation of collagen type I by Smad3 overexpression was observed in cardiac myoblast H9c2 cells but not in cardiac fibroblasts. Gallic acid reduced the DNA binding activity of phosphorylated Smad3 in Smad binding sites of collagen type I promoter in rat cardiac fibroblasts. Furthermore, it decreased the ISP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) protein in mice. JNK2 overexpression reduced collagen type I and Smad3 expression as well as GATA4 expression in H9c2 cells and cardiac fibroblasts. Gallic acid might be a novel therapeutic agent for the prevention of cardiac hypertrophy and fibrosis by regulating the JNK2 and Smad3 signaling pathway. PMID:27703224

  12. Effect of Polyglycolic Acid Mesh for Prevention of Pancreatic Fistula Following Distal Pancreatectomy: A Randomized Clinical Trial.

    PubMed

    Jang, Jin-Young; Shin, Yong Chan; Han, Youngmin; Park, Joon Seong; Han, Ho-Seong; Hwang, Ho Kyoung; Yoon, Dong Sup; Kim, Jae Keun; Yoon, Yoo Seok; Hwang, Dae Wook; Kang, Chang Moo; Lee, Woo Jung; Heo, Jin Seok; Kang, Mee Joo; Chang, Ye Rim; Chang, Jihoon; Jung, Woohyun; Kim, Sun-Whe

    2017-02-01

    The rate of postoperative pancreatic fistula (POPF) after distal pancreatectomy ranges from 13% to 64%. To prevent POPF, polyglycolic acid (PGA) mesh was introduced, but its effect has been evaluated only in small numbers of patients and retrospective studies. To evaluate the efficacy of PGA mesh in preventing POPF after distal pancreatectomy. Prospective randomized clinical, single-blind (participant), parallel-group trial at 5 centers between November 2011 and April 2014. The pancreatic parenchyma was divided using a stapling device; no patient was given prophylactic octreotide. Perioperative and clinical outcomes were compared including POPF, which was graded according to the criteria of the International Study Group For Pancreatic Fistulas. A total of 97 patients aged 20 to 85 years with curable benign, premalignant, or malignant disease of the pancreatic body or tail were enrolled (44 in the PGA group and 53 in the control group). Patients in the PGA group underwent transection of the pancreas and application of fibrin glue followed by wrapping the PGA mesh around the remnant pancreatic stump. The primary end point of this study was the development of a clinically relevant POPF (grade B or C by the International Study Group grading system). The secondary end point was the evaluation of risk factors for POPF. The study therefore evaluated a total of 97 patients, 44 in the PGA group and 53 in the control group. Thirty-nine patients were women and 58 patients were men. There were no differences in mean (SD) age (59.9 [12.0] years vs 54.5 [14.1] years, P = .05), male to female ratio (1.0:1.3 vs 1.0:1.7, P = .59), malignancy (40.9% vs 32.1%, P = .37), mean (SD) pancreatic duct diameter (1.92 [0.75] mm vs 1.94 [0.95] mm, P = .47), soft pancreatic texture (90.9% vs 83.0%, P = .17), and mean (SD) thickness of the transection margin (16.9 [5.4] mm vs 16.4 [4.9] mm, P = .63) between the PGA and control groups. The rate of clinically relevant POPF

  13. Dihomo-γ-linolenic acid prevents the development of atopic dermatitis through prostaglandin D1 production in NC/Tnd mice.

    PubMed

    Amagai, Yosuke; Oida, Kumiko; Matsuda, Akira; Jung, Kyungsook; Kakutani, Saki; Tanaka, Takao; Matsuda, Kenshiro; Jang, Hyosun; Ahn, Ginae; Xia, Yan; Kawashima, Hiroshi; Shibata, Hiroshi; Matsuda, Hiroshi; Tanaka, Akane

    2015-07-01

    Atopic dermatitis (AD) is a chronic and relapsing skin disorder with pruritic skin symptoms. We previously reported that dihomo-γ-linolenic acid (DGLA) prevented the development of AD in NC/Tnd mice, though the mechanism remained unclear. We attempted to investigate the mechanism of preventive effect of DGLA on AD development in NC/Tnd mice. The clinical outcomes of NC/Tnd mice that were given diets containing DGLA, arachidonic acid, or eicosapentaenoic acid were compared. Lipid mediator contents in the skin in each group were also quantified. In addition, release of lipid mediators from RBL-2H3 mast cells treated with either DGLA or prostaglandin D1 (PGD1) was measured. Furthermore, effect of PGD1 on gene expression of thymic stromal lymphopoietin (TSLP) in PAM212 keratinocyte cells was determined. Only DGLA containing diet suppressed the development of dermatitis in vivo. By quantifying the 20-carbon fatty acid-derived eicosanoids in the skin, the application of DGLA was found to upregulate PGD1, which correlated with a better outcome in NC/Tnd mice. Moreover, we confirmed that mast cells produced PGD1 after DGLA exposure, thereby exerting a suppressive effect on immunoglobulin E-mediated degranulation. PGD1 also suppressed gene expression of TSLP in keratinocytes. These results suggest that oral administration of DGLA causes preventive effects on AD development in NC/Tnd mice by regulating the PGD1 supply. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  14. A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation.

    PubMed

    Alai, Milind; Lin, Wen Jen

    2013-01-01

    The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration.

  15. Omega-3 polyunsaturated fatty acids in the prevention of postoperative complications in colorectal cancer: a meta-analysis

    PubMed Central

    Xie, Hai; Chang, Yan-na

    2016-01-01

    Objective To evaluate systematically the clinical efficacy of omega-3 polyunsaturated fatty acids (PUFAs) in the prevention of postoperative complications in colorectal cancer (CRC) patients. Materials and methods Published articles were identified by using search terms in online databases – PubMed, Embase, and the Cochrane Library – up to March 2016. Only randomized controlled trials investigating the efficacy of omega-3 PUFAs in CRC were selected and analyzed through a meta-analysis. Subgroup, sensitivity, and inverted funnel-plot analyses were also conducted. Results Eleven articles with 694 CRC patients were finally included. Compared with control, omega-3 PUFA-enriched enteral or parenteral nutrition during the perioperative period reduced infectious complications (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.47–0.86; P=0.004), tumor necrosis factor alpha (standard mean difference [SMD] −0.37, 95% CI −0.66 to −0.07; P=0.01), interleukin-6 (SMD −0.36, 95% CI −0.66 to −0.07; P=0.02), and hospital stay (MD −2.09, 95% CI −3.71 to −0.48; P=0.01). No significant difference was found in total complications, surgical site infection, or CD4+:CD8+ cell ratio. Conclusion Short-term omega-3 PUFA administration was associated with reduced postoperative infectious complications, inflammatory cytokines, and hospital stay after CRC surgery. Due to heterogeneity and relatively small sample size, the optimal timing and route of administration deserve further study. PMID:28003759

  16. Oleanolic Acid Prevents Increase in Blood Pressure and Nephrotoxicity in Nitric Oxide Dependent Type of Hypertension in Rats

    PubMed Central

    Bachhav, Sagar S.; Bhutada, Mukesh S.; Patil, Sachin P.; Sharma, Kinjal S.; Patil, Savita D.

    2015-01-01

    Background: Recently, we have reported antihypertensive activity of oleanolic acid (OA) in glucocorticoid-induced hypertension with restoration of nitric oxide (NO) level. However, the involvement of NO-releasing action of OA was unclear. Objective: To explore antihypertensive activity of OA in Nω-nitro-L-arginine methyl ester (L-NAME) hypertensive rats wherein NO is completely blocked, which would allow exploring the possibility of involvement of NO-releasing action of OA. Materials and Methods: Five groups of rats were investigated as normal control, L-NAME (40 mg/kg/day), L-NAME + enalapril (15 mg/kg/day), L-NAME + l-arginine (100 mg/kg/day), and L-NAME + OA (60 mg/kg/day) for 4 weeks. The systolic blood pressure, body weight, and heart rate were measured weekly for 4 weeks. Serum nitrate/nitrite (NOx) level, urine electrolytes concentration, cardiac mass index, and serum creatinine level were determined followed by organ histopathology. Results: OA and enalapril delayed the rise in blood pleasure following L-NAME administration. Decreased serum NOx level was not significantly increased with any of the treatment. OA produced a small, though nonsignificant, increase in the NOx level. L-NAME administration did not affect cardiac mass index. There was an increase in serum creatinine upon L-NAME administration which was prevented by OA. Decreased urine volume, urine sodium and potassium were reversed by OA. Conclusion: These results suggest that the antihypertensive effect of OA in L-NAME hypertension is due to diuresis and nephroprotection. However, OA has nonsignificantly affected the NO levels. PMID:26692754

  17. Evaluation of preventive and control measures for lead exposure in a South African lead-acid battery recycling smelter.

    PubMed

    Dyosi, Sindiswa

    2007-10-01

    In South Africa, new lead regulations released in February 2002 served as motivation for a cross-sectional study investigating the effectiveness of preventive and control measures implemented in a lead smelter that recycles lead-acid batteries. Twenty-two workers were observed and interviewed. Structured questionnaires were used to gather workers' personal information, perception about their work environment, health risks, and work practices. Retrospective data from air monitoring and medical surveillance programs were obtained from the plant's records. The smelter implemented a number of control measures for lead exposure, including engineering controls, administrative controls, and, as a last resort, personal protective equipment. Engineering controls were rated the best control measure and included local exhaust ventilation systems and wet methods. Positive pressure systems were used in the offices and laboratory. The local exhaust ventilation system was rated the best engineering control measure. Although control measures were used, areas such as smelting and refinery had average lead in air levels above 0.15 mg/m(3), the occupational exposure limit for lead. This was a concern especially with regard to the smelting area because those workers had the second highest mean blood lead levels; workers in the battery breaking area had the highest. Regular use of personal protective equipment by some workers in the "lead exposure zones" was not observed. Although the mean blood lead levels had been below 40 micro g/dL for more than 90% of the workers since 2001, more than 70% of workers reported concerns about their health while working in the smelter. Even though control measures were implemented, they were not adequate because in some areas lead in air exceeded the occupational exposure limit. Therefore, improvement of existing measures and regular monitoring of personal protective equipment use were included in the recommendations given to the smelter.

  18. Prevention of hepatic fibrosis with liver microsomal triglyceride transfer protein deletion in liver fatty acid binding protein null mice.

    PubMed

    Newberry, Elizabeth P; Xie, Yan; Kennedy, Susan M; Graham, Mark J; Crooke, Rosanne M; Jiang, Hui; Chen, Anping; Ory, Daniel S; Davidson, Nicholas O

    2017-03-01

    Blocking hepatic very low-density lipoprotein secretion through genetic or pharmacologic inhibition of microsomal triglyceride transfer protein (Mttp) causes hepatic steatosis, yet the risks for developing hepatic fibrosis are poorly understood. We report that liver-specific Mttp knockout mice (Mttp-LKO) exhibit both steatosis and fibrosis, which is exacerbated by a high-transfat/fructose diet. When crossed into germline liver fatty acid (FA) binding protein null mice (Mttp-LKO, i.e., double knockout mice) hepatic steatosis was greatly diminished and fibrosis prevented, on both low-fat and high-fat diets. The mechanisms underlying protection include reduced long chain FA uptake, shifts in FA distribution (lipidomic profiling), and metabolic turnover, specifically decreased hepatic 18:2 FA and triglyceride species and a shift in 18:2 FA use for oxidation versus incorporation into newly synthesized triglyceride. Double knockout mice were protected against fasting-induced hepatic steatosis (a model of enhanced exogenous FA delivery) yet developed steatosis upon induction of hepatic de novo lipogenesis with fructose feeding. Mttp-LKO mice, on either the liver FA binding protein null or Apobec-1 null background (i.e., apolipoprotein B100 only) exhibited only subtle increases in endoplasmic reticulum stress, suggesting that an altered unfolded protein response is unlikely to account for the attenuated phenotype in double knockout mice. Acute, antisense-mediated liver FA binding protein knockdown in Mttp-LKO mice also reduced FA uptake, increased oxidation versus incorporation of 18:2 species with complete reversal of hepatic steatosis, increased hepatic injury, and worsened fibrosis. Perturbing exogenous hepatic FA use modulates both hepatic steatosis and fibrosis in the setting of hepatic Mttp deletion, adding new insight into the pathophysiological mechanisms and consequences of defective very low-density lipoprotein secretion. (Hepatology 2017;65:836-852). © 2016 by

  19. Ganglioside-monosialic acid (GM1) prevents oxaliplatin-induced peripheral neurotoxicity in patients with gastrointestinal tumors.

    PubMed

    Zhu, Yanyun; Yang, Junlan; Jiao, Shunchang; Ji, Tiefeng

    2013-01-25

    Oxaliplatin, an effective antineoplastic agent againstgastrointestinal tumors, can cause severe peripheral neurotoxicity, which seriously limits its clinical application. To date, there are no effective treatments for this complication. Ganglioside-monosialic acid (GM1) has been shown to protect neurons against injuries and degeneration. The aim of this study was to evaluate the effects of GM1 on preventing oxaliplatin-induced neurotoxicity in patients with gastrointestinal tumors. In this study, 120 patients with gastrointestinal tumors were enrolled, andthey received the treatment of XELOX (oxaliplatin and capecitabine) and FOLFOX4 (oxaliplatin, leukovolin and 5-fluorouracil). The patients were randomly divided into two groups, the experimental group and control group, with60 patients ineach. On the day chemotherapy was initiated, the experimental group received GM1 intravenously (100 mg once daily) for 3 days, while no neuroprotective agents were applied in the control group. The incidence rates and classification of neurotoxicity in the two groups were evaluated and the differences between the two groups were examined. Furthermore, whether GM1 affected the therapeutic effects of chemotherapy was also examined. The grade of neurotoxicity in the experimental group was significantly lower than in the control group (P<0.05, Mann-Whitney U test). The probability of occurrence of low-grade neurotoxicity (grade 0 and 1) in the experimental group was higher than that in the control group (logistic ordinal regression); whereas the probability of occurrence of high-grade neurotoxicity (grade 2 and 3) in the experimental group was lower than in the control group (logistic ordinal regression). The data suggested that GM1 could reduce the grade of oxaliplatin-induced neurotoxicity and was an effective neuroprotective agent against oxaliplatin-induced high-grade neurotoxicity in patients with gastrointestinal tumors.

  20. Ganglioside-monosialic acid (GM1) prevents oxaliplatin-induced peripheral neurotoxicity in patients with gastrointestinal tumors

    PubMed Central

    2013-01-01

    Background Oxaliplatin, an effective antineoplastic agent againstgastrointestinal tumors, can cause severe peripheral neurotoxicity, which seriously limits its clinical application. To date, there are no effective treatments for this complication. Ganglioside-monosialic acid (GM1) has been shown to protect neurons against injuries and degeneration. The aim of this study was to evaluate the effects of GM1 on preventing oxaliplatin-induced neurotoxicity in patients with gastrointestinal tumors. Methods In this study, 120 patients with gastrointestinal tumors were enrolled, andthey received the treatment of XELOX (oxaliplatin and capecitabine) and FOLFOX4 (oxaliplatin, leukovolin and 5-fluorouracil). The patients were randomly divided into two groups, the experimental group and control group, with60 patients ineach. On the day chemotherapy was initiated, the experimental group received GM1 intravenously (100 mg once daily) for 3 days, while no neuroprotective agents were applied in the control group. The incidence rates and classification of neurotoxicity in the two groups were evaluated and the differences between the two groups were examined. Furthermore, whether GM1 affected the therapeutic effects of chemotherapy was also examined. Results The grade of neurotoxicity in the experimental group was significantly lower than in the control group (P<0.05, Mann–Whitney U test). The probability of occurrence of low-grade neurotoxicity (grade 0 and 1) in the experimental group was higher than that in the control group (logistic ordinal regression); whereas the probability of occurrence of high-grade neurotoxicity (grade 2 and 3) in the experimental group was lower than in the control group (logistic ordinal regression). Conclusion The data suggested that GM1 could reduce the grade of oxaliplatin-induced neurotoxicity and was an effective neuroprotective agent against oxaliplatin-induced high-grade neurotoxicity in patients with gastrointestinal tumors. PMID:23351188

  1. Atherosclerosis-preventing activity of lactic acid bacteria-fermented milk-soymilk supplemented with Momordica charantia.

    PubMed

    Tsai, Tsung-Yu; Chu, Li-Han; Lee, Chun-Lin; Pan, Tzu-Ming

    2009-03-11

    In this study, the milk-soymilk and milk-soymilk supplemented with Momordica charantia , a common oriental vegetable possessing medicinal activities, were fermented by lactic bacteria. The objective of this study was to investigate the effects of milk-soymilk and fermented milk-soymilk with or without M. charantia on atherosclerosis in hyperlipidemic hamsters. Fermented 25% milk and 75% soymilk combinations, supplemented with 1% M. charantia solution, can improve the acceptability of the fermented beverage. A total of 72 male Golden Syrian hamsters were divided into 9 groups (n = 8/group), and experimental diets were provided with a normal diet for the normal group and a high-cholesterol diet for others. The milk-soymilk and fermented milk-soymilk with or without M. charantia were administrated for 8 weeks. The milk-soymilk and fermented milk-soymilk with and without M. charantia were able to significantly decrease (p < 0.05) the serum cholesterol and the atherosclerotic plaque in aorta based on the comparison to the high-cholesterol diet (H) group. The groups on fermented milk-soymilk by Lactobacillus plantarum NTU 102 with or without M. charantia could significantly decrease (p < 0.05) the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C). The femented milk-soymilk by Lactobacillus paracasei subsp. paracasei NTU 101 supplemented with M. charantia had an anti-atherosclerotic activity by increasing superoxide dismutase (SOD) and total antioxidant status (TAS) activity of the blood and relieving the degree of thiobarbituric acid reactive substances (TBARS) compared to the other treatments. It is concluded that the milk-soymilk and the fermented milk-soymilk supplemented with or without M. charantia by L. paracasei subsp. paracasei NTU 101 are effective in preventing and retarding the hyperlipidemia-induced oxidative stress and atherosclerosis.

  2. Prevention of pancreatic fistula using polyethylene glycolic acid mesh reinforcement around pancreatojejunostomy: the propensity score-matched analysis.

    PubMed

    Kang, Jae Seung; Han, Youngmin; Kim, Hongbeom; Kwon, Wooil; Kim, Sun-Whe; Jang, Jin-Young

    2017-03-01

    Several small-scale studies have shown that wrapping polyethylene glycolic acid (PGA) mesh around the anastomotic site reinforced pancreaticojejunostomy following pancreatoduodenectomy (PD) with favorable outcomes. This study investigated the efficacy of PGA mesh for reducing postoperative pancreatic fistula (POPF) and evaluated other risk factors for POPF. This study enrolled 464 consecutive patients who underwent PD performed by one surgeon between 2006 and 2015, including a PGA group of 281 patients (60.6%) and a control group of 183 patients (39.4%). All pancreatico-enteric anastomoses were performed using double-layered, duct-to-mucosa, end-to-side pancreaticojejunostomy. Mean patient age was 63.1 years. The rates of overall (27.0% vs. 37.2%, P = 0.024) and clinically relevant (Grades B, C; 13.9% vs. 24.0%, P = 0.006) POPF were significantly lower in the PGA than in the control group. Following propensity score matching, the rates of clinically relevant POPF (12.6% vs. 22.4%, P = 0.024) and complications (40.2% vs. 63.8%, P < 0.001) remained significantly lower in the PGA group. Multivariate analysis showed that non-pancreatic disease, greater blood loss, higher body mass index, and non-application of PGA mesh were significantly associated with the development of clinically relevant POPF. PGA mesh reinforcement of pancreaticojejunostomy may prevent POPF as well as reducing overall abdominal complications after PD. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  3. Salvianolic acid B functioned as a competitive inhibitor of matrix metalloproteinase-9 and efficiently prevented cardiac remodeling

    PubMed Central

    2010-01-01

    Background Infarct-induced left ventricular (LV) remodeling is a deleterious consequence after acute myocardial infarction (MI) which may further advance to congestive heart failure. Therefore, new therapeutic strategies to attenuate the effects of LV remodeling are urgently needed. Salvianolic acid B (SalB) from Salviae mitiorrhizae, which has been widely used in China for the treatment of cardiovascular diseases, is a potential candidate for therapeutic intervention of LV remodeling targeting matrix metalloproteinase-9 (MMP-9). Results Molecular modeling and LIGPLOT analysis revealed in silico docking of SalB at the catalytic site of MMP-9. Following this lead, we expressed truncated MMP-9 which contains only the catalytic domain, and used this active protein for in-gel gelatin zymography, enzymatic analysis, and SalB binding by Biacore. Data generated from these assays indicated that SalB functioned as a competitive inhibitor of MMP-9. In our rat model for cardiac remodeling, western blot, echocardiography, hemodynamic measurement and histopathological detection were used to detect the effects and mechanism of SalB on cardio-protection. Our results showed that in MI rat, SalB selectively inhibited MMP-9 activities without affecting MMP-9 expression while no effect of SalB was seen on MMP-2. Moreover, SalB treatment in MI rat could efficiently increase left ventricle wall thickness, improve heart contractility, and decrease heart fibrosis. Conclusions As a competitive inhibitor of MMP-9, SalB presents significant effects on preventing LV structural damage and preserving cardiac function. Further studies to develop SalB and its analogues for their potential for cardioprotection in clinic are warranted. PMID:20735854

  4. Conjugated linoleic acid prevents ovariectomy-induced bone loss in mice by modulating both osteoclastogenesis and osteoblastogenesis

    PubMed Central

    Rahman, Md Mizanur; Fernandes, Gabriel; Williams, Paul

    2014-01-01

    Postmenopausal osteoporosis due to estrogen deficiency is associated with severe morbidity and mortality. Beneficial effects of conjugated linoleic acid (CLA) on bone mineral density (BMD) have been reported in mice, rats and humans, but the effect of long term CLA supplementation against ovariectomy-induced bone loss in mice and the mechanisms underlying this effect have not been studied yet. Eight weeks old ovariectomized (Ovx) and sham operated C57BL/6 mice were fed either a diet containing 0.5% safflower oil (SFO) or 0.5% CLA for 24 weeks to examine BMD, bone turn over markers and osteotropic factors. Bone marrow (BM) cells were cultured to determine the effect on inflammation, osteoclastogenesis, and osteoblastogenesis. SFO/Ovx mice had significantly lower femoral, tibial and lumbar BMD compared to SFO/Sham mice; whereas, no difference was found between CLA/OVX and CLA/Sham mice. CLA inhibited bone resorption markers whereas enhanced bone formation markers in Ovx mice as compared to SFO fed mice. RT-PCR and FACS analyses of splenocytes revealed that CLA inhibited pro-osteoclastogenic RANKL and stimulated decoy receptor of RANKL, OPG expression. CLA also inhibited pro-inflammatory cytokine and enhanced anti-inflammatory cytokine production of LPS-stimulated splenocytes and bone marrow cells. Furthermore, CLA inhibited osteoclast differentiation in BM and stimulated osteoblast differentiation in BM stromal cells as confirmed by TRAP and Alizarin Red staining, respectively. In conclusion, CLA may prevent postmenopausal bone loss not only by inhibiting excessive bone resorption due to estrogen deficiency but also by stimulating new bone formation. CLA might be a potential alternative therapy against osteoporotic bone loss. PMID:24338525

  5. Weekly iron-folic acid supplements to prevent anemia among Cambodian women in three settings: process and outcomes of social marketing and community mobilization.

    PubMed

    Kanal, Koum; Busch-Hallen, Jennifer; Cavalli-Sforza, Tommaso; Crape, Byron; Smitasiri, Suttilak

    2005-12-01

    Social marketing and community mobilization approaches were applied in a pilot program to introduce weekly iron-folic acid supplementation to prevent anemia in Cambodian women of reproductive age. The program was implemented in three very different environments: secondary school girls, women working in garment factories in the vicinity of Phnom Penh, and women in rural villages. Each population provided its own challenges and obstacles. However, all three groups of women showed substantial improvements in knowledge about the causes, consequences, and prevention of anemia, and the large majority reported interest in continuing to take the supplements.

  6. Preventive effect of a high fluoride toothpaste and arginine-carbonate toothpaste on dentinal tubules exposure followed by acid challenge: a dentine permeability evaluation.

    PubMed

    Pinto, Shelon Cristina Souza; Bandéca, Matheus Coelho; Pinheiro, Michele Carolina; Cavassim, Rodrigo; Tonetto, Mateus Rodrigues; Borges, Alvaro Henrique; Sampaio, José Eduardo Cezar

    2014-06-24

    Considering the current high use of high fluoride toothpastes, the aim of the study was to quantify alterations in the root dentine permeability submitted to treatment with a high fluoride toothpaste and 8% arginine, calcium carbonate, sodium monofluorophosphate toothpaste as a preventive treatment for dentinal tubules exposure followed by acid challenge. Thirty-third molars were sectioned below the cementoenamel. The root segments were connected to a hydraulic pressure apparatus to measure dentine permeability after the following sequential steps (n = 10 per group): I) Baseline; II) treatment with phosphoric acid for 30 s (maximum permeability); III) Toothbrushing (1 min) according to the experimental groups (G1- control; G2- 5000 ppm fluoride toothpaste; G3- 8% arginine-calcium carbonate toothpaste); IV) acid challenge for 5 min (orange juice). The data were converted into percentage, considering stage II as 100%. The results have shown a statistically significant decreasing on dentine permeability after treatment with toothpaste (Friedman test and Dunn's post hoc test). Comparison among groups demonstrated a high increasing on dentine permeability when acid challenge was performed after toothbrushing with distilled water (control group) (Kruskal-Wallis and Dunn's post hoc test). The toothpaste treatment may provide sufficient resistance on dentine surface, preventing dentinal tubules exposure after acid challenge.

  7. Preventive effect of a high fluoride toothpaste and arginine-carbonate toothpaste on dentinal tubules exposure followed by acid challenge: a dentine permeability evaluation

    PubMed Central

    2014-01-01

    Background Considering the current high use of high fluoride toothpastes, the aim of the study was to quantify alterations in the root dentine permeability submitted to treatment with a high fluoride toothpaste and 8% arginine, calcium carbonate, sodium monofluorophosphate toothpaste as a preventive treatment for dentinal tubules exposure followed by acid challenge. Methods Thirty-third molars were sectioned below the cementoenamel. The root segments were connected to a hydraulic pressure apparatus to measure dentine permeability after the following sequential steps (n = 10 per group): I) Baseline; II) treatment with phosphoric acid for 30 s (maximum permeability); III) Toothbrushing (1 min) according to the experimental groups (G1- control; G2- 5000 ppm fluoride toothpaste; G3- 8% arginine-calcium carbonate toothpaste); IV) acid challenge for 5 min (orange juice). The data were converted into percentage, considering stage II as 100%. Results The results have shown a statistically significant decreasing on dentine permeability after treatment with toothpaste (Friedman test and Dunn’s post hoc test). Comparison among groups demonstrated a high increasing on dentine permeability when acid challenge was performed after toothbrushing with distilled water (control group) (Kruskal-Wallis and Dunn’s post hoc test). Conclusion The toothpaste treatment may provide sufficient resistance on dentine surface, preventing dentinal tubules exposure after acid challenge. PMID:24958423

  8. Diabetic HDL-associated myristic acid inhibits acetylcholine-induced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin.

    PubMed

    White, James; Guerin, Theresa; Swanson, Hollie; Post, Steven; Zhu, Haining; Gong, Ming; Liu, Jun; Everson, William V; Li, Xiang-An; Graf, Gregory A; Ballard, Hubert O; Ross, Stuart A; Smart, Eric J

    2008-01-01

    In the current study, we examined whether diabetes affected the ability of HDL to stimulate nitric oxide (NO) production. Using HDL isolated from both diabetic humans and diabetic mouse models, we found that female HDL no longer induced NO synthesis, despite containing equivalent amounts of estrogen as nondiabetic controls. Furthermore, HDL isolated from diabetic females and males prevented acetylcholine-induced stimulation of NO generation. Analyses of both the human and mouse diabetic HDL particles showed that the HDLs contained increased levels of myristic acid. To determine whether myristic acid associated with HDL particles was responsible for the decrease in NO generation, myristic acid was added to HDL isolated from nondiabetic humans and mice. Myristic acid-associated HDL inhibited the generation of NO in a dose-dependent manner. Importantly, diabetic HDL did not alter the levels of endothelial NO synthase or acetylcholine receptors associated with the cells. Surprisingly, diabetic HDL inhibited ionomycin-induced stimulation of NO production without affecting ionomycin-induced increases in intracellular calcium. Further analysis indicated that diabetic HDL prevented calmodulin from interacting with endothelial NO synthase (eNOS) but did not affect the activation of calmodulin kinase or calcium-independent mechanisms for stimulating eNOS. These studies are the first to show that a specific fatty acid associated with HDL inhibits the stimulation of NO generation. These findings have important implications regarding cardiovascular disease in diabetic patients.

  9. The influence of mechanochemical modification on prevention of toxic ability of humic acids towards phenanthrene in aquatic environment

    NASA Astrophysics Data System (ADS)

    Shekhovtsova, N. S.; Maltseva, E. V.; Glyzina, T. S.; Ovchinnikova, I. S.

    2015-11-01

    The aim of the research work is to quantify interaction between phenanthrene with modified humic acids in aquatic environment. The changes in the structure and properties of humic acids after modifications were studied with 1H NMR spectroscopy and potentiometric titration methods. Our research demonstrates that the application of thiourea as a modified agent increases the binding capacity of humic acids towards phenanthrene.

  10. Arjunolic acid, a triterpenoid saponin, prevents acetaminophen (APAP)-induced liver and hepatocyte injury via the inhibition of APAP bioactivation and JNK-mediated mitochondrial protection.

    PubMed

    Ghosh, Jyotirmoy; Das, Joydeep; Manna, Prasenjit; Sil, Parames C

    2010-02-15

    Acetaminophen (APAP) is a widely used analgesic and antipyretic drug and is safe at therapeutic doses but its overdose frequently causes liver injury. In earlier studies, we demonstrated that arjunolic acid (AA) has a protective effect against chemically induced hepatotoxicity. The purpose of this study was to explore whether AA plays any protective role against APAP-induced acute hepatotoxicity and, if so, what molecular pathways it utilizes for the mechanism of its protective action. Exposure of rats to a hepatotoxic dose of acetaminophen (700 mg/kg, ip) altered a number of biomarkers (related to hepatic oxidative stress), increased reactive oxygen species production, reduced cellular adenosine triphosphate level, and induced necrotic cell death. Arjunolic acid pretreatment (80 mg/kg, orally), on the other hand, afforded significant protection against liver injury. Arjunolic acid also prevented acetaminophen-induced hepatic glutathione depletion and APAP metabolite formation although arjunolic acid itself did not affect hepatic glutathione levels. The results suggest that this preventive action of arjunolic acid is due to the metabolic inhibition of specific forms of cytochrome P450 that activate acetaminophen to N-acetyl-p-benzoquinone imine. In addition, administration of arjunolic acid 4 h after acetaminophen intoxication reduced acetaminophen-induced JNK and downstream Bcl-2 and Bcl-xL phosphorylation, thus protecting against mitochondrial permeabilization, loss of mitochondrial membrane potential, and cytochrome c release. In conclusion, the data suggest that arjunolic acid affords protection against acetaminophen-induced hepatotoxicity through inhibition of P450-mediated APAP bioactivation and inhibition of JNK-mediated activation of mitochondrial permeabilization. Copyright 2009 Elsevier Inc. All rights reserved.

  11. An Evaluation of a Teat Dip with Dodecyl Benzene Sulfonic Acid in Preventing Bovine Mammary Gland Infection from Experimental Exposure to Streptococcus agalactiae and Staphylococcus aureus

    PubMed Central

    Barnum, D. A.; Johnson, R. E.; Brooks, B. W.

    1982-01-01

    The effectiveness of a teat dip with dodecyl benzene sulfonic acid (1.94%) for the prevention of intramammary infections was determined in cows experimentally challenged with Streptococcus agalactiae and Staphylococcus aureus. The infection rates with Streptococcus agalactiae and Staphylococcus aureus were 62.5% and 75% in undipped quarters, 12.5% and 21.5% in dipped quarters with a reduction rate of 80% and 71% respectively. The significance of some findings in relation to mastitis control are discussed. PMID:17422110

  12. A cost minimisation analysis of olive oil versus hyperoxygenated fatty acid treatment for the prevention of pressure ulcers in primary health care: A randomised controlled trial.

    PubMed

    Lupiañez-Pérez, Inmaculada; Morilla-Herrera, Juan Carlos; Kaknani-Uttumchanchandani, Shakira; Lupiañez-Perez, Yolanda; Cuevas-Fernandez-Gallego, Magdalena; Martin-Santos, Francisco; Caro-Bautista, Jorge; Morales-Asencio, Jose Miguel

    2017-09-18

    Pressure ulcers represent a major current health problem and cause an important economic impact on the health care system. Most studies on the prevention of pressure ulcers have been carried out in hospital contexts, with respect to the use of hyperoxygenated fatty acids, and to date no studies have specifically examined the use of olive oil-based treatments. To evaluate the cost of using extra virgin olive oil, rather than hyperoxygenated fatty acids, in the prevention of pressure ulcers among persons with impaired mobility and receiving home care. Cost minimisation analysis of the results obtained from a non-inferiority, triple-blind, parallel, multicentre, randomised clinical trial. Population attending primary health care centres in Andalusia (Spain). 831 immobilised patients at risk of suffering pressure ulcers. These persons were included in the study and randomly assigned as follows: 437 to the olive oil group and 394 to the hyperoxygenated fatty acid group. At the end of the follow-up period, the results obtained by the olive oil group were not inferior to those of the hyperoxygenated fatty acid group, and did not exceed the 10% delta limit. The total treatment cost for 16 weeks was €19,758 with hyperoxygenated fatty acids and €9,566 with olive oil. Overall, the olive oil treatment was €10,192 less costly. It has been concluded the non-inferiority of olive oil makes this product an effective alternative for the prevention of pressure ulcers in patients who are immobilised and in a domestic environment. This treatment enables considerable savings in direct costs. This article is protected by copyright. All rights reserved. © 2017 by the Wound Healing Society.

  13. Ellagic acid prevents rat colon carcinogenesis induced by 1, 2 dimethyl hydrazine through inhibition of AKT-phosphoinositide-3 kinase pathway.

    PubMed

    Umesalma, Syed; Sudhandiran, Ganapasam

    2011-06-25

    Colon cancer is the third most malignant neoplasm in the world and chemoprevention through dietary intervention is an emerging option to reduce its mortality. Ellagic acid (EA) a major component of berries possesses attractive biological deeds. This study is aimed to investigate the effect of ellagic acid in fostering apoptosis in 1,2-dimethyl hydrazine (DMH) mediated experimental colon carcinogenesis model. Wistar male rats were segregated into four groups: group I-control rats, group II-rats received ellagic acid (60 mg/kg body weight p.o. every day), rats in group III-induced with DMH (20 mg/kg body weight, s.c.) for 15 weeks, DMH-induced group IV rats were initiated with ellagic acid treatment. The present study is designed to explore the significance of phosphoinositide-3-kinase (PI3K)/Akt molecular pathway as well as ellagic acid's chemopreventive effect in colon cancer. DMH-induced rats exhibited elevated expressions of PI3K and Akt as confirmed by immunofluorescence, immunoblot and confocal microscopic analysis. Mechanistically, ellagic acid was found to prevent PI3K/Akt activation that in turn, results in modulation of its downstream Bcl-2 family proteins. Bax expression and caspase-3 activation was noted after ellagic acid supplementation leading to elevation of cytochrome c (cyt c) levels and finally cell death. These observations were supported by the DNA fragmentation results, which showed the occurrence of apoptosis. This study reveals the involvement of PI3K-Akt signaling through which ellagic acid induces apoptosis and subsequently suppresses colon cancer during DMH-induced rat colon carcinogenesis. In conclusion, our findings demonstrate that ellagic acid begets apoptosis in DMH-induced colon carcinoma.

  14. Caffeic acid prevents acetaminophen-induced liver injury by activating the Keap1-Nrf2 antioxidative defense system.

    PubMed

    Pang, Chun; Zheng, Zhiyong; Shi, Liang; Sheng, Yuchen; Wei, Hai; Wang, Zhengtao; Ji, Lili

    2016-02-01

    Acute liver failure induced by acetaminophen (APAP) overdose is the main cause of drug-induced liver injury (DILI). Caffeic acid (CA) is a phenolic compound from many natural products. This study aims to investigate the protective mechanism of CA in APAP-induced liver injury. The results of serum alanine/aspartate aminotransferases (ALT/AST), liver myeloperoxidase (MPO) activity, liver glutathione (GSH) and reactive oxygen species (ROS) levels demonstrated the protection of CA against APAP-induced liver injury. Liver histological observation provided further evidences of CA-induced protection. CA was found to reverse the APAP-induced decreased cell viability in human normal liver L-02 cells and HepG2 cells. CA also reduced the increased cellular ROS level induced by APAP in hepatocytes. The results of luciferase assay and Western-blot analysis showed that CA increased the transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2) in the presence of APAP. Nrf2 siRNA reduced the protection of CA against APAP-induced hepatotoxicity. CA also reversed the APAP-induced decreased mRNA and protein expression of heme oxygenase 1 (HO-1) and quinone oxidoreductase 1(NQO1). In addition, HO-1 inhibitor zinc protoporphyrin (ZnPP) and NQO1 inhibitor diminutol (Dim) reduced the protection of CA against APAP-induced hepatotoxicity. CA also decreased the expression of kelch-like ECH-associated protein-1(Keap1). Molecular docking indicated the potential interacting of CA with Nrf2 binding site in the Keap1 protein. CA had little effect on the enzymatic activity of cytochrome P450 (CYP) 3A4 and CYP2E1 in vitro. In conclusion, we demonstrated that CA prevented APAP-induced hepatotoxicity by decreasing Keap1 expression, inhibiting binding of Keap1 to Nrf2, and thus activating Nrf2 and leading to increased expression of antioxidative signals including HO-1 and NQO1. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. The Extract of Aster Koraiensis Prevents Retinal Pericyte Apoptosis in Diabetic Rats and Its Active Compound, Chlorogenic Acid Inhibits AGE Formation and AGE/RAGE Interaction

    PubMed Central

    Kim, Junghyun; Jo, Kyuhyung; Lee, Ik-Soo; Kim, Chan-Sik; Kim, Jin Sook

    2016-01-01

    Retinal capillary cell loss is a hallmark of early diabetic retinal changes. Advanced glycation end products (AGEs) are believed to contribute to retinal microvascular cell loss in diabetic retinopathy. In this study, the protective effects of Aster koraiensis extract (AKE) against damage to retinal vascular cells were investigated in streptozotocin (STZ)-induced diabetic rats. To examine this issue further, AGE accumulation, nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) were investigated using retinal trypsin digests from streptozotocin-induced diabetic rats. In the diabetic rats, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling)-positive retinal microvascular cells were markedly increased. Immunohistochemical studies revealed that AGEs were accumulated within the retinal microvascular cells, and this accumulation paralleled the activation of NF-κB and the expression of iNOS in the diabetic rats. However, AKE prevented retinal microvascular cell apoptosis through the inhibition of AGE accumulation and NF-κB activation. Moreover, to determine the active compounds of AKE, two major compounds, chlorogenic acid and 3,5-di-O-caffeoylquinic acid, were tested in an in vitro assay. Among these compounds, chlorogenic acid significantly reduced AGE formation as well as AGE/RAGE (receptor for AGEs) binding activity. These results suggest that AKE, particularly chlorogenic acid, is useful in inhibiting AGE accumulation in retinal vessels and exerts a preventive effect against the injuries of diabetic retinal vascular cells. PMID:27657123

  16. European Stroke Prevention Study 2: A study of low-dose acetylsalicylic acid and of high dose dipyridamole in secondary prevention of cerebro-vascular accidents.

    PubMed

    1995-11-01

    In spite of some data being added to our knowledge of the effect of antiplatelets in secondary prevention of brain ischemic lesion in recent years, the main reasons to perform a second European Stroke Prevention Study (ESPS 2), which started in 1987-1988, were: (a) clarify the relative roles of aspirin (ASA) and dipyridamole (DP) alone or in combination; (b) confirm the efficacy of small doses of ASA and, so doing, decrease the number of drop-outs due to ASA side effects; (c) join information to the effect of antiplatelets in complete stroke. General characteristics of the sample of 6602 patients are presented and compared with other major trials and series. The patients in the four treatment arms (aspirin, dipyridamole, aspirin + dipyridamole and placebo) are compared. The more relevant features and risk factors known to influence long term prognosis are described and discussed. The small proportion of patients included with TIA (23.7%) and the comparability among treatment groups are stressed. No relevant differences have been found, among groups, on the sex or age distribution, prevalence of hypertension, diabetes, previous vascular events or atrial fibrillation, nor in the characteristics of the accident leading to the inclusion in trial.

  17. Long Chain Fatty Acid Acylated Derivatives of Quercetin-3-O-Glucoside as Antioxidants to Prevent Lipid Oxidation

    PubMed Central

    Warnakulasuriya, Sumudu N.; Ziaullah; Rupasinghe, H.P. Vasantha

    2014-01-01

    Flavonoids have shown promise as natural plant-based antioxidants for protecting lipids from oxidation. It was hypothesized that their applications in lipophilic food systems can be further enhanced by esterification of flavonoids with fatty acids. Quercetin-3-O-glucoside (Q3G) was esterified individually with six selected long chain fatty acids: stearic acid (STA), oleic acid (OLA), linoleic acid (LNA), α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA), using Candida antarctica B lipase as the biocatalyst. The antioxidant activity of esterified flavonoids was evaluated using lipid oxidation model systems of poly-unsaturated fatty acids-rich fish oil and human low density lipoprotein (LDL), in vitro. In the oil-in-water emulsion, Q3G esters exhibited 50% to 100% inhibition in primary oxidation and 30% to 75% inhibition in secondary oxidation. In bulk oil, Q3G esters did not provide considerable protection from lipid oxidation; however, Q3G demonstrated more than 50% inhibition in primary oxidation. EPA, DHA and ALA esters of Q3G showed significantly higher inhibition in Cu2+- and peroxyl radical-induced LDL oxidation in comparison to Q3G. PMID:25384198

  18. Iso-α-acids, Bitter Components of Beer, Prevent Inflammation and Cognitive Decline Induced in a Mouse Model of Alzheimer's Disease.

    PubMed

    Ano, Yasuhisa; Dohata, Atsushi; Taniguchi, Yoshimasa; Hoshi, Ayaka; Uchida, Kazuyuki; Takashima, Akihiko; Nakayama, Hiroyuki

    2017-03-03

    Alongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long, healthy life. Here we found that iso-α-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferator-activated receptor γ. In normal mice, oral administration of iso-α-acids led to a significant increase both in CD11b and CD206 double-positive anti-inflammatory type microglia (p < 0.05) and in microglial phagocytosis in the brain. In Alzheimer's model 5xFAD mice, oral administration of iso-α-acids resulted in a 21% reduction in amyloid β in the cerebral cortex as observed by immunohistochemical analysis, a significant reduction in inflammatory cytokines such as IL-1β and chemokines including macrophage inflammatory protein-1α in the cerebral cortex (p < 0.05) and a significant improvement in a novel object recognition test (p < 0.05), as compared with control-fed 5xFAD mice. The differences in iso-α-acid-fed mice were due to the induction of microglia to an anti-inflammatory phenotype. The present study is the first to report that amyloid β deposition and inflammation are suppressed in a mouse model of Alzheimer's disease by a single component, iso-α-acids, via the regulation of microglial activation. The suppression of neuroinflammation and improvement in cognitive function suggests that iso-α-acids contained in beer may be useful for the prevention of dementia. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies.

    PubMed

    Wilson, R Douglas

    2007-12-01

    To provide information regarding the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies, so that physicians, midwives, nurses, and other health care workers can assist in the education of women in the pre-conception phase of their health care. OPTION: Supplementation with folic acid and vitamins is problematic, since 50% of pregnancies are unplanned, and women's health status may not be optimal when they conceive. Folic acid in combination with a multivitamin supplement has been associated with a decrease in specific birth defects. Medline, PubMed, and Cochrane Database were searched for relevant English language articles published between 1985 and 2007. The previous Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of November 1993 and statements from the American College of Obstetrics and Gynecology and Canadian College of Medical Geneticists were also reviewed in developing this clinical practice guideline. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Promoting the use of folic acid and a multivitamin supplement among women of reproductive age will reduce the incidence of birth defects. The costs are those of daily vitamin supplementation and eating a healthy diet. 1. Women in the reproductive age group should be advised about the benefits of folic acid in addition to a multivitamin supplement during wellness visits (birth control renewal, Pap testing, yearly examination) especially if pregnancy is contemplated. (III-A) 2. Women should be advised to maintain a healthy diet, as recommended in Eating Well With Canada's Food Guide (Health Canada). Foods containing excellent to good sources of folic acid are fortified grains, spinach, lentils, chick peas, asparagus, broccoli, peas, Brussels sprouts, corn, and oranges. However, it is unlikely that diet alone can provide

  20. Dietary Omega-3 Polyunsaturated Fatty Acids Prevent Vascular Dysfunction and Attenuate Cytochrome P4501A1 Expression by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin.

    PubMed

    Wiest, Elani F; Walsh-Wilcox, Mary T; Rothe, Michael; Schunck, Wolf-Hagen; Walker, Mary K

    2016-11-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFAs) found in fish protect against cardiovascular morbidity and mortality; however, many individuals avoid fish consumption due to concerns about pollutants. We tested the hypothesis that n-3 PUFAs would prevent vascular dysfunction induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). C57Bl/6 male mice were fed a chow or n-3 PUFA diet for 10 weeks and were exposed to vehicle or 300 ng/kg/d TCDD during the final 2 weeks on each diet. Aortic vasoconstriction mediated by arachidonic acid (AA) ± SKF525 (P450 inhibitor) or SQ29548 (thromboxane/prostanoid [TP] receptor antagonist) was assessed. RBC fatty acids and expression of n-3 and n-6 PUFA metabolites were analyzed. Cytochrome P4501A1 (CYP1A1), CYP1B1, and aryl hydrocarbon receptor (AHR) expression was measured. TCDD significantly increased AA-mediated vasoconstriction on a chow diet by increasing the contribution of P450s and TP receptor to the constriction response. In contrast, the n-3 PUFA diet prevented the TCDD-induced increase in AA vasoconstriction and normalized the contribution of P450s and TP receptor. Although TCDD increased the levels of AA vasoconstrictors on the chow diet, this increase was prevent by the n-3 PUFA diet. Additionally, the n-3 PUFA diet significantly increased the levels of n-3 PUFA-derived vasodilators and TCDD increased these levels further. Interestingly, the n-3 PUFA diet significantly attenuated CYP1A1 induction by TCDD without a significant effect on AHR expression. These data suggest that n-3 PUFAs can prevent TCDD-induced vascular dysfunction by decreasing vasoconstrictors, increasing vasodilators, and attenuating CYP1A1 induction, which has been shown previously to contribute to TCDD-induced vascular dysfunction.

  1. The Extracellular Chaperone Haptoglobin Prevents Serum Fatty Acid-promoted Amyloid Fibril Formation of β2-Microglobulin, Resistance to Lysosomal Degradation, and Cytotoxicity

    PubMed Central

    Sultan, Abdullah; Raman, Bakthisaran; Rao, Ch. Mohan; Tangirala, Ramakrishna

    2013-01-01

    Fibril formation of β2-microglobulin and associated inflammation occur in patients on long term dialysis. We show that the plasma protein haptoglobin prevents the fatty acid-promoted de novo fibril formation of β2-microglobulin even at substoichiometric concentration. The fibrils are cytotoxic, and haptoglobin abolishes the cytotoxicity by preventing fibril formation. Haptoglobin does not alleviate the cytotoxicity of preformed fibrils. Fibrillar β2-microglobulin is resistant to lysosomal degradation. However, the species of β2-microglobulin populated in the presence of haptoglobin is susceptible to degradation. We observed that haptoglobin interacts with oligomeric prefibrillar species of β2-microglobulin but not with monomeric or fibrillar β2-microglobulin that may underlie the molecular mechanism. 1,1′-Bis(4-anilino)naphthalene-5,5′-disulfonic acid cross-linking to haptoglobin significantly compromises its chaperone activity, suggesting the involvement of hydrophobic surfaces. Haptoglobin is an acute phase protein whose level increases severalfold during inflammation, where local acidosis can occur. Our data show that haptoglobin prevents fibril formation of β2-microglobulin under conditions of physiological acidosis (between pH 5.5 and 6.5) but with relatively decreased efficiency. However, compromise in its chaperone activity under these conditions is more than compensated by its increased level of expression under inflammation. Erythrolysis is known to release hemoglobin into the plasma. Haptoglobin forms a 1:1 (mol/mol) complex with hemoglobin. This complex, like haptoglobin, interacts with the prefibrillar species of β2-microglobulin, preventing its fibril formation and the associated cytotoxicity and resistance to intracellular degradation. Thus, our study demonstrates that haptoglobin is a potential extracellular chaperone for β2-microglobulin even in moderately acidic conditions relevant during inflammation, with promising therapeutic

  2. Potential for dietary ω-3 fatty acids to prevent nonalcoholic fatty liver disease and reduce the risk of primary liver cancer.

    PubMed

    Jump, Donald B; Depner, Christopher M; Tripathy, Sasmita; Lytle, Kelli A

    2015-11-01

    Nonalcoholic fatty liver disease (NAFLD) has increased in parallel with central obesity, and its prevalence is anticipated to increase as the obesity epidemic remains unabated. NAFLD is now the most common cause of chronic liver disease in developed countries and is defined as excessive lipid accumulation in the liver, that is, hepatosteatosis. NAFLD ranges in severity from benign fatty liver to nonalcoholic steatohepatitis (NASH), and NASH is characterized by hepatic injury, inflammation, oxidative stress, and fibrosis. NASH can progress to cirrhosis, and cirrhosis is a risk factor for primary hepatocellular carcinoma (HCC). The prevention of NASH will lower the risk of cirrhosis and NASH-associated HCC. Our studies have focused on NASH prevention. We developed a model of NASH by using mice with the LDL cholesterol receptor gene ablated fed the Western diet (WD). The WD induces a NASH phenotype in these mice that is similar to that seen in humans and includes robust induction of hepatic steatosis, inflammation, oxidative stress, and fibrosis. With the use of transcriptomic, lipidomic, and metabolomic approaches, we examined the capacity of 2 dietary ω-3 (n-3) polyunsaturated fatty acids, eicosapentaenoic acid (20:5ω-3; EPA) and docosahexaenoic acid (22:6ω-3; DHA), to prevent WD-induced NASH. Dietary DHA was superior to EPA at attenuating WD-induced changes in plasma lipids and hepatic injury and at reversing WD effects on hepatic metabolism, oxidative stress, and fibrosis. The outcome of these studies suggests that DHA may be useful in preventing NASH and reducing the risk of HCC.

  3. Potential for Dietary ω-3 Fatty Acids to Prevent Nonalcoholic Fatty Liver Disease and Reduce the Risk of Primary Liver Cancer123

    PubMed Central

    Jump, Donald B; Depner, Christopher M; Tripathy, Sasmita; Lytle, Kelli A

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has increased in parallel with central obesity, and its prevalence is anticipated to increase as the obesity epidemic remains unabated. NAFLD is now the most common cause of chronic liver disease in developed countries and is defined as excessive lipid accumulation in the liver, that is, hepatosteatosis. NAFLD ranges in severity from benign fatty liver to nonalcoholic steatohepatitis (NASH), and NASH is characterized by hepatic injury, inflammation, oxidative stress, and fibrosis. NASH can progress to cirrhosis, and cirrhosis is a risk factor for primary hepatocellular carcinoma (HCC). The prevention of NASH will lower the risk of cirrhosis and NASH-associated HCC. Our studies have focused on NASH prevention. We developed a model of NASH by using mice with the LDL cholesterol receptor gene ablated fed the Western diet (WD). The WD induces a NASH phenotype in these mice that is similar to that seen in humans and includes robust induction of hepatic steatosis, inflammation, oxidative stress, and fibrosis. With the use of transcriptomic, lipidomic, and metabolomic approaches, we examined the capacity of 2 dietary ω-3 (n–3) polyunsaturated fatty acids, eicosapentaenoic acid (20:5ω-3; EPA) and docosahexaenoic acid (22:6ω-3; DHA), to prevent WD-induced NASH. Dietary DHA was superior to EPA at attenuating WD-induced changes in plasma lipids and hepatic injury and at reversing WD effects on hepatic metabolism, oxidative stress, and fibrosis. The outcome of these studies suggests that DHA may be useful in preventing NASH and reducing the risk of HCC. PMID:26567194

  4. Acid mine drainage prevention, control and treatment technology development for the Stockett/Sand Coulee area. Topical report, March 1, 1995--March 31, 1996

    SciTech Connect

    Brown, T.

    1996-12-31

    The project was initiated to assist the State of Montana to develop a methodology to ameliorate acid mine drainage problems associated with the abandoned mines located in the Stockett/Sand Coulee area near Great Falls, Montana. Extremely acidic water is continuously discharging from abandoned coal mines in the Stockett/Sand Coulee area at an estimated rate of greater than 600 acre-feet per year (about 350 to 400 gallons per minute). Due to its extreme acidity, the water is unusable and is contaminating other water supplies. Most of the local alluvial aquifers have been contaminated, and nearly 5% of the private wells that were tested in the area during the mid-1980`s showed some degree of contamination. Significant government money has been spent replacing water supplies due to the magnitude of this problem. In addition, millions of dollars have been spent trying to remediate acid mine drainage occurring in this coal field. To date, the techniques used have focused on the management and containment of mine waters, rather than designing technologies that would prevent the formation of acid mine drainage.

  5. The Listeria monocytogenes hemolysin has an acidic pH optimum to compartmentalize activity and prevent damage to infected host cells.

    PubMed

    Glomski, Ian J; Gedde, Margaret M; Tsang, Albert W; Swanson, Joel A; Portnoy, Daniel A

    2002-03-18

    Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from a phagosome and grows in the host cell cytosol. The pore-forming cholesterol-dependent cytolysin, listeriolysin O (LLO), mediates bacterial escape from vesicles and is approximately 10-fold more active at an acidic than neutral pH. By swapping dissimilar residues from a pH-insensitive orthologue, perfringolysin O (PFO), we identified leucine 461 as unique to pathogenic Listeria and responsible for the acidic pH optimum of LLO. Conversion of leucine 461 to the threonine present in PFO increased the hemolytic activity of LLO almost 10-fold at a neutral pH. L. monocytogenes synthesizing LLO L461T, expressed from its endogenous site on the bacterial chromosome, resulted in a 100-fold virulence defect in the mouse listeriosis model. These bacteria escaped from acidic phagosomes and initially grew normally in cells and spread cell to cell, but prematurely permeabilized the host membrane and killed the cell. These data show that the acidic pH optimum of LLO results from an adaptive mutation that acts to limit cytolytic activity to acidic vesicles and prevent damage in the host cytosol, a strategy also used by host cells to compartmentalize lysosomal hydrolases.

  6. Low density lipoprotein rich in oleic acid is protected against oxidative modification: implications for dietary prevention of atherosclerosis.

    PubMed Central

    Parthasarathy, S; Khoo, J C; Miller, E; Barnett, J; Witztum, J L; Steinberg, D

    1990-01-01

    Oxidative modification of low density lipoprotein (LDL) enhances its potential atherogenicity in several ways, notably by enhancing its uptake into macrophages. In vivo studies in the rabbit show that inhibition of LDL oxidation slows the progression of atherosclerotic lesions. In the present studies, rabbits were fed either a newly developed variant sunflower oil (Trisun 80), containing more than 80% oleic acid and only 8% linoleic acid, or conventional sunflower oil, containing only 20% oleic acid and 67% linoleic acid. LDL isolated from the plasma of animals fed the variant sunflower oil was highly enriched in oleic acid and very low in linoleic acid. These oleate-rich LDL particles were remarkably resistant to oxidative modification. Even after 16-hr exposure to copper-induced oxidation or 24-hr incubation with cultured endothelial cells, macrophage uptake of the LDL was only marginally enhanced. The results suggest that diets sufficiently enriched in oleic acid, in addition to their LDL-lowering effect, may slow the progression of atherosclerosis by generating LDL that is highly resistant to oxidative modification. PMID:2339129

  7. Preventive Effects of Omega-3 and Omega-6 Fatty Acids on Peroxide Mediated Oxidative Stress Responses in Primary Human Trabecular Meshwork Cells

    PubMed Central

    Kruse, Friedrich E.; Welge-Lüssen, Ulrich-Christoph; Birke, Kerstin

    2012-01-01

    Pathologic processes in glaucoma include increased apoptosis, accumulation of extracellular material in the trabecular meshwork and optic nerve, condensations of the cytoskeleton and precocious cellular senescence. Oxidative stress was shown to generate these alterations in primary ocular cells. Fatty acids omega-3 and -6 are alleged to constitute a prophylaxis against these deleterious effects. Here, we tested actual preventive effects omega-3 and -6 against peroxide induced stress responses in primary human trabecular meshwork cells. Changes of mitochondrial activity, proliferation, heat shock proteins, extracellular matrix components, and inflammatory markers were evaluated. Alterations of the cytoskeleton were evaluated by phalloidin labeling. Here we report a repressive effect of omega-6 on metabolic activity and proliferation, which was not detected for omega-3. Both agents were able to prevent the anti-proliferative effect of H2O2, but only omega-3 prevented metabolic repression. Expression of heat shock protein 27 was unaltered by both fatty acids, whereas heat shock protein 90 was significantly induced by both. Omega-6 increased fibronectin and connective tissue growth factor synthesis, as well as the amount of secreted fibronectin. Omega-3, instead, induced plasminogen activator inhibitor 1 synthesis. H2O2 further increased fibronectin production in omega-6 supplemented cells, which was not the case in omega-3 treated cells. H2O2 stimulation of plasminogen activator inhibitor 1 and connective tissue growth factor was repressed by both fatty acids. Both fatty acids appeared to abolish H2O2 mediated stimulation of nuclear factor κB and IL-6, but not IL-1α and IL-8. H2O2 induced formation of cross-linked actin networks and stress fibers, which was reduced by preemptive application of omega-3. Omega-6, in contrast, had no protective effect on that, and even seemed to promote condensation. Based on the observed side effects of omega-6, omega-3 appears to be

  8. Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment.

    PubMed

    Oulhaj, Abderrahim; Jernerén, Fredrik; Refsum, Helga; Smith, A David; de Jager, Celeste A

    2016-01-01

    A randomized trial (VITACOG) in people with mild cognitive impairment (MCI) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline. We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment. 266 participants with MCI aged ≥70 years were randomized to B vitamins (folic acid, vitamins B6 and B12) or placebo for 2 years. Baseline cognitive test performance, clinical dementia rating (CDR) scale, and plasma concentrations of total homocysteine, total docosahexaenoic and eicosapentaenoic acids (omega-3 fatty acids) were measured. Final scores for verbal delayed recall, global cognition, and CDR sum-of-boxes were better in the B vitamin-treated group according to increasing baseline concentrations of omega-3 fatty acids, whereas scores in the placebo group were similar across these concentrations. Among those with good omega-3 status, 33% of those on B vitamin treatment had global CDR scores >0 compared with 59% among those on placebo. For all three outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins, while eicosapentaenoic acid appeared less effective. When omega-3 fatty acid concentrations are low, B vitamin treatment has no effect on cognitive decline in MCI, but when omega-3 levels are in the upper normal range, B vitamins interact to slow cognitive decline. A clinical trial of B vitamins combined with omega-3 fatty acids is needed to see whether it is possible to slow the conversion from MCI to AD.

  9. Optimal conjugation of catechol group onto hyaluronic acid in coronary stent substrate coating for the prevention of restenosis.

    PubMed

    Lih, Eugene; Choi, Seul Gi; Ahn, Dong June; Joung, Yoon Ki; Han, Dong Keun

    2016-01-01

    Although endovascular stenting has been used as an interventional therapy to treat cardio- and cerebro-vascular diseases, it is associated with recurrent vascular diseases following stent thrombosis and in-stent restenosis. In this study, a metallic stent was coated with dopamine-conjugated hyaluronic acid with different ratios of catechol group to improve hemocompatibility and re-endothelialization. Especially, we were interested in how much amount of catechol group is appropriate for the above-mentioned purposes. Therefore, a series of dopamine-conjugated hyaluronic acid conjugates with different ratios of catechol group were synthesized via a carbodiimide coupling reaction. Dopamine-conjugated hyaluronic acid conjugates were characterized with (1)H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, and the amount of catechol group in dopamine-conjugated hyaluronic acid was measured by ultraviolet spectrometer. Co-Cr substrates were polished and coated with various dopamine-conjugated hyaluronic acid conjugates under pH 8.5. Dopamine-conjugated hyaluronic acid amounts on the substrate were quantified by micro-bicinchoninic acid assay. Surface characteristics of dopamine-conjugated hyaluronic-acid-coated Co-Cr were evaluated by water contact angle, scanning electron microscopy, and atomic force microscopy. The hemocompatibility of the surface-modified substrates was assessed by protein adsorption and platelet adhesion tests. Adhesion and activation of platelets were confirmed with scanning electron microscopy and lactate dehydrogenase assay. Human umbilical vein endothelial cells were cultured on the substrates, and the viability, adhesion, and proliferation were investigated through cell counting kit-8 assay and fluorescent images. Obtained results demonstrated that optimal amounts of catechol group (100 µmol) in the dopamine-conjugated hyaluronic acid existed in terms of various properties such as hemocompatibility and cellular responses.

  10. Optimal conjugation of catechol group onto hyaluronic acid in coronary stent substrate coating for the prevention of restenosis

    PubMed Central

    Lih, Eugene; Choi, Seul Gi; Ahn, Dong June; Joung, Yoon Ki; Han, Dong Keun

    2016-01-01

    Although endovascular stenting has been used as an interventional therapy to treat cardio- and cerebro-vascular diseases, it is associated with recurrent vascular diseases following stent thrombosis and in-stent restenosis. In this study, a metallic stent was coated with dopamine-conjugated hyaluronic acid with different ratios of catechol group to improve hemocompatibility and re-endothelialization. Especially, we were interested in how much amount of catechol group is appropriate for the above-mentioned purposes. Therefore, a series of dopamine-conjugated hyaluronic acid conjugates with different ratios of catechol group were synthesized via a carbodiimide coupling reaction. Dopamine-conjugated hyaluronic acid conjugates were characterized with 1H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, and the amount of catechol group in dopamine-conjugated hyaluronic acid was measured by ultraviolet spectrometer. Co-Cr substrates were polished and coated with various dopamine-conjugated hyaluronic acid conjugates under pH 8.5. Dopamine-conjugated hyaluronic acid amounts on the substrate were quantified by micro-bicinchoninic acid assay. Surface characteristics of dopamine-conjugated hyaluronic-acid-coated Co-Cr were evaluated by water contact angle, scanning electron microscopy, and atomic force microscopy. The hemocompatibility of the surface-modified substrates was assessed by protein adsorption and platelet adhesion tests. Adhesion and activation of platelets were confirmed with scanning electron microscopy and lactate dehydrogenase assay. Human umbilical vein endothelial cells were cultured on the substrates, and the viability, adhesion, and proliferation were investigated through cell counting kit-8 assay and fluorescent images. Obtained results demonstrated that optimal amounts of catechol group (100 µmol) in the dopamine-conjugated hyaluronic acid existed in terms of various properties such as hemocompatibility and cellular responses

  11. Effect of hypochlorous acid solution on the eradication and prevention of Pseudomonas aeruginosa infection, serum biochemical variables, and cecum microbiota in rats

    PubMed Central

    GOTO, Kazuo; KUWAYAMA, Eri; NOZU, Ryoko; UENO, Masami; HAYASHIMOTO, Nobuhito

    2015-01-01

    In this study, hypochlorous acid solution, a weak acid, provided as drinking water to rats, was evaluated for its ability to eradicate and prevent Pseudomonas aeruginosa infection, while monitoring its simultaneous effect on serum biochemical variables and microbiota in the rat cecum. The results suggest that the solution could not eliminate the bacteria in the experimentally infected rats; however, the administration of a 10-parts-per-million (ppm) hypochlorous acid solution as drinking water was effective in inhibiting horizontal spread of P. aeruginosa infection among cage mates. Additionally, exposure to hypochlorous solution did not have any effect on serum biochemical variables of the rat including levels of total cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin, total bilirubin, lipase, amylase, urea nitrogen, total protein, calcium (Ca), phosphorus (P), sodium (Na), chlorine (Cl), except for potassium (K) levels. The most frequently isolated bacteria in the rat cecum included species belonging to Bacteroidales, Lactobacillus, Clostridiales, Erysipelotrichaceae, Akkermansia, Coriobacteriales, and Firmicutes. The ratio of the terminal restriction fragment length polymorphism (T-RFLP) peaks did not differ across rats administered with 5 and 10 ppm weak acid solution as compared to the control group for any of the bacteria, except for Erysipelotrichaceae and Firmicutes, where the ratio of T-RFLP peaks was higher in the 5 ppm group for Erysipelotrichaceae and in the 10 ppm group for Firmicutes than that in the control group (P<0.01). The results suggest that the weak acid hypochlorous solution could not eradicate P. aeruginosa completely from rats. The solution was effective in preventing infection without affecting serum biochemical variables; however, some of bacterial microbiota may have changed due to administration of the solution. PMID:25736708

  12. Effect of hypochlorous acid solution on the eradication and prevention of Pseudomonas aeruginosa infection, serum biochemical variables, and cecum microbiota in rats.

    PubMed

    Goto, Kazuo; Kuwayama, Eri; Nozu, Ryoko; Ueno, Masami; Hayashimoto, Nobuhito

    2015-01-01

    In this study, hypochlorous acid solution, a weak acid, provided as drinking water to rats, was evaluated for its ability to eradicate and prevent Pseudomonas aeruginosa infection, while monitoring its simultaneous effect on serum biochemical variables and microbiota in the rat cecum. The results suggest that the solution could not eliminate the bacteria in the experimentally infected rats; however, the administration of a 10-parts-per-million (ppm) hypochlorous acid solution as drinking water was effective in inhibiting horizontal spread of P. aeruginosa infection among cage mates. Additionally, exposure to hypochlorous solution did not have any effect on serum biochemical variables of the rat including levels of total cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin, total bilirubin, lipase, amylase, urea nitrogen, total protein, calcium (Ca), phosphorus (P), sodium (Na), chlorine (Cl), except for potassium (K) levels. The most frequently isolated bacteria in the rat cecum included species belonging to Bacteroidales, Lactobacillus, Clostridiales, Erysipelotrichaceae, Akkermansia, Coriobacteriales, and Firmicutes. The ratio of the terminal restriction fragment length polymorphism (T-RFLP) peaks did not differ across rats administered with 5 and 10 ppm weak acid solution as compared to the control group for any of the bacteria, except for Erysipelotrichaceae and Firmicutes, where the ratio of T-RFLP peaks was higher in the 5 ppm group for Erysipelotrichaceae and in the 10 ppm group for Firmicutes than that in the control group (P<0.01). The results suggest that the weak acid hypochlorous solution could not eradicate P. aeruginosa completely from rats. The solution was effective in preventing infection without affecting serum biochemical variables; however, some of bacterial microbiota may have changed due to administration of the solution.

  13. Deletion of the acid-sensing ion channel ASIC3 prevents gastritis-induced acid hyperresponsiveness of the stomach-brainstem axis.

    PubMed

    Wultsch, Thomas; Painsipp, Evelin; Shahbazian, Anaid; Mitrovic, Martina; Edelsbrunner, Martin; Lazdunski, Michel; Waldmann, Rainer; Holzer, Peter

    2008-02-01

    Gastric acid challenge of the rat and mouse stomach is signalled to the brainstem as revealed by expression of c-Fos. The molecular sensors relevant to the detection of gastric mucosal acidosis are not known. Since the acid-sensing ion channels ASIC2 and ASIC3 are expressed by primary afferent neurons, we examined whether knockout of the ASIC2 or ASIC3 gene modifies afferent signalling of a gastric acid insult in the normal and inflamed stomach. The stomach of conscious mice (C57BL/6) was challenged with intragastric HCl; two hours later the activation of neurons in the nucleus tractus solitarii (NTS) of the brainstem was visualized by c-Fos immunocytochemistry. Mild gastritis was induced by addition of iodoacetamide (0.1%) to the drinking water for 7 days. Exposure of the gastric mucosa to HCl (0.25M) caused a 3-fold increase in the number of c-Fos-positive neurons in the NTS. This afferent input to the NTS remained unchanged by ASIC3 knockout, whereas ASIC2 knockout augmented the c-Fos response to gastric HCl challenge by 33% (P<0.01). Pretreatment of wild-type mice with iodoacetamide induced mild gastritis, as revealed by increased myeloperoxidase activity, and enhanced the number of NTS neurons responding to gastric HCl challenge by 41% (P<0.01). This gastric acid hyperresponsiveness was absent in ASIC3 knockout mice but fully preserved in ASIC2 knockout mice. The current data indicate that ASIC3 plays a major role in the acid hyperresponsiveness associated with experimental gastritis. In contrast, ASIC2 appears to dampen acid-evoked input from the stomach to the NTS.

  14. Acid stress damage of DNA is prevented by Dps binding in Escherichia coli O157:H7.

    PubMed

    Jeong, Kwang Cheol; Hung, Kai Foong; Baumler, David J; Byrd, Jeffrey J; Kaspar, Charles W

    2008-10-15

    Acid tolerance in Escherichia coli O157:H7 contributes to persistence in its bovine host and is thought to promote passage through the gastric barrier of humans. Dps (DNA-binding protein in starved cells) mutants of E. coli have reduced acid tolerance when compared to the parent strain although the role of Dps in acid tolerance is unclear. This study investigated the mechanism by which Dps contributes to acid tolerance in E. coli O157:H7. The results from this study showed that acid stress lead to damage of chromosomal DNA, which was accentuated in dps and recA mutants. The use of Bal31, which cleaves DNA at nicks and single-stranded regions, to analyze chromosomal DNA extracted from cells challenged at pH 2.0 provided in vivo evidence of acid damage to DNA. The DNA damage in a recA mutant further corroborated the hypothesis that acid stress leads to DNA strand breaks. Under in vitro assay conditions, Dps was shown to bind plasmid DNA directly and protect it from acid-induced strand breaks. Furthermore, the extraction of DNA from Dps-DNA complexes required a denaturing agent at low pH (2.2 and 3.6) but not at higher pH (>pH4.6). Low pH also restored the DNA-binding activity of heat-denatured Dps. Circular dichroism spectra revealed that at pH 3.6 and pH 2.2 Dps maintains or forms alpha-helices that are important for Dps-DNA complex formation. Results from the present work showed that acid stress results in DNA damage that is more pronounced in dps and recA mutants. The contribution of RecA to acid tolerance indicated that DNA repair was important even when Dps was present. Dps protected DNA from acid damage by binding to DNA. Low pH appeared to strengthen the Dps-DNA association and the secondary structure of Dps retained or formed alpha-helices at low pH. Further investigation into the precise interplay between DNA protection and damage repair pathways during acid stress are underway to gain additional insight.

  15. Vocal cord palsy after vincristine treatment in a child and the inefficacy of glutamic acid in the prevention of relapse: a case report

    PubMed Central

    2012-01-01

    Introduction Vincristine is an antineoplastic drug with a well known efficacy for the treatment of acute lymphoblastic leukemia and many solid tumors. No more than 20 pediatric patients with vincristine-induced vocal cord palsy have been reported, and to the best of our knowledge this is the first case where glutamic acid was administered with the aim of preventing a relapse of laryngeal dysfunction. Case presentation The larynx paralysis presented with hoarseness and stridor in a Caucasian 18-month-old girl and spontaneously resolved in about a month. In order to administer a subsequent full dose of vincristine, our patient received oral glutamic acid whose efficacy against vincristine neurological side effects has been previously reported. Conclusions Since in our patient the amino acid proved to be ineffective in the prevention of laryngeal paralysis relapse, we suggest that a dose reduction of vincristine should be preferred by oncologists as an initial approach after a case of drug-induced vocal cord palsy. PMID:22584039

  16. A hyaluronic acid-based compound inhibits fibroblast senescence induced by oxidative stress in vitro and prevents oral mucositis in vivo.

    PubMed

    Cirillo, Nicola; Vicidomini, Antonio; McCullough, Michael; Gambardella, Antonio; Hassona, Yazan; Prime, Stephen S; Colella, Giuseppe

    2015-07-01

    Virtually all patients receiving radio- and chemotherapy for cancer develop oral mucositis, a severe and highly debilitating condition. The onset of mucositis is thought to involve the production of reactive oxygen species (ROS) in the submucosa. Here we investigated a possible protective effect of a commercial formulation of hyaluronic acid (HA) enriched with amino acids (Mucosamin(®)) against the damage induced by oxidative stress both in vitro and in vivo. Transient exposure of normal human oral fibroblasts to hydrogen peroxide (H(2)O(2)) led to irreversible senescence, as demonstrated by sustained increase in the levels of p16(INK4A) and SA-βGal. Conditioned media from senescent fibroblasts induced detrimental effects on keratinocytes, as shown by reduced metabolic activity and migration capability. Pre-treatment with Mucosamin(®) prevented H(2)O(2) -induced, but not TGF-β-induced, fibroblast senescence with a concomitant reduction of fibroblast-induced loss of keratinocyte vitality and functional activity. Finally, data from a case-series of patients undergoing radio/chemotherapy strongly suggested that prophylactic use of the hyaluronic acid-based compound in the form of a spray may be effective in preventing the onset of oral mucositis.

  17. Teratogenic effects of diabetic conditions in chick heart in ovo and in micromass culture may be prevented by addition of vitamin C and folic acid.

    PubMed

    Memon, Samreen; Pratten, Margaret K

    2013-01-01

    Maternal diseases like diabetes mellitus may cause developmental defects. Supplementation with folic acid and vitamin C during the periconceptional period has been shown to prevent some neural tube and congenital heart defects. Hearts were dissected from 5 days-old White Leghorn chick embryos, the cells isolated and cultured in micromass under diabetic conditions, with and without folic acid and vitamin C. Contractile activity, cell viability (resazurin reduction) and protein assays were performed. Results indicated diabetic conditions reduced contractile activity and cell viability, whilst vitamin C (100 μM) and folic acid (1 mM) administered concurrently significantly improved them to values comparable with the control. Day 3 chick embryos in ovo were injected with glucose+hydroxybutyrate or a combination of these and vitamins. Diabetic conditions caused gross and histological malformations, but these effects were abrogated by vitamin supplement. Teratogenic effects on heart development could possibly be prevented by vitamin supplementation during pregnancy. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. A randomized controlled experimental study of the efficacy of platelet-rich plasma and hyaluronic acid for the prevention of adhesion formation in a rat uterine horn model.

    PubMed

    Oz, Murat; Cetinkaya, Nilufer; Bas, Sevda; Korkmaz, Elmas; Ozgu, Emre; Terzioglu, Gokay Serdar; Buyukkagnici, Umran; Akbay, Serap; Caydere, Muzaffer; Gungor, Tayfun

    2016-09-01

    Platelet-rich plasma (PRP) has been known to possess an efficacy in tissue regeneration. The aim of this study was to determine the role of PRP on post-operative adhesion formation in an experimental rat study. Thirty Sprague-Dawley rats were randomly divided into control, hyaluronic acid, and PRP treatment groups and operated on for uterine horn adhesion modeling. Blood was collected to produce a PRP with platelet counts of 688 × 10(3)/μL, and 1 ml of either hyaluronic acid gel or PRP was administered over the standard lesions, while the control group received no medication. The evaluation of post-operative adhesions was done on the 30th post-operative day. The location, extent, type, and tenacity of adhesions as well as total adhesion scores, tissue inflammation, fibrosis and transforming growth factor-1beta (TGF-1β) expressions were evaluated. The total adhesion score was significantly lower in the PRP group (3.2 ± 1.5) compared with the hyaluronic acid (5.0 ± 1.3) and control (8.1 ± 1.7) groups. The extent of the adhesions was significantly lower in the PRP group. There was no significant difference in the type and tenacity of adhesions between the hyaluronic acid and the PRP group. The level of inflammation was significantly higher in the control group than the others, while there was no difference between the PRP and hyaluronic acid groups. TGF-1β expression was significantly lesser in the PRP group than the control and hyaluronic acid groups. PRP is more effective than hyaluronic acid treatment in preventing post-operative adhesion formation in an experimental rat uterine horn adhesion model.

  19. Dietary long chain n-3 polyunsaturated fatty acids prevent impaired social behaviour and normalize brain dopamine levels in food allergic mice.

    PubMed

    de Theije, Caroline G M; van den Elsen, Lieke W J; Willemsen, Linette E M; Milosevic, Vanja; Korte-Bouws, Gerdien A H; Lopes da Silva, Sofia; Broersen, Laus M; Korte, S Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D

    2015-03-01

    Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the effect of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on food allergy-induced impaired social behaviour and associated deficits in prefrontal dopamine (DA) in mice. Mice were fed either control or n-3