WorldWideScience

Sample records for topical nicotinamide modulates

  1. A case of vesicular cutaneous lupus erythematosus in a Border collie successfully treated with topical tacrolimus and nicotinamide-tetracycline.

    Science.gov (United States)

    Lehner, Georg M; Linek, Monika

    2013-12-01

    Canine vesicular cutaneous lupus erythematosus (VCLE) is an autoimmune skin disease of the Shetland sheepdog and rough collie, which manifests as an erosive dermatitis of sparsely haired skin of the ventrum and concave pinnae. Reported treatment consists of immunosuppression with glucocorticoids alone or in combination with azathioprine, but successful treatment is unpredictable. To report on the treatment of VCLE in a Border collie dog with topical 0.1% tacrolimus and nicotinamide in combination with tetracycline. An 8-year-old male neutered Border collie was presented with multiple coalescing erosions on the ventral abdomen, groin and axillae and ulceration on the oral commissures. Clinical presentation, routine diagnostics, histology and immunohistochemistry were consistent with VCLE. Remission was achieved with topical 0.1% tacrolimus and combination therapy of nicotinamide and tetracycline. This dog responded well to treatment with topical 0.1% tacrolimus, nicotinamide-tetracycline and sun avoidance. Complete remission was achieved after 2.5 months, and the dog was lesion free during a 1 year follow-up period. © 2013 ESVD and ACVD.

  2. Topical verapamil as a scar modulator.

    Science.gov (United States)

    Boggio, Ricardo Frota; Boggio, Leonardo Frota; Galvão, Bruno Luiz; Machado-Santelli, Glaucia Maria

    2014-10-01

    Skin injuries and the consequent loss of tissue integrity triggers a sequence of cellular and biochemical events that lead to a healed wound. Any failure during this rather sophisticated process may result in pathological scarring. To evaluate the efficacy of topical verapamil as a modulator of the healing process, a group of five observers (plastic surgeon, dermatologist, physiotherapist, biologist, and layman) analyzed pictures of 120 patients 3 months after abdominoplasty (60 patients) and mammoplasty (60 patients). Half of each group of patients used the topical verapamil scar modulator. Pictures were rated using the Stony Brook Scale. According to the classification established by us, the scars in patients who used topical verapamil scar modulator showed better results than those who did not (p modulators showed 48 and 51.2 % satisfaction for mammoplasty and abdominoplasty scars, respectively. No adverse reactions were observed or reported after the use of topical verapamil. This is the first clinical trial that reports the use of topical verapamil as a modulator in the healing process in the postoperative period. Based on clinical results and on the high level of reliability and statistical significance, we concluded that verapamil at a concentration of 50 µM is an excellent choice as a scar modulator; its use avoids the development of keloids and hypertrophic scars after plastic surgery.

  3. Identification of gene expression signature modulated by nicotinamide in a mouse bladder cancer model.

    Directory of Open Access Journals (Sweden)

    Seon-Kyu Kim

    Full Text Available BACKGROUND: Urinary bladder cancer is often a result of exposure to chemical carcinogens such as cigarette smoking. Because of histological similarity, chemically-induced rodent cancer model was largely used for human bladder cancer studies. Previous investigations have suggested that nicotinamide, water-soluble vitamin B3, may play a key role in cancer prevention through its activities in cellular repair. However, to date, evidence towards identifying the genetic alterations of nicotinamide in cancer prevention has not been provided. Here, we search for the molecular signatures of cancer prevention by nicotinamide using a N-butyl-N-(4-hydroxybutyl-nitrosamine (BBN-induced urinary bladder cancer model in mice. METHODOLOGY/PRINCIPAL FINDINGS: Via microarray gene expression profiling of 20 mice and 233 human bladder samples, we performed various statistical analyses and immunohistochemical staining for validation. The expression patterns of 893 genes associated with nicotinamide activity in cancer prevention were identified by microarray data analysis. Gene network analyses of these 893 genes revealed that the Myc and its associated genes may be the most important regulator of bladder cancer prevention, and the gene expression signature correlated well with protein expression data. Comparison of gene expression between human and mouse revealed that BBN-induced mouse bladder cancers exhibited gene expression profiles that were more similar to those of invasive human bladder cancers than to those of non-invasive human bladder cancers. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that nicotinamide plays an important role as a chemo-preventive and therapeutic agent in bladder cancer through the regulation of the Myc oncogenic signature. Nicotinamide may represent a promising therapeutic modality in patients with muscle-invasive bladder cancer.

  4. Nicotinamide supplementation phenocopies SIR2 inactivation by modulating carbon metabolism and respiration during yeast chronological aging.

    Science.gov (United States)

    Orlandi, Ivan; Pellegrino Coppola, Damiano; Strippoli, Maurizio; Ronzulli, Rossella; Vai, Marina

    2017-01-01

    Nicotinamide (NAM), a form of vitamin B 3 , is a byproduct and noncompetitive inhibitor of the deacetylation reaction catalyzed by Sirtuins. These represent a family of evolutionarily conserved NAD + -dependent deacetylases that are well-known critical regulators of metabolism and aging and whose founding member is Sir2 of Saccharomyces cerevisiae. Here, we investigated the effects of NAM supplementation in the context of yeast chronological aging, the established model for studying aging of postmitotic quiescent mammalian cells. Our data show that NAM supplementation at the diauxic shift results in a phenocopy of chronologically aging sir2Δ cells. In fact, NAM-supplemented cells display the same chronological lifespan extension both in expired medium and extreme Calorie Restriction. Furthermore, NAM allows the cells to push their metabolism toward the same outcomes of sir2Δ cells by elevating the level of the acetylated Pck1. Both these cells have the same metabolic changes that concern not only anabolic pathways such as an increased gluconeogenesis but also respiratory activity in terms both of respiratory rate and state of respiration. In particular, they have a higher respiratory reserve capacity and a lower non-phosphorylating respiration that in concert with a low burden of superoxide anions can affect positively chronological aging. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes.

    Science.gov (United States)

    Lee, Hee Jae; Hong, Young-Shick; Jun, Woojin; Yang, Soo Jin

    2015-11-01

    Low-grade chronic inflammation (metaflammation) is a major contributing factor for the onset and development of metabolic diseases, such as type 2 diabetes, obesity, and cardiovascular disease. Nicotinamide riboside (NR), which is present in milk and beer, is a functional vitamin B3 having advantageous effects on metabolic regulation. However, the anti-inflammatory capacity of NR is unknown. This study evaluated whether NR modulates hepatic nucleotide binding and oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Male, 8-week-old KK/HlJ mice were allocated to the control or NR group. NR (100 mg/kg/day) or vehicle (phosphate-buffered saline) was administrated by an osmotic pump for 7 days. Glucose control, lipid profiles, NLRP3 inflammasome, and inflammation markers were analyzed, and structural and histological analyses were conducted. NR treatment did not affect body weight gain, food intake, and liver function. Glucose control based on the oral glucose tolerance test and levels of serum insulin and adiponectin was improved by NR treatment. Among tested lipid profiles, NR lowered the total cholesterol concentration in the liver. Histological and structural analysis by hematoxylin and eosin staining and transmission electron microscopy, respectively, showed that NR rescued the disrupted cellular integrity of the mitochondria and nucleus in the livers of obese and diabetic KK mice. In addition, NR treatment significantly improved hepatic proinflammatory markers, including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1. These ameliorations were accompanied by significant shifts of NLRP3 inflammasome components (NLRP3, ASC, and caspase1). These results demonstrate that NR attenuates hepatic metaflammation by modulating the NLRP3 inflammasome.

  6. COMETS Science. Career Oriented Modules to Explore Topics in Science.

    Science.gov (United States)

    Smith, Walter S.; And Others

    COMETS Science (Career Oriented Modules to Explore Topics in Science) was developed to demonstrate to early adolescents that learning mathematics and science concepts can have payoff in a wide variety of careers and to encourage early adolescent students (grades 5-9), especially girls, to consider science-related careers. The program provides 24…

  7. Viewpoint Developing Modules on the Topic of Education for ...

    African Journals Online (AJOL)

    Viewpoint Developing Modules on the Topic of Education for Sustainable Development: A Cross-cultural Approach for Engaging in International Collaboration ... The project is an international collaboration between teachers in primary schools in Cape Town (South Africa) and Toyko (Japan), supported by researchers at two ...

  8. Nicotinamidase modulation of NAD+ biosynthesis and nicotinamide levels separately affect reproductive development and cell survival in C. elegans.

    Science.gov (United States)

    Vrablik, Tracy L; Huang, Li; Lange, Stephanie E; Hanna-Rose, Wendy

    2009-11-01

    Nicotinamide adenine dinucleotide (NAD(+)) is a central molecule in cellular metabolism and an obligate co-substrate for NAD(+)-consuming enzymes, which regulate key biological processes such as longevity and stress responses. Although NAD(+) biosynthesis has been intensely studied, little analysis has been done in developmental models. We have uncovered novel developmental roles for a nicotinamidase (PNC), the first enzyme in the NAD(+) salvage pathway of invertebrates. Mutations in the Caenorhabditis elegans nicotinamidase PNC-1 cause developmental and functional defects in the reproductive system; the development of the gonad is delayed, four uterine cells die by necrosis and the mutant animals are egg-laying defective. The temporal delay in gonad development results from depletion of the salvage pathway product NAD(+), whereas the uv1 cell necrosis and egg-laying defects result from accumulation of the substrate nicotinamide. Thus, regulation of both substrate and product level is key to the biological activity of PNC-1. We also find that diet probably affects the levels of these metabolites, as it affects phenotypes. Finally, we identified a secreted isoform of PNC-1 and confirmed its extracellular localization and functional activity in vivo. We demonstrate that nicotinamide phosphoribosyltransferase (Nampt), the equivalent enzyme in nicotinamide recycling to NAD(+) in vertebrates, can functionally substitute for PNC-1. As Nampt is also secreted, we postulate an evolutionarily conserved extracellular role for NAD(+) biosynthetic enzymes during development and physiology.

  9. A review of nicotinamide: treatment of skin diseases and potential side effects.

    Science.gov (United States)

    Rolfe, Heidi M

    2014-12-01

    Nicotinamide, also known as niacinamide, is the amide form of vitamin B3. It is a precursor of essential coenzymes for numerous reactions in the body including adenosine triphosphate (ATP) production. Nicotinic acid, also known as niacin, is converted into nicotinamide in the body. The use of topical nicotinamide in the treatment of acne vulgaris; melasma; atopic dermatitis; rosacea; and oral nicotinamide in preventing nonmelanoma skin cancer is discussed. The possible side effects and consequences of excessive nicotinamide exposure are reviewed, including suggestions nicotinamide might have a role in the development of diabetes, Parkinson's disease, and liver damage. © 2014 Wiley Periodicals, Inc.

  10. The ORNL Modulating Heat Pump Design Tool User's Guide; TOPICAL

    International Nuclear Information System (INIS)

    Rice, C.K.

    2001-01-01

    The ORNL Modulating Heat Pump Design Tool consists of a Modulating HPDM (Heat Pump Design Model) and a parametric-analysis (contour-data generating) front-end. Collectively the program is also referred to as MODCON which is in reference to the modulating and the contour data generating capabilities. The program was developed by Oak Ridge National Laboratory for the Department of Energy to provide a publicly-available system design tool for variable- and single-speed heat pumps

  11. Topical Treatment of Hair Loss with Formononetin by Modulating Apoptosis.

    Science.gov (United States)

    Kim, Mi Hye; Choi, You Yeon; Lee, Ji Eun; Kim, Kyuseok; Yang, Woong Mo

    2016-01-01

    Formononetin is one of the main components of red clover plants and its role on hair regrowth against hair loss has not been established yet. In the present study, we assessed the potential effects of formononetin on alopecia, along with impaired hair cycles by induction of apoptosis-regression.Depilated C57BL/6 mice were used for monitoring the hair cycles. Formononetin (1 and 100 µM) was topically treated to the dorsal skin for 14 days. Topical formononetin treatment induced miniaturized hair follicles to recover to normal sizes. Tapering hair shaft began to grow newly, emerging from the hair follicles by formononetin. In addition, formononetin inhibited the activation of caspase-8 and decreased the procaspase-9 expression. As a result of formononetin treatment, anti-apoptotic Bcl-2 was up-regulated, whereas pro-apoptotic Bax and p53 were down-regulated, resulting in a decrease of caspase-3 activation. Formononetin showed the obvious inhibition of apoptosis under terminal deoxynucleotidyl transferase dUTP nick end labeling staining thereafter.Taken together, our findings demonstrate that formononetin exerted the hair regrowth effect on hair loss, in which the underlying mechanisms were associated with Fas/Fas L-induced caspase activation, thus inhibiting apoptosis. Georg Thieme Verlag KG Stuttgart · New York.

  12. Photoprotective effects of nicotinamide.

    Science.gov (United States)

    Damian, Diona L

    2010-04-01

    Sun protective measures can reduce numbers of both precancerous actinic keratoses and cutaneous squamous cell carcinomas within relatively short periods of time even in high-risk populations. Sunscreens, which tend to provide greater protection against shortwave UVB than against longer wavelength UVA radiation, can however provide only partial protection from the mutagenic and immune suppressive effects of sunlight. In large part, this reflects poor compliance with proper sunscreen application and reapplication. Skin cancer is by far the most common malignancy in Caucasian populations, and additional strategies to reduce the morbidity and economic burden of this disease are now urgently needed. Nicotinamide, the amide form of vitamin B3, is an inexpensive agent which is used for a variety of dermatological applications with little or no toxicity even at high doses. Nicotinamide has photoprotective effects against carcinogenesis and immune suppression in mice, and is photoimmunoprotective in humans when used as a lotion or orally. UV irradiation depletes keratinocytes of cellular energy and nicotinamide, which is a precursor of nicotinamide adenine dinucleotide, may act at least in part by providing energy repletion to irradiated cells.

  13. Nano-TiO2 modulates the dermal sensitization potency of dinitrochlorobenzene after topical exposure.

    Science.gov (United States)

    Smulders, S; Golanski, L; Smolders, E; Vanoirbeek, J; Hoet, P H M

    2015-02-01

    Little is known about the impact of engineered nanoparticles (ENPs) on skin sensitization caused by chemicals. We determined the ability of different ENPs (TiO2 , Ag and SiO2 ) and aged paint particles containing ENPs to modulate dermal sensitization by a known potent dermal sensitizer. The fur of BALB/c mice in the area around the ears was cut with scissors 1 day prior to topical exposure to ENPs (0·4, 4 or 40 mg mL(-1) ), paint particles containing ENPs (4 mg mL(-1) ) or vehicle (day 0). On days 1, 2 and 3, the mice received dermal applications on the back of both ears of 2,4-dinitrochlorobenzene (DNCB) or vehicle. The stimulation index (SI) was calculated on day 6. Topical exposure to TiO2 , Ag or SiO2 ENPs, or aged paint particles followed by vehicle treatment as a control, did not influence the SI. When 4 mg mL(-1) TiO2 ENPs were applied prior to DNCB sensitization, we found an increased SI compared with vehicle-exposed mice prior to DNCB sensitization. Furthermore, an increased titanium concentration was found in the draining lymph node cells of this group. Topical exposure to Ag or SiO2 ENPs or aged paint particles prior to DNCB sensitization did not influence the SI. We have demonstrated that topical exposure to TiO2 ENPs increases chemical-induced dermal sensitization. © 2014 British Association of Dermatologists.

  14. Simultaneous quantitation of nicotinamide riboside, nicotinamide mononucleotide and nicotinamide adenine dinucleotide in milk by a novel enzyme-coupled assay.

    Science.gov (United States)

    Ummarino, Simone; Mozzon, Massimo; Zamporlini, Federica; Amici, Adolfo; Mazzola, Francesca; Orsomando, Giuseppe; Ruggieri, Silverio; Raffaelli, Nadia

    2017-04-15

    Nicotinamide riboside, the most recently discovered form of vitamin B3, and its phosphorylated form nicotinamide mononucleotide, have been shown to be potent supplements boosting intracellular nicotinamide adenine dinucleotide (NAD) levels, thus preventing or ameliorating metabolic and mitochondrial diseases in mouse models. Here we report for the first time on the simultaneous quantitation of nicotinamide riboside, nicotinamide mononucleotide and NAD in milk by means of a fluorometric, enzyme-coupled assay. Application of this assay to milk from different species revealed that the three vitamers were present in human and donkey milk, while being selectively distributed in the other milks. Human milk was the richest source of nicotinamide mononucleotide. Overall, the three vitamers accounted for a significant fraction of total vitamin B3 content. Pasteurization did not affect the bovine milk content of nicotinamide riboside, whereas UHT processing fully destroyed the vitamin. In human milk, NAD levels were significantly affected by the lactation time. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Potential pharmacokinetic role of organic cation transporters in modulating the transcorneal penetration of its substrates administered topically

    Science.gov (United States)

    Nirmal, J; Singh, S B; Biswas, N R; Thavaraj, V; Azad, R V; Velpandian, T

    2013-01-01

    Purpose We hypothesize organic cation transporters (OCT) may have a potential role in determining the pharmacokinetics and toxicity of organic cation drugs applied topically. Hence, in the present in vivo study, we attempted to evaluate the role of OCT in modulating the transport of its substrates after topical application. Methods New Zealand albino rabbits of either sex were used. Transcorneal penetration of OCT substrates tetraethylammonium and metformin after single instillation was evaluated in the absence and presence of OCT blockers (quinidine and atropine). Aqueous humor (AH) samples were collected through paracentesis amounting to 70–100 μl under topical anesthesia at various time intervals. The samples were subjected for estimation of both substrate as well as blocker concentrations using liquid chromatography mass spectrometry. Results Topical pre-treatment (30 min before substrate) of OCT blockers significantly decreased the transcorneal penetration of OCT substrates after single topical administration. The levels of blockers reaching AH in the presence of substrates were also modulated at 60 min after its administration as compared with its control. Conclusion OCT are functionally active in the uptake of their substrates from tear to AH. Therefore, OCT in the corneal epithelium may be positioned from apical to basolateral. When administering their substrates/blockers topically, both may be competing for OCT for their uptake across the cornea, thereby decreasing the corneal penetration. Hence OCT can have a potential pharmacokinetic role in modulating the ocular bioavailability of their substrates administered topically, which are used as ocular therapeutics. PMID:23846373

  16. Topical Modulation of the Burn Wound Inflammatory Response to Improve Short and Long Term Outcomes

    Science.gov (United States)

    2016-10-01

    Intracellular MAPK Hair-Follicle Apoptosis Local /Dermal Inflammatory Cell Activation SIRS End-Organ Failure Topical MAPK Inhibitors Production of...care providers in a mass- casualty incident. 2. KEYWORDS: Wounds, Burn, topical, wound healing, inflammatory signaling, Mitogen activated protein ...is the key inflammatory intracellular signaling in mammalian cells. In our previous murine models, we demonstrated that topical application of

  17. COMETS Profiles. Career Oriented Modules to Explore Topics in Science. 24 Biographical Sketches of Women in Science Careers plus Accompanying Language Arts Activities.

    Science.gov (United States)

    Noyce, Ruth, Ed.

    Twenty-four biographical sketches of women in scientific professions are included in this COMETS Profiles package. Each biography relates to a science topic dealt with in one of the instructional modules of COMETS Science (Career Oriented Modules to Explore Topics in Science). The purpose of these materials is to demonstrate to early adolescents…

  18. Modulation of cortical activity during comprehension of familiar and unfamiliar text topics in speed reading and speed listening.

    Science.gov (United States)

    Buchweitz, Augusto; Mason, Robert A; Meschyan, Gayane; Keller, Timothy A; Just, Marcel Adam

    2014-12-01

    Brain activation associated with normal and speeded comprehension of expository texts on familiar and unfamiliar topics was investigated in reading and listening. The goal was to determine how brain activation and the comprehension processes it reflects are modulated by comprehension speed and topic familiarity. Passages on more familiar topics differentially activated a set of areas in the anterior temporal lobe and medial frontal gyrus, areas often associated with text-level integration processes, which we interpret to reflect integration of previous knowledge with the passage content. Passages presented at the faster presentation resulted in more activation of a network of frontal areas associated with strategic and working-memory processes (as well as visual or auditory sensory-related regions), which we interpret to reflect maintenance of local coherence among briefly available passage segments. The implications of this research is that the brain system for text comprehension adapts to varying perceptual and knowledge conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Modulation of tumor hypoxia by topical formulations with vasodilators for enhancing therapy.

    Science.gov (United States)

    Abramovic, Zrinka; Hou, Huagang; Julijana, Kristl; Sentjurc, Marjeta; Lariviere, Jean P; Swartz, Harold M; Khan, Nadeem

    2011-01-01

    Tumor hypoxia is a well known therapeutic problem which contributes to radioresistance and aggressive tumor characteristics. Lack of techniques for repeated measurements of tumor oxygenation (pO(2), partial pressure of oxygen) has restricted the optimization of hypoxia modifying methods and their efficacious application with radiotherapy. We have investigated a non-invasive method to enhance tissue pO(2) of peripheral tumors using topical application of formulations with BN (Benzyl Nicotinate), a vasodilator, and have used EPR (Electron Paramagnetic Resonance) oximetry to follow its effect on tumor oxygenation.We incorporated 2.5% BN in both hydrogel and microemulsions and investigated the effects on pO(2) of subcutaneous RIF-1 (Radiation Induced Fibrosarcoma) tumors in C3H mice. The experiments were repeated for five consecutive days. The topical application of BN in hydrogel led to a significant increase from a pre-treatment pO(2) of 9.3 mmHg to 11 - 16 mmHg at 30 - 50 min on day 1. However, the magnitude and the time of significant increase in pO(2) decreased with repeated topical applications. The BN in a microemulsion resulted in a significant increase from a baseline pO(2) of 8.8 mmHg to 13 - 18 mmHg at 10 - 50 min on day 1. Experiments repeated on subsequent days showed a decline in the magnitude of pO(2) increase on repeated applications. No significant change in tumor pO(2) was observed in experiments with formulations without BN (vehicle only).EPR oximetry was successfully used to follow the temporal changes in tumor pO(2) during repeated applications for five consecutive days. This approach can be potentially used to enhance radiotherapeutic outcome by scheduling radiation doses when an increase in tumor pO(2) is observed after topical applications of BN formulations.

  20. Nano-TiO2 modulates the dermal sensitization potency of dinitrochlorobenzene after topical exposure

    NARCIS (Netherlands)

    Smulders, S.; Golanski, L.; Smolders, E.J.; Vanoirbeek, J.; Hoet, P.H.

    2015-01-01

    BACKGROUND: Little is known about the impact of engineered nanoparticles (ENPs) on skin sensitization caused by chemicals. OBJECTIVES: We determined the ability of different ENPs (TiO2 , Ag and SiO2 ) and aged paint particles containing ENPs to modulate dermal sensitization by a known potent dermal

  1. TOPICAL REVIEW: Metallo-supramolecular modules as a paradigm for materials science

    Directory of Open Access Journals (Sweden)

    Dirk G Kurth

    2008-01-01

    Full Text Available Metal ion coordination in discrete or extended metallo-supramolecular assemblies offers ample opportunity to fabricate and study devices and materials that are equally important for fundamental research and new technologies. Metal ions embedded in a specific ligand field offer diverse thermodynamic, kinetic, chemical, physical and structural properties that make these systems promising candidates for active components in functional materials. A key challenge is to improve and develop methodologies for placing these active modules in suitable device architectures, such as thin films or mesophases. This review highlights recent developments in extended, polymeric metallo-supramolecular systems and discrete polyoxometalates with an emphasis on materials science.

  2. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition.

    Science.gov (United States)

    Bogan, Katrina L; Brenner, Charles

    2008-01-01

    Although baseline requirements for nicotinamide adenine dinucleotide (NAD+) synthesis can be met either with dietary tryptophan or with less than 20 mg of daily niacin, which consists of nicotinic acid and/or nicotinamide, there is growing evidence that substantially greater rates of NAD+ synthesis may be beneficial to protect against neurological degeneration, Candida glabrata infection, and possibly to enhance reverse cholesterol transport. The distinct and tissue-specific biosynthetic and/or ligand activities of tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD+ precursor, nicotinamide riboside, reviewed herein, are responsible for vitamin-specific effects and side effects. Because current data suggest that nicotinamide riboside may be the only vitamin precursor that supports neuronal NAD+ synthesis, we present prospects for human nicotinamide riboside supplementation and propose areas for future research.

  3. European Nicotinamide Diabetes Intervention Trial (ENDIT)

    DEFF Research Database (Denmark)

    Gale, E A M; Bingley, P J; Emmett, C L

    2004-01-01

    to assess whether high dose nicotinamide prevents or delays clinical onset of diabetes in people with a first-degree family history of type 1 diabetes. METHOD: We did a randomised double-blind placebo-controlled trial of nicotinamide in 552 relatives with confirmed islet cell antibody (ICA) levels of 20...... Juvenile Diabetes Federation (JDF) units or more, and a non-diabetic oral glucose tolerance test. Participants were recruited from 18 European countries, Canada, and the USA, and were randomly allocated oral modified release nicotinamide (1.2 g/m2) or placebo for 5 years. Random allocation was done...

  4. NICOTINAMIDE IN COMPLEX TREATMENT OF LARGE-PLAQUE PARAPSORIASIS AND EARLY STAGES OF MALIGNANT T-CELL SKIN LYMPHOMAS

    Directory of Open Access Journals (Sweden)

    I. V. Khamaganova

    2014-01-01

    Full Text Available Aim: To assess clinical efficacy of nicotinamide in 2 the treatment of patients with early stages of malignant T-cell skin lymphomas and large-plaque parapsoriasis. Materials and methods: 12 patients with erythematous stage of mycosis fungoides and 14 patients with large-plaque parapsoriasis were treated by nicotinamide 15 mg twice daily during 2 weeks. Treatment cycles were repeated 4–5 times per year; topical therapy was also administrated. Results: Nicotinamide demonstrated high therapeutic effect and good tolerability in patients with early stage of mycosis fungoides and large-plaque parapsoriasis. Stable remission was achieved in 1  woman with malignant T-cell lymphoma and 12  patients with large-plaque parapsoriasis; significant clinical improvement was shown in 8 and 12 patients, respectively. Conclusion: Thus, nicotinamide is recommended for comprehensive treatment of large-plaque parapsoriasis and early stages of mycosis fungoides.

  5. Nicotinamide -Methyltransferase in Health and Cancer

    Directory of Open Access Journals (Sweden)

    David B Ramsden

    2017-06-01

    Full Text Available Over the past decade, the roles of nicotinamide N -methyltransferase and its product 1-methyl nicotinamide have emerged from playing merely minor roles in phase 2 xenobiotic metabolism as actors in some of the most important scenes of human life. In this review, the structures of the gene, messenger RNA, and protein are discussed, together with the role of the enzyme in many of the common cancers that afflict people today.

  6. Hormones and Antibiotics in Nature: A Laboratory Module Designed to Broaden Undergraduate Perspectives on Typically Human-Centered Topics

    Directory of Open Access Journals (Sweden)

    Carolyn F. Weber

    2014-07-01

    Full Text Available Bringing discovery-based research into undergraduate laboratory courses increases student motivation and learning gains over traditional exercises that merely teach technique or demonstrate well-documented phenomena. Laboratory experiences are further enhanced when they are designed to challenge student perspectives on topics relevant to their lives. To this end, a laboratory module on antibiotics and hormones, which are generally discussed in the context of human health, was developed for students to explore the multifaceted roles of antibiotics and hormones in nature (e.g. interspecies communication via reading primary scientific literature and performing discovery-based experiments. The main objective of this module was to increase the general biological literacy of students as determined by their ability to connect the Five Core Concepts of Biological Literacy (American Association for the Advancement of Science, Vision and Change in Undergraduate Education: A Call to Action, 2011 to the topics “hormones” and “antibiotics” in pre- and postmodule surveys. After discussing unpublished research findings, cell biology students performed experiments demonstrating that: 1 fungi may promote fern growth via hormone production, 2 novel bacterial isolates in the genus Streptomyces produce antifungal compounds, and 3 subinhibitory antibiotic concentrations may enhance soil bacterial growth. The third finding provided evidence supporting a hypothesis framed in a scientific article that students read and discussed. Student perspectives on premodule surveys focused on roles of hormones and antibiotics in the human body (e.g. development, fighting infection, but their broadened postmodule perspectives encompassed the roles of these molecules in organismal communication and possibly the evolution of multicellularity.

  7. Hormones and antibiotics in nature: a laboratory module designed to broaden undergraduate perspectives on typically human-centered topics.

    Science.gov (United States)

    Weber, Carolyn F

    2014-12-01

    Bringing discovery-based research into undergraduate laboratory courses increases student motivation and learning gains over traditional exercises that merely teach technique or demonstrate well-documented phenomena. Laboratory experiences are further enhanced when they are designed to challenge student perspectives on topics relevant to their lives. To this end, a laboratory module on antibiotics and hormones, which are generally discussed in the context of human health, was developed for students to explore the multifaceted roles of antibiotics and hormones in nature (e.g. interspecies communication) via reading primary scientific literature and performing discovery-based experiments. The main objective of this module was to increase the general biological literacy of students as determined by their ability to connect the Five Core Concepts of Biological Literacy (American Association for the Advancement of Science, Vision and Change in Undergraduate Education: A Call to Action, 2011) to the topics "hormones" and "antibiotics" in pre- and postmodule surveys. After discussing unpublished research findings, cell biology students performed experiments demonstrating that: 1) fungi may promote fern growth via hormone production, 2) novel bacterial isolates in the genus Streptomyces produce antifungal compounds, and 3) subinhibitory antibiotic concentrations may enhance soil bacterial growth. The third finding provided evidence supporting a hypothesis framed in a scientific article that students read and discussed. Student perspectives on premodule surveys focused on roles of hormones and antibiotics in the human body (e.g. development, fighting infection), but their broadened postmodule perspectives encompassed the roles of these molecules in organismal communication and possibly the evolution of multicellularity.

  8. Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells.

    Science.gov (United States)

    Fletcher, Rachel S; Ratajczak, Joanna; Doig, Craig L; Oakey, Lucy A; Callingham, Rebecca; Da Silva Xavier, Gabriella; Garten, Antje; Elhassan, Yasir S; Redpath, Philip; Migaud, Marie E; Philp, Andrew; Brenner, Charles; Canto, Carles; Lavery, Gareth G

    2017-08-01

    Augmenting nicotinamide adenine dinucleotide (NAD + ) availability may protect skeletal muscle from age-related metabolic decline. Dietary supplementation of NAD + precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) appear efficacious in elevating muscle NAD + . Here we sought to identify the pathways skeletal muscle cells utilize to synthesize NAD + from NMN and NR and provide insight into mechanisms of muscle metabolic homeostasis. We exploited expression profiling of muscle NAD + biosynthetic pathways, single and double nicotinamide riboside kinase 1/2 (NRK1/2) loss-of-function mice, and pharmacological inhibition of muscle NAD + recycling to evaluate NMN and NR utilization. Skeletal muscle cells primarily rely on nicotinamide phosphoribosyltransferase (NAMPT), NRK1, and NRK2 for salvage biosynthesis of NAD + . NAMPT inhibition depletes muscle NAD + availability and can be rescued by NR and NMN as the preferred precursors for elevating muscle cell NAD + in a pathway that depends on NRK1 and NRK2. Nrk2 knockout mice develop normally and show subtle alterations to their NAD+ metabolome and expression of related genes. NRK1, NRK2, and double KO myotubes revealed redundancy in the NRK dependent metabolism of NR to NAD + . Significantly, these models revealed that NMN supplementation is also dependent upon NRK activity to enhance NAD + availability. These results identify skeletal muscle cells as requiring NAMPT to maintain NAD + availability and reveal that NRK1 and 2 display overlapping function in salvage of exogenous NR and NMN to augment intracellular NAD + availability.

  9. Nicotinamide pharmacokinetics in humans and mice

    International Nuclear Information System (INIS)

    Horsman, M.R.; Hoyer, M.; Overgaard, J.; Honess, D.J.; Dennis, A.F.

    1993-01-01

    Healthy human volunteers orally ingested escalating doses of up to 6 g nicotinamide in capsule form on an empty stomach. Some side-effects were seen although these were mild and transient. HPLC analysis of blood samples showed peak plasma levels, typically within 45 min after ingestion, which were linearly dependent on dose ingested. The elimination half-life and AUC were also found to increase with drug dose, although these increases were non-linear. Pharmacokinetic studies were also performed to female CDF1 mice with C3H mammary carcinomas grown in the right rear foot. Analysis of blood and tumour samples taken from mice injected i.p. with nicotinamide doses between 100-1000 mg/kg showed similar characteristics as the human data, although the elimination half-lives were not dose-dependent. The average peak plasma concentration of 160 μg/ml measured in humans after taking 6 g of nicotinamide was equivalent to that seen in mice after injecting 171 mg/kg. Using a regrowth delay assay the enhancement of radiation damage by nicotinamide in this mouse tumour was found to be independent of drug dose from 100-1000 mg/kg, resulting in a constant 1.3-fold increase in radiation response. Doses of nicotinamide that can be tolerated clinically should therefore produce adequate enhancements of radiation damage in human tumours. (author)

  10. Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration.

    Science.gov (United States)

    Mukherjee, Sarmistha; Chellappa, Karthikeyani; Moffitt, Andrea; Ndungu, Joan; Dellinger, Ryan W; Davis, James G; Agarwal, Beamon; Baur, Joseph A

    2017-02-01

    The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers. Intriguingly, NR also ameliorated the steatosis that normally accompanies liver regeneration. To distinguish the role of hepatocyte NAD levels from any systemic effects of NR, we generated mice overexpressing nicotinamide phosphoribosyltransferase, a rate-limiting enzyme for NAD synthesis, specifically in the liver. Nicotinamide phosphoribosyltransferase overexpressing mice were mildly hyperglycemic at baseline and, similar to mice treated with NR, exhibited enhanced liver regeneration and reduced steatosis following partial hepatectomy. Conversely, mice lacking nicotinamide phosphoribosyltransferase in hepatocytes exhibited impaired regenerative capacity that was completely rescued by administering NR. NAD availability is limiting during liver regeneration, and supplementation with precursors such as NR may be therapeutic in settings of acute liver injury. (Hepatology 2017;65:616-630). © 2016 by the American Association for the Study of Liver Diseases.

  11. Anti-Trypanosoma cruzi activity of nicotinamide.

    Science.gov (United States)

    Soares, Milena B P; Silva, Cinara V; Bastos, Tanira M; Guimarães, Elisalva T; Figueira, Claudio P; Smirlis, Despina; Azevedo, Walter F

    2012-05-01

    Inhibition of Trypanosoma brucei and Leishmania spp. sirtuins has shown promising antiparasitic activity, indicating that these enzymes may be used as targets for drug discovery against trypanosomatid infections. In the present work we carried out a virtual screening focused on the C pocket of Sir2 from Trypanosoma cruzi. Using this approach, the best ligand found was nicotinamide. In vitro tests confirmed the anti-T. cruzi activity of nicotinamide on epimastigote and trypomastigote forms. Moreover, treatment of T. cruzi-infected macrophages with nicotinamide caused a significant reduction in the number of amastigotes. In addition, alterations in the mitochondria and an increase in the vacuolization in the cytoplasm were observed in epimastigotes treated with nicotinamide. Analysis of the complex of Sir2 and nicotinamide revealed the details of the possible ligand-target interaction. Our data reveal a potential use of TcSir2 as a target for anti-T. cruzi drug discovery. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. European Nicotinamide Diabetes Intervention Trial (ENDIT)

    DEFF Research Database (Denmark)

    Gale, E A M; Bingley, P J; Emmett, C L

    2004-01-01

    Juvenile Diabetes Federation (JDF) units or more, and a non-diabetic oral glucose tolerance test. Participants were recruited from 18 European countries, Canada, and the USA, and were randomly allocated oral modified release nicotinamide (1.2 g/m2) or placebo for 5 years. Random allocation was done......, and number of islet autoantibodies detected was 1.01 (0.73-1.38; p=0.97). Of 168 (30.4%) participants who withdrew from the trial, 83 were on placebo. The number of serious adverse events did not differ between treatment groups. Nicotinamide treatment did not affect growth in children or first-phase insulin...

  13. 21 CFR 172.315 - Nicotinamide-ascorbic acid complex.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Nicotinamide-ascorbic acid complex. 172.315 Section... HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.315 Nicotinamide-ascorbic acid complex. Nicotinamide-ascorbic acid complex may be safely used in accordance with the following prescribed conditions...

  14. Nicotinamide induces mitochondrial-mediated apoptosis through oxidative stress in human cervical cancer HeLa cells.

    Science.gov (United States)

    Feng, Yi; Wang, Yonghua; Jiang, Chengrui; Fang, Zishui; Zhang, Zhiqiang; Lin, Xiaoying; Sun, Liwei; Jiang, Weiying

    2017-07-15

    Nicotinamide participates in energy metabolism and influences cellular redox status and modulates multiple pathways related with both cellular survival and death. Recent studies have shown that it induced proliferation inhibition and apoptosis in many cancer cells. However, little is known about the effects of nicotinamide on human cervical cancer cells. We aimed to evaluate the effects of the indicated concentrations nicotinamide on cell proliferation, apoptosis and redox-related parameters in HeLa cells and investigated the apoptotic mechanism. After the treatment of the indicated concentrations nicotinamide, HeLa cell proliferation was evaluated by the CCK-8 assay and the production of ROS (reactive oxygen species) was measured using 2',7'-Dichlorofluorescin diacetate. The apoptotic effect was confirmed by observing the cellular and nuclear morphologies with fluorescence microscope and apoptotic rate of HeLa cell apoptosis was measured by flow cytometry using Annexin-V method. Moreover, we examined the mitochondrial membrane potential by JC-1 method and measured the expression of apoptosis related genes using qRT-PCR and immunoblotting. Nicotinamide restrained the HeLa cell proliferation and significantly increased the accumulation of ROS and depletion of GSH at relatively high concentrations. Furthermore, nicotinamide promoted HeLa cell apoptosis via the intrinsic mitochondrial apoptotic pathway. Our study revealed that nicotinamide induced the apoptosis through oxidative stress and intrinsic mitochondrial apoptotic pathways in HeLa cell. The results emerge that nicotinamide may be an inexpensive, safe and promising therapeutic agent or a neoadjuvant chemotherapy for cervical cancer patients, as well useful to find new drugs for cervical cancer therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Nicotinamide ribosyl uptake mutants in Haemophilus influenzae.

    Science.gov (United States)

    Herbert, Mark; Sauer, Elizabeta; Smethurst, Graeme; Kraiss, Anita; Hilpert, Anna-Karina; Reidl, Joachim

    2003-09-01

    The gene for the nicotinamide riboside (NR) transporter (pnuC) was identified in Haemophilus influenzae. A pnuC mutant had only residual NR uptake and could survive in vitro with high concentrations of NR, but could not survive in vivo. PnuC may represent a target for the development of inhibitors for preventing H. influenzae disease.

  16. Modulation of chemical dermal absorption by 14 natural products: a quantitative structure permeation analysis of components often found in topical preparations.

    Science.gov (United States)

    Muhammad, Faqir; Jaberi-Douraki, Majid; de Sousa, Damião Pergentino; Riviere, Jim E

    2017-09-01

    A large number of cosmetics and topical pharmaceuticals contain compounds of natural origin. There is a rising concern if these compounds can interact with the activity of other topically applied components in these formulations. The current study demonstrates modulation of dermal absorption of model components often found in topical preparations ( 14 C caffeine and 14 C salicylic acid) by a set of 14 compounds of natural origin using a flow through in vitro porcine skin diffusion system. The parameters of flux and permeability were calculated and quantitative structure permeation relationship (QSPR) analysis conducted on different molecular descriptors of modulator compounds. Terpinyl acetate was the greatest permeability/flux enhancer for caffeine followed by s-perillyl acetate and limonene 1,2-epoxide. The permeability/flux of salicylic acid was highest with hydroxycitronellal followed by limonene 1,2-epoxide and s-perillyl acetate. The optimum descriptors using stepwise regression analysis for predicting additive modulation on penetrant permeability/flux were polar surface area, log P for caffeine and Henry's Law constant, number of freely rotatable bonds, and water solubility for salicylic acid. In parallel with the experimental techniques, a novel mathematical model was developed to estimate the permeability coefficients and improve the stepwise regression analysis for assessing modulator effects. The r 2 values significantly increased for multicomponent QSPR models. Notably, limonene 1,2-epoxide and s-perillyl acetate were excellent enhancers for both caffeine and salicylic acid. These results confirm that some natural products incorporated into topical formulations will enhance absorption of other components which could affect their safety and efficacy profiles.

  17. Crystal Structure of Human Nicotinamide Riboside Kinase

    Energy Technology Data Exchange (ETDEWEB)

    Khan,J.; Xiang, S.; Tong, L.

    2007-01-01

    Nicotinamide riboside kinase (NRK) has an important role in the biosynthesis of NAD{sup +} as well as the activation of tiazofurin and other NR analogs for anticancer therapy. NRK belongs to the deoxynucleoside kinase and nucleoside monophosphate (NMP) kinase superfamily, although the degree of sequence conservation is very low. We report here the crystal structures of human NRK1 in a binary complex with the reaction product nicotinamide mononucleotide (NMN) at 1.5 {angstrom} resolution and in a ternary complex with ADP and tiazofurin at 2.7 {angstrom} resolution. The active site is located in a groove between the central parallel {beta} sheet core and the LID and NMP-binding domains. The hydroxyl groups on the ribose of NR are recognized by Asp56 and Arg129, and Asp36 is the general base of the enzyme. Mutation of residues in the active site can abolish the catalytic activity of the enzyme, confirming the structural observations.

  18. Crystal structure of human nicotinamide riboside kinase.

    Science.gov (United States)

    Khan, Javed A; Xiang, Song; Tong, Liang

    2007-08-01

    Nicotinamide riboside kinase (NRK) has an important role in the biosynthesis of NAD(+) as well as the activation of tiazofurin and other NR analogs for anticancer therapy. NRK belongs to the deoxynucleoside kinase and nucleoside monophosphate (NMP) kinase superfamily, although the degree of sequence conservation is very low. We report here the crystal structures of human NRK1 in a binary complex with the reaction product nicotinamide mononucleotide (NMN) at 1.5 A resolution and in a ternary complex with ADP and tiazofurin at 2.7 A resolution. The active site is located in a groove between the central parallel beta sheet core and the LID and NMP-binding domains. The hydroxyl groups on the ribose of NR are recognized by Asp56 and Arg129, and Asp36 is the general base of the enzyme. Mutation of residues in the active site can abolish the catalytic activity of the enzyme, confirming the structural observations.

  19. Nicotinamide polymeric nanoemulsified systems: a quality-by-design case study for a sustained antimicrobial activity

    Directory of Open Access Journals (Sweden)

    Zidan AS

    2016-04-01

    demonstrated a sustained release profile for nicotinamide. The Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction demonstrated a significant interaction between the drug and 2-hydroxypropyl-β-cyclodextrin that might modulate the sustained release behavior. Furthermore, the formulations provided a sustained antibacterial activity that depended on nicotinamide-loading concentration, release rate, and incubation time. In conclusion, the study demonstrated the potential of polymeric nanoemulsified system to sustain the release and antibacterial activity of nicotinamide. Keywords: nicotinamide, polymeric nanoemulsified systems, Plackett–Burman design, antibacterial activity, sustained release

  20. In vitro evaluation of nicotinamide riboside analogs against Haemophilus influenzae.

    OpenAIRE

    Godek, C P; Cynamon, M H

    1990-01-01

    Exogenous NAD, nicotinamide mononucleotide, or nicotinamide riboside is required for the growth of Haemophilus influenzae. These compounds have been defined as the V-factor growth requirement. We have previously shown that the internalization of nicotinamide riboside is energy dependent and carrier mediated with saturation kinetics. Thionicotinamide riboside, 3-pyridinealdehyde riboside, 3-acetylpyridine riboside, and 3-aminopyridine riboside were prepared from their corresponding NAD analogs...

  1. NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells.

    Science.gov (United States)

    Ratajczak, Joanna; Joffraud, Magali; Trammell, Samuel A J; Ras, Rosa; Canela, Núria; Boutant, Marie; Kulkarni, Sameer S; Rodrigues, Marcelo; Redpath, Philip; Migaud, Marie E; Auwerx, Johan; Yanes, Oscar; Brenner, Charles; Cantó, Carles

    2016-10-11

    NAD + is a vital redox cofactor and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Supplementation with NAD + precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD + synthesis. Using genetic gain- and loss-of-function models, we further demonstrate that the role of NRK1 in driving NAD + synthesis from other NAD + precursors, such as nicotinamide or nicotinic acid, is dispensable. Using stable isotope-labelled compounds, we confirm NMN is metabolized extracellularly to NR that is then taken up by the cell and converted into NAD + . Our results indicate that mammalian cells require conversion of extracellular NMN to NR for cellular uptake and NAD + synthesis, explaining the overlapping metabolic effects observed with the two compounds.

  2. Undergraduate teaching modules featuring geodesy data applied to critical social topics (GETSI: GEodetic Tools for Societal Issues)

    Science.gov (United States)

    Pratt-Sitaula, B. A.; Walker, B.; Douglas, B. J.; Charlevoix, D. J.; Miller, M. M.

    2015-12-01

    The GETSI project, funded by NSF TUES, is developing and disseminating teaching and learning materials that feature geodesy data applied to critical societal issues such as climate change, water resource management, and natural hazards (serc.carleton.edu/getsi). It is collaborative between UNAVCO (NSF's geodetic facility), Mt San Antonio College, and Indiana University. GETSI was initiated after requests by geoscience faculty for geodetic teaching resources for introductory and majors-level students. Full modules take two weeks but module subsets can also be used. Modules are developed and tested by two co-authors and also tested in a third classroom. GETSI is working in partnership with the Science Education Resource Center's (SERC) InTeGrate project on the development, assessment, and dissemination to ensure compatibility with the growing number of resources for geoscience education. Two GETSI modules are being published in October 2015. "Ice mass and sea level changes" includes geodetic data from GRACE, satellite altimetry, and GPS time series. "Imaging Active Tectonics" has students analyzing InSAR and LiDAR data to assess infrastructure earthquake vulnerability. Another three modules are in testing during fall 2015 and will be published in 2016. "Surface process hazards" investigates mass wasting hazard and risk using LiDAR data. "Water resources and geodesy" uses GRACE, vertical GPS, and reflection GPS data to have students investigating droughts in California and the High Great Plains. "GPS, strain, and earthquakes" helps students learn about infinitesimal and coseismic strain through analysis of horizontal GPS data and includes an extension module on the Napa 2014 earthquake. In addition to teaching resources, the GETSI project is compiling recommendations on successful development of geodesy curricula. The chief recommendations so far are the critical importance of including scientific experts in the authorship team and investing significant resources in

  3. In vitro evaluation of nicotinamide riboside analogs against Haemophilus influenzae.

    Science.gov (United States)

    Godek, C P; Cynamon, M H

    1990-08-01

    Exogenous NAD, nicotinamide mononucleotide, or nicotinamide riboside is required for the growth of Haemophilus influenzae. These compounds have been defined as the V-factor growth requirement. We have previously shown that the internalization of nicotinamide riboside is energy dependent and carrier mediated with saturation kinetics. Thionicotinamide riboside, 3-pyridinealdehyde riboside, 3-acetylpyridine riboside, and 3-aminopyridine riboside were prepared from their corresponding NAD analogs. These compounds and several other nicotinamide riboside analogs were evaluated for their ability to support the growth of H. influenzae and for their ability to block the uptake of [carbonyl-14C]nicotinamide riboside by H. influenzae. 3-Aminopyridine riboside blocked the uptake of [carbonyl-14C]nicotinamide riboside and inhibited the growth of H. influenzae when NAD, nicotinamide mononucleotide, or nicotinamide riboside served as the V factor. The antibacterial activity of 3-aminopyridine riboside was found to be specific for H. influenzae but had no effect on the growth of Staphylococcus aureus or Escherichia coli. In additional experiments by reversed-phase high-performance liquid chromatography, it was determined that whole cells of H. influenzae degrade 3-aminopyridine adenine dinucleotide to 3-aminopyridine riboside, which is then internalized. Inside the cell, 3-aminopyridine riboside has the ability to interfere with the growth of H. influenzae by an undetermined mechanism.

  4. Solar-parabolic dish-Stirling-engine-system module. Task 1: Topical report, market assessment/conceptual design

    Energy Technology Data Exchange (ETDEWEB)

    1982-11-30

    The major activities reported are: a market study to identify an early market for a dish-Stirling module and assess its commercial potential; preparation of a conceptual system and subsystem design to address this market; and preparation of an early sales implementation plan. A study of the reliability of protection from the effects of walk-off, wherein the sun's image leaves the receiver if the dish is not tracking, is appended, along with an optical analysis and structural analysis. Also appended are the relationship between PURPA and solar thermal energy development and electric utility pricing rationale. (LEW)

  5. The NAD(+) precursor nicotinamide riboside decreases exercise performance in rats.

    Science.gov (United States)

    Kourtzidis, Ioannis A; Stoupas, Andreas T; Gioris, Ioannis S; Veskoukis, Aristidis S; Margaritelis, Nikos V; Tsantarliotou, Maria; Taitzoglou, Ioannis; Vrabas, Ioannis S; Paschalis, Vassilis; Kyparos, Antonios; Nikolaidis, Michalis G

    2016-01-01

    Nicotinamide adenine dinucleotide (NAD(+)) and its phosphorylated form (NADP(+)) are key molecules in ubiquitous bioenergetic and cellular signaling pathways, regulating cellular metabolism and homeostasis. Thus, supplementation with NAD(+) and NADP(+) precursors emerged as a promising strategy to gain many and multifaceted health benefits. In this proof-of-concept study, we sought to investigate whether chronic nicotinamide riboside administration (an NAD(+) precursor) affects exercise performance. Eighteen Wistar rats were equally divided in two groups that received either saline vehicle or nicotinamide riboside at a dose of 300 mg/kg body weight/day for 21 days via gavage. At the end of the 21-day administration protocol, both groups performed an incremental swimming performance test. The nicotinamide riboside group showed a tendency towards worse physical performance by 35 % compared to the control group at the final 10 % load (94 ± 53 s for the nicotinamide riboside group and 145 ± 59 s for the control group; P = 0.071). Our results do not confirm the previously reported ergogenic effect of nicotinamide riboside. The potentially negative effect of nicotinamide riboside administration on physical performance may be attributed to the pleiotropic metabolic and redox properties of NAD(+) and NADP(+).

  6. Action of nucleotide phosphotransferase of Escherichia coli on nicotinamide riboside and nicotinamide mononucleotide.

    Science.gov (United States)

    Brunngraber, E F; Chargaff, E

    1977-01-01

    The action of the nucleotide phosphotransferase of Escherichia coli on nicotinamide riboside and on its 5'-phosphate results in the addition of one phosphate moiety to each of the substrates. Although the proof is not conclusive, it is likely that the phosphate group is transferred to the 3'-hydroxyl of the ribose. This is in contrast to the behavior of the enzyme toward NAD in which only the adenylic acid portion is phosphorylated enzymically. PMID:144913

  7. The chemistry of nicotinamide adenine dinucleotide (NAD) analogues containing C-nucleosides related to nicotinamide riboside.

    Science.gov (United States)

    Pankiewicz, Krzysztof W; Watanabe, Kyoichi A; Lesiak-Watanabe, Krystyna; Goldstein, Barry M; Jayaram, Hiremagalur N

    2002-04-01

    Oncolytic C-nucleosides, tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) and benzamide riboside (3-beta-D-ribofuranosylbenzamide) are converted in cell into active metabolites thiazole-4-carboxamide- and benzamide adenine dinucleotide, TAD and BAD, respectively. TAD and BAD as NAD analogues were found to bind at the nicotinamide adenine dinucleotide (cofactor NAD) site of inosine monophosphate dehydrogenase (IMPDH), an important target in cancer treatment. The synthesis and evaluation of anticancer activity of a number of C-nucleosides related to tiazofurin and nicotinamide riboside then followed and are reviewed herein. Interestingly, pyridine C-nucleosides (such as C-nicotinamide riboside) are not metabolized into the corresponding NAD analogues in cell. Their conversion by chemical methods is described. As dinucleotides these compounds show inhibition of IMPDH in low micromolar level. Also, the synthesis of BAD in metabolically stable bis(phosphonate) form is discussed indicating the usefulness of such preformed inhibitors in drug development. Among tiazofurin analogues, Franchetti and Grifantini found, that the replacement of the sulfur by oxygen (as in oxazafurin) but not the removal of nitrogen (tiophenfurin) of the thiazole ring resulted in inactive compounds. The anti cancer activity of their synthetic dinucleotide analogues indicate that inactive compounds are not only poorly metabolized in cell but also are weak inhibitors of IMPDH as dinucleotides.

  8. Extracellular nicotinamide phosphoribosyltransferase, a new cancer metabokine

    Science.gov (United States)

    Grolla, Ambra A; Travelli, Cristina

    2016-01-01

    Abstract In this review, we focus on the secreted form of nicotinamide phosphoribosyltransferase (NAMPT); extracellular NAMPT (eNAMPT), also known as pre‐B cell colony‐enhancing factor or visfatin. Although intracellular NAMPT is a key enzyme in controlling NAD metabolism, eNAMPT has been reported to function as a cytokine, with many roles in physiology and pathology. Circulating eNAMPT has been associated with several metabolic and inflammatory disorders, including cancer. Because cytokines produced in the tumour micro‐environment play an important role in cancer pathogenesis, in part by reprogramming cellular metabolism, future improvements in cancer immunotherapy will require a better understanding of the crosstalk between cytokine action and tumour biology. In this review, the knowledge of eNAMPT in cancer will be discussed, focusing on its immunometabolic function as a metabokine, its secretion, its mechanism of action and possible roles in the cancer micro‐environment. PMID:27128025

  9. An efficient chemical synthesis of nicotinamide riboside (NAR) and analogues.

    Science.gov (United States)

    Tanimori, Shinji; Ohta, Takeshi; Kirihata, Mitsunori

    2002-04-22

    A simple and efficient synthesis of nicotinamide riboside (NAR) 1 and derivatives 4 and 5 via trimethylsilyl trifluoromethanesulfonate (TMSOTf)-mediated N-glycosilation followed by spontaneous deacetylation by treating with methanol is reported.

  10. Recycling nicotinamide. The transition-state structure of human nicotinamide phosphoribosyltransferase

    Science.gov (United States)

    Burgos, Emmanuel S.; Vetticatt, Mathew J.; Schramm, Vern L.

    2013-01-01

    Human nicotinamide phosphoribosyltransferase (NAMPT) replenishes the NAD pool and controls the activities of sirtuins (SIRT), mono- and poly-(ADP-ribose) polymerases (PARP) and NAD nucleosidase (CD38). The nature of the enzymatic transition-state (TS) is central to understanding the function of NAMPT. We determined the TS structure for pyrophosphorolysis of nicotinamide mononucleotide (NMN) by kinetic isotope effects (KIEs). With the natural substrates, NMN and pyrophosphate (PPi), the intrinsic KIEs of [1′-14C], [1-15N], [1′-3H] and [2′-3H] are 1.047, 1.029, 1.154 and 1.093, respectively. A unique quantum computational approach was used for TS analysis that included structural elements of the catalytic site. Without constraints (e.g. imposed torsion angles), the theoretical and experimental data are in good agreement. The quantum-mechanical calculations incorporated a crucial catalytic site residue (D313), two magnesium atoms and coordinated water molecules. The transition state model predicts primary 14C, α-secondary 3H, β-secondary 3H and primary 15N KIE close to the experimental values. The analysis reveals significant ribocation character at the TS. The attacking PPi nucleophile is weakly interacting (rC-O = 2.60 Å) and the N-ribosidic C1′-N bond is highly elongated at the TS (rC-N = 2.35 Å), consistent with an ANDN mechanism. Together with the crystal structure of the NMN•PPi•Mg2•enzyme complex, the reaction coordinate is defined. The enzyme holds the nucleophile and leaving group in relatively fixed positions to create a reaction coordinate with C1′-anomeric migration from nicotinamide to the PPi. The transition state is reached by a 0.85 Å migration of C1′. PMID:23373462

  11. Tavaborole Topical

    Science.gov (United States)

    Tavaborole topical solution is used to treat fungal toenail infections (infections that may cause nail discoloration, splitting, or pain). Tavaborole topical solution is in a class of medications called antifungals. It works by stopping the growth of nail ...

  12. Efinaconazole Topical

    Science.gov (United States)

    Efinaconazole topical solution is used to treat fungal toenail infections (infections that may cause nail discoloration, splitting, or pain). Efinaconazole topical solution is in a class of medications called antifungals. It works by stopping the growth of nail ...

  13. Health Topics

    Science.gov (United States)

    ... Carpal tunnel syndrome Depression Irritable bowel syndrome Migraine Thyroid disease Urinary tract infections All A-Z health topics ... Carpal tunnel syndrome Depression Irritable bowel syndrome Migraine Thyroid disease Urinary tract infections All A-Z health topics ...

  14. Characterization of CobB kinetics and inhibition by nicotinamide.

    Directory of Open Access Journals (Sweden)

    Julia Gallego-Jara

    Full Text Available Lysine acetylation has emerged as a global protein regulation system in all domains of life. Sirtuins, or Sir2-like enzymes, are a family of histone deacetylases characterized by their employing NAD+ as a co-substrate. Sirtuins can deacetylate several acetylated proteins, but a consensus substrate recognition sequence has not yet been established. Product inhibition of many eukaryotic sirtuins by nicotinamide and its analogues has been studied in vitro due to their potential role as anticancer agents. In this work, the kinetics of CobB, the main Escherichia coli deacetylase, have been characterized. To our knowledge, this is the first kinetic characterization of a sirtuin employing a fully acetylated and natively folded protein as a substrate. CobB deacetylated several acetyl-CoA synthetase acetylated lysines with a single kinetic rate. In addition, in vitro nicotinamide inhibition of CobB has been characterized, and the intracellular nicotinamide concentrations have been determined under different growth conditions. The results suggest that nicotinamide can act as a CobB regulator in vivo. A nicotinamidase deletion strain was thus phenotypically characterized, and it behaved similarly to the ΔcobB strain. The results of this work demonstrate the potential regulatory role of the nicotinamide metabolite in vivo.

  15. Characterization of CobB kinetics and inhibition by nicotinamide.

    Science.gov (United States)

    Gallego-Jara, Julia; Écija Conesa, Ana; de Diego Puente, Teresa; Lozano Terol, Gema; Cánovas Díaz, Manuel

    2017-01-01

    Lysine acetylation has emerged as a global protein regulation system in all domains of life. Sirtuins, or Sir2-like enzymes, are a family of histone deacetylases characterized by their employing NAD+ as a co-substrate. Sirtuins can deacetylate several acetylated proteins, but a consensus substrate recognition sequence has not yet been established. Product inhibition of many eukaryotic sirtuins by nicotinamide and its analogues has been studied in vitro due to their potential role as anticancer agents. In this work, the kinetics of CobB, the main Escherichia coli deacetylase, have been characterized. To our knowledge, this is the first kinetic characterization of a sirtuin employing a fully acetylated and natively folded protein as a substrate. CobB deacetylated several acetyl-CoA synthetase acetylated lysines with a single kinetic rate. In addition, in vitro nicotinamide inhibition of CobB has been characterized, and the intracellular nicotinamide concentrations have been determined under different growth conditions. The results suggest that nicotinamide can act as a CobB regulator in vivo. A nicotinamidase deletion strain was thus phenotypically characterized, and it behaved similarly to the ΔcobB strain. The results of this work demonstrate the potential regulatory role of the nicotinamide metabolite in vivo.

  16. Nicotinamide riboside kinase structures reveal new pathways to NAD+.

    Directory of Open Access Journals (Sweden)

    Wolfram Tempel

    2007-10-01

    Full Text Available The eukaryotic nicotinamide riboside kinase (Nrk pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+ by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide riboside. Indeed, nicotinic acid riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+.

  17. Nicotinamide riboside kinase structures reveal new pathways to NAD+.

    Science.gov (United States)

    Tempel, Wolfram; Rabeh, Wael M; Bogan, Katrina L; Belenky, Peter; Wojcik, Marzena; Seidle, Heather F; Nedyalkova, Lyudmila; Yang, Tianle; Sauve, Anthony A; Park, Hee-Won; Brenner, Charles

    2007-10-02

    The eukaryotic nicotinamide riboside kinase (Nrk) pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+) by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide riboside. Indeed, nicotinic acid riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+.

  18. Protein Engineering for Nicotinamide Coenzyme Specificity in Oxidoreductases: Attempts and Challenges.

    Science.gov (United States)

    Chánique, Andrea M; Parra, Loreto P

    2018-01-01

    Oxidoreductases are ubiquitous enzymes that catalyze an extensive range of chemical reactions with great specificity, efficiency, and selectivity. Most oxidoreductases are nicotinamide cofactor-dependent enzymes with a strong preference for NADP or NAD. Because these coenzymes differ in stability, bioavailability and costs, the enzyme preference for a specific coenzyme is an important issue for practical applications. Different approaches for the manipulation of coenzyme specificity have been reported, with different degrees of success. Here we present various attempts for the switching of nicotinamide coenzyme preference in oxidoreductases by protein engineering. This review covers 103 enzyme engineering studies from 82 articles and evaluates the accomplishments in terms of coenzyme specificity and catalytic efficiency compared to wild type enzymes of different classes. We analyzed different protein engineering strategies and related them with the degree of success in inverting the cofactor specificity. In general, catalytic activity is compromised when coenzyme specificity is reversed, however when switching from NAD to NADP, better results are obtained. In most of the cases, rational strategies were used, predominantly with loop exchange generating the best results. In general, the tendency of removing acidic residues and incorporating basic residues is the strategy of choice when trying to change specificity from NAD to NADP, and vice versa . Computational strategies and algorithms are also covered as helpful tools to guide protein engineering strategies. This mini review aims to give a general introduction to the topic, giving an overview of tools and information to work in protein engineering for the reversal of coenzyme specificity.

  19. Protein Engineering for Nicotinamide Coenzyme Specificity in Oxidoreductases: Attempts and Challenges

    Directory of Open Access Journals (Sweden)

    Andrea M. Chánique

    2018-02-01

    Full Text Available Oxidoreductases are ubiquitous enzymes that catalyze an extensive range of chemical reactions with great specificity, efficiency, and selectivity. Most oxidoreductases are nicotinamide cofactor-dependent enzymes with a strong preference for NADP or NAD. Because these coenzymes differ in stability, bioavailability and costs, the enzyme preference for a specific coenzyme is an important issue for practical applications. Different approaches for the manipulation of coenzyme specificity have been reported, with different degrees of success. Here we present various attempts for the switching of nicotinamide coenzyme preference in oxidoreductases by protein engineering. This review covers 103 enzyme engineering studies from 82 articles and evaluates the accomplishments in terms of coenzyme specificity and catalytic efficiency compared to wild type enzymes of different classes. We analyzed different protein engineering strategies and related them with the degree of success in inverting the cofactor specificity. In general, catalytic activity is compromised when coenzyme specificity is reversed, however when switching from NAD to NADP, better results are obtained. In most of the cases, rational strategies were used, predominantly with loop exchange generating the best results. In general, the tendency of removing acidic residues and incorporating basic residues is the strategy of choice when trying to change specificity from NAD to NADP, and vice versa. Computational strategies and algorithms are also covered as helpful tools to guide protein engineering strategies. This mini review aims to give a general introduction to the topic, giving an overview of tools and information to work in protein engineering for the reversal of coenzyme specificity.

  20. 4-Hydroxy-3-methoxybenzaldehyde–nicotinamide (1/1

    Directory of Open Access Journals (Sweden)

    Fiona N.-F. How

    2011-12-01

    Full Text Available In the title compound, C6H6N2O·C8H8O3, an equimolar co-crystal of nicotinamide and vanillin, the aromatic ring and the amide fragment of the nicotinamide molecule make a dihedral angle of 32.6 (2°. The vanillin molecule is almost planar, with an r.m.s. deviation for all non-H atoms of 0.0094 Å. The vaniline and nicotinamide aromatic rings are nearly coplanar, the dihedral angle between them being 3.20 (9°. In the crystal, the two components are linked through N—H...O and O—H...N hydrogen bonds into chains along the a axis. The chains are connected via C—H...O interactions, forming a three-dimensional polymeric structure.

  1. Nicotinamide riboside phosphorylase from beef liver: purification and characterization.

    Science.gov (United States)

    Imai, T; Anderson, B M

    1987-04-01

    Nicotinamide riboside phosphorylase (NR phosphorylase) from beef liver has been purified to apparent homogeneity at 300-fold purification with a 35% yield. Kinetic constants for the enzyme-catalyzed phosphorolysis were as follows Knicotinamide riboside, 2.5 +/- 0.4 mM; Kinorganic phosphate, 0.50 +/- 0.12 mM; Vmax, 410 +/- 30 X 10(-6) mol min-1 mg protein-1, respectively. The molecular weights of the native enzyme and subunit structure were determined to be 131,000 and 32,000, respectively, suggesting the beef liver NR phosphorylase to be tetrameric in structure and consistent with the presence of identical subunits. The amino acid composition was shown to be very similar to that reported for human erythrocyte purine-nucleoside phosphorylase but differing considerably from that found for rat liver purine-nucleoside phosphorylase. In addition to catalytic activity with nicotinamide riboside, the beef liver enzyme catalyzed a phosphorolytic reaction with inosine and guanosine exhibiting activity ratios, nicotinamide riboside:inosine: guanosine of 1.00:0.35:0.29, respectively. These ratios of activity remained constant throughout purification of the beef liver enzyme and no separation of these activities was detected. Phosphorolysis of nicotinamide riboside was inhibited competitively by inosine (Ki = 75 microM) and guanosine (Ki = 75 microM). Identical rates of thermal denaturation of the beef liver enzyme were observed when determined for the phosphorolysis of either nicotinamide riboside or inosine. These observations coupled with studies of pH and specific buffer effects indicate the phosphorolysis of nicotinamide riboside, inosine, and guanosine to be catalyzed by the same enzyme.

  2. Syntheses of nicotinamide riboside and derivatives: effective agents for increasing nicotinamide adenine dinucleotide concentrations in mammalian cells.

    Science.gov (United States)

    Yang, Tianle; Chan, Noel Yan-Ki; Sauve, Anthony A

    2007-12-27

    A new two-step methodology achieves stereoselective synthesis of beta-nicotinamide riboside and a series of related amide, ester, and acid nucleosides. Compounds were prepared through a triacetylated-nicotinate ester nucleoside, via coupling of either ethylnicotinate or phenylnicotinate with 1,2,3,5-tetra-O-acetyl-beta-D-ribofuranose. Nicotinamide riboside, nicotinic acid riboside, O-ethylnicotinate riboside, O-methylnicotinate riboside, and several N-alkyl derivatives increased NAD+ concentrations from 1.2-2.7-fold in several mammalian cell lines. These findings establish bioavailability and potent effects of these nucleosides in stimulating the increase of NAD+ concentrations in mammalian cells.

  3. Assimilation of endogenous nicotinamide riboside is essential for calorie restriction-mediated life span extension in Saccharomyces cerevisiae.

    Science.gov (United States)

    Lu, Shu-Ping; Kato, Michiko; Lin, Su-Ju

    2009-06-19

    NAD(+) (nicotinamide adenine dinucleotide) is an essential cofactor involved in various biological processes including calorie restriction-mediated life span extension. Administration of nicotinamide riboside (NmR) has been shown to ameliorate deficiencies related to aberrant NAD(+) metabolism in both yeast and mammalian cells. However, the biological role of endogenous NmR remains unclear. Here we demonstrate that salvaging endogenous NmR is an integral part of NAD(+) metabolism. A balanced NmR salvage cycle is essential for calorie restriction-induced life span extension and stress resistance in yeast. Our results also suggest that partitioning of the pyridine nucleotide flux between the classical salvage cycle and the NmR salvage branch might be modulated by the NAD(+)-dependent Sir2 deacetylase. Furthermore, two novel deamidation steps leading to nicotinic acid mononucleotide and nicotinic acid riboside production are also uncovered that further underscore the complexity and flexibility of NAD(+) metabolism. In addition, utilization of extracellular nicotinamide mononucleotide requires prior conversion to NmR mediated by a periplasmic phosphatase Pho5. Conversion to NmR may thus represent a strategy for the transport and assimilation of large nonpermeable NAD(+) precursors. Together, our studies provide a molecular basis for how NAD(+) homeostasis factors confer metabolic flexibility.

  4. Assimilation of Endogenous Nicotinamide Riboside Is Essential for Calorie Restriction-mediated Life Span Extension in Saccharomyces cerevisiae*

    Science.gov (United States)

    Lu, Shu-Ping; Kato, Michiko; Lin, Su-Ju

    2009-01-01

    NAD+ (nicotinamide adenine dinucleotide) is an essential cofactor involved in various biological processes including calorie restriction-mediated life span extension. Administration of nicotinamide riboside (NmR) has been shown to ameliorate deficiencies related to aberrant NAD+ metabolism in both yeast and mammalian cells. However, the biological role of endogenous NmR remains unclear. Here we demonstrate that salvaging endogenous NmR is an integral part of NAD+ metabolism. A balanced NmR salvage cycle is essential for calorie restriction-induced life span extension and stress resistance in yeast. Our results also suggest that partitioning of the pyridine nucleotide flux between the classical salvage cycle and the NmR salvage branch might be modulated by the NAD+-dependent Sir2 deacetylase. Furthermore, two novel deamidation steps leading to nicotinic acid mononucleotide and nicotinic acid riboside production are also uncovered that further underscore the complexity and flexibility of NAD+ metabolism. In addition, utilization of extracellular nicotinamide mononucleotide requires prior conversion to NmR mediated by a periplasmic phosphatase Pho5. Conversion to NmR may thus represent a strategy for the transport and assimilation of large nonpermeable NAD+ precursors. Together, our studies provide a molecular basis for how NAD+ homeostasis factors confer metabolic flexibility. PMID:19416965

  5. Simvastatin-nicotinamide co-crystal: design, preparation and ...

    African Journals Online (AJOL)

    Purpose: To improve the solubility of simvastatin (SV) by co-crystallization using nicotinamide (Nic) as co-crystal agent (co-former). Methods: In silico molecular modeling of Nic counter to SV were investigated using Auto Dock 4.2. Cocrystal of Nic-SV was obtained by solvent evaporation (SE) using an equimolar ratio of Nic ...

  6. Bimatoprost Topical

    Science.gov (United States)

    ... not use a cotton swab or any other brush or applicator to apply topical bimatoprost.To use the solution, follow these steps: Wash your hands and face thoroughly with soap and water. Be sure that ...

  7. Ciclopirox Topical

    Science.gov (United States)

    Ciclopirox topical solution is used along with regular nail trimming to treat fungal infections of the fingernails and toenails (an infection that may cause nail discoloration, splitting and pain). Ciclopirox is in a ...

  8. Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)

    DEFF Research Database (Denmark)

    Bingley, Polly J; Mahon, Jeffrey L; Gale, Edwin A M

    2008-01-01

    OBJECTIVE: Insulin resistance can modulate progression to type 1 diabetes in individuals with ongoing islet autoimmunity. We wanted to see whether measures of insulin resistance improved risk assessment in islet cell antibody (ICA)-positive relatives when added to other immune and metabolic markers....... RESEARCH DESIGN AND METHODS: The retrospective cohort analysis included 213 family members participating in the European Nicotinamide Diabetes Intervention Trial. All were aged or=20 Juvenile Diabetes Foundation units. Median length of follow......-up was 4.21 years, and 105 individuals developed diabetes. Oral and intravenous glucose tolerance tests were performed at baseline; antibodies to GAD, IA-2, and insulin were determined by radioimmunoassay; and insulin resistance was estimated by homeostasis model assessment. Risk was assessed by Cox...

  9. Saccharomyces cerevisiae YOR071C encodes the high affinity nicotinamide riboside transporter Nrt1.

    Science.gov (United States)

    Belenky, Peter A; Moga, Tiberiu G; Brenner, Charles

    2008-03-28

    NAD(+) is an essential coenzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD(+)-consuming enzymes. Nicotinamide riboside is a recently discovered eukaryotic NAD(+) precursor converted to NAD(+) via the nicotinamide riboside kinase pathway and by nucleosidase activity and nicotinamide salvage. Nicotinamide riboside supplementation of yeast extends replicative life span on high glucose medium. The molecular basis for nicotinamide riboside uptake was unknown in any eukaryote. Here, we show that deletion of a single gene, YOR071C, abrogates nicotinamide riboside uptake without altering nicotinic acid or nicotinamide import. The gene, which is negatively regulated by Sum1, Hst1, and Rfm1, fully restores nicotinamide riboside import and utilization when resupplied to mutant yeast cells. The encoded polypeptide, Nrt1, is a predicted deca-spanning membrane protein related to the thiamine transporter, which functions as a pH-dependent facilitator with a K(m) for nicotinamide riboside of 22 microm. Nrt1-related molecules are conserved in particular fungi, suggesting a similar basis for nicotinamide riboside uptake.

  10. Nicotinamide Riboside and Nicotinic Acid Riboside Salvage in Fungi and Mammals

    Science.gov (United States)

    Belenky, Peter; Christensen, Kathryn C.; Gazzaniga, Francesca; Pletnev, Alexandre A.; Brenner, Charles

    2009-01-01

    NAD+ is a co-enzyme for hydride transfer enzymes and an essential substrate of ADP-ribose transfer enzymes and sirtuins, the type III protein lysine deacetylases related to yeast Sir2. Supplementation of yeast cells with nicotinamide riboside extends replicative lifespan and increases Sir2-dependent gene silencing by virtue of increasing net NAD+ synthesis. Nicotinamide riboside elevates NAD+ levels via the nicotinamide riboside kinase pathway and by a pathway initiated by splitting the nucleoside into a nicotinamide base followed by nicotinamide salvage. Genetic evidence has established that uridine hydrolase, purine nucleoside phosphorylase, and methylthioadenosine phosphorylase are required for Nrk-independent utilization of nicotinamide riboside in yeast. Here we show that mammalian purine nucleoside phosphorylase but not methylthioadenosine phosphorylase is responsible for mammalian nicotinamide riboside kinase-independent nicotinamide riboside utilization. We demonstrate that so-called uridine hydrolase is 100-fold more active as a nicotinamide riboside hydrolase than as a uridine hydrolase and that uridine hydrolase and mammalian purine nucleoside phosphorylase cleave nicotinic acid riboside, whereas the yeast phosphorylase has little activity on nicotinic acid riboside. Finally, we show that yeast nicotinic acid riboside utilization largely depends on uridine hydrolase and nicotinamide riboside kinase and that nicotinic acid riboside bioavailability is increased by ester modification. PMID:19001417

  11. Diflorasone Topical

    Science.gov (United States)

    ... area, do not use tight-fitting diapers or plastic pants. Such use may increase side effects.Do not apply other skin preparations or products ... doctor.if you are having surgery, including dental surgery, tell the doctor or dentist that you are using betamethasone topical.

  12. Betamethasone Topical

    Science.gov (United States)

    ... area, do not use tight-fitting diapers or plastic pants. Such use may increase side effects.Do not apply other skin preparations or products ... immediately.if you are having surgery, including dental surgery, tell the doctor or dentist that you are using betamethasone topical.

  13. Halcinonide Topical

    Science.gov (United States)

    ... area, do not use tight-fitting diapers or plastic pants. Such use may increase side effects.Do not wrap or bandage the treated area ... doctor.if you are having surgery, including dental surgery, tell the doctor or dentist that you are using halcinonide topical.

  14. Fluocinonide Topical

    Science.gov (United States)

    ... area, do not use tight-fitting diapers or plastic pants. Such use may increase side effects.Do not apply other skin preparations or products ... immediately.if you are having surgery, including dental surgery, tell the doctor or dentist that you are using fluocinonide topical.

  15. Dapsone Topical

    Science.gov (United States)

    ... go away: skin redness or burning skin drying skin oiliness and peeling itching Some side effects can be serious. If you experience any of these symptoms, stop using dapsone and call ... yellow or pale skin Dapsone topical may cause other side effects. Call ...

  16. Mometasone Topical

    Science.gov (United States)

    ... a few drops on the affected areas and massage lightly until it disappears.This medication is only for use on the skin. Do not let mometasone topical get into your eyes or mouth and do not swallow it. Avoid use on the face, in the genital and rectal areas, and in ...

  17. Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease.

    Science.gov (United States)

    Yao, Zhiwen; Yang, Wenhao; Gao, Zhiqiang; Jia, Peng

    2017-04-24

    Amyloid-β (Aβ) oligomers have been accepted as major neurotoxic agents in the therapy of Alzheimer's disease (AD). It has been shown that the activity of nicotinamide adenine dinucleotide (NAD+) is related with the decline of Aβ toxicity in AD. Nicotinamide mononucleotide (NMN), the important precursor of NAD+, is produced during the reaction of nicotinamide phosphoribosyl transferase (Nampt). This study aimed to figure out the potential therapeutic effects of NMN and its underlying mechanisms in APPswe/PS1dE9 (AD-Tg) mice. We found that NMN gave rise to a substantial improvement in behavioral measures of cognitive impairments compared to control AD-Tg mice. In addition, NMN treatment significantly decreased β-amyloid production, amyloid plaque burden, synaptic loss, and inflammatory responses in transgenic animals. Mechanistically, NMN effectively controlled JNK activation. Furthermore, NMN potently progressed nonamyloidogenic amyloid precursor protein (APP) and suppressed amyloidogenic APP by mediating the expression of APP cleavage secretase in AD-Tg mice. Based on our findings, it was suggested that NMN substantially decreases multiple AD-associated pathological characteristically at least partially by the inhibition of JNK activation. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Nicotinamide and WLDS Act Together to Prevent Neurodegeneration in Glaucoma

    Directory of Open Access Journals (Sweden)

    Simon W. M. John

    2017-04-01

    Full Text Available Glaucoma is a complex neurodegenerative disease characterized by progressive visual dysfunction leading to vision loss. Retinal ganglion cells are the primary affected neuronal population, with a critical insult damaging their axons in the optic nerve head. This insult is typically secondary to harmfully high levels of intraocular pressure (IOP. We have previously determined that early mitochondrial abnormalities within retinal ganglion cells lead to neuronal dysfunction, with age-related declines in NAD (NAD+ and NADH rendering retinal ganglion cell mitochondria vulnerable to IOP-dependent stresses. The Wallerian degeneration slow allele, WldS, decreases the vulnerability of retinal ganglion cells in eyes with elevated IOP, but the exact mechanism(s of protection from glaucoma are not determined. Here, we demonstrate that WldS increases retinal NAD levels. Coupled with nicotinamide administration (an NAD precursor, it robustly protects from glaucomatous neurodegeneration in a mouse model of glaucoma (94% of eyes having no glaucoma, more than WldS or nicotinamide alone. Importantly, nicotinamide and WldS protect somal, synaptic, and axonal compartments, prevent loss of anterograde axoplasmic transport, and protect from visual dysfunction as assessed by pattern electroretinogram. Boosting NAD production generally benefits major compartments of retinal ganglion cells, and may be of value in other complex, age-related, axonopathies where multiple neuronal compartments are ultimately affected.

  19. Nicotinamide adenine dinucleotide replenishment rescues colon degeneration in aged mice.

    Science.gov (United States)

    Zhu, Xudong; Shen, Weiyan; Wang, Ying; Jaiswal, Amit; Ju, Zhenyu; Sheng, Qinsong

    2017-01-01

    Susceptibility of gastrointestinal dysmotility increases with age-associated colonic degeneration. A paucity of remedies reversing colonic degeneration per se hinders the fundamental relief of symptoms. Here we discovered the correlation between colon degeneration and altered nicotinamide adenine dinucleotide (NAD) level in aged mice. Compared to 3-month-old young controls, 2-year-old mice showed a spectrum of degenerative colonic phenotypes and exhibited a significant elongated transit time and slowed stool frequency in the context of Lomotil-induced slow-transit constipation. Despite upregulated colonic tryptophan hydroxylases expression, serotonin release and expression of colon-predominant type IV serotonin receptor, reduced viability of interstitial cells of Cajal while enhanced aquaporins (Aqp1, 3 and 11) led to a less colonic motility and increased luminal dehydration in aged mice. Notably, this colonic degeneration was accompanied with reduced key NAD + -generating enzyme expression and lowered NAD + /NADH ratio in aged colon. Three-month continuous administration of beta nicotinamide mononucleotide, a NAD + precursor, elevated colonic NAD + level and improved defecation in aged mice. In contrast, pharmacological inhibition of nicotinamide phosphoribosyltransferase, the rate-limiting enzyme for NAD + biosynthesis, induced a reduction in colonic NAD content and impaired gastrointestinal function in young mice. Taken together, these findings suggest the beneficial effect of NAD + in maintaining colonic homoeostasis and reactivating NAD + biosynthesis may represent a promising strategy to counteract age-related gastrointestinal degeneration.

  20. Topical anesthesia

    Science.gov (United States)

    Kumar, Mritunjay; Chawla, Rajiv; Goyal, Manish

    2015-01-01

    Topical anesthetics are being widely used in numerous medical and surgical sub-specialties such as anesthesia, ophthalmology, otorhinolaryngology, dentistry, urology, and aesthetic surgery. They cause superficial loss of pain sensation after direct application. Their delivery and effectiveness can be enhanced by using free bases; by increasing the drug concentration, lowering the melting point; by using physical and chemical permeation enhancers and lipid delivery vesicles. Various topical anesthetic agents available for use are eutectic mixture of local anesthetics, ELA-max, lidocaine, epinephrine, tetracaine, bupivanor, 4% tetracaine, benzocaine, proparacaine, Betacaine-LA, topicaine, lidoderm, S-caine patch™ and local anesthetic peel. While using them, careful attention must be paid to their pharmacology, area and duration of application, age and weight of the patients and possible side-effects. PMID:26702198

  1. Topical anesthesia

    Directory of Open Access Journals (Sweden)

    Mritunjay Kumar

    2015-01-01

    Full Text Available Topical anesthetics are being widely used in numerous medical and surgical sub-specialties such as anesthesia, ophthalmology, otorhinolaryngology, dentistry, urology, and aesthetic surgery. They cause superficial loss of pain sensation after direct application. Their delivery and effectiveness can be enhanced by using free bases; by increasing the drug concentration, lowering the melting point; by using physical and chemical permeation enhancers and lipid delivery vesicles. Various topical anesthetic agents available for use are eutectic mixture of local anesthetics, ELA-max, lidocaine, epinephrine, tetracaine, bupivanor, 4% tetracaine, benzocaine, proparacaine, Betacaine-LA, topicaine, lidoderm, S-caine patch™ and local anesthetic peel. While using them, careful attention must be paid to their pharmacology, area and duration of application, age and weight of the patients and possible side-effects.

  2. Double blind clinical trial in a series of 115 patients with seborrheic dermatitis: prevention of relapses using a topical modulator of Toll like receptor 2.

    Science.gov (United States)

    Ionescu, M A; Baroni, A; Brambilla, L; Cannavò, S P; Cristaudo, A; Vedove, C Dalle; Frasca, M; Girolomoni, G; Gnecchi, L; Peris, K; Trifirò, C; Matta, A M; Robert, G

    2011-06-01

    Seborrheic dermatitis is a chronic inflammatory disease aggravated by Malassezia species. Toll-like receptors (TLR) are part of innate immune system that can be activated by yeasts. Previous studies showed that an association of Umbelliferae extract with a lipid (TLR2-Regul™) decreases the IL-8 expression in human skin in contact with M. furfur. The aim of this study was to assess the activity of a topical formulated with TLR2-Regul™ in the prevention of seborrheic dermatitis (SD) relapses. Immune-competent SD adult patients were treated for SD (topical imidazoles or steroids). Cleared patients were randomized and received a topical containing TLR2-Regul™ (A) or its vehicle (B). Erythema, scales and pruritus were assessed during two months. The study included 115 patients, mean age 43.4, sex ratio m/f 1.5. At week 4 the relapse rate was 26% (N.=15) in group A and 43% (N.=25) in group B. At W8 the relapse rate was 21% (N.=12) in group A and 40% (N.=23) (P=0.0309). In this series of 115 adults with seborrheic dermatitis, patients treated with a topical containing TLR-Regul™ showed a significantly less relapse rate compared with the excipient group (Pseborrheic dermatitis relapses.

  3. S-Adenosyl-L-Homocysteine Hydrolase Inhibition by a Synthetic Nicotinamide Cofactor Biomimetic

    Directory of Open Access Journals (Sweden)

    Lyn L. Kailing

    2018-03-01

    Full Text Available S-adenosyl-L-homocysteine (SAH hydrolases (SAHases are involved in the regulation of methylation reactions in many organisms and are thus crucial for numerous cellular functions. Consequently, their dysregulation is associated with severe health problems. The SAHase-catalyzed reaction is reversible and both directions depend on the redox activity of nicotinamide adenine dinucleotide (NAD+ as a cofactor. Therefore, nicotinamide cofactor biomimetics (NCB are a promising tool to modulate SAHase activity. In the present in vitro study, we investigated 10 synthetic truncated NAD+ analogs against a SAHase from the root-nodulating bacterium Bradyrhizobium elkanii. Among this set of analogs, one was identified to inhibit the SAHase in both directions. Isothermal titration calorimetry (ITC and crystallography experiments suggest that the inhibitory effect is not mediated by a direct interaction with the protein. Neither the apo-enzyme (i.e., deprived of the natural cofactor, nor the holo-enzyme (i.e., in the NAD+-bound state were found to bind the inhibitor. Yet, enzyme kinetics point to a non-competitive inhibition mechanism, where the inhibitor acts on both, the enzyme and enzyme-SAH complex. Based on our experimental results, we hypothesize that the NCB inhibits the enzyme via oxidation of the enzyme-bound NADH, which may be accessible through an open molecular gate, leaving the enzyme stalled in a configuration with oxidized cofactor, where the reaction intermediate can be neither converted nor released. Since the reaction mechanism of SAHase is quite uncommon, this kind of inhibition could be a viable pharmacological route, with a low risk of off-target effects. The NCB presented in this work could be used as a template for the development of more potent SAHase inhibitors.

  4. Biosynthesis and Recycling of Nicotinamide Cofactors in Mycobacterium tuberculosis

    Science.gov (United States)

    Boshoff, Helena I. M.; Xu, Xia; Tahlan, Kapil; Dowd, Cynthia S.; Pethe, Kevin; Camacho, Luis R.; Park, Tae-Ho; Yun, Chang-Soo; Schnappinger, Dirk; Ehrt, Sabine; Williams, Kerstin J.; Barry, Clifton E.

    2008-01-01

    Despite the presence of genes that apparently encode NAD salvage-specific enzymes in its genome, it has been previously thought that Mycobacterium tuberculosis can only synthesize NAD de novo. Transcriptional analysis of the de novo synthesis and putative salvage pathway genes revealed an up-regulation of the salvage pathway genes in vivo and in vitro under conditions of hypoxia. [14C]Nicotinamide incorporation assays in M. tuberculosis isolated directly from the lungs of infected mice or from infected macrophages revealed that incorporation of exogenous nicotinamide was very efficient in in vivo-adapted cells, in contrast to cells grown aerobically in vitro. Two putative nicotinic acid phosphoribosyltransferases, PncB1 (Rv1330c) and PncB2 (Rv0573c), were examined by a combination of in vitro enzymatic activity assays and allelic exchange studies. These studies revealed that both play a role in cofactor salvage. Mutants in the de novo pathway died upon removal of exogenous nicotinamide during active replication in vitro. Cell death is induced by both cofactor starvation and disruption of cellular redox homeostasis as electron transport is impaired by limiting NAD. Inhibitors of NAD synthetase, an essential enzyme common to both recycling and de novo synthesis pathways, displayed the same bactericidal effect as sudden NAD starvation of the de novo pathway mutant in both actively growing and nonreplicating M. tuberculosis. These studies demonstrate the plasticity of the organism in maintaining NAD levels and establish that the two enzymes of the universal pathway are attractive chemotherapeutic targets for active as well as latent tuberculosis. PMID:18490451

  5. Aquabis(nicotinamide-κN(thiocyanato-κNcopper(II

    Directory of Open Access Journals (Sweden)

    Changlun Shao

    2008-02-01

    Full Text Available In the title compound, [Cu(NCS2(C6H6N2O2(H2O], the Cu atom adopts a square-based pyramidal CuN4O coordination, with the water O atom in the apical position. The pairs of N-bonded nicotinamide ligands and thiocyanate anions in the basal plane are in a trans configuration. In the crystal structure, the molecules are connected into sheets by N—H...O and O—H...O hydrogen bonds.

  6. Deracemization of Axially Chiral Nicotinamides by Dynamic Salt Formation with Enantiopure Dibenzoyltartaric Acid (DBTA

    Directory of Open Access Journals (Sweden)

    Fumitoshi Yagishita

    2013-11-01

    Full Text Available Dynamic atroposelective resolution of chiral salts derived from oily racemic nicotinamides and enantiopure dibenzoyltartaric acid (DBTA was achieved by crystallization. The absolute structures of the axial chiral nicotinamides were determined by X-ray structural analysis. The chirality could be controlled by the selection of enantiopure DBTA as a chiral auxiliary. The axial chirality generated by dynamic salt formation was retained for a long period after dissolving the chiral salt in solution even after removal of the chiral acid. The rate of racemization of nicotinamides could be controlled based on the temperature and solvent properties, and that of the salts was prolonged compared to free nicotinamides, as the molecular structure of the pyridinium ion in the salts was different from that of acid-free nicotinamides.

  7. Immune Modulating Topical S100A8/A9 Inhibits Growth of Pseudomonas aeruginosa and Mitigates Biofilm Infection in Chronic Wounds

    DEFF Research Database (Denmark)

    Trøstrup, Hannah; Lerche, Christian Johann; Christophersen, Lars

    2017-01-01

    . Treatment slightly augmented key inflammatory cytokine Tumor Necrosis Factor-α (TNF-α), but dampened interferon-γ (IFN-γ) levels and blood polymorphonuclear count. In conclusion, topical S100A8/A9 displays remarkable novel immune stimulatory and anti-infective properties in vivo and in vitro. Importantly......Pseudomonas aeruginosa biofilm maintains and perturbs local host defense, hindering timely wound healing. Previously, we showed that P. aeruginosa suppressed S100A8/A9 of the murine innate host defense. We assessed the potential antimicrobial effect of S100A8/A9 on biofilm-infected wounds...... murine S100A8/A9 and a group of vehicle controls (phosphate-buffered saline, PBS) all treated with s.c. injections daily for up to five days. Wounds were analyzed for quantitative bacteriology and contents of key inflammatory markers. Count of blood polymorphonuclear leukocytes was included. S100A8/A9...

  8. Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection.

    Science.gov (United States)

    Chi, Yuling; Sauve, Anthony A

    2013-11-01

    This review focuses upon the biology and metabolism of a trace component in foods called nicotinamide riboside. Nicotinamide riboside is a precursor of nicotinamide adenine dinucleotide (NAD), and is a source of Vitamin B3. Evidence indicates that nicotinamide riboside has unique properties as a Vitamin B3. We review knowledge of the metabolism of this substance, as well as recent work suggesting novel health benefits that might be associated with nicotinamide riboside taken in larger quantities than is found naturally in foods. Recent work investigating the effects of nicotinamide riboside in yeast and mammals established that it is metabolized by at least two types of metabolic pathways. The first of these is degradative and produces nicotinamide. The second pathway involves kinases called nicotinamide riboside kinases (Nrk1 and Nrk2, in humans). The likely involvement of the kinase pathway is implicated in the unique effects of nicotinamide riboside in raising tissue NAD concentrations in rodents and for potent effects in eliciting insulin sensitivity, mitochondrial biogenesis, and enhancement of sirtuin functions. Additional studies with nicotinamide riboside in models of Alzheimer's disease indicate bioavailability to brain and protective effects, likely by stimulation of brain NAD synthesis. Initial studies have clarified the potential for a lesser-known Vitamin B3 called nicotinamide riboside that is available in selected foods, and possibly available to humans by supplements. It has properties that are insulin sensitizing, enhancing to exercise, resisting to negative effects of high-fat diet, and neuroprotecting.

  9. In vivo and in situ modulation of the expression of genes involved in metastasis and angiogenesis in a patient treated with topical imiquimod for melanoma skin metastases.

    Science.gov (United States)

    Hesling, C; D'Incan, M; Mansard, S; Franck, F; Corbin-Duval, A; Chèvenet, C; Déchelotte, P; Madelmont, J-C; Veyre, A; Souteyrand, P; Bignon, Y-J

    2004-04-01

    There is a growing body of evidence to support the efficacy of topical imiquimod in the treatment of primary skin carcinomas. Conflicting data exist concerning the use of imiquimod for the treatment of skin melanoma metastases. To date, only the impact of imiquimod on cytokines involved in immunological processes has been studied extensively. We report a woman successfully treated with imiquimod (once daily for 8 weeks) for skin melanoma metastases in whom we investigated the expression of molecules involved in metastasis and angiogenesis. Before and after treatment, a skin lesion was biopsied and the expression of the following molecules was investigated using real-time reverse transcription-polymerase chain reaction: matrix metalloproteinase (MMP)-1, 2 and 9 and their inhibitors KiSS-1 and tissue inhibitor of metalloproteinase (TIMP)-1, vascular endothelial growth factor (VEGF), fibroblast growth factor-2, and angiogenesis inhibitors (thrombospondin-1 and 2). Interferon (IFN)-alpha was also investigated as an in vivo marker of imiquimod activity. IFN-alpha was upregulated by the treatment. Under imiquimod, the following molecules were upregulated: TIMP-1, KiSS-1 and MMP-1. MMP-2 expression was not modified. MMP-9 expression was dramatically decreased. The expression of angiogenesis inhibitors was slightly increased but VEGF expression remained at a basal level. These results suggest that imiquimod could downregulate metastasis invasion and angiogenesis. However, these data were obtained at a transcriptional level and from a single case, and further investigations should include migration assays and additional cases in order to confirm that imiquimod may be safely used for treatment of melanoma metastases.

  10. PnuC and the Utilization of the Nicotinamide Riboside Analog 3-Aminopyridine in Haemophilus influenzae

    OpenAIRE

    Sauer, Elizabeta; Merdanovic, Melisa; Price Mortimer, Anne; Bringmann, Gerhard; Reidl, Joachim

    2004-01-01

    The utilization pathway for the uptake of NAD and nicotinamide riboside was previously characterized for Haemophilus influenzae. We now report on the cellular location, topology, and substrate specificity of PnuC. pnuC of H. influenzae is only distantly related to pnuC of Escherichia coli and Salmonella enterica serovar Typhimurium. When E. coli PnuC was expressed in an H. influenzae pnuC mutant, it was able to take up only nicotinamide riboside and not nicotinamide mononucleotide. Therefore,...

  11. pHP-Tethered N-Acyl Carbamate: A Photocage for Nicotinamide.

    Science.gov (United States)

    Salahi, Farbod; Purohit, Vatsal; Ferraudi, Guillermo; Stauffacher, Cynthia; Wiest, Olaf; Helquist, Paul

    2018-04-13

    The synthesis of a new photocaged nicotinamide having an N-acyl carbamate linker and a p-hydroxyphenacyl (pHP) chromophore is described. The photophysical and photochemical studies showed an absorption maximum at λ = 330 nm and a quantum yield for release of 11% that are dependent upon both pH and solvent. While the acyl carbamate releases nicotinamide efficiently, a simpler amide linker was inert to photocleavage. This photocaged nicotinamide has significant advantages with respect to quantum yield, absorbance wavelength, rate of release, and solubility that make it the first practical example of a photocaged amide.

  12. Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated silencing and longevity.

    Science.gov (United States)

    Gallo, Christopher M; Smith, Daniel L; Smith, Jeffrey S

    2004-02-01

    The Saccharomyces cerevisiae Sir2 protein is an NAD(+)-dependent histone deacetylase (HDAC) that functions in transcriptional silencing and longevity. The NAD(+) salvage pathway protein, Npt1, regulates Sir2-mediated processes by maintaining a sufficiently high intracellular NAD(+) concentration. However, another NAD(+) salvage pathway component, Pnc1, modulates silencing independently of the NAD(+) concentration. Nicotinamide (NAM) is a by-product of the Sir2 deacetylase reaction and is a natural Sir2 inhibitor. Pnc1 is a nicotinamidase that converts NAM to nicotinic acid. Here we show that recombinant Pnc1 stimulates Sir2 HDAC activity in vitro by preventing the accumulation of NAM produced by Sir2. In vivo, telomeric, rDNA, and HM silencing are differentially sensitive to inhibition by NAM. Furthermore, PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, life span, and Hst1-mediated transcriptional repression. Finally, we show that stress suppresses the inhibitory effect of NAM through the induction of PNC1 expression. Pnc1, therefore, positively regulates Sir2-mediated silencing and longevity by preventing the accumulation of intracellular NAM during times of stress.

  13. Modulating the properties of sunflower oil based novel emulgels using castor oil fatty acid ester: prospects for topical antimicrobial drug delivery.

    Science.gov (United States)

    Behera, B; Biswal, D; Uvanesh, K; Srivastava, A K; Bhattacharya, Mrinal K; Paramanik, K; Pal, K

    2015-04-01

    The current study describes the effect of polyglycerol polyricinoleate (PGPR) on the properties of sunflower oil and span-40 based emulgels. The prepared emulgels contained PGPR in varied concentrations. The microstructure of the emulgels was characterized by bright-field microscopy. The molecular interactions amongst the components of the emulgels were studied using FTIR spectroscopy. The flow and mechanical behaviors of the emulgels were studied using cone-and-plate viscometer and static mechanical tester, respectively. The efficiency of the metronidazole-loaded emulgels as antimicrobial formulations was tested in vitro. E. coli was used as the model microorganism for the antimicrobial study. The emulgels were also explored for iontophoretic delivery applications. The biocompatibility of the emulgels was tested using human keratinocytes (HaCaT). The microscopic evaluation of the emulgels indicated formation of biphasic formulations. FTIR studies suggested a decrease in the hydrogen bonding amongst the components of the emulgels as the concentration of the PGPR was increased. Viscosity studies indicated shear-thinning property of the emulgels. An increase in the PGPR concentration resulted in the reduction in the mechanical properties of the emulgels. Incorporation of PGPR resulted in the decrease in the drug released (both passive and iontophoresis) from the emulgels. The emulgels were found to be cytocompatible in the presence of keratinocytes. The drug loaded emulgels showed good antimicrobial activity against E. coli. In gist, the developed emulgels can be tried for controlled delivery of antimicrobial drugs. The physical and the release properties of the emulgels can be modulated by incorporating PGPR in varied proportions. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. [Nicotinamide coenzymes in the regulation of cellular metabolism in various types of diabetes].

    Science.gov (United States)

    Velikiĭ, N N; Obrosova, I G; Efimov, A S; Babicheva, E I; Sokil, O P

    1992-01-01

    Hypoglycemic and hypolipidemic effects of nicotinamide in insulin-dependent and noninsulin-dependent types of diabetes have been investigated. Hypoglycemic effect of nicotinamide in alloxan- and streptozotocin-induced diabetes resulted in activation of NAD+ biosynthesis and corresponding alterations in the redox state of free nicotinamide coenzymes. Increase in the free NAD+/NADH ratio was accompanied by inhibition of key gluconeogenic enzymes and by a decrease in the rate of 2-14C-incorporation into glucose in liver tissue and by inhibition of sorbitol formation in lens tissue. Nicotinamide exhibited hypolipidemic effect in db/db mice with noninsulin-dependent diabetes. The agent inhibited the enzyme of primary steps of lipogenesis, altered the structure of intercellular CoA pool and lowered the rate of lipid biosynthesis in liver tissue, thus normalizing blood lipoprotein compositions.

  15. Glaucoma as a Metabolic Optic Neuropathy: Making the Case for Nicotinamide Treatment in Glaucoma.

    Science.gov (United States)

    Williams, Pete A; Harder, Jeffrey M; John, Simon W M

    2017-12-01

    Mitochondrial dysfunction may be an important, if not essential, component of human glaucoma. Using transcriptomics followed by molecular and neurobiological techniques, we have recently demonstrated that mitochondrial dysfunction within retinal ganglion cells is an early feature in the DBA/2J mouse model of inherited glaucoma. Guided by these findings, we discovered that the retinal level of nicotinamide adenine dinucleotide (NAD, a key molecule for mitochondrial health) declines in an age-dependent manner. We hypothesized that this decline in NAD renders retinal ganglion cells susceptible to damage during periods of elevated intraocular pressure. To replete NAD levels in this glaucoma, we administered nicotinamide (the amide of vitamin B3). At the lowest dose tested, nicotinamide robustly protected from glaucoma (~70% of eyes had no detectable glaucomatous neurodegeneration). At this dose, nicotinamide had no influence on intraocular pressure and so its effect was neuroprotective. At the highest dose tested, 93% of eyes had no detectable glaucoma. This represents a ~10-fold decrease in the risk of developing glaucoma. At this dose, intraocular pressure still became elevated but there was a reduction in the degree of elevation showing an additional benefit. Thus, nicotinamide is unexpectedly potent at preventing this glaucoma and is an attractive option for glaucoma therapeutics. Our findings demonstrate the promise for both preventing and treating glaucoma by interventions that bolster metabolism during increasing age and during periods of elevated intraocular pressure. Nicotinamide prevents age-related declines in NAD (a decline that occurs in different genetic contexts and species). NAD precursors are reported to protect from a variety of neurodegenerative conditions. Thus, nicotinamide may provide a much needed neuroprotective treatment against human glaucoma. This manuscript summarizes human data implicating mitochondria in glaucoma, and argues for studies to

  16. Structural Basis of Substrate Recognition in Human Nicotinamide N-Methyltransferase

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Yi; Sartini, Davide; Pozzi, Valentina; Wilk, Dennis; Emanuelli, Monica; Yee, Vivien C. (Case Western); (Politecnica Valencia)

    2012-05-02

    Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of nicotinamide, pyridines, and other analogues using S-adenosyl-L-methionine as donor. NNMT plays a significant role in the regulation of metabolic pathways and is expressed at markedly high levels in several kinds of cancers, presenting it as a potential molecular target for cancer therapy. We have determined the crystal structure of human NNMT as a ternary complex bound to both the demethylated donor S-adenosyl-L-homocysteine and the acceptor substrate nicotinamide, to 2.7 {angstrom} resolution. These studies reveal the structural basis for nicotinamide binding and highlight several residues in the active site which may play roles in nicotinamide recognition and NNMT catalysis. The functional importance of these residues was probed by mutagenesis. Of three residues near the nicotinamide's amide group, substitution of S201 and S213 had no effect on enzyme activity while replacement of D197 dramatically decreased activity. Substitutions of Y20, whose side chain hydroxyl interacts with both the nicotinamide aromatic ring and AdoHcy carboxylate, also compromised activity. Enzyme kinetics analysis revealed k{sub cat}/K{sub m} decreases of 2-3 orders of magnitude for the D197A and Y20A mutants, confirming the functional importance of these active site residues. The mutants exhibited substantially increased K{sub m} for both NCA and AdoMet and modestly decreased k{sub cat}. MD simulations revealed long-range conformational effects which provide an explanation for the large increase in K{sub m}(AdoMet) for the D197A mutant, which interacts directly only with nicotinamide in the ternary complex crystal structure.

  17. Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy.

    Science.gov (United States)

    Sasaki, Yo; Araki, Toshiyuki; Milbrandt, Jeffrey

    2006-08-16

    Axonal degeneration occurs in many neurodegenerative diseases and after traumatic injury and is a self-destructive program independent from programmed cell death. Previous studies demonstrated that overexpression of nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) or exogenous application of nicotinamide adenine dinucleotide (NAD) can protect axons of cultured dorsal root ganglion (DRG) neurons from degeneration caused by mechanical or neurotoxic injury. In mammalian cells, NAD can be synthesized from multiple precursors, including tryptophan, nicotinic acid, nicotinamide, and nicotinamide riboside (NmR), via multiple enzymatic steps. To determine whether other components of these NAD biosynthetic pathways are capable of delaying axonal degeneration, we overexpressed each of the enzymes involved in each pathway and/or exogenously administered their respective substrates in DRG cultures and assessed their capacity to protect axons after axotomy. Among the enzymes tested, Nmnat1 had the strongest protective effects, whereas nicotinamide phosphoribosyl transferase and nicotinic acid phosphoribosyl transferase showed moderate protective activity in the presence of their substrates. Strong axonal protection was also provided by Nmnat3, which is predominantly located in mitochondria, and an Nmnat1 mutant localized to the cytoplasm, indicating that the subcellular location of NAD production is not crucial for protective activity. In addition, we showed that exogenous application of the NAD precursors that are the substrates of these enzymes, including nicotinic acid mononucleotide, nicotinamide mononucleotide, and NmR, can also delay axonal degeneration. These results indicate that stimulation of NAD biosynthetic pathways via a variety of interventions may be useful in preventing or delaying axonal degeneration.

  18. Cyclic voltammetric response of nicotinic acid and nicotinamide on a polycrystalline gold electrode

    International Nuclear Information System (INIS)

    Wang Xiaoxia; Yang Nianjun; Wan Qijin

    2006-01-01

    The oxidation of nicotinic acid and nicotinamide on a polycrystalline gold electrode occurred at almost same potentials but their reduction did at different peak potentials. The redox reaction mechanisms of nicotinic acid and nicotinamide were rationalized by the formation/disappearance of the new nitrogen-oxygen bonds in the pyridine rings by means of cyclic voltammetry and bulk electrolysis. The anodic currents of nicotinic acid and nicotinamide were controlled by diffusion, while the cathodic ones by adsorption. The difference in the cathodic peak potentials of nicotinic acid and nicotinamide on the polycrystalline gold electrode is attributed to the effect of the electron densities of remote substituents on the pyridine rings. The cathodic peak currents at about 0.20 V were linear with their concentrations in the range of 2.4 mM to 2.7 μM and 2.4 mM to 3.3 μM with detection limits of 0.27 and 0.33 μM for nicotinic acid and nicotinamide, respectively. Voltammetry was then adopted for the selective monitoring the content of nicotinic acid and nicotinamide in pharmaceuticals

  19. Identification of Isn1 and Sdt1 as Glucose- and Vitamin-regulated Nicotinamide Mononucleotide and Nicotinic Acid Mononucleotide 5′-Nucleotidases Responsible for Production of Nicotinamide Riboside and Nicotinic Acid Riboside*

    OpenAIRE

    Bogan, Katrina L.; Evans, Charles; Belenky, Peter; Song, Peng; Burant, Charles F.; Kennedy, Robert; Brenner, Charles

    2009-01-01

    Recently, we discovered that nicotinamide riboside and nicotinic acid riboside are biosynthetic precursors of NAD+, which are utilized through two pathways consisting of distinct enzymes. In addition, we have shown that exogenously supplied nicotinamide riboside is imported into yeast cells by a dedicated transporter, and it extends replicative lifespan on high glucose medium. Here, we show that nicotinamide riboside and nicotinic acid riboside are authentic intracellular metabolites in yeast...

  20. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice.

    Science.gov (United States)

    Trammell, Samuel A J; Weidemann, Benjamin J; Chadda, Ankita; Yorek, Matthew S; Holmes, Amey; Coppey, Lawrence J; Obrosov, Alexander; Kardon, Randy H; Yorek, Mark A; Brenner, Charles

    2016-05-27

    Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD(+) metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP(+) and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies.

  1. Effect of nicotinamide on early graft failure following intraportal islet transplantation

    Science.gov (United States)

    Jung, Da-Yeon; Park, Jae Berm; Joo, Sung-Yeon; Joh, Jae-Won; Kwon, Choon-Hyuck; Kwon, Ghee-Young

    2009-01-01

    Intraportal islet transplantation (IPIT) may potentially cure Type 1 diabetes mellitus; however, graft failure in the early post-transplantation period presents a major obstacle. In this study, we tested the ability of nicotinamide to prevent early islet destruction in a syngeneic mouse model. Mice (C57BL/6) with chemically-induced diabetes received intraportal transplants of syngeneic islet tissue in various doses. Islets were cultured for 24 h in medium with or without 10 mM nicotinamide supplementation. Following IPIT, islet function was confirmed by an intraperitoneal glucose tolerance test (IPGTT) and hepatectomy. The effects of nicotinamide were evaluated by blood glucose concentration, serum monocyte chemoattractant protein-1 (MCP-1) concentration, and immunohistology at 3 h and 24 h after IPIT. Among the various islet doses, an infusion of 300 syngeneic islets treated with nicotinamide exhibited the greatest differences in glucose tolerance between recipients of treated and untreated (i.e., control) islets. One day after 300 islet equivalent (IEQ) transplantation, islets treated with nicotinamide were better granulated than the untreated islets (P = 0.01), and the recipients displayed a slight decrease in serum MCP-1 concentration, as compared to controls. After 15 days, recipients of nicotinamide-pretreated islets showed higher levels of graft function (as measured by IPGTT) than controls. The pretreatment also prolonged graft survival (> 100 days) and function; these were confirmed by partial hepatectomy, which led to the recurrence of diabetes. Pretreatment of islet grafts with nicotinamide may prevent their deterioration on the early period following IPIT in a syngeneic mouse model. PMID:19641379

  2. Topical Treatment with Xiaozheng Zhitong Paste (XZP Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

    Directory of Open Access Journals (Sweden)

    Yanju Bao

    2015-01-01

    Full Text Available To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05. Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were detected in the XZP-treated rats (P<0.05 for all. Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.

  3. Nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2 regulates axon integrity in the mouse embryo.

    Directory of Open Access Journals (Sweden)

    Amy N Hicks

    Full Text Available Using transposon-mediated gene-trap mutagenesis, we have generated a novel mouse mutant termed Blad (Bloated Bladder. Homozygous mutant mice die perinatally showing a greatly distended bladder, underdeveloped diaphragm and a reduction in total skeletal muscle mass. Wild type and heterozygote mice appear normal. Using PCR, we identified a transposon insertion site in the first intron of Nmnat2 (Nicotinamide mononucleotide adenyltransferase 2. Nmnat2 is expressed predominantly in the brain and nervous system and has been linked to the survival of axons. Expression of this gene is undetectable in Nmnat2(blad/blad mutants. Examination of the brains of E18.5 Nmnat2(blad/blad mutant embryos did not reveal any obvious morphological changes. In contrast, E18.5 Nmnat2(blad/blad homozygotes showed an approximate 60% reduction of spinal motoneurons in the lumbar region and a more than 80% reduction in the sensory neurons of the dorsal root ganglion (DRG. In addition, facial motoneuron numbers were severely reduced, and there was virtually a complete absence of axons in the hind limb. Our observations suggest that during embryogenesis, Nmnat2 plays an important role in axonal growth or maintenance. It appears that in the absence of Nmnat2, major target organs and tissues (e.g., muscle are not functionally innervated resulting in perinatal lethality. In addition, neither Nmnat1 nor 3 can compensate for the loss of Nmnat2. Whilst there have been recent suggestions that Nmnat2 may be an endogenous modulator of axon integrity, this work represents the first in vivo study demonstrating that Nmnat2 is involved in axon development or survival in a mammal.

  4. PnuC and the utilization of the nicotinamide riboside analog 3-aminopyridine in Haemophilus influenzae.

    Science.gov (United States)

    Sauer, Elizabeta; Merdanovic, Melisa; Mortimer, Anne Price; Bringmann, Gerhard; Reidl, Joachim

    2004-12-01

    The utilization pathway for the uptake of NAD and nicotinamide riboside was previously characterized for Haemophilus influenzae. We now report on the cellular location, topology, and substrate specificity of PnuC. pnuC of H. influenzae is only distantly related to pnuC of Escherichia coli and Salmonella enterica serovar Typhimurium. When E. coli PnuC was expressed in an H. influenzae pnuC mutant, it was able to take up only nicotinamide riboside and not nicotinamide mononucleotide. Therefore, we postulated that PnuC transporters in general possess specificity for nicotinamide riboside. Earlier studies showed that 3-aminopyridine derivatives (e.g., 3-aminopyridine adenine dinucleotide) are inhibitory for H. influenzae growth. By testing characterized strains with mutations in the NAD utilization pathway, we show that 3-aminopyridine riboside is inhibitory to H. influenzae and is taken up by the NAD-processing and nicotinamide riboside route. 3-Aminopyridine riboside is utilized effectively in a pnuC+ background. In addition, we demonstrate that 3-aminopyridine adenine dinucleotide resynthesis is produced by NadR. 3-Aminopyridine riboside-resistant H. influenzae isolates were characterized, and mutations in nadR could be detected. We also tested other species of the family Pasteurellaceae, Pasteurella multocida and Actinobacillus actinomycetemcomitans, and found that 3-aminopyridine riboside does not act as a growth inhibitor; hence, 3-aminopyridine riboside represents an anti-infective agent with a very narrow host range.

  5. Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics

    Directory of Open Access Journals (Sweden)

    Adrian C Williams

    2017-04-01

    Full Text Available Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B 3 /nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the ‘de novo’ tryptophan-to-kynurenine-nicotinamide ‘immune tolerance’ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital.

  6. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin.

    Science.gov (United States)

    Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2013-05-01

    Nicotinamide (vitamin B3) protects from ultraviolet (UV) radiation-induced carcinogenesis in mice and from UV-induced immunosuppression in mice and humans. Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD(+)), an essential coenzyme in adenosine triphosphate (ATP) production. Previously, we showed that nicotinamide prevents UV-induced ATP decline in HaCaT keratinocytes. Energy-dependent DNA repair is a key determinant of cellular survival after exposure to DNA-damaging agents such as UV radiation. Hence, in this study we investigated whether nicotinamide protection from cellular energy loss influences DNA repair. We treated HaCaT keratinocytes with nicotinamide and exposed them to low-dose solar-simulated UV (ssUV). Excision repair was quantified using an assay of unscheduled DNA synthesis. Nicotinamide increased both the proportion of cells undergoing excision repair and the repair rate in each cell. We then investigated ssUV-induced cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxoG) formation and repair by comet assay in keratinocytes and with immunohistochemistry in human skin. Nicotinamide reduced CPDs and 8oxoG in both models and the reduction appeared to be due to enhancement of DNA repair. These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention.

  7. Nicotinamide; antioxidative and DNA hypomethylation effects in plant cells.

    Science.gov (United States)

    Berglund, Torkel; Wallström, Anders; Nguyen, Tuong-Van; Laurell, Cecilia; Ohlsson, Anna B

    2017-09-01

    The effects of nicotinamide (NIC) and its natural plant metabolites nicotinic acid (NIA) and trigonelline (TRIG) were studied with respect to defense in plant cell cultures. NIC and NIA could protect against oxidative stress damage caused by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), which generates free radicals. Damage was analyzed as DNA strand breaks in cell cultures of Pisum sativum (garden pea), Daucus carota (carrot), Populus tremula L. × P. tremuloides (hybrid aspen) and Catharanthus roseus (Madagascar periwinkle), monitored by single cell gel electrophoresis (comet assay), and assays of cell leakage in C. roseus. The activities of aconitase and fumarase enzymes, which have key roles in energy metabolism, were analyzed in P. sativum cultures after treatment with NIC or NIA. Aconitase activity was increased by NIA, and fumarase activity was increased by both compounds. These compounds were shown to promote glutathione metabolism in P. sativum cultures, and NIC was shown to have a global DNA hypomethylating effect. Neither TRIG nor poly(ADP-ribose) polymerase (PARP) inhibitor 3-aminobenzamide offered any protection against DNA damage or cell leakage, nor did they promote aconitase or fumarase activities, or glutathione metabolism. By this broad approach addressing multiple biochemical factors and different plant species, we demonstrate that NIC and NIA protect plant cells from oxidative stress, and that NIC clearly exerts an epigenetic effect; decreased DNA methylation. This indicates that these compounds have important roles in the regulation of metabolism in plant cells, especially in connection to stress. Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  8. Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+.

    Science.gov (United States)

    Belenky, Peter; Racette, Frances G; Bogan, Katrina L; McClure, Julie M; Smith, Jeffrey S; Brenner, Charles

    2007-05-04

    Although NAD(+) biosynthesis is required for Sir2 functions and replicative lifespan in yeast, alterations in NAD(+) precursors have been reported to accelerate aging but not to extend lifespan. In eukaryotes, nicotinamide riboside is a newly discovered NAD(+) precursor that is converted to nicotinamide mononucleotide by specific nicotinamide riboside kinases, Nrk1 and Nrk2. In this study, we discovered that exogenous nicotinamide riboside promotes Sir2-dependent repression of recombination, improves gene silencing, and extends lifespan without calorie restriction. The mechanism of action of nicotinamide riboside is totally dependent on increased net NAD(+) synthesis through two pathways, the Nrk1 pathway and the Urh1/Pnp1/Meu1 pathway, which is Nrk1 independent. Additionally, the two nicotinamide riboside salvage pathways contribute to NAD(+) metabolism in the absence of nicotinamide-riboside supplementation. Thus, like calorie restriction in the mouse, nicotinamide riboside elevates NAD(+) and increases Sir2 function.

  9. Biosynthesis of NAD from nicotinic acid and nicotinamide by resting cells of Arthrobacter globiformis

    International Nuclear Information System (INIS)

    Kuwahara, Masaaki

    1978-01-01

    Isotopically labeled nicotinic acid and nicotinamide were incorporated into the metabolites of nicotinic acid-dependent pathway (Preiss-Handler pathway) of the NAD biosynthesis by resting cells of Arthrobacter globiformis. Azaserine and adenosine markedly stimulated the accumulation of NAD in the cells. Radioactive nicotinic acid and nicotinamide were also incorporated into an unknown compound when the cells were incubated in the presence of azaserine. Cell-free extract of the organism showed the NAD synthetase activity, which required ammonium ion and ATP for the amidation of deamido-NAD. Adenosine inhibited the enzyme activity. The organism possessed nicotinamidase, suggesting deamidation is the first step in the biosynthesis of NAD from nicotinamide. The activity was inhibited by NAD, NADP and NMN. (auth.)

  10. Optimization of nicotinamide and riboflavin in the biodesulfurization of dibenzothiophene using response surface methodology

    Directory of Open Access Journals (Sweden)

    Hossein Saber

    2013-01-01

    Full Text Available Introduction: Dibenzothiophene (DBT is a sulfuric compound and resistant to Hydrodesulfurization process.Rhodococcuserythropolis R1, a previously isolated bacterial strain, is capable to bioconversion of DBT to 2-hydroxybiphenyl (2-HBP.Materials and methods: The effect of nicotinamide (precursor of NAD and riboflavin (precursor of FMN on DBT biodesulfurization and growth rate by this strain was studied using Gibbs assay and turbidimeteric assay respectively. The level of cofactor precursors were optimized using response surface methodology (RSM. Results: Analyses showed that both nicotinamide and riboflavin were statistically significant and could enhance the biodesulfurization rate of DBT by induction of dsz operon. The optimum level of nicotinamide and riboflavin was obtained at 10.67 mM and 34.2 µM respectively. Discussion and conclusion: In spite of increasing in BDS, the addition of these cofactor precursors led to decreased growth rate and biomass production due to limitated effect of produced 2-HBP.

  11. Temperature Dependence in the Terahertz Spectrum of Nicotinamide: Anharmonicity and Hydrogen-Bonded Network.

    Science.gov (United States)

    Takahashi, Masae; Okamura, Nubuyuki; Fan, Xinyi; Shirakawa, Hitoshi; Minamide, Hiroaki

    2017-04-06

    We have investigated the terahertz-spectral property of nicotinamide focusing on the temperature dependence in the range of 14-300 K. We observed that almost all peaks in the terahertz spectrum of the nicotinamide crystal showed a remarkable shift with temperature, whereas the lowest-frequency peak at 34.8 cm -1 showed a negligible shift with temperature. By analyzing the terahertz spectrum with the dispersion-corrected density functional theory calculations, we found that the difference in the temperature dependence of the peak shift is well understood in terms of the presence/absence of stretching vibration of the intermolecular hydrogen bond in the mode and the change of cell parameters. The anharmonicity in the dissociation potential energy of very weak intermolecular hydrogen bonding causes the remarkable peak shift with temperature in the terahertz spectrum of nicotinamide. This finding suggests that the assignment and identification of peaks in the terahertz spectrum are systematically enabled by temperature-dependent measurements.

  12. Nicotinamide "protects" resting lymphocytes exposed to hydrogen peroxide from necrosis but not from apoptosis.

    Science.gov (United States)

    Tronov, V A; Konstantinov, E M; Petrakou, E; Tsilimigaki, S; Piperakis, S M

    2002-01-01

    The aim of this work was to investigate the relationship between mechanisms of DNA repair and apoptosis induced by oxidative stress (H2O2) in human lymphocytes. Using the comet assay, fluorescent microscopy, and DNA electrophoresis, we studied the DNA damage induced by hydrogen peroxide (H2O2) treatment, the time and the amount of repair of strand breaks, the type of cell death, and the influence of inhibitors of repair (nicotinamide). When lymphocytes were treated with H2O2, we observed an increased in necrosis compared to apoptosis. However, when nicotinamide (which inhibits DNA repair) was added, the mode of death reversed to increased apoptosis. These results indicate that nicotinamide "protects" resting lymphocytes exposed to H2O2 from necrosis but not from apoptosis.

  13. Nicotinamide inhibits vasculogenic mimicry, an alternative vascularization pathway observed in highly aggressive melanoma.

    Directory of Open Access Journals (Sweden)

    Orit Itzhaki

    Full Text Available Vasculogenic mimicry (VM describes functional vascular channels composed only of tumor cells and its presence predicts poor prognosis in melanoma patients. Inhibition of this alternative vascularization pathway might be of clinical importance, especially as several anti-angiogenic therapies targeting endothelial cells are largely ineffective in melanoma. We show the presence of VM structures histologically in a series of human melanoma lesions and demonstrate that cell cultures derived from these lesions form tubes in 3D cultures ex vivo. We tested the ability of nicotinamide, the amide form of vitamin B3 (niacin, which acts as an epigenetic gene regulator through unique cellular pathways, to modify VM. Nicotinamide effectively inhibited the formation of VM structures and destroyed already formed ones, in a dose-dependent manner. Remarkably, VM formation capacity remained suppressed even one month after the complete withdrawal of Nicotimamid. The inhibitory effect of nicotinamide on VM formation could be at least partially explained by a nicotinamide-driven downregulation of vascular endothelial cadherin (VE-Cadherin, which is known to have a central role in VM. Further major changes in the expression profile of hundreds of genes, most of them clustered in biologically-relevant clusters, were observed. In addition, nicotinamide significantly inhibited melanoma cell proliferation, but had an opposite effect on their invasion capacity. Cell cycle analysis indicated moderate changes in apoptotic indices. Therefore, nicotinamide could be further used to unravel new biological mechanisms that drive VM and tumor progression. Targeting VM, especially in combination with anti-angiogenic strategies, is expected to be synergistic and might yield substantial anti neoplastic effects in a variety of malignancies.

  14. Application of a coupled enzyme assay to characterize nicotinamide riboside kinases.

    Science.gov (United States)

    Dölle, Christian; Ziegler, Mathias

    2009-02-15

    The recently identified nicotinamide riboside kinases (Nrks) constitute a distinct pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. Here we present the combination of an established optical adenosine triphosphatase (ATPase) test, the pyruvate kinase/lactate dehydrogenase system, with the Nrk-catalyzed reaction to determine kinetic properties of these enzymes, in particular affinities for ATP. The assay allows variation of both nucleoside and phosphate donor substrates, thereby providing major advantages for the characterization of these enzymes. We confirm previously established kinetic parameters and identify differences in substrate selectivity between the two human Nrk isoforms. The proposed assay is inexpensive and may be applied for high-throughput screening.

  15. In situ enzymatic removal of orthophosphate by the nucleoside phosphorylase catalyzed phosphorolysis of nicotinamide riboside.

    Science.gov (United States)

    Shriver, J W; Sykes, B D

    1982-09-01

    An enzymatic orthophosphate removal system is described which can be effectively used to continuously remove orthophosphate from biochemical samples. The phosphorolysis of nicotinamide riboside is catalyzed by calf spleen nucleoside phosphorylase to give ribose-1-PO4 and nicotinamide along with a proton. At pH 8 the production of ribose-1-PO4 from orthophosphate is essentially quantitative. This reaction can be monitored optically or by 31P nuclear magnetic resonance (NMR). Equations are given for determining the time required to remove a given amount of phosphate from a typical NMR sample with a known amount of nucleoside phosphorylase. The effects of a competing orthophosphate-producing reaction are considered.

  16. Nicotinamide homeostasis: a xenobiotic pathway that is key to development and degenerative diseases.

    Science.gov (United States)

    Williams, A C; Ramsden, D B

    2005-01-01

    Monkeys and man are very closely related genetically. Yet intellectually there are big differences and they suffer from a broad range of different diseases. For example, monkeys do not get Parkinson's or Alzheimer's disease. The former is surprising given that both get parkinsonism from MPTP poisoning and the latter initially less surprising as the cortex predominantly affected in Alzheimer's never developed as fully in the monkey. Man is an omnivore whilst other primates are predominantly herbivores. The one primate who was almost wholly carnivorous was Neanderthal man who became extinct. Red meat has a high content of Nicotinamide, Choline, and methyl donors. The enzyme NNMT converts nicotinamide to N-methyl-nicotinamide using SAM as the methyl donor. It is not present to any degree in herbivores. It has recently been shown to be present in human brain and up regulated in Parkinson's disease. Omnivores presumably need it for nicotinamide homeostasis but the production of N-methyl-nicotinamide will also be beneficial as it will reduce the export of Choline from neurones. Both will aid brain growth and development. However, as N-methyl-nicotinamide resembles MPTP it could cause parkinsonism later in life for man but not monkeys as they would be predicted not to have as much NNMT. Humans with a diet low in Nicotinamide,Choline or methyl donors early in life and low enzyme activity may be prone to Alzheimer's as their brain and therefore its reserves may never have developed as fully. The possession of NNMT plus a diet rich in Nicotinamide, Choline and methyl providers may explain many of the advantages but also the disadvantages of the human condition. One prediction is that a diet rich in these micronutrients whilst young will improve brain development and reduce the risk of Alzheimer's but that a lower dose later in life will reduce the risk of Parkinsonism. A second prediction is that it will become clear that dietary factors including vitamins are signalers and

  17. Diclofenac Topical (osteoarthritis pain)

    Science.gov (United States)

    Diclofenac topical gel (Voltaren) is used to relieve pain from osteoarthritis (arthritis caused by a breakdown of ... the knees, ankles, feet, elbows, wrists, and hands. Diclofenac topical liquid (Pennsaid) is used to relieve osteoarthritis ...

  18. Women's Health Topics

    Science.gov (United States)

    ... Information by Audience For Women Women's Health Topics Women's Health Topics Share Tweet Linkedin Pin it More ... State & Local Officials Consumers Health Professionals Science & Research Industry Scroll back to top Popular Content Home Latest ...

  19. Child Development & Behavior Topics

    Science.gov (United States)

    ... Your Child Topics Commentaries Featured Links Contact Us Child Development & Behavior Topics A B C D E F ... Seat Safety Carbon Monoxide Chewing Tobacco Child Care Child Development Milestones Child Development, What Do Grown-Ups Know ...

  20. Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats.

    Science.gov (United States)

    Madkor, Hafez R; Mansour, Sherif W; Ramadan, Gamal

    2011-04-01

    Spices which show hypoglycaemic, hypolipidaemic and antioxidant activities may have a role in the treatment of diabetes and its complications. The present study aimed to compare the modulatory effects of garlic, ginger, turmeric and their mixture on the metabolic syndrome and oxidative stress in streptozotocin (STZ)-nicotinamide diabetic rats. Diabetes was induced in overnight fasted rats by a single intraperitoneal injection of STZ (65 mg/kg body weight) and nicotinamide (110 mg/kg body weight, 15 min before STZ injection). Diabetic rats orally received either distilled water (as vehicle) or 200 mg/kg body weight of garlic bulb, ginger rhizome or turmeric rhizome powder suspension separately or mixed together (GGT mixture) for twenty-eight consecutive days. The results showed that these spices and their mixture significantly alleviated (80-97 %, P diabetic rats by increasing the production of insulin (26-37 %), enhancing the antioxidant defence system (31-52 %, especially GSH) and decreasing lipid peroxidation (60-97 %). The greatest modulation was seen in diabetic rats that received garlic and the GGT mixture (10-23 % more than that in the ginger and turmeric groups). In conclusion, garlic or the mix including garlic appears to have an impact on each of the measures more effectively than ginger and turmeric and may have a role in alleviating the risks of the metabolic syndrome and cardiovascular complications.

  1. Freshman Health Topics

    Science.gov (United States)

    Hovde, Karen

    2011-01-01

    This article examines a cluster of health topics that are frequently selected by students in lower division classes. Topics address issues relating to addictive substances, including alcohol and tobacco, eating disorders, obesity, and dieting. Analysis of the topics examines their interrelationships and organization in the reference literature.…

  2. NadN and e (P4) Are Essential for Utilization of NAD and Nicotinamide Mononucleotide but Not Nicotinamide Riboside in Haemophilus influenzae

    Science.gov (United States)

    Kemmer, Gabriele; Reilly, Thomas J.; Schmidt-Brauns, Joachim; Zlotnik, Gary W.; Green, Bruce A.; Fiske, Michael J.; Herbert, Mark; Kraiß, Anita; Schlör, Stefan; Smith, Arnold; Reidl, Joachim

    2001-01-01

    Haemophilus influenzae has an absolute requirement for NAD (factor V) because it lacks almost all the biosynthetic enzymes necessary for the de novo synthesis of that cofactor. Factor V can be provided as either nicotinamide adenosine dinucleotide (NAD), nicotinamide mononucleotide (NMN), or nicotinamide riboside (NR) in vitro, but little is known about the source or the mechanism of uptake of these substrates in vivo. As shown by us earlier, at least two gene products are involved in the uptake of NAD, the outer membrane lipoprotein e (P4), which has phosphatase activity and is encoded by hel, and a periplasmic NAD nucleotidase, encoded by nadN. It has also been observed that the latter gene product is essential for H. influenzae growth on media supplemented with NAD. In this report, we describe the functions and substrates of these two proteins as they act together in an NAD utilization pathway. Data are provided which indicate that NadN harbors not only NAD pyrophosphatase but also NMN 5′-nucleotidase activity. The e (P4) protein is also shown to have NMN 5′-nucleotidase activity, recognizing NMN as a substrate and releasing NR as its product. Insertion mutants of nadN or deletion and site-directed mutants of hel had attenuated growth and a reduced uptake phenotype when NMN served as substrate. A hel and nadN double mutant was only able to grow in the presence of NR, whereas no uptake of NMN was observed. PMID:11395461

  3. NadN and e (P4) are essential for utilization of NAD and nicotinamide mononucleotide but not nicotinamide riboside in Haemophilus influenzae.

    Science.gov (United States)

    Kemmer, G; Reilly, T J; Schmidt-Brauns, J; Zlotnik, G W; Green, B A; Fiske, M J; Herbert, M; Kraiss, A; Schlör, S; Smith, A; Reidl, J

    2001-07-01

    Haemophilus influenzae has an absolute requirement for NAD (factor V) because it lacks almost all the biosynthetic enzymes necessary for the de novo synthesis of that cofactor. Factor V can be provided as either nicotinamide adenosine dinucleotide (NAD), nicotinamide mononucleotide (NMN), or nicotinamide riboside (NR) in vitro, but little is known about the source or the mechanism of uptake of these substrates in vivo. As shown by us earlier, at least two gene products are involved in the uptake of NAD, the outer membrane lipoprotein e (P4), which has phosphatase activity and is encoded by hel, and a periplasmic NAD nucleotidase, encoded by nadN. It has also been observed that the latter gene product is essential for H. influenzae growth on media supplemented with NAD. In this report, we describe the functions and substrates of these two proteins as they act together in an NAD utilization pathway. Data are provided which indicate that NadN harbors not only NAD pyrophosphatase but also NMN 5'-nucleotidase activity. The e (P4) protein is also shown to have NMN 5'-nucleotidase activity, recognizing NMN as a substrate and releasing NR as its product. Insertion mutants of nadN or deletion and site-directed mutants of hel had attenuated growth and a reduced uptake phenotype when NMN served as substrate. A hel and nadN double mutant was only able to grow in the presence of NR, whereas no uptake of NMN was observed.

  4. Topical Melatonin for Treatment of Androgenetic Alopecia

    OpenAIRE

    Fischer, Tobias W; Tr?eb, Ralph M; H?nggi, Gabriella; Innocenti, Marcello; Elsner, Peter

    2012-01-01

    Background: In the search for alternative agents to oral finasteride and topical minoxidil for the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth modulator, was identified as a promising candidate based on in vitro and in vivo studies. Materials and Methods: One pharmacodynamic study on topical application of melatonin and four clinical pre-post studies were performed in patients with androgenetic alopecia or general hair loss and evaluated by standardise...

  5. Identification of Isn1 and Sdt1 as Glucose- and Vitamin-regulated Nicotinamide Mononucleotide and Nicotinic Acid Mononucleotide 5′-Nucleotidases Responsible for Production of Nicotinamide Riboside and Nicotinic Acid Riboside*

    Science.gov (United States)

    Bogan, Katrina L.; Evans, Charles; Belenky, Peter; Song, Peng; Burant, Charles F.; Kennedy, Robert; Brenner, Charles

    2009-01-01

    Recently, we discovered that nicotinamide riboside and nicotinic acid riboside are biosynthetic precursors of NAD+, which are utilized through two pathways consisting of distinct enzymes. In addition, we have shown that exogenously supplied nicotinamide riboside is imported into yeast cells by a dedicated transporter, and it extends replicative lifespan on high glucose medium. Here, we show that nicotinamide riboside and nicotinic acid riboside are authentic intracellular metabolites in yeast. Secreted nicotinamide riboside was detected with a biological assay, and intracellular levels of nicotinamide riboside, nicotinic acid riboside, and other NAD+ metabolites were determined by a liquid chromatography-mass spectrometry method. A biochemical genomic screen indicated that three yeast enzymes possess nicotinamide mononucleotide 5′-nucleotidase activity in vitro. Metabolic profiling of knock-out mutants established that Isn1 and Sdt1 are responsible for production of nicotinamide riboside and nicotinic acid riboside in cells. Isn1, initially classified as an IMP-specific 5′-nucleotidase, and Sdt1, initially classified as a pyrimidine 5′-nucleotidase, are additionally responsible for dephosphorylation of pyridine mononucleotides. Sdt1 overexpression is growth-inhibitory to cells in a manner that depends on its active site and correlates with reduced cellular NAD+. Expression of Isn1 protein is positively regulated by the availability of nicotinic acid and glucose. These results reveal unanticipated and highly regulated steps in NAD+ metabolism. PMID:19846558

  6. Identification of Isn1 and Sdt1 as glucose- and vitamin-regulated nicotinamide mononucleotide and nicotinic acid mononucleotide [corrected] 5'-nucleotidases responsible for production of nicotinamide riboside and nicotinic acid riboside.

    Science.gov (United States)

    Bogan, Katrina L; Evans, Charles; Belenky, Peter; Song, Peng; Burant, Charles F; Kennedy, Robert; Brenner, Charles

    2009-12-11

    Recently, we discovered that nicotinamide riboside and nicotinic acid riboside are biosynthetic precursors of NAD(+), which are utilized through two pathways consisting of distinct enzymes. In addition, we have shown that exogenously supplied nicotinamide riboside is imported into yeast cells by a dedicated transporter, and it extends replicative lifespan on high glucose medium. Here, we show that nicotinamide riboside and nicotinic acid riboside are authentic intracellular metabolites in yeast. Secreted nicotinamide riboside was detected with a biological assay, and intracellular levels of nicotinamide riboside, nicotinic acid riboside, and other NAD(+) metabolites were determined by a liquid chromatography-mass spectrometry method. A biochemical genomic screen indicated that three yeast enzymes possess nicotinamide mononucleotide 5'-nucleotidase activity in vitro. Metabolic profiling of knock-out mutants established that Isn1 and Sdt1 are responsible for production of nicotinamide riboside and nicotinic acid riboside in cells. Isn1, initially classified as an IMP-specific 5'-nucleotidase, and Sdt1, initially classified as a pyrimidine 5'-nucleotidase, are additionally responsible for dephosphorylation of pyridine mononucleotides. Sdt1 overexpression is growth-inhibitory to cells in a manner that depends on its active site and correlates with reduced cellular NAD(+). Expression of Isn1 protein is positively regulated by the availability of nicotinic acid and glucose. These results reveal unanticipated and highly regulated steps in NAD(+) metabolism.

  7. Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis.

    Science.gov (United States)

    Wang, Shu-Na; Xu, Tian-Ying; Li, Wen-Lin; Miao, Chao-Yu

    2016-06-01

    Adult neurogenesis is the process of generating new neurons throughout life in the olfactory bulb and hippocampus of most mammalian species, which is closely related to aging and disease. Nicotinamide phosphoribosyltransferase (NAMPT), also an adipokine known as visfatin, is the rate-limiting enzyme for mammalian nicotinamide adenine dinucleotide (NAD) salvage synthesis by generating nicotinamide mononucleotide (NMN) from nicotinamide. Recent findings from our laboratory and other laboratories have provided much evidence that NAMPT might serve as a therapeutic target to restore adult neurogenesis. NAMPT-mediated NAD biosynthesis in neural stem/progenitor cells is important for their proliferation, self-renewal, and formation of oligodendrocytes in vivo and in vitro. Therapeutic interventions by the administration of NMN, NAD, or recombinant NAMPT are effective for restoring adult neurogenesis in several neurological diseases. We summarize adult neurogenesis in aging, ischemic stroke, traumatic brain injury, and neurodegenerative disease and review the advances of targeting NAMPT in restoring neurogenesis. Specifically, we provide emphasis on the P7C3 family, a class of proneurogenic compounds that are potential NAMPT activators, which might shed light on future drug development in neurogenesis restoration. © 2016 John Wiley & Sons Ltd.

  8. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae.

    Science.gov (United States)

    Anderson, Rozalyn M; Bitterman, Kevin J; Wood, Jason G; Medvedik, Oliver; Sinclair, David A

    2003-05-08

    Calorie restriction extends lifespan in a broad range of organisms, from yeasts to mammals. Numerous hypotheses have been proposed to explain this phenomenon, including decreased oxidative damage and altered energy metabolism. In Saccharomyces cerevisiae, lifespan extension by calorie restriction requires the NAD+-dependent histone deacetylase, Sir2 (ref. 1). We have recently shown that Sir2 and its closest human homologue SIRT1, a p53 deacetylase, are strongly inhibited by the vitamin B3 precursor nicotinamide. Here we show that increased expression of PNC1 (pyrazinamidase/nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is both necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress. We also identify PNC1 as a longevity gene that is responsive to all stimuli that extend lifespan. We provide evidence that nicotinamide depletion is sufficient to activate Sir2 and that this is the mechanism by which PNC1 regulates longevity. We conclude that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms.

  9. Increasing NAD synthesis in muscle via nicotinamide phosphoribosyltransferase is not sufficient to promote oxidative metabolism.

    Science.gov (United States)

    Frederick, David W; Davis, James G; Dávila, Antonio; Agarwal, Beamon; Michan, Shaday; Puchowicz, Michelle A; Nakamaru-Ogiso, Eiko; Baur, Joseph A

    2015-01-16

    The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Safety assessment of nicotinamide riboside, a form of vitamin B3.

    Science.gov (United States)

    Conze, D B; Crespo-Barreto, J; Kruger, C L

    2016-01-20

    Nicotinamide riboside (NR) is a naturally occurring form of vitamin B 3 present in trace amounts in some foods. Like niacin, it has been shown to be a precursor in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). The safety of Niagen™, a synthetic form of NR, was determined using a bacterial reverse mutagenesis assay (Ames), an in vitro chromosome aberration assay, an in vivo micronucleus assay, and acute, 14-day and 90-day rat toxicology studies. NR was not genotoxic. There was no mortality at an oral dose of 5000 mg/kg. Based on the results of a 14-day study, a 90-day study was performed comparing NR at 300, 1000, and 3000 mg/kg/day to an equimolar dose of nicotinamide at 1260 mg/kg/day as a positive control. Results from the study show that NR had a similar toxicity profile to nicotinamide at the highest dose tested. Target organs of toxicity were liver, kidney, ovaries, and testes. The lowest observed adverse effect level for NR was 1000 mg/kg/day, and the no observed adverse effect level was 300 mg/kg/day. © The Author(s) 2016.

  11. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae

    Science.gov (United States)

    Anderson, Rozalyn M.; Bitterman, Kevin J.; Wood, Jason G.; Medvedik, Oliver; Sinclair, David A.

    2016-01-01

    Calorie restriction extends lifespan in a broad range of organisms, from yeasts to mammals. Numerous hypotheses have been proposed to explain this phenomenon, including decreased oxidative damage and altered energy metabolism. In Saccharomyces cerevisiae, lifespan extension by calorie restriction requires the NAD+-dependent histone deacetylase, Sir2 (ref. 1). We have recently shown that Sir2 and its closest human homologue SIRT1, a p53 deacetylase, are strongly inhibited by the vitamin B3 precursor nicotinamide2. Here we show that increased expression of PNC1 (pyrazinamidase/nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is both necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress. We also identify PNC1 as a longevity gene that is responsive to all stimuli that extend lifespan. We provide evidence that nicotinamide depletion is sufficient to activate Sir2 and that this is the mechanism by which PNC1 regulates longevity. We conclude that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms. PMID:12736687

  12. Phosphorylation of 3-deazaguanosine by nicotinamide riboside kinase in Chinese hamster ovary cells.

    Science.gov (United States)

    Saunders, P P; Tan, M T; Spindler, C D; Robins, R K

    1989-12-01

    The growth inhibitory activity of 3-deazaguanosine toward a mutant line (TGR-3) of Chinese hamster ovary cells deficient in hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) was substantially reversed by the simultaneous addition of nicotinamide riboside. The activities of most other ribonucleoside analogues tested were unaffected. The formation of cellular 3-deazaGMP and 3-deazaGTP from the ribonucleoside analogue, as measured by high-pressure liquid chromatography, was inhibited by the presence of nicotinamide riboside. The inhibition was dependent on concentration of 3-deazaguanosine and could also be demonstrated by following the metabolism of 3-deazaguanosine, labeled with 14C in the ribose moiety, to [14C]3-deazaGTP. In the presence of 100 microM nicotinamide riboside formation of the labeled triphosphate derivative of 3-deazaguanosine was undetectable. A 3-deazaguanosine phosphorylating activity was separated from other cellular kinases by DEAE-cellulose chromatography. Contaminating purine nucleoside phosphorylase (EC 2.4.2.1) was subsequently removed by sucrose density gradient centrifugation. The resulting enzyme preparation demonstrated the greatest activities with nicotinamide riboside and 3-deazaguanosine and, in addition, could also phosphorylate tiazofurin and guanosine to lesser, but significant, degrees. These and other observations suggest that 3-deazaguanosine, and perhaps other agents such as tiazofurin, may, at least in part, be phosphorylated by a nicotinamide ribonucleoside kinase in these cells. If so, it is possible that the activity of this agent in other types of cells in vivo could be dependent upon the presence of this enzyme and that it could be influenced by cellular concentrations of the natural pyridine nucleoside.

  13. The modification of human tumour blood flow using pentoxifylline, nicotinamide and carbogen

    International Nuclear Information System (INIS)

    Sibtain, Amen; Hill, Sally; Goodchild, Kate; Shah, Nihal; Saunders, Michele; Hoskin, Peter J.

    2002-01-01

    Aim: To assess the effect of combining oral nicotinamide, oral pentoxifylline and carbogen gas (2% CO 2 , 98% O 2 ) breathing on human tumour red cell flux. Methods and materials: Microregional red blood cell flux was measured in accessible tumour nodules using laser Doppler microprobes in 11 patients with histologically proven malignancy. Patients received single oral doses of nicotinamide 40 mg kg -1 and pentoxifylline 1200 mg 2 h before a 10-min period of carbogen gas breathing, corresponding to peak plasma concentrations of these drugs. Red cell flux in up to six microregions in each tumour was measured for 30 min, recording pre-, during and post-carbogen breathing for 10 min each. Results: Data from ten of the 11 patients could be assessed. The red cell flux in 48 microregions was analysed and the mean red cell flux was calculated. A mean relative increase in red cell flux of 1.18 (±0.09, 95% confidence interval (CI)) was observed after 6 min of carbogen breathing, 2 h after the administration of nicotinamide and pentoxifylline. This compares to relative increases of 1.4 (±0.39, 95%CI) after nicotinamide with carbogen and 1.15 (±0.10, 95%CI) after pentoxifylline with carbogen. These differences are not statistically significant (P>0.05). The increased red cell flux persisted after the cessation of carbogen gas breathing. Conclusions: A combination of pentoxifylline, nicotinamide and carbogen produces an increase in human tumour red cell flux, similar to that observed when each of the drugs are used alone with carbogen breathing

  14. Nicotinamide and other benzamide analogs as agents for overcoming hypoxic cell radiation resistance in tumours

    International Nuclear Information System (INIS)

    Horsman, M.

    1996-01-01

    Oxygen deficient hypoxic cells, which are resistant to sparsely ionising radiation, have now been identified in most animal and some human solid tumours and will influence the response of those tumours to radiation treatment. This hypoxia can be either chronic, arising from an oxygen diffusion limitation, or acute, resulting from transient stoppages in microregional blood flow. Extensive experimental studies, especially in the last decade, have shown that nicotinamide and structurally related analogs can effectively sensitize murine tumours to both single and fractionated radiation treatments and that they do so in preference to the effects seen in mouse normal tissues. The earliest studies suggested that this enhancement of radiation damage was the result of an inhibition of the repair mechanisms. However, recent studies in mouse tumours have shown that these drugs prevent transient cessations in blood flow, thus inhibiting the development of acute hypoxia. This novel discovery led to the suggestion that the potential role of these agents as radiosensitizers would be when combined with treatments that overcame chronic hypoxia. The combined nicotinamide with hyperthermia proved that the enhancement of radiation damage by both agents together was greater than that seen with each agent alone. Similar results were later seen for nicotinamide combined with a perfluorochemical emulsion, carbogen breathing, and pentoxifylline, and in all these studies the effects in tumours were always greater than those seen in appropriate normal tissues. Of all the analogs, it is nicotinamide itself which has been the most extensively studied as a radiosensitizer in vivo and the one that shows the greatest effect in animal tumours. It is also an agent that has been well established clinically, with daily doses of up to 6 g, associated with a low incidence of side effects. This human dose is equivalent to 100-200 mg/kg in mice and such doses will maximally sensitize murine tumours to

  15. Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession.

    Science.gov (United States)

    Liu, Dong; Pitta, Michael; Jiang, Haiyang; Lee, Jong-Hwan; Zhang, Guofeng; Chen, Xinzhi; Kawamoto, Elisa M; Mattson, Mark P

    2013-06-01

    Impaired brain energy metabolism and oxidative stress are implicated in cognitive decline and the pathologic accumulations of amyloid β-peptide (Aβ) and hyperphosphorylated tau in Alzheimer's disease (AD). To determine whether improving brain energy metabolism will forestall disease progress in AD, the impact of the β-nicotinamide adenine dinucleotide precursor nicotinamide on brain cell mitochondrial function and macroautophagy, bioenergetics-related signaling, and cognitive performance were studied in cultured neurons and in a mouse model of AD. Oxidative stress resulted in decreased mitochondrial mass, mitochondrial degeneration, and autophagosome accumulation in neurons. Nicotinamide preserved mitochondrial integrity and autophagy function, and reduced neuronal vulnerability to oxidative/metabolic insults and Aβ toxicity. β-Nicotinamide adenine dinucleotide biosynthesis, autophagy, and phosphatidylinositol-3-kinase signaling were required for the neuroprotective action of nicotinamide. Treatment of 3xTgAD mice with nicotinamide for 8 months resulted in improved cognitive performance, and reduced Aβ and hyperphosphorylated tau pathologies in hippocampus and cerebral cortex. Nicotinamide treatment preserved mitochondrial integrity, and improved autophagy-lysosome procession by enhancing lysosome/autolysosome acidification to reduce autophagosome accumulation. Treatment of 3xTgAD mice with nicotinamide resulted in elevated levels of activated neuroplasticity-related kinases (protein kinase B [Akt] and extracellular signal-regulated kinases) and the transcription factor cyclic adenosine monophosphate (AMP) response element-binding protein in the hippocampus and cerebral cortex. Thus, nicotinamide suppresses AD pathology and cognitive decline in a mouse model of AD by a mechanism involving improved brain bioenergetics with preserved functionality of mitochondria and the autophagy system. Published by Elsevier Inc.

  16. The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity

    Science.gov (United States)

    Cantó, Carles; Houtkooper, Riekelt H.; Pirinen, Eija; Youn, Dou Y.; Oosterveer, Maaike H.; Cen, Yana; Fernandez-Marcos, Pablo J.; Yamamoto, Hiroyasu; Andreux, Pénélope A.; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A.; Auwerx, Johan

    2013-01-01

    SUMMARY As NAD+ is a rate-limiting co-substrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38 —both NAD+ consumers— increases NAD+ bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD+ precursor with the ability to increase NAD+ levels, Sir2-dependent gene silencing and replicative lifespan in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD+ levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin, NR, could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function. PMID:22682224

  17. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity.

    Science.gov (United States)

    Cantó, Carles; Houtkooper, Riekelt H; Pirinen, Eija; Youn, Dou Y; Oosterveer, Maaike H; Cen, Yana; Fernandez-Marcos, Pablo J; Yamamoto, Hiroyasu; Andreux, Pénélope A; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A; Auwerx, Johan

    2012-06-06

    As NAD(+) is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38-both NAD(+) consumers-increases NAD(+) bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD(+) precursor with the ability to increase NAD(+) levels, Sir2-dependent gene silencing, and replicative life span in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD(+) levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin NR could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Expose Mechanical Engineering Students to Biomechanics Topics

    Science.gov (United States)

    Shen, Hui

    2011-01-01

    To adapt the focus of engineering education to emerging new industries and technologies nationwide and in the local area, a biomechanics module has been developed and incorporated into a mechanical engineering technical elective course to expose mechanical engineering students at ONU (Ohio Northern University) to the biomedical engineering topics.…

  19. Syntacticized topics in Kurmuk

    DEFF Research Database (Denmark)

    Andersen, Torben

    2015-01-01

    This article argues that Kurmuk, a little-described Western Nilotic language, is characterized by a syntacticized topic whose grammatical relation is variable. In this language, declarative clauses have as topic an obligatory preverbal NP which is either a subject, an object or an adjunct. The gr...

  20. Torpedo: topic periodicity discovery from text data

    Science.gov (United States)

    Wang, Jingjing; Deng, Hongbo; Han, Jiawei

    2015-05-01

    Although history may not repeat itself, many human activities are inherently periodic, recurring daily, weekly, monthly, yearly or following some other periods. Such recurring activities may not repeat the same set of keywords, but they do share similar topics. Thus it is interesting to mine topic periodicity from text data instead of just looking at the temporal behavior of a single keyword/phrase. Some previous preliminary studies in this direction prespecify a periodic temporal template for each topic. In this paper, we remove this restriction and propose a simple yet effective framework Torpedo to mine periodic/recurrent patterns from text, such as news articles, search query logs, research papers, and web blogs. We first transform text data into topic-specific time series by a time dependent topic modeling module, where each of the time series characterizes the temporal behavior of a topic. Then we use time series techniques to detect periodicity. Hence we both obtain a clear view of how topics distribute over time and enable the automatic discovery of periods that are inherent in each topic. Theoretical and experimental analyses demonstrate the advantage of Torpedo over existing work.

  1. Nicotinamide riboside and nicotinic acid riboside salvage in fungi and mammals. Quantitative basis for Urh1 and purine nucleoside phosphorylase function in NAD+ metabolism.

    Science.gov (United States)

    Belenky, Peter; Christensen, Kathryn C; Gazzaniga, Francesca; Pletnev, Alexandre A; Brenner, Charles

    2009-01-02

    NAD+ is a co-enzyme for hydride transfer enzymes and an essential substrate of ADP-ribose transfer enzymes and sirtuins, the type III protein lysine deacetylases related to yeast Sir2. Supplementation of yeast cells with nicotinamide riboside extends replicative lifespan and increases Sir2-dependent gene silencing by virtue of increasing net NAD+ synthesis. Nicotinamide riboside elevates NAD+ levels via the nicotinamide riboside kinase pathway and by a pathway initiated by splitting the nucleoside into a nicotinamide base followed by nicotinamide salvage. Genetic evidence has established that uridine hydrolase, purine nucleoside phosphorylase, and methylthioadenosine phosphorylase are required for Nrk-independent utilization of nicotinamide riboside in yeast. Here we show that mammalian purine nucleoside phosphorylase but not methylthioadenosine phosphorylase is responsible for mammalian nicotinamide riboside kinase-independent nicotinamide riboside utilization. We demonstrate that so-called uridine hydrolase is 100-fold more active as a nicotinamide riboside hydrolase than as a uridine hydrolase and that uridine hydrolase and mammalian purine nucleoside phosphorylase cleave nicotinic acid riboside, whereas the yeast phosphorylase has little activity on nicotinic acid riboside. Finally, we show that yeast nicotinic acid riboside utilization largely depends on uridine hydrolase and nicotinamide riboside kinase and that nicotinic acid riboside bioavailability is increased by ester modification.

  2. Cleavage of nicotinamide adenine dinucleotide by the ribosome-inactivating protein from Momordica charantia.

    Science.gov (United States)

    Vinkovic, M; Dunn, G; Wood, G E; Husain, J; Wood, S P; Gill, R

    2015-09-01

    The interaction of momordin, a type 1 ribosome-inactivating protein from Momordica charantia, with NADP(+) and NADPH has been investigated by X-ray diffraction analysis of complexes generated by co-crystallization and crystal soaking. It is known that the proteins of this family readily cleave the adenine-ribose bond of adenosine and related nucleotides in the crystal, leaving the product, adenine, bound to the enzyme active site. Surprisingly, the nicotinamide-ribose bond of oxidized NADP(+) is cleaved, leaving nicotinamide bound in the active site in the same position but in a slightly different orientation to that of the five-membered ring of adenine. No binding or cleavage of NADPH was observed at pH 7.4 in these experiments. These observations are in accord with current views of the enzyme mechanism and may contribute to ongoing searches for effective inhibitors.

  3. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.

    Science.gov (United States)

    Trammell, Samuel A J; Schmidt, Mark S; Weidemann, Benjamin J; Redpath, Philip; Jaksch, Frank; Dellinger, Ryan W; Li, Zhonggang; Abel, E Dale; Migaud, Marie E; Brenner, Charles

    2016-10-10

    Nicotinamide riboside (NR) is in wide use as an NAD + precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD + metabolism in humans. We report that human blood NAD + can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD + with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD + metabolome in the first clinical trial of NR pharmacokinetics in humans. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for the conversion of NR to NAD + , is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD + repletion.

  4. Metabolomics analysis of metabolic effects of nicotinamide phosphoribosyltransferase (NAMPT inhibition on human cancer cells.

    Directory of Open Access Journals (Sweden)

    Vladimir Tolstikov

    Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT plays an important role in cellular bioenergetics. It is responsible for converting nicotinamide to nicotinamide adenine dinucleotide, an essential molecule in cellular metabolism. NAMPT has been extensively studied over the past decade due to its role as a key regulator of nicotinamide adenine dinucleotide-consuming enzymes. NAMPT is also known as a potential target for therapeutic intervention due to its involvement in disease. In the current study, we used a global mass spectrometry-based metabolomic approach to investigate the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on metabolic perturbations in human cancer cells. We treated A2780 (ovarian cancer and HCT-116 (colorectal cancer cell lines with FK866 in the presence and absence of nicotinic acid. Significant changes were observed in the amino acids metabolism and the purine and pyrimidine metabolism. We also observed metabolic alterations in glycolysis, the citric acid cycle (TCA, and the pentose phosphate pathway. To expand the range of the detected polar metabolites and improve data confidence, we applied a global metabolomics profiling platform by using both non-targeted and targeted hydrophilic (HILIC-LC-MS and GC-MS analysis. We used Ingenuity Knowledge Base to facilitate the projection of metabolomics data onto metabolic pathways. Several metabolic pathways showed differential responses to FK866 based on several matches to the list of annotated metabolites. This study suggests that global metabolomics can be a useful tool in pharmacological studies of the mechanism of action of drugs at a cellular level.

  5. beta-1,2,3-Triazolyl-nucleosides as nicotinamide riboside mimics.

    Science.gov (United States)

    Amigues, E J; Armstrong, E; Dvorakova, M; Migaud, M E; Huang, M

    2009-03-01

    The synthesis of a series of pyridine- and piperidine-substituted 1,2,3-triazolides linked to a riboside moiety is described. The presence of a triazolide substituent on the pyridine moiety permitted the facile reduction of the latter under mild hydrogenation conditions. These analogues were modelled as to define their similarity to nicotinamide riboside and quantify their ability to bind NAD-dependent protein deacetylases.

  6. Metabolomics analysis of metabolic effects of nicotinamide phosphoribosyltransferase (NAMPT) inhibition on human cancer cells.

    Science.gov (United States)

    Tolstikov, Vladimir; Nikolayev, Alexander; Dong, Sucai; Zhao, Genshi; Kuo, Ming-Shang

    2014-01-01

    Nicotinamide phosphoribosyltransferase (NAMPT) plays an important role in cellular bioenergetics. It is responsible for converting nicotinamide to nicotinamide adenine dinucleotide, an essential molecule in cellular metabolism. NAMPT has been extensively studied over the past decade due to its role as a key regulator of nicotinamide adenine dinucleotide-consuming enzymes. NAMPT is also known as a potential target for therapeutic intervention due to its involvement in disease. In the current study, we used a global mass spectrometry-based metabolomic approach to investigate the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on metabolic perturbations in human cancer cells. We treated A2780 (ovarian cancer) and HCT-116 (colorectal cancer) cell lines with FK866 in the presence and absence of nicotinic acid. Significant changes were observed in the amino acids metabolism and the purine and pyrimidine metabolism. We also observed metabolic alterations in glycolysis, the citric acid cycle (TCA), and the pentose phosphate pathway. To expand the range of the detected polar metabolites and improve data confidence, we applied a global metabolomics profiling platform by using both non-targeted and targeted hydrophilic (HILIC)-LC-MS and GC-MS analysis. We used Ingenuity Knowledge Base to facilitate the projection of metabolomics data onto metabolic pathways. Several metabolic pathways showed differential responses to FK866 based on several matches to the list of annotated metabolites. This study suggests that global metabolomics can be a useful tool in pharmacological studies of the mechanism of action of drugs at a cellular level.

  7. Uptake of [14C]nicotinic acid and [14C]nicotinamide by Bordetella pertussis

    International Nuclear Information System (INIS)

    McPheat, W.L.; Wardlaw, A.C.

    1980-01-01

    Bordetella pertussis has an absolute requirement for either nicotinic acid (NA) or nicotinamide (ND), both being equally effective in supporting growth. The results of an investigation to compare the rates of uptake of NA and ND, to determine the influence of factors such as energy source and temperature on uptake, and to measure the Ksub(m) and Vsub(max) values are reported. (Auth.)

  8. Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration.

    Science.gov (United States)

    Vaur, Pauline; Brugg, Bernard; Mericskay, Mathias; Li, Zhenlin; Schmidt, Mark S; Vivien, Denis; Orset, Cyrille; Jacotot, Etienne; Brenner, Charles; Duplus, Eric

    2017-12-01

    NAD + depletion is a common phenomenon in neurodegenerative pathologies. Excitotoxicity occurs in multiple neurologic disorders and NAD + was shown to prevent neuronal degeneration in this process through mechanisms that remained to be determined. The activity of nicotinamide riboside (NR) in neuroprotective models and the recent description of extracellular conversion of NAD + to NR prompted us to probe the effects of NAD + and NR in protection against excitotoxicity. Here, we show that intracortical administration of NR but not NAD + reduces brain damage induced by NMDA injection. Using cortical neurons, we found that provision of extracellular NR delays NMDA-induced axonal degeneration (AxD) much more strongly than extracellular NAD + Moreover, the stronger effect of NR compared to NAD + depends of axonal stress since in AxD induced by pharmacological inhibition of nicotinamide salvage, both NAD + and NR prevent neuronal death and AxD in a manner that depends on internalization of NR. Taken together, our findings demonstrate that NR is a better neuroprotective agent than NAD + in excitotoxicity-induced AxD and that axonal protection involves defending intracellular NAD + homeostasis.-Vaur, P., Brugg, B., Mericskay, M., Li, Z., Schmidt, M. S., Vivien, D., Orset, C., Jacotot, E., Brenner, C., Duplus, E. Nicotinamide riboside, a form of vitamin B 3 , protects against excitotoxicity-induced axonal degeneration. © FASEB.

  9. Docetaxel-nicotinamide complex-loaded nanostructured lipid carriers for transdermal delivery.

    Science.gov (United States)

    Fan, Xiucong; Chen, Jinjin; Shen, Qi

    2013-12-31

    Docetaxel (DTX) proved one of the most effective active pharmaceutical ingredients (APIs) for the treatment of cancers. However, in respect of its low solubility and high lipophilic property, nicotinamide (NCT) was chosen as the co-former to form the docetaxel-nicotinamide complex to handle the drawbacks. As was analyzed by Fourier Transform Infrared spectrometer, thermal analysis and saturated solubility, the complex proved stable. Then, docetaxel-nicotinamide complex nanostructured lipid carriers (DN-NLCs) were prepared by emulsion-evaporation at low temperature method. The average drug entrapment efficiency, particle size and drug loading of docetaxel-NLCs (D-NLCs) and DN-NLCs were 81.41-79.48%, 61.45-59.48nm and 1.60-1.63%, respectively. The physicochemical characteristics of nanoparticles were valued by transmission electron microscope and Powder X Ray Diffraction. The in vitro drug-release profile of nanoparticle formulations fitted the Weibull dynamic equation. The skin permeability test was performed by Vertical Franz-type diffusion cells. It demonstrated that DN-NLCs transported drugs more easily than D-NLCs. Confocal Laser Scanning Microscopy observation showed DN-NLCs permeated more effectively than D-NLCs. In vivo study demonstrated that DN-NLCs maintained most in the skin. These results suggest that the DN-NLCs can be a useful method to increase skin permeation of docetaxel. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  10. Topical Pain Medications

    Science.gov (United States)

    ... skin Learn about the various types of topical pain medications available for pain relief. Can they ease your ... hurt even though you take your usual arthritis pain medication. Reluctant to pop another pill, you might wonder ...

  11. Topics in Nuclear Astrophysics

    International Nuclear Information System (INIS)

    Chung, K.C.

    1982-01-01

    Some topics in nuclear astrophysics are discussed, e.g.: highly evolved stellar cores, stellar evolution (through the temperature analysis of stellar surface), nucleosynthesis and finally the solar neutrino problem. (L.C.) [pt

  12. Topical approaches to cellulite

    OpenAIRE

    ALĞIN YAPAR, Evren

    2017-01-01

    Today, topical application of pharmacologically active chemicals and local application of physical, mechanical and thermal methods are available in order to eliminate cellulite which is an aesthetic problem that affects the majority of women. Many products on natural or synthetic originated anti-cellulite active ingredients have been developed with topical application studies performed on cellulite developed parts. Formulations developed against cellulite are usually in the form of gel...

  13. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans.

    Science.gov (United States)

    Bieganowski, Pawel; Brenner, Charles

    2004-05-14

    NAD+ is essential for life in all organisms, both as a coenzyme for oxidoreductases and as a source of ADPribosyl groups used in various reactions, including those that retard aging in experimental systems. Nicotinic acid and nicotinamide were defined as the vitamin precursors of NAD+ in Elvehjem's classic discoveries of the 1930s. The accepted view of eukaryotic NAD+ biosynthesis, that all anabolism flows through nicotinic acid mononucleotide, was challenged experimentally and revealed that nicotinamide riboside is an unanticipated NAD+ precursor in yeast. Nicotinamide riboside kinases from yeast and humans essential for this pathway were identified and found to be highly specific for phosphorylation of nicotinamide riboside and the cancer drug tiazofurin. Nicotinamide riboside was discovered as a nutrient in milk, suggesting that nicotinamide riboside is a useful compound for elevation of NAD+ levels in humans.

  14. Special Attachments. Module 19.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on special attachments, one in a series dealing with industrial sewing machines, their attachments, and operation, covers four topics: gauges; cording attachment; zipper foot; and hemming, shirring, and binding. For each topic these components are provided: an introduction, directions, an objective, learning activities, student…

  15. Special Operation. Module 20.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on special operations, one in a series dealing with industrial sewing machines, their attachments, and operation, covers two topics: topstitching and mitering. For each topic these components are provided: an introduction, directions, an objective, learning activities, student information, a student self-check, and a check-out…

  16. Topical treatment of melasma

    Directory of Open Access Journals (Sweden)

    Bandyopadhyay Debabrata

    2009-01-01

    Full Text Available Melasma is a common hypermelanotic disorder affecting the face that is associated with considerable psychological impacts. The management of melasma is challenging and requires a long-term treatment plan. In addition to avoidance of aggravating factors like oral pills and ultraviolet exposure, topical therapy has remained the mainstay of treatment. Multiple options for topical treatment are available, of which hydroquinone (HQ is the most commonly prescribed agent. Besides HQ, other topical agents for which varying degrees of evidence for clinical efficacy exist include azelaic acid, kojic acid, retinoids, topical steroids, glycolic acid, mequinol, and arbutin. Topical medications modify various stages of melanogenesis, the most common mode of action being inhibition of the enzyme, tyrosinase. Combination therapy is the preferred mode of treatment for the synergism and reduction of untoward effects. The most popular combination consists of HQ, a topical steroid, and retinoic acid. Prolonged HQ usage may lead to untoward effects like depigmentation and exogenous ochronosis. The search for safer alternatives has given rise to the development of many newer agents, several of them from natural sources. Well-designed controlled clinical trials are needed to clarify their role in the routine management of melasma.

  17. Nicotinamide Riboside and Nicotinic Acid Riboside Salvage in Fungi and Mammals: QUANTITATIVE BASIS FOR Urh1 AND PURINE NUCLEOSIDE PHOSPHORYLASE FUNCTION IN NAD+METABOLISM*S⃞

    OpenAIRE

    Belenky, Peter; Christensen, Kathryn C.; Gazzaniga, Francesca; Pletnev, Alexandre A.; Brenner, Charles

    2009-01-01

    NAD+ is a co-enzyme for hydride transfer enzymes and an essential substrate of ADP-ribose transfer enzymes and sirtuins, the type III protein lysine deacetylases related to yeast Sir2. Supplementation of yeast cells with nicotinamide riboside extends replicative lifespan and increases Sir2-dependent gene silencing by virtue of increasing net NAD+ synthesis. Nicotinamide riboside elevates NAD+ levels via the nicotinamide riboside kinase pathway and by a pathway initiate...

  18. Interactive effects of salinity stress and nicotinamide on physiological and biochemical parameters of Faba bean plant

    International Nuclear Information System (INIS)

    Abdelhamid, Magdi T; Sadak, Mervat Sh; Schmidhalter, Urs; El Saady, Abdel Kareem M.

    2013-01-01

    A possible survival strategy for plants under saline conditions is to use some compounds that could alleviate the salt stress effect. One of these compounds is nicotinamide (vitamin B3/niacin). The effect of exogenous application of nicotinamide with different concentrations (0,200 or 400 mg l-1) on faba bean (Vicia faba L.) plant grown at different NaCl levels (0,50 or 100 mM) was investigated in the wire house of the National Research Centre, Cairo, Egypt. Salinity stress significantly reduced the photosynthetic pigments, polysaccharides, total carbohydrates, total-N contents of shoot, plant height, leaves number, fresh and dry weights of shoot, seed yield, total carbohydrates and total crude protein of the yielded seeds compared with those of the control plants. In contrast, salinity induced marked increases in sucrose, total soluble sugars, total free amino acids, proline, lipid peroxidation product (MDA) and some oxidative enzymes (polyphenol-oxidase and peroxidase). Also, salinity stress increased Na+ contents with the decreases of other macro and micro elements contents (P, K+, Mg 2 +, Ca 2 +, Fe 2 +, Mn 2 +, Zn 2 + and Cu 2 +) of shoots and the yielded seeds of faba bean. Foliar spraying of nicotinamide alleviated the adverse effects of salinity stress through increased the photosynthetic pigments, polysaccharides, total carbohydrates, total N concentration of shoot, plant height, leaves number, fresh and dry weights of shoot, and seed yield as well as, sucrose, total soluble sugars, total free amino acids and proline, compared with those of the corresponding salinity levels, while decreased lipid peroxidation product as malondialdehyde (MDA) and the oxidative enzymes (polyphenol oxidase and peroxidase enzymes). Nicotinamide inhibited the uptake of Na+ and accelerated the accumulation of P, K+, Mg 2 +, Ca 2 +, Fe 2 +, Mn 2 +, Zn 2 + and Cu 2 + concentrations in the shoots of salt stressed plants and enhanced total carbohydrate and total crude protein

  19. Purification and characterization of the enzymes involved in nicotinamide adenine dinucleotide degradation by Penicillium brevicompactum NRC 829.

    Science.gov (United States)

    Ali, Thanaa Hamed; El-Ghonemy, Dina Helmy

    2016-06-01

    The present study was conducted to investigate a new pathway for the degradation of nicotinamide adenine dinucleotide (NAD) by Penicillium brevicompactum NRC 829 extracts. Enzymes involved in the hydrolysis of NAD, i.e. alkaline phosphatase, aminohydrolase and glycohydrolase were determined. Alkaline phosphatase was found to catalyse the sequential hydrolysis of two phosphate moieties of NAD molecule to nicotinamide riboside plus adenosine. Adenosine was then deaminated by aminohydrolase to inosine and ammonia. While glycohydrolase catalyzed the hydrolysis of the nicotinamide-ribosidic bond of NAD+ to produce nicotinamide and ADP-ribose in equimolar amounts, enzyme purification through a 3-step purification procedure revealed the existence of two peaks of alkaline phosphatases, and one peak contained deaminase and glycohydrolase activities. NAD deaminase was purified to homogeneity as estimated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis with an apparent molecular mass of 91 kDa. Characterization and determination of some of NAD aminohydrolase kinetic properties were conducted due to its biological role in the regulation of cellular NAD level. The results also revealed that NAD did not exert its feedback control on nicotinamide amidase produced by P. brevicompactum.

  20. Inhibitory effect of nicotinamide on in vitro and in vivo production of tumor necrosis factor-alpha.

    Science.gov (United States)

    Fukuzawa, M; Satoh, J; Muto, G; Muto, Y; Nishimura, S; Miyaguchi, S; Qiang, X L; Toyota, T

    1997-10-01

    Nicotinamide, a pellagra-preventive factor, has multiple functions such as inhibition of poly-ADP-ribose synthetase, inhibition of inducible nitric oxide synthase, free radical scavenging and suppression of major histocompatibility complex class II expression and ICAM-1 expression on endothelial cells. In addition to these, we have found an inhibitory effect of nicotinamide on production of tumor necrosis factor-alpha (TNF-alpha) in vitro and in vivo. Lipopolysaccharide (LPS)-induced in vitro TNF-alpha production by human peripheral blood mononuclear cells, measured by enzyme-linked immunosorbent assay (ELISA), was significantly inhibited with more than 1 x 10(-3) mol/l of nicotinamide, while interleukin-1-beta was not inhibited and interleukin-6 was slightly inhibited even with 10(-2) mol/l. Oral administration of nicotinamide with more than 62.5 mg/kg also significantly inhibited LPS-induced serum TNF-alpha production measured by ELISA and bioassay in Balb/c mice. Thus, nicotinamide has an inhibitory effect on TNF-alpha production that may be beneficial to TNF-alpha-mediated diseases.

  1. Clinical study of 89Sr therapy with radiosensitization by nicotinamide and carbogen in multiple bone metastasis of malignant neoplasms

    International Nuclear Information System (INIS)

    Liu Yajie; Wang Shubin; Guo Yiling; Chen Zuowei; Zhang Yingnan

    2005-01-01

    Objective: To evaluate the curative effect and side effects of 89 Sr therapy with radiosensitization by nicotinamide and carbogen in multiple bone metastasis of malignant neoplasms. Methods: Ninety-seven patients were divided into 4 groups respectively: group A, 89 Sr + nicotinamide + carbogen (24 patients); group B, 89 Sr + nicotinamide(22 patients); group C, 89 Sr + carbogen (25 patients); group D, 89 Sr, (26 patients). 89 SrCl was intravenously injected at a dose of 1.48-2.22 MBq/kg. Nicotinamide was taken orally 1 hour before 89 SrCl injection, 6 g/day, tid, d1-d5. Aspiration of carbogen(95%O 2 + 5%CO 2 ) gases, 6 L/min, 10 minutes, qd, d1-d5. Results: The effective rate of pain control and QOL improvement in A group were higher than in groups B, C and D (91.7% VS 77.3%, 76.0% and 69.2%, P=0.048). The lesions assessed by SPECT imaging in every group was not significantly different at three months after treatment. I to II degree toxic effect on bone marrow appeared in every group and there were no significantly inter-group differences. Conclusions: Combinative therapy using 89 Sr + nicotinamide + carbogen is more effective to treat multiple metastatic bone pain and for improvement of QOL. The side effects are not increased. (authors)

  2. Salicylic Acid Topical

    Science.gov (United States)

    ... the package label for more information.Apply a small amount of the salicylic acid product to one or two small areas you want to treat for 3 days ... know that children and teenagers who have chicken pox or the flu should not use topical salicylic ...

  3. Conditionals Are Topics

    Science.gov (United States)

    Haiman, John

    1978-01-01

    A review of analyses of conditionals (in the philosophical literature) and of topics (primarily in linguistics) reveals that their definitions are very similar. This paper justifies the method of basing semantic analysis of a construction on a cross-linguistic examination of its superficial form. (Author/NCR)

  4. Advanced Topics in Aerodynamics

    DEFF Research Database (Denmark)

    Filippone, Antonino

    1999-01-01

    "Advanced Topics in Aerodynamics" is a comprehensive electronic guide to aerodynamics,computational fluid dynamics, aeronautics, aerospace propulsion systems, design and relatedtechnology. We report data, tables, graphics, sketches,examples, results, photos, technical andscientific literature......, for higher education, learning, reference, research and engineering services....

  5. Characters and Topical Diversity

    DEFF Research Database (Denmark)

    Eriksson, Rune

    2014-01-01

    The purpose of this article is to contribute to our understanding of the difference between the bestseller and the non-bestseller in nonfiction. It is noticed that many bestsellers in nonfiction belongs to the sub-genre of creative nonfiction, but also that the topics in this kind of literature i...

  6. Topical immunomodulators in dermatology

    Directory of Open Access Journals (Sweden)

    Khandpur Sujay

    2004-04-01

    Full Text Available Topical immunomodulators are agents that regulate the local immune response of the skin. They are now emerging as the therapy of choice for several immune-mediated dermatoses such as atopic dermatitis, contact allergic dermatitis, alopecia areata, psoriasis, vitiligo, connective tissue disorders such as morphea and lupus erythematosus, disorders of keratinization and several benign and malignant skin tumours, because of their comparable efficacy, ease of application and greater safety than their systemic counterparts. They can be used on a domiciliary basis for longer periods without aggressive monitoring. In this article, we have discussed the mechanism of action, common indications and side-effects of the commonly used topical immunomodulators, excluding topical steroids. Moreover, newer agents, which are still in the experimental stages, have also been described. A MEDLINE search was undertaken using the key words "topical immunomodulators, dermatology" and related articles were also searched. In addition, a manual search for many Indian articles, which are not indexed, was also carried out. Wherever possible, the full article was reviewed. If the full article could not be traced, the abstract was used.

  7. New function for Escherichia coli xanthosine phophorylase (xapA): genetic and biochemical evidences on its participation in NAD+ salvage from nicotinamide

    Science.gov (United States)

    2014-01-01

    Background In an effort to reconstitute the NAD+ synthetic pathway in Escherichia coli (E. coli), we produced a set of gene knockout mutants with deficiencies in previously well-defined NAD+de novo and salvage pathways. Unexpectedly, the mutant deficient in NAD+de novo and salvage pathway I could grow in M9/nicotinamide medium, which was contradictory to the proposed classic NAD+ metabolism of E. coli. Such E. coli mutagenesis assay suggested the presence of an undefined machinery to feed nicotinamide into the NAD+ biosynthesis. We wanted to verify whether xanthosine phophorylase (xapA) contributed to a new NAD+ salvage pathway from nicotinamide. Results Additional knockout of xapA further slowed down the bacterial growth in M9/nicotinamide medium, whereas the complementation of xapA restored the growth phenotype. To further validate the new function of xapA, we cloned and expressed E. coli xapA as a recombinant soluble protein. Biochemical assay confirmed that xapA was capable of using nicotinamide as a substrate for nicotinamide riboside formation. Conclusions Both the genetic and biochemical evidences indicated that xapA could convert nicotinamide to nicotinamide riboside in E. coli, albeit with relatively weak activity, indicating that xapA may contribute to a second NAD+ salvage pathway from nicotinamide. We speculate that this xapA-mediated NAD+ salvage pathway might be significant in some bacteria lacking NAD+de novo and NAD+ salvage pathway I or II, to not only use nicotinamide riboside, but also nicotinamide as precursors to synthesize NAD+. However, this speculation needs to be experimentally tested. PMID:24506841

  8. New function for Escherichia coli xanthosine phophorylase (xapA): genetic and biochemical evidences on its participation in NAD(+) salvage from nicotinamide.

    Science.gov (United States)

    Dong, Wei-Ren; Sun, Cen-Cen; Zhu, Guan; Hu, Shi-Hua; Xiang, Li-Xin; Shao, Jian-Zhong

    2014-02-08

    In an effort to reconstitute the NAD(+) synthetic pathway in Escherichia coli (E. coli), we produced a set of gene knockout mutants with deficiencies in previously well-defined NAD(+)de novo and salvage pathways. Unexpectedly, the mutant deficient in NAD(+) de novo and salvage pathway I could grow in M9/nicotinamide medium, which was contradictory to the proposed classic NAD(+) metabolism of E. coli. Such E. coli mutagenesis assay suggested the presence of an undefined machinery to feed nicotinamide into the NAD(+) biosynthesis. We wanted to verify whether xanthosine phophorylase (xapA) contributed to a new NAD(+) salvage pathway from nicotinamide. Additional knockout of xapA further slowed down the bacterial growth in M9/nicotinamide medium, whereas the complementation of xapA restored the growth phenotype. To further validate the new function of xapA, we cloned and expressed E. coli xapA as a recombinant soluble protein. Biochemical assay confirmed that xapA was capable of using nicotinamide as a substrate for nicotinamide riboside formation. Both the genetic and biochemical evidences indicated that xapA could convert nicotinamide to nicotinamide riboside in E. coli, albeit with relatively weak activity, indicating that xapA may contribute to a second NAD(+) salvage pathway from nicotinamide. We speculate that this xapA-mediated NAD(+) salvage pathway might be significant in some bacteria lacking NAD(+) de novo and NAD(+) salvage pathway I or II, to not only use nicotinamide riboside, but also nicotinamide as precursors to synthesize NAD(+). However, this speculation needs to be experimentally tested.

  9. Alteration in substrate specificity of horse liver alcohol dehydrogenase by an acyclic nicotinamide analog of NAD(+).

    Science.gov (United States)

    Malver, Olaf; Sebastian, Mina J; Oppenheimer, Norman J

    2014-11-01

    A new, acyclic NAD-analog, acycloNAD(+) has been synthesized where the nicotinamide ribosyl moiety has been replaced by the nicotinamide (2-hydroxyethoxy)methyl moiety. The chemical properties of this analog are comparable to those of β-NAD(+) with a redox potential of -324mV and a 341nm λmax for the reduced form. Both yeast alcohol dehydrogenase (YADH) and horse liver alcohol dehydrogenase (HLADH) catalyze the reduction of acycloNAD(+) by primary alcohols. With HLADH 1-butanol has the highest Vmax at 49% that of β-NAD(+). The primary deuterium kinetic isotope effect is greater than 3 indicating a significant contribution to the rate limiting step from cleavage of the carbon-hydrogen bond. The stereochemistry of the hydride transfer in the oxidation of stereospecifically deuterium labeled n-butanol is identical to that for the reaction with β-NAD(+). In contrast to the activity toward primary alcohols there is no detectable reduction of acycloNAD(+) by secondary alcohols with HLADH although these alcohols serve as competitive inhibitors. The net effect is that acycloNAD(+) has converted horse liver ADH from a broad spectrum alcohol dehydrogenase, capable of utilizing either primary or secondary alcohols, into an exclusively primary alcohol dehydrogenase. This is the first example of an NAD analog that alters the substrate specificity of a dehydrogenase and, like site-directed mutagenesis of proteins, establishes that modifications of the coenzyme distance from the active site can be used to alter enzyme function and substrate specificity. These and other results, including the activity with α-NADH, clearly demonstrate the promiscuity of the binding interactions between dehydrogenases and the riboside phosphate of the nicotinamide moiety, thus greatly expanding the possibilities for the design of analogs and inhibitors of specific dehydrogenases. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy.

    Science.gov (United States)

    Diguet, Nicolas; Trammell, Samuel A J; Tannous, Cynthia; Deloux, Robin; Piquereau, Jérôme; Mougenot, Nathalie; Gouge, Anne; Gressette, Mélanie; Manoury, Boris; Blanc, Jocelyne; Breton, Marie; Decaux, Jean-François; Lavery, Gareth; Baczkó, István; Zoll, Joffrey; Garnier, Anne; Li, Zhenlin; Brenner, Charles; Mericskay, Mathias

    2017-12-07

    Background -Myocardial metabolic impairment is a major feature in chronic heart failure (HF). As the major coenzyme in fuel oxidation and oxidative phosphorylation and a substrate for enzymes signaling energy stress and oxidative stress response, NAD + is emerging as a metabolic target in a number of diseases including HF. Little is known on mechanisms regulating homeostasis of NAD + in the failing heart. Methods -To explore possible alterations of NAD + homeostasis in the failing heart, we quantified expression of NAD + biosynthetic enzymes in human failing heart and in the heart of a mouse model of dilated cardiomyopathy (DCM) triggered by SRF transcription factor depletion in the heart (SRF HKO ) or of cardiac hypertrophy triggered by transverse aorta constriction (TAC). We studied the impact of NAD + precursor supplementation on cardiac function in both mouse models. Results -We observed a 30% loss in levels of NAD + in the murine failing heart of both DCM and TAC mice that was accompanied by a decrease in expression of the NAMPT enzyme that recycles the nicotinamide (NAM) precursor whereas the nicotinamide riboside kinase 2 (NMRK2) that phosphorylates the nicotinamide riboside (NR) precursor is increased, to a higher level in the DCM (40 fold) than in TAC (4 fold). This shift was also observed in human failing heart biopsies compared to non-failing controls. We show that the Nmrk2 gene is an AMPK and PPARalpha responsive gene that is activated by energy stress and NAD + depletion in isolated rat cardiomyocytes. NR efficiently rescues NAD + synthesis in response to FK866-mediated inhibition of NAMPT and stimulates glycolysis in cardiomyocytes. Accordingly, we show that NR supplementation in food attenuates the development of HF in mice, more robustly in DCM, and partially after TAC, by stabilizing myocardial NAD + levels in the failing heart. NR treatment also robustly increases the myocardial levels of three metabolites, nicotinic acid adenine dinucleotide

  11. No evidence for cognitive improvement from oral nicotinamide adenine dinucleotide (NADH) in dementia.

    Science.gov (United States)

    Rainer, M; Kraxberger, E; Haushofer, M; Mucke, H A; Jellinger, K A

    2000-01-01

    Reduced nicotinamide adenine dinucleotide (NADH) is advertised as an over-the-counter product or dietary supplement to treat Alzheimer's disease. We performed a 3-month open-label study with oral 10 mg/day NADH with 25 patients with mild to moderate dementia of the Alzheimer, vascular, and fronto-temporal types in addition to their current cholinomimetic drug medication. In 19 patients who completed the study, we found no evidence for any cognitive effect as defined by established psychometric tests. We conclude that NADH is unlikely to achieve cognitive improvements in an extent reported earlier, and present theoretical arguments against an effectiveness of this compound in dementia disorders.

  12. SAR and characterization of non-substrate isoindoline urea inhibitors of nicotinamide phosphoribosyltransferase (NAMPT)

    Energy Technology Data Exchange (ETDEWEB)

    Curtin, Michael L.; Heyman, H. Robin; Clark, Richard F.; Sorensen, Bryan K.; Doherty, George A.; Hansen, T. Matthew; Frey, Robin R.; Sarris, Kathy A.; Aguirre, Ana L.; Shrestha, Anurupa; Tu, Noah; Woller, Kevin; Pliushchev, Marina A.; Sweis, Ramzi F.; Cheng, Min; Wilsbacher, Julie L.; Kovar, Peter J.; Guo, Jun; Cheng, Dong; Longenecker, Kenton L.; Raich, Diana; Korepanova, Alla V.; Soni, Nirupama B.; Algire, Mikkel A.; Richardson, Paul L.; Marin, Violeta L.; Badagnani, Ilaria; Vasudevan, Anil; Buchanan, F.Greg; Maag, David; Chiang, Gary G.; Tse, Chris; Michaelides, Michael R. (AbbVie)

    2017-08-01

    Herein we disclose SAR studies that led to a series of isoindoline ureas which we recently reported were first-in-class, non-substrate nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. Modification of the isoindoline and/or the terminal functionality of screening hit 5 provided inhibitors such as 52 and 58 with nanomolar antiproliferative activity and preclinical pharmacokinetics properties which enabled potent antitumor activity when dosed orally in mouse xenograft models. X-ray crystal structures of two inhibitors bound in the NAMPT active-site are discussed.

  13. PREFACE: CEWQO Topical Issue CEWQO Topical Issue

    Science.gov (United States)

    Bozic, Mirjana; Man'ko, Margarita

    2009-09-01

    This topical issue of Physica Scripta collects selected peer-reviewed contributions based on invited and contributed talks and posters presented at the 15th Central European Workshop on Quantum Optics (CEWQO) which took place in Belgrade 29 May-3 June 2008 (http://cewqo08.phy.bg.ac.yu). On behalf of the whole community took place in Belgrade 29 May-3 June 2008 (http://cewqo08.phy.bg.ac.yu, cewqo08.phy.bg.ac.yu). On behalf of the whole community of the workshop, we thank the referees for their careful reading and useful suggestions which helped to improve all of the submitted papers. A brief description of CEWQO The Central European Workshop on Quantum Optics is a series of conferences started informally in Budapest in 1992. Sometimes small events transform into important conferences, as in the case of CEWQO. Professor Jozsef Janszky, from the Research Institute of Solid State Physics and Optics, is the founder of this series. Margarita Man'ko obtained the following information from Jozsef Janszky during her visit to Budapest, within the framework of cooperation between the Russian and Hungarian Academies of Sciences in 2005. He organized a small workshop on quantum optics in Budapest in 1992 with John Klauder as a main speaker. Then, bearing in mind that a year before Janszky himself was invited by Vladimir Buzek to give a seminar on the same topic in Bratislava, he decided to assign the name 'Central European Workshop on Quantum Optics', considering the seminar in Bratislava to be the first workshop and the one in Budapest the second. The third formal workshop took place in Bratislava in 1993 organized by Vladimir Buzek, then in 1994 (Budapest, by Jozsef Janszky), 1995 and 1996 (Budmerice, Slovakia, by Vladimir Buzek), 1997 (Prague, by Igor Jex), 1999 (Olomouc, Czech Republic, by Zdenek Hradil), 2000 (Balatonfüred, Hungary, by Jozsef Janszky ), 2001 (Prague, by Igor Jex), 2002 (Szeged, Hungary, by Mihaly Benedict), 2003 (Rostock,Germany, by Werner Vogel and

  14. Combined experimental and computational studies of pyrazinamide and nicotinamide in the context of crystal engineering and thermodynamics

    DEFF Research Database (Denmark)

    Jarzembska, Katarzyna N.; Hoser, Anna Agnieszka; Kamiński, Radosław

    2014-01-01

    Pyrazinamide and nicotinamide constitute small, rigid molecules, which are of importance in several areas of science, including crystal engineering, chemical synthesis, biochemistry, and pharmacy. This contribution is dedicated to the comprehensive study of experimental charge density distributions...... features of both crystals, such as atomic charges, bond critical points, electrostatic potential and experimentally derived intermolecular interactions are described and compared. The presence of the additional nitrogen atom in the aromatic ring of pyrazinamide, when compared to nicotinamide, has...... different crystal packing motifs. These considerations were quantified in terms of computational methods (periodic DFT and PIXEL approaches), resulting in the conclusion of the α form of nicotinamide crystal being more energetically advantageous. Additionally, a proper deconvolution of thermal motion from...

  15. Topics in industrial mathematics

    International Nuclear Information System (INIS)

    Vatsya, S.R.

    1992-01-01

    Mathematical methods are widely used to solve practical problems arising in modern industry. This article outlines some of the topics relevant to AECL programmes. This covers the applications of transmission and neutron transport tomography to determine density distributions in rocks and two phase flow situations. Another example covered is the use of variational methods to solve the problems of aerosol migration and control theory. (author). 7 refs

  16. Formation of nicotinamide ribose diphosphate ribose, a new metabolite of the NAD pathway, by growing mycelium of Aspergillus niger

    International Nuclear Information System (INIS)

    Kuwahara, Masaaki

    1976-01-01

    A new step of NAD metabolism was shown in Aspergillus niger. Radioactive nicotinic acid and nicotinamide were incorporated into nicotinamide ribose diphosphate ribose (NAm-RDPR), which had been isolated from the culture filtrate. Its content in the culture medium increased with an increase of culture time, and this compound was proved to be a terminal metabolite in the NAD pathway. The experimental results also showed that the Preiss-Handler pathway and the NAD cycling system function in the NAD biosynthesis in A. niger. A part of the radioactive precursors was also incorporated into an unknown compound. (auth.)

  17. Topic Visualization and Survival Analysis

    OpenAIRE

    Wang, Ping Jr

    2017-01-01

    Latent semantic structure in a text collection is called a topic. In this thesis, we aim to visualize topics in the scientific literature and detect active or inactive research areas based on their lifetime. Topics were extracted from over 1 million abstracts from the arXiv.org database using Latent Dirichlet Allocation (LDA). Hellinger distance measures similarity between two topics. Topics are determined to be relevant if their pairwise distances are smaller than the threshold of Hellinger ...

  18. Synthesis and antifungal activity of nicotinamide derivatives as succinate dehydrogenase inhibitors.

    Science.gov (United States)

    Ye, Yong-Hao; Ma, Liang; Dai, Zhi-Cheng; Xiao, Yu; Zhang, Ying-Ying; Li, Dong-Dong; Wang, Jian-Xin; Zhu, Hai-Liang

    2014-05-07

    Thirty-eight nicotinamide derivatives were designed and synthesized as potential succinate dehydrogenase inhibitors (SDHI) and precisely characterized by (1)H NMR, ESI-MS, and elemental analysis. The compounds were evaluated against two phytopathogenic fungi, Rhizoctonia solani and Sclerotinia sclerotiorum, by mycelia growth inhibition assay in vitro. Most of the compounds displayed moderate activity, in which, 3a-17 exhibited the most potent antifungal activity against R. solani and S. sclerotiorum with IC50 values of 15.8 and 20.3 μM, respectively, comparable to those of the commonly used fungicides boscalid and carbendazim. The structure-activity relationship (SAR) of nicotinamide derivatives demonstrated that the meta-position of aniline was a key position contributing to the antifungal activity. Inhibition activities against two fungal SDHs were tested and achieved the same tendency with the data acquired from in vitro antifungal assay. Significantly, 3a-17 was demonstrated to successfully suppress disease development in S. sclerotiorum infected cole in vivo. In the molecular docking simulation, sulfur and chlorine of 3a-17 were bound with PHE291 and PRO150 of the SDH homology model, respectively, which could explain the probable mechanism of action between the inhibitory and target protein.

  19. Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk.

    Science.gov (United States)

    Trammell, Samuel Aj; Yu, Liping; Redpath, Philip; Migaud, Marie E; Brenner, Charles

    2016-05-01

    Nicotinamide riboside (NR) is a recently discovered NAD(+) precursor vitamin with a unique biosynthetic pathway. Although the presence of NR in cow milk has been known for more than a decade, the concentration of NR with respect to the other NAD(+) precursors was unknown. We aimed to determine NAD(+) precursor vitamin concentration in raw samples of milk from individual cows and from commercially available cow milk. LC tandem mass spectrometry and isotope dilution technologies were used to quantify NAD(+) precursor vitamin concentration and to measure NR stability in raw and commercial milk. Nuclear magnetic resonance (NMR) spectroscopy was used to test for NR binding to substances in milk. Cow milk typically contained ∼12 μmol NAD(+) precursor vitamins/L, of which 60% was present as nicotinamide and 40% was present as NR. Nicotinic acid and other NAD(+) metabolites were below the limits of detection. Milk from samples testing positive for Staphylococcus aureus contained lower concentrations of NR (Spearman ρ = -0.58, P = 0.014), and NR was degraded by S. aureus Conventional milk contained more NR than milk sold as organic. Nonetheless, NR was stable in organic milk and exhibited an NMR spectrum consistent with association with a protein fraction in skim milk. NR is a major NAD(+) precursor vitamin in cow milk. Control of S. aureus may be important to preserve the NAD(+) precursor vitamin concentration of milk. © 2016 American Society for Nutrition.

  20. YCL047C/POF1 is a novel nicotinamide mononucleotide adenylyltransferase (NMNAT) in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kato, Michiko; Lin, Su-Ju

    2014-05-30

    NAD(+) is an essential metabolic cofactor involved in various cellular biochemical processes. Nicotinamide riboside (NR) is an endogenously produced key pyridine metabolite that plays important roles in the maintenance of NAD(+) pool. Using a NR-specific cell-based screen, we identified mutants that exhibit altered NR release phenotype. Yeast cells lacking the ORF YCL047C/POF1 release considerably more NR compared with wild type, suggesting that POF1 plays an important role in NR/NAD(+) metabolism. The amino acid sequence of Pof1 indicates that it is a putative nicotinamide mononucleotide adenylyltransferase (NMNAT). Unlike other yeast NMNATs, Pof1 exhibits NMN-specific adenylyltransferase activity. Deletion of POF1 significantly lowers NAD(+) levels and decreases the efficiency of NR utilization, resistance to oxidative stress, and NR-induced life span extension. We also show that NR is constantly produced by multiple nucleotidases and that the intracellular NR pools are likely to be compartmentalized, which contributes to the regulation of NAD(+) homeostasis. Our findings may contribute to the understanding of the molecular basis and regulation of NAD(+) metabolism in higher eukaryotes. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. YCL047C/POF1 Is a Novel Nicotinamide Mononucleotide Adenylyltransferase (NMNAT) in Saccharomyces cerevisiae*

    Science.gov (United States)

    Kato, Michiko; Lin, Su-Ju

    2014-01-01

    NAD+ is an essential metabolic cofactor involved in various cellular biochemical processes. Nicotinamide riboside (NR) is an endogenously produced key pyridine metabolite that plays important roles in the maintenance of NAD+ pool. Using a NR-specific cell-based screen, we identified mutants that exhibit altered NR release phenotype. Yeast cells lacking the ORF YCL047C/POF1 release considerably more NR compared with wild type, suggesting that POF1 plays an important role in NR/NAD+ metabolism. The amino acid sequence of Pof1 indicates that it is a putative nicotinamide mononucleotide adenylyltransferase (NMNAT). Unlike other yeast NMNATs, Pof1 exhibits NMN-specific adenylyltransferase activity. Deletion of POF1 significantly lowers NAD+ levels and decreases the efficiency of NR utilization, resistance to oxidative stress, and NR-induced life span extension. We also show that NR is constantly produced by multiple nucleotidases and that the intracellular NR pools are likely to be compartmentalized, which contributes to the regulation of NAD+ homeostasis. Our findings may contribute to the understanding of the molecular basis and regulation of NAD+ metabolism in higher eukaryotes. PMID:24759102

  2. Nicotinamide phosphoribosyltransferase may be involved in age-related brain diseases.

    Directory of Open Access Journals (Sweden)

    Li-Ying Liu

    Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT is a key enzyme for nicotinamide adenine dinucleotide (NAD biosynthesis, and can be found either intracellularly (iNAMPT or extracellularly (eNAMPT. Studies have shown that both iNAMPT and eNAMPT are implicated in aging and age-related diseases/disorders in the peripheral system. However, their functional roles in aged brain remain to be established. Here we showed that upon aging, NAMPT level increased in serum but decreased in brain, decreased in cortex and hippocampus but remained unchanged in cerebellum and striatum in brain, and increased in microglia but likely decreased in neuron. Accordingly, total NAD (tNAD level significantly decreased in hippocampus, cerebellum and striatum in aged brain. Application of recombinant NAMPT, mimicking the elevated serum NAMPT level, enhanced the susceptibility of cerebral endothelial cells to ischemic injury, while inhibition of iNAMPT by FK866, a specific inhibitor, reduced intracellular NAD level and induced neuronal death. Taken together, we have revealed a region- and cell-specific change of NAMPT level in brain and serum upon aging, deduced its potential consequences, which suggests that NAMPT is a regulatory factor in aging and age-related brain diseases.

  3. Ulcer healing properties of different extracts of Origanum majorana in streptozotocin-nicotinamide induced diabetic rats

    Directory of Open Access Journals (Sweden)

    BP Pimple

    2012-08-01

    Full Text Available Objective: The aim of the present investigation was to evaluate the ulcer healing properties of different extracts of Origannum majorana, viz., hydrodistilled volatile oil (OMO, methanolic (OMM and aqueous extract (OMW in streptozotocin-nicotinamide induced diabetic rats. Methods: All the extracts were administered in different doses (100, 200 and 400 mg/kg, p.o. to investigate the ulcer healing potential. Streptozotocin (STZ; 65 mg/kg, i.p. along with nicotinamide (120 mg/kg, i.p. was used to induce non-insulin dependent diabetes mellitus in rats. Aspirin (200 mg/kg, i.p. was administered for initial 7 d to induce gastric ulcerations in the diabetic rats. Various biochemical markers of blood and tissue origin were estimated to compare the ulcer healing potential of these extracts. Results: The OMO and OMM exhibited dose dependent significant (P<0.01 ulcer healing property than the OMW. Additionally, the antidiabetic property of OMO and OMM was better than OMW. Conclusions: The OMO and OMM of Origanum majorana leaves can prove to be beneficial in the concomitant treatment of gastric ulcers and diabetes.

  4. Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise.

    Science.gov (United States)

    Uddin, Golam Mezbah; Youngson, Neil A; Doyle, Bronte M; Sinclair, David A; Morris, Margaret J

    2017-11-08

    Maternal overnutrition increases the risk of long-term metabolic dysfunction in offspring. Exercise improves metabolism partly by upregulating mitochondrial biogenesis or function, via increased levels of nicotinamide adenine dinucleotide (NAD + ). We have shown that the NAD + precursor, nicotinamide mononucleotide (NMN) can reverse some of the negative consequences of high fat diet (HFD) consumption. To investigate whether NMN can impact developmentally-set metabolic deficits, we compared treadmill exercise and NMN injection in offspring of obese mothers. Five week old lean and obese female C57BL6/J mice were mated with chow fed males. Female offspring weaned onto HFD were given treadmill exercise for 9 weeks, or NMN injection daily for 18 days. Maternal obesity programmed increased adiposity and liver triglycerides, with decreased glucose tolerance, liver NAD + levels and citrate synthase activity in offspring. Both interventions reduced adiposity, and showed a modest improvement in glucose tolerance and improved markers of mitochondrial function. NMN appeared to have stronger effects on liver fat catabolism (Hadh) and synthesis (Fasn) than exercise. The interventions appeared to exert the most global benefit in mice that were most metabolically challenged (HFD-consuming offspring of obese mothers). This work encourages further study to confirm the suitability of NMN for use in reversing metabolic dysfunction linked to programming by maternal obesity.

  5. Effect of the Polyphenol Rich Ethyl Acetate Fraction from the Leaves of Lycium chinenseMill. on Oxidative Stress, Dyslipidemia, and Diabetes Mellitus in Streptozotocin-Nicotinamide Induced Diabetic Rats.

    Science.gov (United States)

    Olatunji, Opeyemi J; Chen, Hongxia; Zhou, Yifeng

    2017-10-01

    Lycium chinenseMill., popularly known as boxthorn, is a plant that is traditionally used for treating night sweat, cough, inflammation and diabetes mellitus. However, the leaves have received little or no attention despite their potentials as a potent therapeutic agent. This study was aimed at investigating the hypoglycemic and hypolipidemic effects of the polyphenols-rich ethyl acetate fraction from the leaves of Lycium chinenseMill. on streptozotocin-nicotinamide induced diabetic rats. The ethyl acetate fraction (LFE) was selected and orally gavaged at 100, 200, and 400 mg/kg dose to streptozotocin (STZ)-nicotinamide induced diabetic rats. The rats' body weight, fasting blood glucose (FBG), lipid profile and oxidative stress markers were evaluated after the treatment period. Treatment with LFE resulted in a significant decrease in the FBG level, altered lipid profiles, and reduced the activities of the enzymes alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT) in the treated diabetic rats. Furthermore, LFE significantly elevated the antioxidant status (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities) and reducing malondialdehyde (MDA) levels in the treated rats. The present study has revealed that L. chinenseMill. possess anti-hyperglycemic and anti-hyperlipidemic properties which is mediated through modulation of oxidative stress and polyphenolics might be responsible for the action. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  6. Model theory and modules

    CERN Document Server

    Prest, M

    1988-01-01

    In recent years the interplay between model theory and other branches of mathematics has led to many deep and intriguing results. In this, the first book on the topic, the theme is the interplay between model theory and the theory of modules. The book is intended to be a self-contained introduction to the subject and introduces the requisite model theory and module theory as it is needed. Dr Prest develops the basic ideas concerning what can be said about modules using the information which may be expressed in a first-order language. Later chapters discuss stability-theoretic aspects of module

  7. Topics in Nonlinear Dynamics

    DEFF Research Database (Denmark)

    Mosekilde, Erik

    Through a significant number of detailed and realistic examples this book illustrates how the insights gained over the past couple of decades in the fields of nonlinear dynamics and chaos theory can be applied in practice. Aomng the topics considered are microbiological reaction systems, ecological...... food-web systems, nephron pressure and flow regulation, pulsatile secretion of hormones, thermostatically controlled radiator systems, post-stall maneuvering of aircrafts, transfer electron devices for microwave generation, economic long waves, human decision making behavior, and pattern formation...... in chemical reaction-diffusion systems....

  8. Topics in CP violation

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, H.R.

    1993-02-01

    Given the varied backgrounds of the members of this audience this talk will be a grab bag of topics related to the general theme of CP Violation. I do not have time to dwell in detail on any of them. First, for the astronomers and astrophysicists among you, I want to begin by reviewing the experimental status of evidence for CP violation in particle processes. There is only one system where this has been observed, and that is in the decays of neutral K mesons.

  9. Topics in Operator Theory

    CERN Document Server

    Ball, Joseph A; Helton, JWilliam; Rodman, Leiba; Spitkovsky, Iiya

    2010-01-01

    This is the first volume of a collection of original and review articles on recent advances and new directions in a multifaceted and interconnected area of mathematics and its applications. It encompasses many topics in theoretical developments in operator theory and its diverse applications in applied mathematics, physics, engineering, and other disciplines. The purpose is to bring in one volume many important original results of cutting edge research as well as authoritative review of recent achievements, challenges, and future directions in the area of operator theory and its applications.

  10. Topics on continua

    CERN Document Server

    Macias, Sergio

    2005-01-01

    Specialized as it might be, continuum theory is one of the most intriguing areas in mathematics. However, despite being popular journal fare, few books have thoroughly explored this interesting aspect of topology. In Topics on Continua, Sergio Macías, one of the field's leading scholars, presents four of his favorite continuum topics: inverse limits, Jones's set function T, homogenous continua, and n-fold hyperspaces, and in doing so, presents the most complete set of theorems and proofs ever contained in a single topology volume. Many of the results presented have previously appeared only in research papers, and some appear here for the first time. After building the requisite background and exploring the inverse limits of continua, the discussions focus on Professor Jones''s set function T and continua for which T is continuous. An introduction to topological groups and group actions lead to a proof of Effros''s Theorem, followed by a presentation of two decomposition theorems. The author then offers an...

  11. Topic and Topic-Comment Constructions in Mandarin Chinese.

    Science.gov (United States)

    Shi, Dingxu

    2000-01-01

    Attempts to provide a precise definition for topic and to derive most of the properties of topic from this definition. The main assumption is that the topic-comment construction is a syntactic device employed to fulfill certain discourse functions. (Author/VWL)

  12. Replicatively senescent human fibroblasts reveal a distinct intracellular metabolic profile with alterations in NAD+ and nicotinamide metabolism.

    Science.gov (United States)

    James, Emma L; Lane, James A E; Michalek, Ryan D; Karoly, Edward D; Parkinson, E Kenneth

    2016-12-07

    Cellular senescence occurs by proliferative exhaustion (PEsen) or following multiple cellular stresses but had not previously been subject to detailed metabolomic analysis. Therefore, we compared PEsen fibroblasts with proliferating and transiently growth arrested controls using a combination of different mass spectroscopy techniques. PEsen cells showed many specific alterations in both the NAD+ de novo and salvage pathways including striking accumulations of nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) in the amidated salvage pathway despite no increase in nicotinamide phosphoribosyl transferase or in the NR transport protein, CD73. Extracellular nicotinate was depleted and metabolites of the deamidated salvage pathway were reduced but intracellular NAD+ and nicotinamide were nevertheless maintained. However, sirtuin 1 was downregulated and so the accumulation of NMN and NR was best explained by reduced flux through the amidated arm of the NAD+ salvage pathway due to reduced sirtuin activity. PEsen cells also showed evidence of increased redox homeostasis and upregulated pathways used to generate energy and cellular membranes; these included nucleotide catabolism, membrane lipid breakdown and increased creatine metabolism. Thus PEsen cells upregulate several different pathways to sustain their survival which may serve as pharmacological targets for the elimination of senescent cells in age-related disease.

  13. Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects

    NARCIS (Netherlands)

    Smedts, H.P.M.; Rakhshandehroo, M.; Verkleij-Hagoort, A.C.; Vries, de J.H.M.; Ottenkamp, J.; Steegers, E.A.P.; Steegers-Theunissen, R.P.M.

    2008-01-01

    With the exception of studies on folic acid, little evidence is available concerning other nutrients in the pathogenesis of congenital heart defects (CHDs). Fatty acids play a central role in embryonic development, and the B-vitamins riboflavin and nicotinamide are co-enzymes in lipid metabolism.

  14. Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects.

    Science.gov (United States)

    Smedts, Huberdina P M; Rakhshandehroo, Maryam; Verkleij-Hagoort, Anna C; de Vries, Jeanne H M; Ottenkamp, Jaap; Steegers, Eric A P; Steegers-Theunissen, Régine P M

    2008-10-01

    With the exception of studies on folic acid, little evidence is available concerning other nutrients in the pathogenesis of congenital heart defects (CHDs). Fatty acids play a central role in embryonic development, and the B-vitamins riboflavin and nicotinamide are co-enzymes in lipid metabolism. To investigate associations between the maternal dietary intake of fats, riboflavin and nicotinamide, and CHD risk in the offspring. A case-control family study was conducted in 276 mothers of a child with a CHD comprising of 190 outflow tract defects (OTD) and 86 non-outflow tract defects (non-OTD) and 324 control mothers of a non-malformed child. Mothers filled out general and food frequency questionnaires at 16 months after the index-pregnancy, as a proxy of the habitual food intake in the preconception period. Nutrient intakes (medians) were compared between cases and controls by Mann-Whitney U test. Odds ratios (OR) for the association between CHDs and nutrient intakes were estimated in a logistic regression model. Case mothers, in particular mothers of a child with OTD, had higher dietary intakes of saturated fat, 30.9 vs. 29.8 g/d; P riboflavin and nicotinamide were lower in mothers of a child with an OTD than in controls (1.32 vs. 1.41 mg/d; P riboflavin (riboflavin and nicotinamide seems to contribute to CHD risk, in particular OTDs.

  15. Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects

    NARCIS (Netherlands)

    Smedts, Huberdina P. M.; Rakhshandehroo, Maryam; Verkleij-Hagoort, Anna C.; de Vries, Jeanne H. M.; Ottenkamp, Jaap; Steegers, Eric A. P.; Steegers-Theunissen, Régine P. M.

    2008-01-01

    BACKGROUND: With the exception of studies on folic acid, little evidence is available concerning other nutrients in the pathogenesis of congenital heart defects (CHDs). Fatty acids play a central role in embryonic development, and the B-vitamins riboflavin and nicotinamide are co-enzymes in lipid

  16. Progression to type 1 diabetes in islet cell antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial

    DEFF Research Database (Denmark)

    Bingley, P J; Gale, E A M; Reimers, Jesper Irving

    2006-01-01

    AIMS/HYPOTHESIS: To examine the role of additional immune, genetic and metabolic risk markers in determining risk of diabetes in islet cell antibody (ICA)-positive individuals with a family history of type 1 diabetes recruited into the European Nicotinamide Diabetes Intervention Trial. METHODS...

  17. Establishment of Bioprocess for Synthesis of Nicotinamide by Recombinant Escherichia coli Expressing High-Molecular-Mass Nitrile Hydratase.

    Science.gov (United States)

    Wang, Zhe; Liu, Zhongmei; Cui, Wenjing; Zhou, Zhemin

    2017-08-01

    Application of engineered bacteria expressing nitrile hydratase for the production of amide is getting tremendous attention due to the rapid development of recombinant DNA technique. This study evaluated the effect of 3-cyanopyridine concentrations on nicotinamide production using recombinant Escherichia coli strain (BAG) expressing high-molecular-mass nitrile hydratase from Rhodococcus rhodochrous J1, and established proper process of whole-cell catalysis of 3-cyanopyridine and high cell-density cultivation. The process of substrate fed-batch was applied in the production of nicotinamide, and the concentration of product reached 390 g/L under the condition of low cell-density. After the high cell-density cultivation of BAG in 5 L bioreactor, the OD 600 of cell attained 200 and the total activity reached 2813 U/mL. Different high density of BAG after fermentation in the tank was used to catalyze 3-cyanopyridine, and the concentration of nicotinamide reached to 508 g/L in just 60 min. The productivity of BAG was 212% higher than that of R. rhodochrous J1, and it is possible that BAG is able to achieve industrial production of nicotinamide.

  18. Poly(amido amine)s as gene delivery vectors: effects of quaternary nicotinamide moieties in the side chains

    NARCIS (Netherlands)

    Mateos timoneda, Miguel; Lok, Martin C.; Hennink, Wim E.; Feijen, Jan; Engbersen, Johannes F.J.

    2008-01-01

    To evaluate the effect of quaternary nicotinamide pendant groups on gene delivery properties, a series of poly(amido amine) (co)polymers were synthesized by Michael addition polymerization of N, N-cystaminebisacrylamide with variable ratios of 1-(4-aminobutyl)-3-carbamoylpyridinium (Nic-BuNH2), and

  19. Vulnerability to a Metabolic Challenge Following Perinatal Asphyxia Evaluated by Organotypic Cultures: Neonatal Nicotinamide Treatment.

    Science.gov (United States)

    Perez-Lobos, R; Lespay-Rebolledo, C; Tapia-Bustos, A; Palacios, E; Vío, V; Bustamante, D; Morales, P; Herrera-Marschitz, M

    2017-10-01

    The hypothesis of enhanced vulnerability following perinatal asphyxia was investigated with a protocol combining in vivo and in vitro experiments. Asphyxia-exposed (AS) (by 21 min water immersion of foetuses containing uterine horns) and caesarean-delivered control (CS) rat neonates were used at P2-3 for preparing triple organotypic cultures (substantia nigra, neostriatum and neocortex). At DIV 18, cultures were exposed to different concentrations of H 2 O 2 (0.25-45 mM), added to the culture medium for 18 h. After a 48-h recovery period, the cultures were either assessed for cell viability or for neurochemical phenotype by confocal microscopy. Energy metabolism (ADP/ATP ratio), oxidative stress (GSH/GSSG) and a modified ferric reducing/antioxidant power assay were applied to homogenates of parallel culture series. In CS cultures, the number of dying cells was similar in substantia nigra, neostriatum and neocortex, but it was several times increased in AS cultures evaluated under the same conditions. A H 2 O 2 challenge led to a concentration-dependent increase in cell death (>fourfold after 0.25 mM of H 2 O 2 ) in CS cultures. In AS cultures, a significant increase in cell death was only observed after 0.5 mM of H 2 O 2 . At higher than 1 mM of H 2 O 2 (up to 45 mM), cell death increased several times in all cultures, but the effect was still more prominent in CS than in AS cultures. The cell phenotype of dying/alive cells was investigated in formalin-fixed cultures exposed to 0 or 1 mM of H 2 O 2 , co-labelling for TUNEL (apoptosis), MAP-2 (neuronal phenotype), GFAP (astroglial phenotype) and TH (tyrosine hydroxylase; for dopamine phenotype), counterstaining for DAPI (nuclear staining), also evaluating the effect of a single dose of nicotinamide (0.8 nmol/kg, i.p. injected in 100 μL, 60 min after delivery). Perinatal asphyxia produced a significant increase in the number of DAPI/TUNEL cells/mm 3 , in substantia nigra and neostriatum. One millimolar of

  20. Topical Acne Treatments and Pregnancy

    Science.gov (United States)

    Topical Acne Treatments and Pregnancy In every pregnancy, a woman starts out with a 3-5% chance of having ... This sheet talks about whether exposure to topical acne treatments may increase the risk for birth defects ...

  1. Topics in orbit equivalence

    CERN Document Server

    Kechris, Alexander S

    2004-01-01

    This volume provides a self-contained introduction to some topics in orbit equivalence theory, a branch of ergodic theory. The first two chapters focus on hyperfiniteness and amenability. Included here are proofs of Dye's theorem that probability measure-preserving, ergodic actions of the integers are orbit equivalent and of the theorem of Connes-Feldman-Weiss identifying amenability and hyperfiniteness for non-singular equivalence relations. The presentation here is often influenced by descriptive set theory, and Borel and generic analogs of various results are discussed. The final chapter is a detailed account of Gaboriau's recent results on the theory of costs for equivalence relations and groups and its applications to proving rigidity theorems for actions of free groups.

  2. Topics in atomic physics

    CERN Document Server

    Burkhardt, Charles E

    2006-01-01

    The study of atomic physics propelled us into the quantum age in the early twentieth century and carried us into the twenty-first century with a wealth of new and, in some cases, unexplained phenomena. Topics in Atomic Physics provides a foundation for students to begin research in modern atomic physics. It can also serve as a reference because it contains material that is not easily located in other sources. A distinguishing feature is the thorough exposition of the quantum mechanical hydrogen atom using both the traditional formulation and an alternative treatment not usually found in textbooks. The alternative treatment exploits the preeminent nature of the pure Coulomb potential and places the Lenz vector operator on an equal footing with other operators corresponding to classically conserved quantities. A number of difficult to find proofs and derivations are included as is development of operator formalism that permits facile solution of the Stark effect in hydrogen. Discussion of the classical hydrogen...

  3. Topics in mathematical biology

    CERN Document Server

    Hadeler, Karl Peter

    2017-01-01

    This book analyzes the impact of quiescent phases on biological models. Quiescence arises, for example, when moving individuals stop moving, hunting predators take a rest, infected individuals are isolated, or cells enter the quiescent compartment of the cell cycle. In the first chapter of Topics in Mathematical Biology general principles about coupled and quiescent systems are derived, including results on shrinking periodic orbits and stabilization of oscillations via quiescence. In subsequent chapters classical biological models are presented in detail and challenged by the introduction of quiescence. These models include delay equations, demographic models, age structured models, Lotka-Volterra systems, replicator systems, genetic models, game theory, Nash equilibria, evolutionary stable strategies, ecological models, epidemiological models, random walks and reaction-diffusion models. In each case we find new and interesting results such as stability of fixed points and/or periodic orbits, excitability...

  4. Analytical Method Validation and Determination of Pyridoxine, Nicotinamide, and Caffeine in Energy Drinks Using Thin Layer Chromatography-Densitometry

    Directory of Open Access Journals (Sweden)

    Florentinus Dika Octa Riswanto

    2015-03-01

    Full Text Available Food supplement which contains vitamins and stimulants such as caffeine were classified as energy drink. TLC-densitometry method was chosen to determine the pyridoxine, nicotinamide, and caffeine in the energy drink sample. TLC plates of silica gel 60 F254 was used as the stationary phase and methanol : ethyl acetate : ammonia 25% (134:77:10 was used as the mobile phase. The correlation coefficient for each pyridoxine, nicotinamide, and caffeine were 0.9982, 0.9997, and 0.9966, respectively. Detection and quantitation limits of from the three analytes were 4.05 and 13.51 µg/mL; 13.15 and 43.83 µg/mL; 5.43 and 18.11 µg/mL, respectively. The recovery of pyridoxine, nicotinamide, and caffeine were within the required limit range of 95-105%. The percent of RSD were below the limit value of 5.7% for caffeine and nicotinamide and 8% for pyridoxine. The content amount of pyridoxine in the sample 1 and 2 were 33.59 ± 0.981 and 30.29 ± 2.061 µg/mL, respectively. The content amount of nicotinamide in the sample 1 and 2 were 106.53 ± 3.521 and 98.20 ± 3.648 µg/mL, respectively. The content amount of caffeine in the sample 1 and 2 were 249.50 ± 5.080 and 252.80 ± 2.640 µg/mL, respectively. Robustness test results showed that the most optimal method conditions should be applied for the analysis.

  5. Rings and their modules

    CERN Document Server

    Bland, Paul E

    2011-01-01

    This book is an introduction to the theory of rings and modules that goes beyond what one normally obtains in a graduate course in abstract algebra. In addition to the presentation of standard topics in ring and module theory, it also covers category theory, homological algebra and even more specialized topics like injective envelopes and projective covers, reflexive modules and quasi-Frobenius rings, and graded rings and modules. The book is a self-contained volume written in a very systematic style: allproofs are clear and easy for the reader to understand and allarguments are based onmaterials contained in the book. A problem sets follow each section. It is suitable for graduate and PhD students who have chosen ring theory for their research subject.

  6. Topical melatonin for treatment of androgenetic alopecia.

    Science.gov (United States)

    Fischer, Tobias W; Trüeb, Ralph M; Hänggi, Gabriella; Innocenti, Marcello; Elsner, Peter

    2012-10-01

    In the search for alternative agents to oral finasteride and topical minoxidil for the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth modulator, was identified as a promising candidate based on in vitro and in vivo studies. One pharmacodynamic study on topical application of melatonin and four clinical pre-post studies were performed in patients with androgenetic alopecia or general hair loss and evaluated by standardised questionnaires, TrichoScan, 60-second hair count test and hair pull test. FIVE CLINICAL STUDIES SHOWED POSITIVE EFFECTS OF A TOPICAL MELATONIN SOLUTION IN THE TREATMENT OF AGA IN MEN AND WOMEN WHILE SHOWING GOOD TOLERABILITY: (1) Pharmacodynamics under once-daily topical application in the evening showed no significant influence on endogenous serum melatonin levels. (2) An observational study involving 30 men and women showed a significant reduction in the degree of severity of alopecia after 30 and 90 days (P melatonin solution can be considered as a treatment option in androgenetic alopecia.

  7. Groups, rings, modules

    CERN Document Server

    Auslander, Maurice

    2014-01-01

    This classic monograph is geared toward advanced undergraduates and graduate students. The treatment presupposes some familiarity with sets, groups, rings, and vector spaces. The four-part approach begins with examinations of sets and maps, monoids and groups, categories, and rings. The second part explores unique factorization domains, general module theory, semisimple rings and modules, and Artinian rings. Part three's topics include localization and tensor products, principal ideal domains, and applications of fundamental theorem. The fourth and final part covers algebraic field extensions

  8. Effect of tetrahydrocurcumin on lipid peroxidation and lipids in streptozotocin-nicotinamide-induced diabetic rats.

    Science.gov (United States)

    Murugan, Pidaran; Pari, Leelavinothan

    2006-08-01

    Hyperlipidaemia is an associated complication of diabetes mellitus. We recently reported that tetrahydrocurcumin lowered the blood glucose in diabetic rats. In the present study, we have investigated the effect of tetrahydrocurcumin, one of the active metabolites of curcumin on lipid profile and lipid peroxidation in streptozotocin-nicotinamide-induced diabetic rats. Tetrahydrocurcumin 80 mg/kg body weight was administered orally to diabetic rats for 45 days, resulted a significant reduction in blood glucose and significant increase in plasma insulin in diabetic rats, which proved its antidiabetic effect. Tetrahydrocurcumin also caused a significant reduction in lipid peroxidation (thiobarbituric acid reactive substances and hydroperoxides) and lipids (cholesterol, triglycerides, free fatty acids and phospholipids) in serum and tissues, suggesting its role in protection against lipid peroxidation and its antihyperlipidemic effect. Tetrahydrocurcumin showed a better effect when compared with curcumin. Results of the present study indicate that tetrahydrocurcumin showed antihyperlipidaemic effect in addition to its antidiabetic effect in type 2 diabetic rats.

  9. Target enzyme mutations are the molecular basis for resistance towards pharmacological inhibition of nicotinamide phosphoribosyltransferase

    DEFF Research Database (Denmark)

    Olesen, Uffe H; Petersen, Jakob G; Garten, Antje

    2010-01-01

    BACKGROUND: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT) are promising cancer drugs currently in clinical trials in oncology, including APO866, CHS-828 and the CHS-828 prodrug EB1627/GMX1777, but cancer cell resistance to these drugs has not been studied in detail. METHODS: Here, we...... introduce an analogue of CHS-828 called TP201565 with increased potency in cellular assays. Further, we describe and characterize a panel of cell lines with acquired stable resistance towards several NAMPT inhibitors of 18 to 20,000 fold compared to their parental cell lines. RESULTS: We find that 4 out...... of 5 of the resistant sublines display mutations of NAMPT located in the vicinity of the active site or in the dimer interface of NAMPT. Furthermore, we show that these mutations are responsible for the resistance observed. All the resistant cell lines formed xenograft tumours in vivo. Also, we confirm...

  10. The generation of myricetin-nicotinamide nanococrystals by top down and bottom up technologies.

    Science.gov (United States)

    Liu, Mingyu; Hong, Chao; Li, Guowen; Ma, Ping; Xie, Yan

    2016-09-30

    Myricetin-nicotinamide (MYR-NIC) nanococrystal preparation methods were developed and optimized using both top down and bottom up approaches. The grinding (top down) method successfully achieved nanococrystals, but there were some micrometer range particles and aggregation. The key consideration of the grinding technology was to control the milling time to determine a balance between the particle size and distribution. In contrast, a modified bottom up approach based on a solution method in conjunction with sonochemistry resulted in a uniform MYR-NIC nanococrystal that was confirmed by powder x-ray diffraction, scanning electron microscopy, dynamic light scattering, and differential scanning calorimeter, and the particle dissolution rate and amount were significantly greater than that of MYR-NIC cocrystal. Notably, this was a simple method without the addition of any non-solvent. We anticipate our findings will provide some guidance for future nanococrystal preparation as well as its application in both chemical and pharmaceutical area.

  11. Conducting polymer and its composite materials based electrochemical sensor for Nicotinamide Adenine Dinucleotide (NADH).

    Science.gov (United States)

    Omar, Fatin Saiha; Duraisamy, Navaneethan; Ramesh, K; Ramesh, S

    2016-05-15

    Nicotinamide Adenine Dinucleotide (NADH) is an important coenzyme in the human body that participates in many metabolic reactions. The impact of abnormal concentrations of NADH significantly causes different diseases in human body. Electrochemical detection of NADH using bare electrode is a challenging task especially in the presence of main electroactive interferences such as ascorbic acid (AA), uric acid (UA) and dopamine (DA). Modified electrodes have been widely explored to overcome the problems of poor sensitivity and selectivity occurred from bare electrodes. This review gives an overview on the progress of using conducting polymers, polyelectrolyte and its composites (co-polymer, carbonaceous, metal, metal oxide and clay) based modified electrodes for the sensing of NADH. In addition, developments on the fabrication of numerous conducting polymer composites based modified electrodes are clearly described. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Cancer stem cell overexpression of nicotinamide N-methyltransferase enhances cellular radiation resistance

    DEFF Research Database (Denmark)

    D’Andrea, Filippo P.; Safwat, Akmal; Kassem, Moustapha

    2011-01-01

    BackgroundCancer stem cells are thought to be a radioresistant population and may be the seeds for recurrence after radiotherapy. Using tumorigenic clones of retroviral immortalized human mesenchymal stem cell with small differences in their phenotype, we investigated possible genetic expression...... that could explain cancer stem cell radiation resistance. MethodsTumorigenic mesenchymal cancer stem cell clones BB3 and CE8 were irradiated at varying doses and assayed for clonogenic surviving fraction. Altered gene expression before and after 2Gy was assessed by Affymetric exon chip analysis and further...... found the genes involved in cancer, proliferation, DNA repair and cell death. ConclusionsThe higher radiation resistance in clone CE8 is likely due to NNMT overexpression. The higher levels of NNMT could affect the cellular damage resistance through depletion of the accessible amounts of nicotinamide...

  13. Isotope effect studies of the chemical mechanism of nicotinamide adenine dinucleotide malic enzyme from Crassula

    International Nuclear Information System (INIS)

    Grissom, C.B.; Willeford, O.; Wedding, R.T.

    1987-01-01

    The 13 C primary kinetic isotope effect on the decarboxylation of malate by nicotinamide adenine dinucleotide malic enzyme from Crassula argentea is 1.0199 +/- 0.0006 with proteo L-malate-2-H and 1.0162 +/- 0.0003 with malate-2-d. The primary deuterium isotope effect is 1.45 +/- 0.10 on V/K and 1.93 +/- 0.13 on V/sub max/. This indicates a stepwise conversion of malate to pyruvate and CO 2 with hydride transfer preceding decarboxylation, thereby suggesting a discrete oxaloacetate intermediate. This is in agreement with the stepwise nature of the chemical mechanism of other malic enzymes despite the Crassula enzyme's inability to reduce or decarboxylate oxaloacetate. Differences in morphology and allosteric regulation between enzymes suggest specialization of the Crassula malic enzyme for the physiology of crassulacean and acid metabolism while maintaining the catalytic events founds in malic enzymes from animal sources

  14. Nicotinamide riboside, an unusual, non-typical, substrate of purified purine-nucleoside phosphorylases.

    Science.gov (United States)

    Wielgus-Kutrowska, B; Kulikowska, E; Wierzchowski, J; Bzowska, A; Shugar, D

    1997-01-15

    Nicotinamide 1-beta-D-riboside (Nir), the cationic, reducible moiety of the coenzyme NAD+, has been confirmed as an unusual substrate for purified purine-nucleoside phosphorylase (PNP) from a mammalian source (calf spleen). It is also a substrate of the enzyme from Escherichia coli. The Km values at pH 7, 1.48 mM and 0.62 mM, respectively, were 1-2 orders of magnitude higher than for the natural substrate inosine, but the Vmax values were comparable, 96% and 35% that for Ino. The pseudo first-order rate constants, Vmax/Km, were 1.1% and 2.5% for the calf spleen and E. coli enzymes. The aglycon, nicotinamide, was neither a substrate nor an inhibitor of PNP. Nir was a weak inhibitor of inosine phosphorolysis catalyzed by both enzymes, with Ki values close to the Km for its phosphorolysis, consistent with simple competitive inhibition; this was further confirmed by Dixon plots. Phosphorolysis of the fluorescent positively charged substrate 7-methylguanosine was also inhibited in a competitive manner by both Ino and Nir. Phosphorolysis of Nir by both enzymes was inhibited competitively by several specific inhibitors of calf spleen and E. coli PNP, with Ki values similar to those for inhibition of other natural substrates. The pH dependence of the kinetic constants for the phosphorolysis of Nir and of a variety of other substrates, was extensively investigated, particularly in the alkaline pH range, where Nir exhibited abnormally high substrate activity relative to the reduced reaction rates of both enzymes towards other anionic or neutral substrates. The overall results are discussed in relation to present concepts regarding binding and phosphorolysis of substrates by PNP based on crystallographic data of enzyme-inhibitor complexes, and current studies on enzymatic and nonenzymatic mechanisms of the cleavage of the Nir glycosidic bond.

  15. Nicotinamide Phosphoribosyltransferase Upregulation by Phenylephrine Reduces Radiation Injury in Submandibular Gland

    International Nuclear Information System (INIS)

    Xiang, Bin; Han, Lichi; Wang, Xinyue; Tang, Ling; Li, Kailiang; Li, Xiuxiu; Zhao, Xibo; Xia, Miaomiao; Zhou, Xixi; Zhang, Fuyin; Liu, Ke Jian

    2016-01-01

    Purpose: Radiation therapy for head and neck cancer commonly leads to radiation sialadenitis. Emerging evidence has indicated that phenylephrine pretreatment reduces radiosensitivity in the salivary gland; however, the underlying cytoprotective mechanism remains unclear. Nicotinamide phosphoribosyltransferase (NAMPT) is not only a key enzyme for the nicotinamide adenine dinucleotide salvage pathway, but also a cytokine participating in cell survival, metabolism, and longevity, with a broad effect on cellular functions in physiology and pathology. However, the regulatory events of NAMPT in response to the irradiated salivary gland are unknown. Methods and Materials: The cell viability of primary cultured submandibular gland cells was determined using the PrestoBlue assay. NAMPT expression was measured using reverse transcriptase polymerase chain reaction and Western blotting in vitro and in vivo. Silent information regulator 1 (SIRT1) and phosphorylated Akt protein levels were examined by Western blotting. The cellular locations of NAMPT and SIRT1 were detected by immunohistochemistry. NAMPT promoter activity was assessed using the luciferase reporter gene assay. Results: NAMPT was mainly distributed in the cytoplasm of granular convoluted tubule cells and ductal cells in normal submandibular glands. mRNA and protein expression of NAMPT was downregulated after radiation but upregulated with phenylephrine pretreatment both in vivo and in vitro. Moreover, the protein expression of phosphorylated Akt and SIRT1 was decreased in irradiated glands, and phenylephrine pretreatment restored the expression of both. SIRT1 was mainly located in the cell nucleus and cytoplasm in the normal submandibular gland. Phenylephrine dramatically enhanced the expression of SIRT1, which was significantly reduced by radiation. Furthermore, phenylephrine induced a marked increase of NAMPT promoter activity. Conclusions: These findings reveal the regulatory mechanisms of NAMPT expression

  16. Nicotinamide adenine dinucleotide assisted shape-controlled synthesis of catalytically active raspberry-like gold nanostructures

    International Nuclear Information System (INIS)

    Das, Ashok Kumar; Layek, Rama K.; Kim, Nam Hoon; Samdani, Jitendra; Kang, Myung Chul; Lee, Joong Hee

    2015-01-01

    Graphical abstract: A facile method was developed for the synthesis of raspberry-like Au nanostructure and it was used as an electrocatalyst for the oxidation of methanol and reduction of oxygen. - Highlights: • Raspberry-like gold nanostructures have been synthesized. • Nicotinamide adenine dinucleotide plays an important role in the synthesis. • Raspberry-like Au nanostructure has an excellent electrocatalytic activity in methanol oxidation and oxygen reduction. - Abstract: We describe the shape-controlled growth of raspberry-like gold (Au) nanostructures and their application in the electrochemical oxidation of methanol and reduction of oxygen. Nicotinamide adenine dinucleotide (NAD + ) plays a vital role in the growth of raspberry-like Au nanostructures. The preferential adsorption of NAD + onto the (011) facets of Au favors the growth of raspberry-like morphology. In the absence of NAD + , icosahedral Au nanostructures were obtained. The raspberry-like Au nanostructures have been characterized by UV-visible spectroscopy, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and electrochemical measurements. The FESEM image shows that the raspberry-like morphology has an average size of 170 nm. The spectral profile shows a broad band between 650 and 795 nm. Compared to Au nanoseeds and icosahedral Au nanostructures that were grown in the absence of NAD + , the raspberry-like morphology has excellent catalytic activity towards the electrochemical oxidation of methanol and reduction of oxygen. On the raspberry-like nanoparticle-based electrode, the oxidation of methanol was observed at 0.35 V in alkaline pH, and the reduction of oxygen was observed at -0.06 and -0.4 V in 0.1 M PBS. The electrochemical reduction of oxygen occurs in two steps: (i) reduction of oxygen to H 2 O 2 and (ii) further reduction of electrogenerated H 2 O 2 to water. The electrochemical performance of the raspberry-like nanostructure-based electrode is highly

  17. Cobalt(II) and strontium(II) complexes of three isomers, nicotinamide, isonicotinamide and picolinamide

    Science.gov (United States)

    Xue, Junhui; Hua, Xiaohui; Yang, Limin; Li, Weihong; Xu, Yizhuang; Zhao, Guozhong; Zhang, Gaohui; Liu, Liming; Liu, Kexin; Chen, Jia'er; Wu, Jinguang

    2014-02-01

    Novel coordination structures formed by cobalt(II) and strontium(II) complexes with nicotinamide (na), isonicotinamide (ina) and picolinamide (pa) are reported. The structures of these complexes (CoCl2·(C6H6N2O)2·6H2O (Co-na), CoCl2·(C6H6N2O)2 (Co-ina), CoCl2·(C6H6N2O)2·2H2O, (Co-pa), SrCl2·(C6H6N2O)2·4H2O (Sr-na), SrCl2·(C6H6N2O)2·3H2O (Sr-ina) and SrCl2·C6H6N2O·H2O (Sr-pa)) in the solid state have been characterized by X-ray single crystal diffraction, FTIR, FIR, THz, Raman and UV-Vis spectroscopies. Pyridyl nitrogen of nicotinamide is coordinated to Co2+, but pyridyl nitrogen and carbonyl oxygen are used for coordination to Sr2+, and each Sr2+ is coordinated to four ligands. For isonicotinamide, pyridyl nitrogen is coordinated to Co2+, carbonyl oxygen is coordinated to Sr2+ and the ligand is also hydrogen-bonded in Sr-ina. Pyridyl nitrogen and carbonyl oxygen of picolinamide are coordinated to Co2+ to form a five-membered ring structure, but the carbonyl oxygen is coordinated to two Sr2+ ions in Sr-pa. Some of the complexes can form chain or network structures. The experiments results indicate the differences of the coordination of Co and Sr ions, the changes of hydrogen bonds and conformation of the ligands induced by complexation.

  18. Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin.

    Science.gov (United States)

    Domínguez-Gómez, G; Díaz-Chávez, J; Chávez-Blanco, A; Gonzalez-Fierro, A; Jiménez-Salazar, J E; Damián-Matsumura, P; Gómez-Quiroz, L E; Dueñas-González, A

    2015-02-01

    Poly(ADP-ribose) polymerase (PARP) inhibitors enhance the effect of DNA alkylating agents on BRCA1‑ and BRCA2-deficient cell lines. The aim of this study was to analyze the effect of the PARP inhibitor nicotinamide (NAM) on breast cancer cells with different BRCA1 expression or function, such as BRCA1‑deficient MDA-MB-436 cells, low expression BRCA1 MCF-7 cells, and the BRCA1 wild‑type MDA-MB-231 cells, to demonstrate its effects as a chemo‑ or radiosensitizing agent. PARP activity was analyzed in MDA-MB-436, MCF-7 and MDA-MB-231 breast cancer cells subjected or not to NAM. Inhibition of PARP by NAM in the presence of DNA damage was examined by Alexa Fluor 488 immunofluorescence. Crystal violet assays were used to test growth inhibition and the chemo‑ and radiosensitization effects of NAM were investigated using clonogenic assays. Significant differences among data sets were determined using two-tailed ANOVA and Bonferroni tests. We demonstrated that NAM reduces PARP activity in vitro, and in cells subjected or not to DNA damage, it also reduces the viability of breast cancer cell lines and synergyzes the cytotoxicity of cisplatin in MDA-MB-436 and MCF-7 cells. Downregulation of PARP1 with siRNA led to modest growth inhibition, which was further increased by cisplatin. Nicotinamide also induced radiosensitization in MDA-MB-436 and MDA-MB-231 cells. In conclusion, NAM may be used as a chemo‑ or radiosensitizing agent regardless of the BRCA1 status in breast cancer.

  19. Nicotinamide Phosphoribosyltransferase Upregulation by Phenylephrine Reduces Radiation Injury in Submandibular Gland

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Bin, E-mail: xiangbin72@163.com [Laboratory of Oral and Maxillofacial Disease, Second Hospital of Dalian Medical University, Dalian (China); Han, Lichi [Department of Oral Medicine and Medical Research Center of Medical College, Dalian University, Dalian (China); Wang, Xinyue [Laboratory of Oral and Maxillofacial Disease, Second Hospital of Dalian Medical University, Dalian (China); Tang, Ling [Life Sciences and Technology College, Dalian University, Dalian (China); Li, Kailiang [Department of Oral and Maxillofacial Surgery, Second Hospital of Dalian Medical University, Dalian (China); Li, Xiuxiu [Department of Oral Medicine and Medical Research Center of Medical College, Dalian University, Dalian (China); Zhao, Xibo [Department of Oral and Maxillofacial Surgery, Second Hospital of Dalian Medical University, Dalian (China); Xia, Miaomiao [Department of Oral Medicine and Medical Research Center of Medical College, Dalian University, Dalian (China); Zhou, Xixi [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico (United States); Zhang, Fuyin [Department of Oral and Maxillofacial Surgery, Second Hospital of Dalian Medical University, Dalian (China); Liu, Ke Jian, E-mail: kliu@salud.unm.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico (United States)

    2016-11-01

    Purpose: Radiation therapy for head and neck cancer commonly leads to radiation sialadenitis. Emerging evidence has indicated that phenylephrine pretreatment reduces radiosensitivity in the salivary gland; however, the underlying cytoprotective mechanism remains unclear. Nicotinamide phosphoribosyltransferase (NAMPT) is not only a key enzyme for the nicotinamide adenine dinucleotide salvage pathway, but also a cytokine participating in cell survival, metabolism, and longevity, with a broad effect on cellular functions in physiology and pathology. However, the regulatory events of NAMPT in response to the irradiated salivary gland are unknown. Methods and Materials: The cell viability of primary cultured submandibular gland cells was determined using the PrestoBlue assay. NAMPT expression was measured using reverse transcriptase polymerase chain reaction and Western blotting in vitro and in vivo. Silent information regulator 1 (SIRT1) and phosphorylated Akt protein levels were examined by Western blotting. The cellular locations of NAMPT and SIRT1 were detected by immunohistochemistry. NAMPT promoter activity was assessed using the luciferase reporter gene assay. Results: NAMPT was mainly distributed in the cytoplasm of granular convoluted tubule cells and ductal cells in normal submandibular glands. mRNA and protein expression of NAMPT was downregulated after radiation but upregulated with phenylephrine pretreatment both in vivo and in vitro. Moreover, the protein expression of phosphorylated Akt and SIRT1 was decreased in irradiated glands, and phenylephrine pretreatment restored the expression of both. SIRT1 was mainly located in the cell nucleus and cytoplasm in the normal submandibular gland. Phenylephrine dramatically enhanced the expression of SIRT1, which was significantly reduced by radiation. Furthermore, phenylephrine induced a marked increase of NAMPT promoter activity. Conclusions: These findings reveal the regulatory mechanisms of NAMPT expression

  20. Nicotinamide Phosphoribosyltransferase Upregulation by Phenylephrine Reduces Radiation Injury in Submandibular Gland.

    Science.gov (United States)

    Xiang, Bin; Han, Lichi; Wang, Xinyue; Tang, Ling; Li, Kailiang; Li, Xiuxiu; Zhao, Xibo; Xia, Miaomiao; Zhou, Xixi; Zhang, Fuyin; Liu, Ke Jian

    2016-11-01

    Radiation therapy for head and neck cancer commonly leads to radiation sialadenitis. Emerging evidence has indicated that phenylephrine pretreatment reduces radiosensitivity in the salivary gland; however, the underlying cytoprotective mechanism remains unclear. Nicotinamide phosphoribosyltransferase (NAMPT) is not only a key enzyme for the nicotinamide adenine dinucleotide salvage pathway, but also a cytokine participating in cell survival, metabolism, and longevity, with a broad effect on cellular functions in physiology and pathology. However, the regulatory events of NAMPT in response to the irradiated salivary gland are unknown. The cell viability of primary cultured submandibular gland cells was determined using the PrestoBlue assay. NAMPT expression was measured using reverse transcriptase polymerase chain reaction and Western blotting in vitro and in vivo. Silent information regulator 1 (SIRT1) and phosphorylated Akt protein levels were examined by Western blotting. The cellular locations of NAMPT and SIRT1 were detected by immunohistochemistry. NAMPT promoter activity was assessed using the luciferase reporter gene assay. NAMPT was mainly distributed in the cytoplasm of granular convoluted tubule cells and ductal cells in normal submandibular glands. mRNA and protein expression of NAMPT was downregulated after radiation but upregulated with phenylephrine pretreatment both in vivo and in vitro. Moreover, the protein expression of phosphorylated Akt and SIRT1 was decreased in irradiated glands, and phenylephrine pretreatment restored the expression of both. SIRT1 was mainly located in the cell nucleus and cytoplasm in the normal submandibular gland. Phenylephrine dramatically enhanced the expression of SIRT1, which was significantly reduced by radiation. Furthermore, phenylephrine induced a marked increase of NAMPT promoter activity. These findings reveal the regulatory mechanisms of NAMPT expression, which help to understand the mechanism of the

  1. The Buttonhole Machine. Module 13.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the bottonhole machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers two topics: performing special operations on the buttonhole machine (parts and purpose) and performing special operations on the buttonhole machine (gauged buttonholes). For each topic these components are…

  2. Superconcentration and related topics

    CERN Document Server

    Chatterjee, Sourav

    2014-01-01

    A certain curious feature of random objects, introduced by the author as “super concentration,” and two related topics, “chaos” and “multiple valleys,” are highlighted in this book. Although super concentration has established itself as a recognized feature in a number of areas of probability theory in the last twenty years (under a variety of names), the author was the first to discover and explore its connections with chaos and multiple valleys. He achieves a substantial degree of simplification and clarity in the presentation of these findings by using the spectral approach. Understanding the fluctuations of random objects is one of the major goals of probability theory and a whole subfield of probability and analysis, called concentration of measure, is devoted to understanding these fluctuations. This subfield offers a range of tools for computing upper bounds on the orders of fluctuations of very complicated random variables. Usually, concentration of measure is useful when more direct prob...

  3. Topics in statistical mechanics

    International Nuclear Information System (INIS)

    Elser, V.

    1984-05-01

    This thesis deals with four independent topics in statistical mechanics: (1) the dimer problem is solved exactly for a hexagonal lattice with general boundary using a known generating function from the theory of partitions. It is shown that the leading term in the entropy depends on the shape of the boundary; (2) continuum models of percolation and self-avoiding walks are introduced with the property that their series expansions are sums over linear graphs with intrinsic combinatorial weights and explicit dimension dependence; (3) a constrained SOS model is used to describe the edge of a simple cubic crystal. Low and high temperature results are derived as well as the detailed behavior near the crystal facet; (4) the microscopic model of the lambda-transition involving atomic permutation cycles is reexamined. In particular, a new derivation of the two-component field theory model of the critical behavior is presented. Results for a lattice model originally proposed by Kikuchi are extended with a high temperature series expansion and Monte Carlo simulation. 30 references

  4. Advanced verification topics

    CERN Document Server

    Bhattacharya, Bishnupriya; Hall, Gary; Heaton, Nick; Kashai, Yaron; Khan Neyaz; Kirshenbaum, Zeev; Shneydor, Efrat

    2011-01-01

    The Accellera Universal Verification Methodology (UVM) standard is architected to scale, but verification is growing and in more than just the digital design dimension. It is growing in the SoC dimension to include low-power and mixed-signal and the system integration dimension to include multi-language support and acceleration. These items and others all contribute to the quality of the SOC so the Metric-Driven Verification (MDV) methodology is needed to unify it all into a coherent verification plan. This book is for verification engineers and managers familiar with the UVM and the benefits it brings to digital verification but who also need to tackle specialized tasks. It is also written for the SoC project manager that is tasked with building an efficient worldwide team. While the task continues to become more complex, Advanced Verification Topics describes methodologies outside of the Accellera UVM standard, but that build on it, to provide a way for SoC teams to stay productive and profitable.

  5. Topics in inflationary cosmology

    International Nuclear Information System (INIS)

    Kahn, R.N.

    1985-01-01

    This thesis examines several topics in the theory of inflationary cosmology. It first proves the existence of Hawking Radiation during the slow-rolling period of a new inflationary universe. It then derives and somewhat extends Bardeen's gauge invariant formalism for calculating the growth of linear gravitational perturbations in a Friedmann-Robertson-Walker cosmological background. This formalism is then applied, first to several new inflationary universe models all of which show a Zel'dovich spectrum of fluctuations, but with amplitude sigma(100 4 ) above observational limits. The general formalism is next applied to models that exhibit primordial inflation. Fluctuations in these models also exhibit a Zel'dovich spectrum here with an acceptable amplitude. Finally the thesis presents the results of new, numerical calculations. A classical, (2 + 1) dimensional computer model is developed that includes a Higgs field (which drives inflation) along with enough auxiliary fields to generate dynamically not only a thermal bath, but also the fluctuations that naturally accompany that bath. The thesis ends with a discussion of future prospects

  6. Discovering health topics in social media using topic models.

    Directory of Open Access Journals (Sweden)

    Michael J Paul

    Full Text Available By aggregating self-reported health statuses across millions of users, we seek to characterize the variety of health information discussed in Twitter. We describe a topic modeling framework for discovering health topics in Twitter, a social media website. This is an exploratory approach with the goal of understanding what health topics are commonly discussed in social media. This paper describes in detail a statistical topic model created for this purpose, the Ailment Topic Aspect Model (ATAM, as well as our system for filtering general Twitter data based on health keywords and supervised classification. We show how ATAM and other topic models can automatically infer health topics in 144 million Twitter messages from 2011 to 2013. ATAM discovered 13 coherent clusters of Twitter messages, some of which correlate with seasonal influenza (r = 0.689 and allergies (r = 0.810 temporal surveillance data, as well as exercise (r =  .534 and obesity (r =  -.631 related geographic survey data in the United States. These results demonstrate that it is possible to automatically discover topics that attain statistically significant correlations with ground truth data, despite using minimal human supervision and no historical data to train the model, in contrast to prior work. Additionally, these results demonstrate that a single general-purpose model can identify many different health topics in social media.

  7. Topics in Bethe Ansatz

    Science.gov (United States)

    Wang, Chunguang

    Integrable quantum spin chains have close connections to integrable quantum field. theories, modern condensed matter physics, string and Yang-Mills theories. Bethe. ansatz is one of the most important approaches for solving quantum integrable spin. chains. At the heart of the algebraic structure of integrable quantum spin chains is. the quantum Yang-Baxter equation and the boundary Yang-Baxter equation. This. thesis focuses on four topics in Bethe ansatz. The Bethe equations for the isotropic periodic spin-1/2 Heisenberg chain with N. sites have solutions containing ±i/2 that are singular: both the corresponding energy and the algebraic Bethe ansatz vector are divergent. Such solutions must be carefully regularized. We consider a regularization involving a parameter that can be. determined using a generalization of the Bethe equations. These generalized Bethe. equations provide a practical way of determining which singular solutions correspond. to eigenvectors of the model. The Bethe equations for the periodic XXX and XXZ spin chains admit singular. solutions, for which the corresponding eigenvalues and eigenvectors are ill-defined. We use a twist regularization to derive conditions for such singular solutions to bephysical, in which case they correspond to genuine eigenvalues and eigenvectors of. the Hamiltonian. We analyze the ground state of the open spin-1/2 isotropic quantum spin chain. with a non-diagonal boundary term using a recently proposed Bethe ansatz solution. As the coefficient of the non-diagonal boundary term tends to zero, the Bethe roots. split evenly into two sets: those that remain finite, and those that become infinite. We. argue that the former satisfy conventional Bethe equations, while the latter satisfy a. generalization of the Richardson-Gaudin equations. We derive an expression for the. leading correction to the boundary energy in terms of the boundary parameters. We argue that the Hamiltonians for A(2) 2n open quantum spin chains

  8. Pyridine nucleotide cycle of Salmonella typhimurium: isolation and characterization of pncA, pncB, and pncC mutants and utilization of exogenous nicotinamide adenine dinucleotide.

    Science.gov (United States)

    Foster, J W; Kinney, D M; Moat, A G

    1979-03-01

    Mutants of Salmonella typhimurium LT-2 deficient in nicotinamidase activity (pncA) or nicotinic acid phosphoribosyltransferase activity (pncB) were isolated as resistant to analogs of nicotinic acid and nicotinamide. Information obtained from interrupted mating experiments placed the pncA gene at 27 units and the pncB gene at 25 units on the S. typhimurium LT-2 linkage map. A major difference in the location of the pncA gene was found between the S. typhimurium and Escherichia coli linkage maps. The pncA gene is located in a region in which there is a major inversion of the gene order in S. typhimurium as compared to that in E. coli. Growth experiments using double mutants blocked in the de novo pathway to nicotinamide adenine dinucleotide (NAD) (nad) and in the pyridine nucleotide cycle (pnc) at either the pncA or pncB locus, or both, have provided evidence for the existence of an alternate recycling pathway in this organism. Mutants lacking this alternate cycle, pncC, have been isolated and mapped via cotransduction at 0 units. Utilization of exogenous NAD was examined through the use of [14C]carbonyl-labeled NAD and [14C]adenine-labeled NAD. The results of these experiments suggest that NAD is degraded to nicotinamide mononucleotide at the cell surface. A portion of this extracellular nicotinamide mononucleotide is then transported across the cell membrane by nicotinamide mononucleotide glycohydrolase and degraded to nicotinamide in the process. The remaining nicotinamide mononucleotide accumulates extracellularly and will support the growth of nadA pncB mutants which cannot utilize the nicotinamide resulting from the major pathway of NAD degradation. A model is presented for the utilization of exogenous NAD by S. typhimurium LT-2.

  9. Application of a new method for detecting streptococcal nicotinamide adenine dinucleotide glycohydrolase to various M types of Streptoccus pyogenes.

    Science.gov (United States)

    Lütticken, R; Lütticken, D; Johnson, D R; Wannamaker, L W

    1976-05-01

    The production of extracellular nicotinamide adenine dinucleotide glycohydrolase (NADase) by Streptococcus pyogenes can easily be demonstrated using the fluorescence of nicotinamide adenine dinucleotide in ultraviolet light occurring on addition of strong alkali. The new method described here uses microtiter plates and can be read with the naked eye. It permits the screening of large numbers of strains in a short time and with minimal amounts of reagents. The sensitivity of the new method proved to be good in comparison with the bisulfite spectrophotometric method. Culture supernatants of 177 group A streptococci were tested for NADase production by the microtiter fluorescence method. We could confirm former findings that strains within a certain M type of S. pyogenes are usually either producers or nonproducers of the enzyme. The usefulness of the test for screening of streptococcal NADase production is discussed.

  10. Design, synthesis and biological evaluation of N-(4-alkoxy-3-cyanophenyl)isonicotinamide/nicotinamide derivatives as novel xanthine oxidase inhibitors.

    Science.gov (United States)

    Zhang, Ting-Jian; Li, Song-Ye; Wang, Lin; Sun, Qi; Wu, Qing-Xia; Zhang, Yi; Meng, Fan-Hao

    2017-12-01

    A series of N-(4-alkoxy-3-cyanophenyl)isonicotinamide/nicotinamide derivatives was designed, synthesized and evaluated for inhibitory potency in vitro against xanthine oxidase. The isonicotinamide series was considerably more effective than the nicotinamide series. SARs analysis revealed that the isonicotinoyl moiety played a significant role on the inhibition and that a benzyl ether tail (e.g., ortho-cyanobenzoxy) linked to the benzonitrile moiety benefits the inhibitory potency. Among these compounds, 10q (IC 50  = 0.3 μM) was identified to be the most potent in this work and was observed to be 28.3-fold more potent than allopurinol but 20-fold less potent than topiroxostat. The Lineweaver-Burk plot showed that 10q acted as a mixed-type inhibitor on xanthine oxidase. Molecular modeling provided a reasonable explanation for the SARs observed in this study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Nicotinamide-functionalized multiwalled carbon nanotubes increase insulin production in pancreatic beta cells via MIF pathway

    Directory of Open Access Journals (Sweden)

    Ilie I

    2013-08-01

    Full Text Available Ioana Ilie,1 Razvan Ilie,2 Teodora Mocan,3 Flaviu Tabaran,4 Cornel Iancu,4 Lucian Mocan4 1Department of Endocrinology, 2Department of Microbiology, 3Department of Physiology, 4Third Surgery Clinic, Department of Nanomedicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania Abstract: Recent data in the literature support the role of nicotinamide (NA as a pharmacologic agent that stimulates pancreatic beta-cells to produce insulin in vitro. There are data showing that carbon nanotubes may be useful in initiating and maintaining cellular metabolic responses. This study shows that administration of multiwalled carbon nanotubes (MWCNTs functionalized with nicotinamide (NA-MWCNTs leads to significant insulin production compared with individual administration of NA, MWCNTs, and a control solution. Treatment of 1.4E7 cells for 30 minutes with NA-MWCNTs at concentrations ranging from 1 mg/L to 20 mg/L resulted in significantly increased insulin release (0.18 ± 0.026 ng/mL for 1 mg/L, 0.21 ± 0.024 ng/mL for 5 mg/L, and 0.27 ± 0.028 ng/mL for 20 mg/L. Thus, compared with cells treated with NA only (0.1 ± 0.01 ng/mL for 1 mg/L, 0.12 ± 0.017 ng/mL for 5 mg/L, and 0.17 ± 0.01 ng/mL for 20 mg/L we observed a significant positive effect on insulin release in cells treated with NA-MWCNTs. The results were confirmed using flow cytometry, epifluorescence microscopy combined with immunochemistry staining, and enzyme-linked immunosorbent assay techniques. In addition, using immunofluorescence microscopy techniques, we were able to demonstrate that MWCNTs enhance insulin production via the macrophage migration inhibitory factor pathway. The application and potential of NA combined with MWCNTs as an antidiabetic agent may represent the beginning of a new chapter in the nanomediated treatment of diabetes mellitus. Keywords: carbon nanotubes, NA, insulin-producing cells, insulin, macrophage migration inhibitory factor, diabetes mellitus

  12. Combination of hydrotropic nicotinamide with nanoparticles for enhancing tacrolimus percutaneous delivery

    Directory of Open Access Journals (Sweden)

    Pan W

    2016-08-01

    Full Text Available Wenhui Pan, Mengyao Qin, Guoguang Zhang, Yueming Long, Wenyi Ruan, Jingtong Pan, Zushuai Wu, Tao Wan, Chuanbin Wu, Yuehong Xu Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: Tacrolimus (FK506, an effective immunosuppressant for treating inflammatory skin diseases, hardly penetrates into and through the skin owing to its high hydrophobicity and molecular weight. The aim of this study was to develop a hybrid system based on nicotinamide (NIC and nanoparticles (NPs encapsulating FK506, such as FK506–NPs–NIC, for facilitating percutaneous delivery, which exploited virtues of both NIC and NPs to obtain the synergetic effect. Solubility and percutaneous permeation studies were carried out. The results showed that NIC could increase the solubility and permeability of FK506 and that 20% (w/v NIC presented higher FK506 permeability and was thus chosen as the hydrotropic solution to solubilize FK506 and prepare FK506–NPs–NIC. Hyaluronic acid (HA was chemically conjugated with cholesterol (Chol to obtain amphiphilic conjugate of HA–Chol, which self-assembled NPs in 20% NIC solution containing FK506. The particle size, zeta potential, and morphology of NPs were characterized. The encapsulation efficiency and in vitro percutaneous permeation of NPs were evaluated in the presence and absence of NIC. The results demonstrated that hydrotropic solubilizing FK506 was readily encapsulated into NPs with a higher encapsulation efficiency of 79.2%±4.2%, and the combination of NPs with NIC exhibited a significantly synergistic effect on FK506 deposition within the skin (2.39±0.53 µg/cm2 and penetration through the skin (13.38±2.26 µg/cm2. The effect of the combination of NPs with NIC on drug permeation was further visualized by confocal laser scanning microscope through in vivo permeation studies, and the results confirmed that NPs–NIC synergistically enhanced

  13. Topics of Evolutionary Computation 2001

    DEFF Research Database (Denmark)

    Ursem, Rasmus Kjær

    This booklet contains the student reports from the course: Topics of Evolutionary Computation, Fall 2001, given by Thiemo Krink, Rene Thomsen and Rasmus K. Ursem......This booklet contains the student reports from the course: Topics of Evolutionary Computation, Fall 2001, given by Thiemo Krink, Rene Thomsen and Rasmus K. Ursem...

  14. L-glutamine supplementation prevents the development of experimental diabetic cardiomyopathy in streptozotocin-nicotinamide induced diabetic rats.

    Directory of Open Access Journals (Sweden)

    Sachin L Badole

    Full Text Available The objective of the present investigation was to evaluate the effect of L-glutamine on cardiac myopathy in streptozotocin-nicotinamide induced diabetic rats. Diabetes was induced in overnight fasted Sprague Dawely rats by using intraperitonial injection of streptozotocin (55 mg/kg. Nicotinamide (100 mg/kg, i.p. was administered 20 min before administration of streptozotocin. Experimental rats were divided into Group I: non-diabetic control (distilled water; 10 ml/kg, p.o., II: diabetic control (distilled water, 10 ml/kg, p.o., III: L-glutamine (500 mg/kg, p.o. and IV: L-glutamine (1000 mg/kg, p.o.. All groups were diabetic except group I. The plasma glucose level, body weight, electrocardiographic abnormalities, hemodynamic changes and left ventricular contractile function, biological markers of cardiotoxicity, antioxidant markers were determined after 4 months after STZ with nicotinamide injection. Histopathological changes of heart tissue were carried out by using H and E stain. L-glutamine treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters and histological changes in STZ induced diabetic rats. Results from the present investigation demonstrated that L-glutamine has seemed a cardioprotective activity.

  15. Mitigation of gamma-radiation induced abasic sites in genomic DNA by dietary nicotinamide supplementation: Metabolic up-regulation of NAD{sup +} biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Batra, Vipen, E-mail: batravipen@gmail.com; Kislay, Binita

    2013-09-15

    Highlights: • Dietary nicotinamide increases enzyme dependent NAD{sup +} synthesis after irradiation. • Enhanced NAD{sup +} levels mitigate gamma (γ)-radiation induced abasic sites in DNA. • Dietary nicotinamide induces and prolongs expression of excision repair enzymes. • Nicotinamide reduces radiation-generated biomarker (8-oxo-dG) of DNA base damage. • Dietary nicotinamide reduces radiation inflicted DNA damage and delays apoptosis. - Abstract: The search for non-toxic radio-protective drugs has yielded many potential agents but most of these compounds have certain amount of toxicity. The objective of the present study was to investigate dietary nicotinamide enrichment dependent adaptive response to potential cytotoxic effect of {sup 60}Co γ-radiation. To elucidate the possible underlying mechanism(s), male Swiss mice were maintained on control diet (CD) and nicotinamide supplemented diet (NSD). After 6 weeks of CD and NSD dietary regimen, we exposed the animals to γ-radiation (2, 4 and 6 Gy) and investigated the profile of downstream metabolites and activities of enzymes involved in NAD{sup +} biosynthesis. Increased activities of nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase (NMNAT) were observed up to 48 h post-irradiation in NSD fed irradiated mice. Concomitant with increase in liver NAMPT and NMNAT activities, NAD{sup +} levels were replenished in NSD fed and irradiated animals. However, NAMPT and NMNAT-mediated NAD{sup +} biosynthesis and ATP levels were severely compromised in liver of CD fed irradiated mice. Another major finding of these studies revealed that under γ-radiation stress, dietary nicotinamide supplementation might induce higher and long-lasting poly(ADP)-ribose polymerase 1 (PARP1) and poly(ADP-ribose) glycohydrolase (PARG) activities in NSD fed animals compared to CD fed animals. To investigate liver DNA damage, number of apurinic/apyrimidinic sites (AP sites) and level of

  16. Topic modelling in the information warfare domain

    CSIR Research Space (South Africa)

    De Waal, A

    2013-11-01

    Full Text Available In this paper the authors provide context to Topic Modelling as an Information Warfare technique. Topic modelling is a technique that discovers latent topics in unstructured and unlabelled collection of documents. The topic structure can be searched...

  17. Diaquabis(4-bromobenzoato-κObis(nicotinamide-κN1copper(II

    Directory of Open Access Journals (Sweden)

    Hacali Necefoğlu

    2011-07-01

    Full Text Available The asymmetric unit of the title mononuclear CuII complex, [Cu(C7H4BrO22(C6H6N2O2(H2O2], contains one half-molecule, the CuII atom being located on an inversion center. The unit cell contains two nicotinamide (NA, two 4-bromobenzoate (PBB ligands and two coordinated water molecules. The four O atoms in the equatorial plane around the CuII ion form a slightly distorted square-planar arrangement, while the slightly distorted octahedral coordination is completed by the two N atoms of the NA ligands in the axial positions. The dihedral angle between the carboxylate group and the adjacent benzene ring is 22.17 (16°, while the pyridine ring and the benzene ring are oriented at a dihedral angle of 82.80 (6°. In the crystal, N—H...O, O—H...O and C—H...O hydrogen bonds link the molecules into a three-dimensional network. A weak C—H...π interaction is also observed.

  18. Synthesis of β-Nicotinamide Riboside Using an Efficient Two-Step Methodology.

    Science.gov (United States)

    Zhang, Ning; Sauve, Anthony A

    2017-12-24

    A two-step chemical method for the synthesis of β-nicotinamide riboside (NR) is described. NR has achieved wide use as an NAD + precursor (vitamin B3) and can significantly increase central metabolite NAD + concentrations in mammalian cells. β-NR can be prepared with an efficient two-step procedure. The synthesis is initiated via coupling of commercially available 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose with ethyl nicotinate in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf). 1 H NMR showed that the product was formed with complete stereoselectivity to produce only the β-isomer in high yield (>90% versus starting sugar). The clean stereochemical result suggests that the coupling proceeds via a cationic cis-1,2-acyloxonium-sugar intermediate, which controls addition by nucleophiles to generate predominantly β-stereochemistry. The subsequent deprotection of esters in methanolic ammonia generates the desired product in 85% overall yield versus sugar. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  19. Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3.

    Science.gov (United States)

    Khan, Nahid A; Auranen, Mari; Paetau, Ilse; Pirinen, Eija; Euro, Liliya; Forsström, Saara; Pasila, Lotta; Velagapudi, Vidya; Carroll, Christopher J; Auwerx, Johan; Suomalainen, Anu

    2014-06-01

    Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD(+)/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD(+) precursor, was previously shown to boost NAD(+) levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early- and late-stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD(+) levels are a promising treatment strategy for mitochondrial myopathy. © 2014 The Authors. Published under the terms of the CC BY license.

  20. Cerebral ischemia is exacerbated by extracellular nicotinamide phosphoribosyltransferase via a non-enzymatic mechanism.

    Directory of Open Access Journals (Sweden)

    Bing Zhao

    Full Text Available Intracellular nicotinamide phosphoribosyltransferase (iNAMPT in neuron has been known as a protective factor against cerebral ischemia through its enzymatic activity, but the role of central extracellular NAMPT (eNAMPT is not clear. Here we show that eNAMPT protein level was elevated in the ischemic rat brain after middle-cerebral-artery occlusion (MCAO and reperfusion, which can be traced to at least in part from blood circulation. Administration of recombinant NAMPT protein exacerbated MCAO-induced neuronal injury in rat brain, while exacerbated oxygen-glucose-deprivation (OGD induced neuronal injury only in neuron-glial mixed culture, but not in neuron culture. In the mixed culture, NAMPT protein promoted TNF-α release in a time- and concentration-dependent fashion, while TNF-α neutralizing antibody protected OGD-induced, NAMPT-enhanced neuronal injury. Importantly, H247A mutant of NAMPT with essentially no enzymatic activity exerted similar effects on ischemic neuronal injury and TNF-α release as the wild type protein. Thus, eNAMPT is an injurious and inflammatory factor in cerebral ischemia and aggravates ischemic neuronal injury by triggering TNF-α release from glia cells, via a mechanism not related to NAMPT enzymatic activity.

  1. Expression patterns of nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase in human malignant lymphomas.

    Science.gov (United States)

    Olesen, Uffe Høgh; Hastrup, Nina; Sehested, Maxwell

    2011-04-01

    The purpose of the study was to determine in human malignant lymphomas the expression patterns of nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT), the primary, rate-limiting enzymes in the synthesis of NAD+. NAMPT is a potential biomarker for sensitivity to NAMPT inhibitors and NAPRT is a biomarker for the use of nicotinic acid as a chemoprotectant in treatment with NAMPT inhibitors. The NAMPT inhibitor, APO866, is currently in clinical phase II trials in lymphomas. The expression of NAMPT and NAPRT was investigated in 53 samples of malignant lymphomas (diffuse large B-cell lymphoma, follicular B-cell lymphoma, Hodgkin's lymphoma and peripheral T-cell lymphoma). The expression of NAMPT was generally high in the more aggressive malignant lymphomas, with >80% strong expression, whereas the expression in the more indolent follicular lymphoma (FL) was significantly lower (>75% moderate or low expression, p = 0.0002). NAMPT was very highly expressed in Hodgkin Reed-Sternberg cells in Hodgkin's lymphoma. NAPRT expression was more varied (p > 0.0001) with 30-50% low expression except for Hodgkin's lymphoma where 85% displayed low expression (p = 0.0024). In conclusion, FL are a promising target for NAMPT inhibitors whereas substantial subsets of malignant lymphomas especially in Hodgkin lymphoma may be suitable for a combination treatment with nicotinic acid and NAMPT inhibitors. © 2011 The Authors. APMIS © 2011 APMIS.

  2. The Binary System of Ibuprofen-Nicotinamide Under Nanoscale Confinement: From Cocrystal to Coamorphous State.

    Science.gov (United States)

    Bi, Yanping; Xiao, Deli; Ren, Shuai; Bi, Shuyan; Wang, Jianzhu; Li, Fei

    2017-10-01

    Coamorphous systems have gained success in stabilizing amorphous drugs and improving their solubility and dissolution. Here we proposed to confine a binary mixture of drug and coformer (CF) within nanopores to obtain a nanoconfined coamorphous (NCA) system. For proving feasibility of this proposal, a poorly water-soluble drug (ibuprofen) and a frequently used pharmaceutical CF (nicotinamide) were loaded into nanopores of mesoporous silica microspheres. The solid state of NCA system was characterized by differential scanning calorimetry, X-ray powder diffraction, infrared spectrum, and solid-state nuclear magnetic resonance. With large numbers of nanopores, mesoporous silica microspheres appear to be a feasible carrier to transform a cocrystal system into coamorphism by nanoscale confinement. Benefiting from both nanoscale confinement and CF, the NCA system of ibuprofen achieved synchronic increase in dissolution properties and physical stability. Consequently, the NCA strategy is effective in achieving coamorphous state and offers a promising alternative for formulating poorly water-soluble drugs. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. Antioxidant effect of pomegranate against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Anahita Aboonabi

    2014-01-01

    Full Text Available Oxidative stress attributes a crucial role in chronic complication of diabetes. The aim of this study was to determine the most effective part of pomegranate on oxidative stress markers and antioxidant enzyme activities against streptozotocin-nicotinamide (STZ-NA-induced diabetic rats. Male Sprague-Dawley rats were randomly divided into six groups. Experimental diabetes was induced by a single intraperitoneal injection (i.p, 15 min after the i.p administration of NA. Diabetic rats showed significant increase in plasma glucose level, and the significant decrease in plasma insulin level. The activities of antioxidant enzymes such as total antioxidant status (TAS, superoxide dismutase (SOD, and catalase (CAT reduced while the levels of biomarkers of oxidative stress such as gamma-glutamyle transferase (GGT, and malondialdehyde (MDA increased in diabetic control rats as compared to normal control rats. Oral treatment with pomegranate seed-juice for 21 days demonstrated significant protective effects on all the biochemical parameters studied. Besides, biochemical findings were supported by histopathological study. These results revealed that pomegranate has potential protective effect against oxidative stress induced diabetic rats.

  4. Magnitude of malate-aspartate reduced nicotinamide adenine dinucleotide shuttle activity in intact respiring tumor cells.

    Science.gov (United States)

    Greenhouse, W V; Lehninger, A L

    1977-11-01

    Measurements of respiration, CO2 and lactate production, and changes in the levels of various key metabolites of the glycolytic sequence and tricarboxylic acid cycle were made on five lines of rodent ascites tumor cells (two strains of Ehrlich ascites tumor cells, Krebs II carcinoma, AS-30D carcinoma, and L1210 cells) incubated aerobically in the presence of uniformly labeled D-[14C]glucose. From these data, as well as earlier evidence demonstrating that the reduced nicotinamide adenine dinucleotide (NADH) shuttle in these cells requires a transaminase step and is thus identified as the malate-aspartate shuttle (W.V.V. Greenhouse and A.L. Lehninger, Cancer Res., 36: 1392-1396, 1976), metabolic flux diagrams were constructed for the five cell lines. These diagrams show the relative rates of glycolysis, the tricarboxylic acid cycle, electron transport, and the malate-aspartate shuttle in these tumors. Large amounts of cytosolic NADH were oxidized by the mitochondrial respiratory chain via the NADH shuttle, comprising anywhere from about 20 to 80% of the total flow of reducing equivalents to oxygen in these tumors. Calculations of the sources of energy for adenosine triphosphate synthesis indicated that on the average about one-third of the respiratory adenosine triphosphate is generated by electron flow originating from cytosolic NADH via the malate-aspartate shuttle.

  5. Studies of yeast cell oxygenation and energetics by laser fluorometry of reduced nicotinamide adenine dinucleotide

    Science.gov (United States)

    Pan, Fu-shih; Chen, Stephen; Mintzer, Robert A.; Chen, Chin-Tu; Schumacker, Paul

    1991-03-01

    It is of fundamental importance for biological scientists to assess cellular energetics. Under aerobic conditions, the tricarboxylic acid cycle (TCA cycle) is coupled with the mitochondrial electron cascade pathway to provide the cell with energy. The nicotinamide adenine dinucleotide-conjugated pair (NAD and NADH) is the coenzyme in numerous important biomedical reactions which include several important dehydrogenase reactions in the TCA cycle. Based on Le Chatelier's principle, NADH will accumulate when this energy production mechanism is impaired. The relative amounts of NAD and NADH in a cell are defined as the redox state of the cell (Williamson et.al. 1967) which provides a valuable index of cellular energetics. The sum of the amounts of NAD and NADH in a cell may be assumed to be constant during a finite time; therefore, a reliable means of measuring the NADH concentration would provide us with a useful indicator of tissue viability. Traditionally, the quantities of NADH and NAD may be measured by chemical assay methods. We can avoid these tediois analyses by exploiting the significant difference between the ultraviolet absorption spectra of this redox pair. However, because of the opacity of biological samples and the interference of other biochemicals that also absorb ultraviolet radiation, measurement of NADH and NAD+ concentrations in vivo by absorption spectroscopy is not feasible.

  6. The Adsorption of Calmoduline via Nicotinamide Immobilized Poly(HEMA-GMA Cryogels

    Directory of Open Access Journals (Sweden)

    Kadir Erol

    2016-12-01

    Full Text Available The separation and purification methods for the isolation of an important biomolecule calmoduline protein is extremely important. Among these methods, the adsorption technique is extremely popular, and the cryogels as adsorbents with the macro porous structure and interconnected flow channels cryogel they have are preferred in this field. In this study, the adsorption of calmoduline via Ca(II immobilized poly (2-hydroxyethyl methacrylate-glycidyl methacrylate, poly (HEMA-GMA, cryogels through changing interaction time, calmoduline initial concentration and temperature conditions. For the characterization of cryogels, the swelling test, Fourier Transform Infrared (FT-IR Spectroscopy, Scanning Electron Microscopy (SEM, surface area (BET, elemental analysis and ICP-OES methods were performed. Nicotinamide molecule was used as Ca (II chelating agent and the adsorption capacity of the cryogels was estimated as 1.812 mg calmoduline / g cryogel. The adsorption models of the adsorption reaction were examined by the Langmuir and Freundlich isotherm models and was determined to be more appropriate for Langmuir isotherm model.

  7. Association between Nicotinamide N-Methyltransferase Gene Polymorphisms and Obesity in Chinese Han Male College Students

    Directory of Open Access Journals (Sweden)

    Qiong Zhou

    2017-01-01

    Full Text Available Some reports have shown that nicotinamide N-methyltransferase (NNMT is associated with the body mass index (BMI and energy metabolism. Here we explored the association between NNMT gene polymorphisms and obesity. The subjects were recruited from male Chinese Han college student. 289 of them (19 ≤ body fat percentage (BF% were selected as the high body fat group (HBFG, 494 of them (3 ≤ BF% < 13.5 were selected as the low body fat group (LBFG, and then a case-control study (fat versus thin was carried out to explore the association between the NNMT gene polymorphism and the body composition using tagSNPs method. A tagSNP (rs10891644 in NNMT gene was found significantly associated with the body composition (P<0.0026. At this locus, the BF% for the genotype GT, TT, and GG were 14.56±8.35, 13.47±8.11, and 12.42±7.50, respectively, and the differences between the GT and the GG + TT were highly significant (P<0.01; the ORadjusted value of the GT versus (GG + TT was 1.716 (Padjusted=0.002, 95% CI = 1.240–2.235. Therefore, the variation of the tagSNP, rs10891644, is significantly associated with obesity and the GT carriers are the susceptible population.

  8. Target enzyme mutations are the molecular basis for resistance towards pharmacological inhibition of nicotinamide phosphoribosyltransferase

    Directory of Open Access Journals (Sweden)

    Christensen Mette K

    2010-12-01

    Full Text Available Abstract Background Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT are promising cancer drugs currently in clinical trials in oncology, including APO866, CHS-828 and the CHS-828 prodrug EB1627/GMX1777, but cancer cell resistance to these drugs has not been studied in detail. Methods Here, we introduce an analogue of CHS-828 called TP201565 with increased potency in cellular assays. Further, we describe and characterize a panel of cell lines with acquired stable resistance towards several NAMPT inhibitors of 18 to 20,000 fold compared to their parental cell lines. Results We find that 4 out of 5 of the resistant sublines display mutations of NAMPT located in the vicinity of the active site or in the dimer interface of NAMPT. Furthermore, we show that these mutations are responsible for the resistance observed. All the resistant cell lines formed xenograft tumours in vivo. Also, we confirm CHS-828 and TP201565 as competitive inhibitors of NAMPT through docking studies and by NAMPT precipitation from cellular lysate by an analogue of TP201565 linked to sepharose. The NAMPT precipitation could be inhibited by addition of APO866. Conclusion We found that CHS-828 and TP201565 are competitive inhibitors of NAMPT and that acquired resistance towards NAMPT inhibitors can be expected primarily to be caused by mutations in NAMPT.

  9. Experimental and Computational Studies on Non-Covalent Imprinted Microspheres as Recognition System for Nicotinamide Molecules

    Directory of Open Access Journals (Sweden)

    Giuseppe Vasapollo

    2009-07-01

    Full Text Available Molecularly imprinted microspheres obtained by precipitation polymerization using nicotinamide (nia as template have been prepared and characterised by SEM. How various experimental parameters can affect microsphere morphology, reaction yield and re-binding capacity have been evaluated. Pre-polymerization interactions between template and functional monomer in chloroform and MeCN have been studied by 1H-NMR. The results suggest that the interaction between nia and methacrylic acid (MAA is mainly based on hydrogen-bonding between amide protons and MAA. Computational density functional theory (DFT studies on MAA-nia complexes have been also performed to better understand hydrogen-bonding interactions. The imprinted activity of the microspheres, synthesized in chloroform or acetonitrile (MeCN, has been evaluated by spectrophotometric analysis of nia solutions when chloroform or MeCN are used as incubation solvents. The results suggest that MeCN interferes with hydrogen bonding between template and MAA during either the polymerization step or re-binding process as also observed from theoretical results. Finally, the selectivity towards selected nia analogues has been also confirmed.

  10. Mental Mechanisms for Topics Identification

    Directory of Open Access Journals (Sweden)

    Louis Massey

    2014-01-01

    Full Text Available Topics identification (TI is the process that consists in determining the main themes present in natural language documents. The current TI modeling paradigm aims at acquiring semantic information from statistic properties of large text datasets. We investigate the mental mechanisms responsible for the identification of topics in a single document given existing knowledge. Our main hypothesis is that topics are the result of accumulated neural activation of loosely organized information stored in long-term memory (LTM. We experimentally tested our hypothesis with a computational model that simulates LTM activation. The model assumes activation decay as an unavoidable phenomenon originating from the bioelectric nature of neural systems. Since decay should negatively affect the quality of topics, the model predicts the presence of short-term memory (STM to keep the focus of attention on a few words, with the expected outcome of restoring quality to a baseline level. Our experiments measured topics quality of over 300 documents with various decay rates and STM capacity. Our results showed that accumulated activation of loosely organized information was an effective mental computational commodity to identify topics. It was furthermore confirmed that rapid decay is detrimental to topics quality but that limited capacity STM restores quality to a baseline level, even exceeding it slightly.

  11. A Study of Topic and Topic Change in Conversational Threads

    Science.gov (United States)

    2009-09-01

    ture or content of a relationship changes. The ability to detect topic change would support investigations of sexual predators, where a conversation...often starts out platonic and then turns sexual [21], as well as investigations into the techniques of recruitment for criminal or religious activity. If...conditions such as Autism or Attention Deficit Disorder be detected via long term studies of topics in individuals’ personal communications? 62 CHAPTER 6

  12. Topical steroid-damaged skin

    Directory of Open Access Journals (Sweden)

    Anil Abraham

    2014-01-01

    Full Text Available Topical steroids, commonly used for a wide range of skin disorders, are associated with side effects both systemic and cutaneous. This article aims at bringing awareness among practitioners, about the cutaneous side effects of easily available, over the counter, topical steroids. This makes it important for us as dermatologists to weigh the usefulness of topical steroids versus their side effects, and to make an informed decision regarding their use in each individual based on other factors such as age, site involved and type of skin disorder.

  13. Topics in lightwave transmission systems

    CERN Document Server

    Li, Tingye

    1991-01-01

    Topics in Lightwave Transmission Systems is a second volume of a treatise on optical fiber communications that is devoted to the science, engineering, and application of information transmission via optical fibers. The first volume, published in 1985, dealt exclusively with fiber fabrication. The present volume contains topics that pertain to subsystems and systems. The book contains five chapters and begins with discussions of transmitters and receivers, which are basic to systems now operating in the field. Subsequent chapters cover topics relating to coherent systems: frequency and phase m

  14. Does topical voriconazole trigger dysplastic changes on the ocular surface?

    Science.gov (United States)

    Palamar, Melis; Egrilmez, Sait; Yilmaz, Suzan Guven; Polat, Suleyha Hilmioglu; Gunduz, Omur Ucakhan

    2015-02-01

    Systemic voriconazole treatment was reported to cause photosensitivity and related cutaneous malignancies. The aim of this report is to demonstrate a graft-related Candida endophthalmitis case that developed ocular surface dysplastic changes after receiving topical 1% voriconazole treatment. Full ocular examination, photography, and in vivo confocal microscopy examination (Rostock Cornea Module/HRT II, Heidelberg, Germany) were performed. A 73-year-old male with graft-related Candida endophthalmitis that was on topical 1% voriconazole for 4 months developed a whitish gelatinous lesion on the cornea originating from the nasal limbus. In vivo confocal microscopy examination revealed mild dysplastic changes in the cornea epithelium. Topical voriconazole might trigger neoplastic changes on the ocular surface as reported with systemic use in other sun-exposed parts of the body. Further studies are needed to relate topical use of voriconazole with ocular surface dysplasia.

  15. Inhibition of Nicotinamide Phosphoribosyltransferase (NAMPT) Activity by Small Molecule GMX1778 Regulates Reactive Oxygen Species (ROS)-mediated Cytotoxicity in a p53- and Nicotinic Acid Phosphoribosyltransferase1 (NAPRT1)-dependent Manner*

    Science.gov (United States)

    Cerna, David; Li, Hongyun; Flaherty, Siobhan; Takebe, Naoko; Coleman, C. Norman; Yoo, Stephen S.

    2012-01-01

    Cancer cells undergo mitosis more frequently than normal cells and thus have increased metabolic needs, which in turn lead to higher than normal reactive oxygen species (ROS) production. Higher ROS production increases cancer cell dependence on ROS scavenging systems to balance the increased ROS. Selectively modulating intracellular ROS in cancers by exploiting cancer dependence on ROS scavenging systems provides a useful therapeutic approach. Essential to developing these therapeutic strategies is to maintain physiologically low ROS levels in normal tissues while inducing ROS in cancer cells. GMX1778 is a specific inhibitor of nicotinamide phosphoribosyltransferase, a rate-limiting enzyme required for the regeneration of NAD+ from nicotinamide. We show that GMX1778 increases intracellular ROS in cancer cells by elevating the superoxide level while decreasing the intracellular NAD+ level. Notably, GMX1778 treatment does not induce ROS in normal cells. GMX1778-induced ROS can be diminished by adding nicotinic acid (NA) in a NA phosphoribosyltransferase 1 (NAPRT1)-dependent manner, but NAPRT1 is lost in a high frequency of glioblastomas, neuroblastomas, and sarcomas. In NAPRT1-deficient cancer cells, ROS induced by GMX1778 was not susceptible to treatment with NA. GMX1778-mediated ROS induction is p53-dependent, suggesting that the status of both p53 and NAPRT1 might affect tumor apoptosis, as determined by annexin-V staining. However, as determined by colony formation, GMX1778 long term cytotoxicity in cancer cells was only prevented by the addition of NA to NAPRT1-expressing cells. Exposure to GMX1778 may be a novel way of inducing ROS selectively in NAPRT1-negative tumors without inducing cytotoxic ROS in normal tissue. PMID:22570471

  16. Perinatal asphyxia leads to PARP-1 overactivity, p65 translocation, IL-1β and TNF-α overexpression, and apoptotic-like cell death in mesencephalon of neonatal rats: prevention by systemic neonatal nicotinamide administration.

    Science.gov (United States)

    Neira-Peña, T; Rojas-Mancilla, E; Munoz-Vio, V; Perez, R; Gutierrez-Hernandez, M; Bustamante, D; Morales, P; Hermoso, M A; Gebicke-Haerter, P; Herrera-Marschitz, M

    2015-05-01

    Perinatal asphyxia (PA) is a leading cause of neuronal damage in newborns, resulting in long-term neurological and cognitive deficits, in part due to impairment of mesostriatal and mesolimbic neurocircuitries. The insult can be as severe as to menace the integrity of the genome, triggering the overactivation of sentinel proteins, including poly (ADP-ribose) polymerase-1 (PARP-1). PARP-1 overactivation implies increased energy demands, worsening the metabolic failure and depleting further NAD(+) availability. Using a global PA rat model, we report here evidence that hypoxia increases PARP-1 activity, triggering a signalling cascade leading to nuclear translocation of the NF-κB subunit p65, modulating the expression of IL-1β and TNF-α, pro-inflammatory molecules, increasing apoptotic-like cell death in mesencephalon of neonate rats, monitored with Western blots, qPCR, TUNEL and ELISA. PARP-1 activity increased immediately after PA, reaching a maximum 1-8 h after the insult, while activation of the NF-κB signalling pathway was observed 8 h after the insult, with a >twofold increase of p65 nuclear translocation. IL-1β and TNF-α mRNA levels were increased 24 h after the insult, together with a >twofold increase in apoptotic-like cell death. A single dose of the PARP-1 inhibitor nicotinamide (0.8 mmol/kg, i.p.), 1 h post delivery, prevented the effect of PA on PARP-1 activity, p65 translocation, pro-inflammatory cytokine expression and apoptotic-like cell death. The present study demonstrates that PA leads to PARP-1 overactivation, increasing the expression of pro-inflammatory cytokines and cell death in mesencephalon, effects prevented by systemic neonatal nicotinamide administration, supporting the idea that PARP-1 inhibition represents a therapeutic target against the effects of PA.

  17. Topic structure for information retrieval

    NARCIS (Netherlands)

    He, J.; Sanderson, M.; Zhai, C.; Zobel, J.; Allan, J.; Aslam, J.A.

    2009-01-01

    In my research, I propose a coherence measure, with the goal of discovering and using topic structures within and between documents, of which I explore its extensions and applications in information retrieval.

  18. Selected topics in nuclear structure

    International Nuclear Information System (INIS)

    1994-01-01

    The collection of abstracts on selected topics in nuclear structure are given. Special attention pays to collective excitations and high-spin states of nuclei, giant resonance structure, nuclear reaction mechanisms and so on

  19. Conversational topics in transsexual persons.

    Science.gov (United States)

    Van Borsel, John; Cayzeele, Miet; Heirman, Eva; T'sjoen, Guy

    2014-06-01

    Abstract In general, speech language therapy for transsexual persons focuses on pitch and pitch variation and more recently also on resonance. Other communicative aspects are dealt with far less often, especially language. This study investigated to what extent conversational topics might need attention in therapy for transsexual persons. A total of 111 males, 116 females, 28 male-to-female and 18 female-to-male transsexuals were asked to indicate on a list with 34 topics how often they speak about each topic (never, sometimes, often) in conversations with males, with females and in a gender mixed group. Results showed that transsexual persons behave in accordance with the desired gender. However, they also tend to adopt a position depending on the gender of their conversational partner. It can be concluded that in general it is not necessary to pay attention to conversational topics in therapy for transsexual persons.

  20. Special topics in spectral distributions

    International Nuclear Information System (INIS)

    French, J.B.

    1980-01-01

    We discuss two problems which relate to the foundations of the subject, and a third about asymptotic properties of spectral distributions. We give also a brief list of topics which should be further explored

  1. Topics of Bioengineering in Wikipedia

    Directory of Open Access Journals (Sweden)

    Vassia Atanassova

    2009-10-01

    Full Text Available The present report aims to give a snapshot of how topics from the field of bioengineering (bioinformatics, bioprocess systems, biomedical engineering, biotechnology, etc. are currently covered in the free electronic encyclopedia Wikipedia. It also offers insights and information about what Wikipedia is, how it functions, how and when to cite Wikipedian articles, if necessary. Several external wikis, devoted to topics of bioengineering, are also listed and reviewed.

  2. Key Topics in Sports Medicine

    OpenAIRE

    2006-01-01

    Key Topics in Sports Medicine is a single quick reference source for sports and exercise medicine. It presents the essential information from across relevant topic areas, and includes both the core and emerging issues in this rapidly developing field. It covers: 1) Sports injuries, rehabilitation and injury prevention, 2) Exercise physiology, fitness testing and training, 3) Drugs in sport, 4) Exercise and health promotion, 5) Sport and exercise for special and clinical populations, 6) The ps...

  3. Topics in modern differential geometry

    CERN Document Server

    Verstraelen, Leopold

    2017-01-01

    A variety of introductory articles is provided on a wide range of topics, including variational problems on curves and surfaces with anisotropic curvature. Experts in the fields of Riemannian, Lorentzian and contact geometry present state-of-the-art reviews of their topics. The contributions are written on a graduate level and contain extended bibliographies. The ten chapters are the result of various doctoral courses which were held in 2009 and 2010 at universities in Leuven, Serbia, Romania and Spain.

  4. TopicPanorama: A Full Picture of Relevant Topics.

    Science.gov (United States)

    Wang, Xiting; Liu, Shixia; Liu, Junlin; Chen, Jianfei; Zhu, Jun; Guo, Baining

    2016-12-01

    This paper presents a visual analytics approach to analyzing a full picture of relevant topics discussed in multiple sources, such as news, blogs, or micro-blogs. The full picture consists of a number of common topics covered by multiple sources, as well as distinctive topics from each source. Our approach models each textual corpus as a topic graph. These graphs are then matched using a consistent graph matching method. Next, we develop a level-of-detail (LOD) visualization that balances both readability and stability. Accordingly, the resulting visualization enhances the ability of users to understand and analyze the matched graph from multiple perspectives. By incorporating metric learning and feature selection into the graph matching algorithm, we allow users to interactively modify the graph matching result based on their information needs. We have applied our approach to various types of data, including news articles, tweets, and blog data. Quantitative evaluation and real-world case studies demonstrate the promise of our approach, especially in support of examining a topic-graph-based full picture at different levels of detail.

  5. Stimulation of the Fibrillar Collagen and Heat Shock Proteins by Nicotinamide or Its Derivatives in Non-Irradiated or UVA Radiated Fibroblasts, and Direct Anti-Oxidant Activity of Nicotinamide Derivatives

    Directory of Open Access Journals (Sweden)

    Neena Philips

    2015-05-01

    Full Text Available In skin aging, from intrinsic factors or exposure to ultraviolet (UV radiation, there is loss of structural fibrillar collagen and regulatory heat shock proteins. Phenolic compounds, with hydroxyl groups attached to an aromatic ring, have antioxidative and anti-inflammatory properties. Nicotinamide is an amide derivative of niacin or vitamin B3, with an amide linked to an aromatic ring, with UV absorptive, antioxidant, anti-inflammatory and anti-cell death/apoptosis properties. The goal of this research was to investigate the anti-skin aging mechanism of nicotinamide and its derivatives, 2,6-dihydroxynicotinamide, 2,4,5,6-tetrahydroxynicotinamide, and 3-hydroxypicolinamide (collectively niacin derivatives, through the stimulation of fibrillar collagens (type I, III and V, at protein and/or promoter levels and the expression of heat shock proteins (HSP-27, 47, 70, and 90 in non-irradiated or UVA radiated dermal fibroblasts; and from its direct antioxidant activity. UVA radiation inhibited the expression of types I and III collagen, and HSP-47 in dermal fibroblasts. The niacin derivatives significantly and similarly stimulated the expression of types I (transcriptionally, III and V collagens in non-irradiated, and UVA radiated fibroblasts indicating predominant effects. The 2,6-dihydroxynicotinamide had greater stimulatory effect on types I and III collagen in the non-irradiated, and UVA radiated fibroblasts, as well as greater direct antioxidant activity than the other niacin derivatives. The niacin derivatives, with a few exceptions, stimulated the expression of HSP-27, 47, 70 and 90 in non-irradiated, and UVA radiated fibroblasts. However, they had varied effects on the expression of the different HSPs in non-irradiated, and UVA radiated fibroblasts indicating non-predominant, albeit stimulatory, effect. Overall, nicotinamide and its derivatives have anti skin aging potential through the stimulation of fibrillar collagen and HSPs.

  6. Training Module on the Evaluation of Best Modeling Practices

    Science.gov (United States)

    Building upon the fundamental concepts outlined in previous modules, the objectives of this module are to explore the topic of model evaluation and identify the 'best modeling practices' and strategies for the Evaluation Stage of the model life-cycle.

  7. Isolation and characterization of Avibacterium paragallinarum with different nicotinamide adenine dinucleotide requirements.

    Science.gov (United States)

    Jeong, Ok-Mi; Kang, Min-Su; Jeon, Byung-Woo; Choi, Byung-Kook; Kwon, Yong-Kuk; Yoon, So-Youn; Blackall, Patrick J; Lee, Hee-Soo; Jung, Suk-Chan; Kim, Jae-Hong

    2017-06-01

    Twenty field isolates of Avibacterium paragallinarum were obtained from chickens in South Korea during 2011-2015. The isolates were identified by a HPG-2 PCR assay specific for A. paragallinarum and by biochemical tests. Growth requirements, Page serovars, carbohydrate fermentation patterns, and antimicrobial susceptibility were also examined. Most isolates (16/20) showed the typical requirement for nicotinamide adenine dinucleotide (NAD) and an enriched CO 2 atmosphere for growth. One isolate needed increased levels of NAD and serum for good growth. Three isolates showed NAD-independent growth on blood agar under aerobic conditions. In terms of carbohydrate fermentation patterns, three biochemical biovars were recognized; these varied with respect to acid production from maltose and D-xylose. The 16 typical NAD-dependent isolates were serovar A while the variants, both NAD-independent isolates and the isolate with increased NAD dependency were non-typeable. All isolates were sensitive to amoxicillin-clavulanic acid, ceftiofur, gentamicin, and spectinomycin. High rates of resistance, including intermediate resistance, to lincomycin (100%), cloxacillin (75%), and erythromycin (70%) were observed. The four variant strains (the three NAD-independent isolates and the isolate showing unusual growth requirements) were more resistant to antibiotics than the typical NAD-dependent strains. The finding of NAD-independent forms of A. paragallinarum extends the known distribution of this form, previously only reported in South Africa, Mexico and Peru. There is clearly a need for increased caution in the diagnosis and, possibly, the control of infectious coryza. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Lack of nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2): consequences for mouse bladder development and function.

    Science.gov (United States)

    Hicks, Amy N; Campeau, Lysanne; Burmeister, David; Bishop, Colin E; Andersson, Karl-Erik

    2013-11-01

    To describe the morphological and functional consequences for bladder development and function when nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2) is lacking or reduced. The Bloated Bladder (Blad) mouse, lacking Nmnat2, and heterozygotes were utilized for this investigation. Morphology and development of the bladder were studied using immunohistochemistry against urothelial, smooth muscle, and nerve markers. Functional effects were assessed by organ bath experiments and cystometry. Homozygote mutants were malformed and died at birth, whereas heterozygotes survived and morphologically did not differ from wild-type controls. Morphological bladder changes appeared in the Blad mutants as early as embryonic day 15.5 (E15.5) with an extremely distended bladder at E18.5. Staining revealed that all the bladder layers were present and expressed mature markers in all three genotypes. No nerves could be demonstrated by immunohistochemistry in the Blad mutant bladder at E18.5. Organ bath analysis showed that bladders from Blad mutant showed signs of denervation supersensitivity in response to carbachol, and no response to electrical stimulation of nerves at E18.5. Adult heterozygotes, which have a reduced expression of Nmnat2 at E18.5, showed decreased responses to carbachol and electrical stimulation compared to wild-type controls. The latter also retained their ability to empty their bladders, but showed increased micturition pressures compared to controls. Complete loss of Nmnat2 leads to a mature but distended bladder in utero and is not compatible with survival. Moderate loss of Nmnat2 has no effect on bladder development, survival, and has only modest effects on bladder function later in life. © 2013 Wiley Periodicals, Inc.

  9. Salt Specificity of a Reduced Nicotinamide Adenine Dinucleotide Oxidase Prepared from a Halophilic Bacterium1

    Science.gov (United States)

    Hochstein, L. I.; Dalton, B. P.

    1968-01-01

    Extracts prepared from a halophilic bacterium contained a reduced nicotinamide adenine dinucleotide (NADH2) oxidase active at high solute concentrations. The cation requirement was nonspecific, since KCl, RbCl, and CsCl replaced NaCl with little or no loss of activity, and NH4Cl was only partially effective. Only LiCl failed to replace NaCl. No specific chloride requirement was observed although not all anions replaced chloride. Bromide, nitrate, and iodide were essentially ineffective, whereas acetate, formate, citrate, and sulfate proved suitable. The presence of sulfate affected the ability of a cation to satisfy the solute requirement. Sulfate enhanced the rate of NADH2 oxidation when compared with the rate observed in the presence of chloride. Cations which were inactive as chlorides (LiCl and MgCl2 at high concentrations) satisfied the cation requirement when added as sulfate salts. Although magnesium satisfied the cation requirement, a concentration effect, as well as an anion effect, was observed. In the presence of MgCl2, little NADH2 oxidation was observed at concentrations greater than 1 m. At lower concentrations, the rate of oxidation increased, reaching a maximal value at 0.1 m and remaining constant up to a concentration of 0.05 m MgCl2. Magnesium acetate and MgSO4 also replaced NaCl, and the maximal rate of oxidation occurred at 0.05 m with respect to magnesium. There was no change in the rate of oxidation at high magnesium acetate concentrations, whereas the rate of NADH2 oxidation increased at higher concentrations of MgSO4. PMID:5636829

  10. Nicotinamide phosphoribosyltransferase inhibition reduces intraplaque CXCL1 production and associated neutrophil infiltration in atherosclerotic mice.

    Science.gov (United States)

    Nencioni, Alessio; da Silva, Rafaela F; Fraga-Silva, Rodrigo A; Steffens, Sabine; Fabre, Mathias; Bauer, Inga; Caffa, Irene; Magnone, Mirko; Sociali, Giovanna; Quercioli, Alessandra; Pelli, Graziano; Lenglet, Sébastien; Galan, Katia; Burger, Fabienne; Vázquez Calvo, Sara; Bertolotto, Maria; Bruzzone, Santina; Ballestrero, Alberto; Patrone, Franco; Dallegri, Franco; Santos, Robson A; Stergiopulos, Nikolaos; Mach, François; Vuilleumier, Nicolas; Montecucco, Fabrizio

    2014-02-01

    Pharmacological treatments targeting CXC chemokines and the associated neutrophil activation and recruitment into atherosclerotic plaques hold promise for treating cardiovascular disorders. Therefore, we investigated whether FK866, a nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with anti-inflammatory properties that we recently found to reduce neutrophil recruitment into the ischaemic myocardium, would exert beneficial effects in a mouse atherosclerosis model. Atherosclerotic plaque formation was induced by carotid cast implantation in ApoE-/- mice that were fed with a Western-type diet. FK866 or vehicle were administrated intraperitoneally from week 8 until week 11 of the diet. Treatment with FK866 reduced neutrophil infiltration and MMP-9 content and increased collagen levels in atherosclerotic plaques compared to vehicle. No effect on other histological parameters, including intraplaque lipids or macrophages, was observed. These findings were associated with a reduction in both systemic and intraplaque CXCL1 levels in FK866-treated mice. In vitro, FK866 did not affect MMP-9 release by neutrophils, but it strongly reduced CXCL1 production by endothelial cells which, in the in vivo model, were identified as a main CXCL1 source at the plaque level. CXCL1 synthesis inhibition by FK866 appears to reflect interference with nuclear factor-κB signalling as shown by reduced p65 nuclear levels in endothelial cells pre-treated with FK866. In conclusion, pharmacological inhibition of NAMPT activity mitigates inflammation in atherosclerotic plaques by reducing CXCL1-mediated activities on neutrophils. These results support further assessments of NAMPT inhibitors for the potential prevention of plaque vulnerability.

  11. Enhancement of in vivo Radiosensitization by Combination with Pentoxifylline and Nicotinamide

    International Nuclear Information System (INIS)

    Lee, In Tae; Cho, Moon June

    1991-01-01

    Pentoxifylline (PENTO) has been known to improve RBC fluidity, and thus improve the flux of RBC through narrow capillaries. Additionally, PENTO also decreases the O2 release from RBC. Nicotinamide (N4) has been reported to decrease the number of acutely hypoxic cells in tumors by temporarily increasing tumor blood flow. Therefore, the purpose of this study was to examine whether the combination of PENTO and NA (PENTO+NA) would reduce the radioresistance of the the FSa II murine fibrosarcoma by oxygenation the hypoxic cells. We observed a significantly enhanced radiation-induced growth delay of the FSa II tumors by PENTO-NA. Thus the enhancement ration was between 2.5 and 2.8 in growth delay assay. The TCD 50 of control tumors was about 57 Gy, but that of PENTO-NA treated tumors was about 32 Gy. The TCD50 was modified by a factor of 1.8. We also observed that PENTO+NA, changes in tumor blood flow and intratumor pO2 were measured using laser Doppler flowmetry and O2 microelectrode methods. The tumor blood flow significantly increased at 10 min. after injection of PENTO+NA. Furthermore, we also found that PENTO+NA significantly increased intratumor pO2 from 8 to 19 mmHg. We concluded that PENTO+NA was far more effective than NA alone or PENTO alone. The increase in the response of tumor in vivo to X-irradiation appeared to be due mainly to an increase in the tumor oxygenation. Further studies using various concentrations of PENTO alone and in combination with NA to obtain better sequencing and maximal radiosensitization are warranted

  12. "The Strawberry Caper": Using Scenario-Based Problem Solving to Integrate Middle School Science Topics

    Science.gov (United States)

    Gonda, Rebecca L.; DeHart, Kyle; Ashman, Tia-Lynn; Legg, Alison Slinskey

    2015-01-01

    Achieving a deep understanding of the many topics covered in middle school biology classes is difficult for many students. One way to help students learn these topics is through scenario-based learning, which enhances students' performance. The scenario-based problem-solving module presented here, "The Strawberry Caper," not only…

  13. Eugenosedin-A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Kuo-Ping Shen

    2018-03-01

    Full Text Available This study examined the effects of eugenosedin-A (Eu-A in a streptozotocin (STZ/nicotinamide-induced rat model of type II diabetes mellitus (T2DM. Six-week-old Sprague–Dawley rats were randomly divided into three groups: (1 RD group, normal rats fed a regular diet (RD, (2 DM group, T2DM rats fed a high-fat diet, and (3 Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day. After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK in liver and skeletal muscle and decreased protein expression of insulin receptor (IR, insulin receptor substrate-1 (IRS-1, IRS-2, AMP-activated protein kinase (AMPK, glucose transporter-4 (GLUT-4, glucokinase (GCK, and peroxisome proliferator-activated receptor γ (PPAR-γ. STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.

  14. Auxotrophic Actinobacillus pleurpneumoniae grows in multispecies biofilms without the need for nicotinamide-adenine dinucleotide (NAD) supplementation.

    Science.gov (United States)

    Loera-Muro, Abraham; Jacques, Mario; Avelar-González, Francisco J; Labrie, Josée; Tremblay, Yannick D N; Oropeza-Navarro, Ricardo; Guerrero-Barrera, Alma L

    2016-06-27

    Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, which causes important worldwide economic losses in the swine industry. Several respiratory tract infections are associated with biofilm formation, and A. pleuropneumoniae has the ability to form biofilms in vitro. Biofilms are structured communities of bacterial cells enclosed in a self-produced polymer matrix that are attached to an abiotic or biotic surface. Virtually all bacteria can grow as a biofilm, and multi-species biofilms are the most common form of microbial growth in nature. The goal of this study was to determine the ability of A. pleuropneumoniae to form multi-species biofilms with other bacteria frequently founded in pig farms, in the absence of pyridine compounds (nicotinamide mononucleotide [NMN], nicotinamide riboside [NR] or nicotinamide adenine dinucleotide [NAD]) that are essential for the growth of A. pleuropneumoniae. For the biofilm assay, strain 719, a field isolate of A. pleuropneumoniae serovar 1, was mixed with swine isolates of Streptococcus suis, Bordetella bronchiseptica, Pasteurella multocida, Staphylococcus aureus or Escherichia coli, and deposited in 96-well microtiter plates. Based on the CFU results, A. pleuropneumoniae was able to grow with every species tested in the absence of pyridine compounds in the culture media. Interestingly, A. pleuropneumoniae was also able to form strong biofilms when mixed with S. suis, B. bronchiseptica or S. aureus. In the presence of E. coli, A. pleuropneumoniae only formed a weak biofilm. The live and dead populations, and the matrix composition of multi-species biofilms were also characterized using fluorescent markers and enzyme treatments. The results indicated that poly-N-acetyl-glucosamine remains the primary component responsible for the biofilm structure. In conclusion, A. pleuropneumoniae apparently is able to satisfy the requirement of pyridine compounds through of other swine pathogens by

  15. Topical application of hemostatic paste

    Directory of Open Access Journals (Sweden)

    Mohammad Mizanur Rahman

    2017-02-01

    Full Text Available As a measure to control minor surgical bleeding, surgeons usually depend on a number of hemostatic aids. Topical use of bovine thrombin is a widely used procedure to arrest such minor bleeding. A 35 year old male sergeant of Bangladesh Air Force presented with repeated development of hematoma in his left thigh without any history of trauma or previous history of bleeding. Critical analysis of the patient’s history, routine and sophisticated hematological investigations revealed that the patient developed anti-thrombin antibody following the application of hemostatic paste in the tooth socket five years back during minor dental procedure to stop ignorable bleeding episodes. Therefore, topical use of hemostatic glue/paste or bovine thrombin should be avoided to desist minor bleeding as recombinant human thrombin is now available for topical use.

  16. Quantum mechanics II advanced topics

    CERN Document Server

    Rajasekar, S

    2015-01-01

    Quantum Mechanics II: Advanced Topics uses more than a decade of research and the authors’ own teaching experience to expound on some of the more advanced topics and current research in quantum mechanics. A follow-up to the authors introductory book Quantum Mechanics I: The Fundamentals, this book begins with a chapter on quantum field theory, and goes on to present basic principles, key features, and applications. It outlines recent quantum technologies and phenomena, and introduces growing topics of interest in quantum mechanics. The authors describe promising applications that include ghost imaging, detection of weak amplitude objects, entangled two-photon microscopy, detection of small displacements, lithography, metrology, and teleportation of optical images. They also present worked-out examples and provide numerous problems at the end of each chapter.

  17. Red algae (Gelidium amansii) reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide

    OpenAIRE

    Tsung-Han Yang; Hsien-Tsung Yao; Meng-Tsan Chiang

    2015-01-01

    Gelidium amansii (GA) is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1) rats without diabetes fed a high-fat diet (control group); (2) rats with diabetes fed a high-fat diet; (3) rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4) rats with...

  18. Identification of malic enzyme mutants depending on 1,2,3-triazole moiety-containing nicotinamide adenine dinucleotide analogs.

    Science.gov (United States)

    Hou, Shuhua; Ji, Debin; Liu, Wujun; Wang, Lei; Zhao, Zongbao Kent

    2014-03-01

    An activity screening between 1,2,3-triazole moiety-containing nicotinamide adenine dinucleotide (NAD) analogs and malic enzyme (ME) mutants identified some mutants capable of taking NAD analogs as the cofactor. One particular pair, ME-L310K/L404S and the analog B-8 had good catalytic efficiency and cofactor specificity. The new system gained about 1200-fold cofactor specificity shift from NAD toward B-8 in terms of oxidative decarboxylation of l-malate. Our results provided insightful information for the development of orthogonal redox system that is of particular important to precisely control engineered metabolic pathways. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Topics in millimeter wave technology

    CERN Document Server

    Button, Kenneth

    1988-01-01

    Topics in Millimeter Wave Technology, Volume 1 presents topics related to millimeter wave technology, including fin-lines and passive components realized in fin-lines, suspended striplines, suspended substrate microstrips, and modal power exchange in multimode fibers. A miniaturized monopulse assembly constructed in planar waveguide with multimode scalar horn feeds is also described. This volume is comprised of five chapters; the first of which deals with the analysis and synthesis techniques for fin-lines as well as the various passive components realized in fin-line. Tapers, discontinuities,

  20. Topics in current aerosol research

    CERN Document Server

    Hidy, G M

    1971-01-01

    Topics in Current Aerosol Research deals with the fundamental aspects of aerosol science, with emphasis on experiment and theory describing highly dispersed aerosols (HDAs) as well as the dynamics of charged suspensions. Topics covered range from the basic properties of HDAs to their formation and methods of generation; sources of electric charges; interactions between fluid and aerosol particles; and one-dimensional motion of charged cloud of particles. This volume is comprised of 13 chapters and begins with an introduction to the basic properties of HDAs, followed by a discussion on the form

  1. Topical therapies in hyperhidrosis care.

    Science.gov (United States)

    Pariser, David M; Ballard, Angela

    2014-10-01

    Primary focal hyperhidrosis affects 3% of the US population; about the same number as psoriasis. More than half of these patients have primary focal axillary hyperhidrosis: sweating that is beyond what is anticipated or necessary for thermoregulation. Most topical therapies are based on aluminum salts, which work by a chemical reaction that forms plugs in the eccrine sweat ducts. Topical anticholinergics may also be used. Instruction on proper methods and timing of antiperspirants enhances effect and may be effective alone or in combination with other treatments in patients with hyperhidrosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Selected topics in nuclear structure

    International Nuclear Information System (INIS)

    Solov'ev, V.G.; Gromov, K.Ya.; Malov, L.A.; Shilov, V.M.

    1994-01-01

    The Fourth International Conference on selected topics in nuclear structure was held at Dubna in July 1994 on recent experimental and theoretical investigations in nuclear structure. Topics discussed were the following: nuclear structure at low-energy excitations (collective quasiparticle phenomena, proton-neutron interactions, microscopic and phenomenological theories of nuclear structure; nuclear structure studies with charged particles. heavy ions, neutrons and photons; nuclei at high angular momenta and superdeformation, structure and decay properties of giant resonances, charge-exchange resonances and β-decay; semiclassical approach of large amplitude collective motion and structure of hot nuclei

  3. Health Occupations Module. The Skeletal System--II.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on the skeletal system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, two objectives (e.g., list the types of joints and movements, and give examples), and two learning…

  4. Health Occupations Module. The Skeletal System--I.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on the skeletal system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, three objectives (e.g., define the skeletal system and list its functions), and three learning…

  5. Environmental Health Topics from A to Z

    Science.gov (United States)

    ... help. Explore Brochures & Fact Sheets Environmental Health Topics Environmental Health Topics Explore Environmental Health Topics A to ... Sessions Speakers Bureau Kids Environment | Kids Health Kids Environment | Kids Health A resource for kids, parents, and ...

  6. Genotype-dependent variability in flow cytometric evaluation of reduced nicotinamide adenine dinucleotide phosphate oxidase function in patients with chronic granulomatous disease.

    Science.gov (United States)

    Vowells, S J; Fleisher, T A; Sekhsaria, S; Alling, D W; Maguire, T E; Malech, H L

    1996-01-01

    We studied phagocyte reduced nicotinamide adenine dinucleotide phosphate function to evaluate production of reactive oxygen species in both X-linked and autosomal forms of chronic granulomatous disease. We found a consistent and significant difference between the activated granulocyte response of the X-linked (gp91-phagocyte oxidase) form of chronic granulomatous disease (n = 18) and that of the most common autosomal recessive (p47-phagocyte oxidase) form of the disease (n = 17). The data indicate that mutations in the p47-phagocyte oxidase component of the reduced nicotinamide adenine dinucleotide phosphate oxidase component do not completely prevent oxidation despite severe defects in superoxide generation.

  7. Vocational Education Today: Topical Issues.

    Science.gov (United States)

    Kenway, Jane, Ed.; Tregenza, Karen, Ed.; Watkins, Peter, Ed.

    This book contains 13 papers examining topical issues in vocational education and training (VET) in Victoria, Australia. The following papers are included: "Vocational Education and Schooling: The Changing Scene" (Jane Kenway, Sue Willis, Peter Watkins, Karen Tregenza); "The Enterprise Approach" (James Mulraney); "VET…

  8. Two topics in quantum chromodynamics

    International Nuclear Information System (INIS)

    Bjorken, J.D.

    1989-12-01

    The two topics are (1) estimates of perturbation theory coefficients for R(e + e - → hadrons), and (2) the virtual-photon structure function, with emphasis on the analytic behavior in its squared mass. 20 refs., 4 figs., 2 tabs

  9. Selected topics in nuclear structure

    International Nuclear Information System (INIS)

    Stachura, Z.

    1984-09-01

    19. winter school in Zakopane was devoted to selected topics in nuclear structure such as: production of spin resonances, heavy ions reactions and their applications to the investigation of high spin states, octupole deformations, excited states and production of new elements etc. The experimental data are ofen compared with theoretical predictions. Report contains 28 papers. (M.F.W.)

  10. Evaluating topic models with stability

    CSIR Research Space (South Africa)

    De Waal, A

    2008-11-01

    Full Text Available on unlabelled data, so that a ground truth does not exist and (b) "soft" (probabilistic) document clusters are created by state-of-the-art topic models, which complicates comparisons even when ground truth labels are available. Perplexity has often been used...

  11. Topical bevacizumab treatment in aniridia

    NARCIS (Netherlands)

    Lapid-Gortzak, Ruth; Santana, Nathalie T. Y.; Nieuwendaal, Carla P.; Mourits, Maarten P.; van der Meulen, Ivanka J. E.

    2017-01-01

    To report the results of long-term topical treatment with bevacizumab (Avastin) 5 mg/mL eyedrops in a case of aniridia-related neovacularization of the cornea. Interventional case report. A female patient with aniridia had a decrease in the best corrected visual acuity from 0.32 to 0.02 in the OS

  12. Topics in advanced quantum mechanics

    CERN Document Server

    Holstein, Barry R

    1992-01-01

    This graduate-level text is based on a course in advanced quantum mechanics, taught many times at the University of Massachusetts, Amherst. Topics include propagator methods, scattering theory, charged particle interactions, alternate approximate methods, and Klein-Gordon and Dirac equations. Problems appear in the flow of the discussion, rather than at the end of chapters.

  13. Lattice quantum chromodynamics: Some topics

    Indian Academy of Sciences (India)

    For reasons of both time and interest, I have chosen to limit this review to some se- lected topics. I will begin with a lightning quick overview of the basic lattice gauge theory and then go on to discuss the recent results on the QCD phase diagram, quark number susceptibility and the screening lengths. A short summary is ...

  14. Topic Map for Authentic Travel

    OpenAIRE

    Wandsvik, Atle; Zare, Mehdi

    2007-01-01

    E-business is a new trend in Internet use. Authentic travel is an approach to travel and travel business which helps the traveler experience what is authentic in the travel destination. But how can the traveler find those small authentic spots and organize them together to compose a vacation? E-business techniques, combined withTopic Maps, can help.

  15. Hot Topics in Science Teaching

    Science.gov (United States)

    Ediger, Marlow

    2018-01-01

    There are vital topics in science teaching and learning which are mentioned frequently in the literature. Specialists advocate their importance in the curriculum as well as science teachers stress their saliency. Inservice education might well assist new and veteran teachers in knowledge and skills. The very best science lessons and units of…

  16. The pharmacology of topical analgesics.

    Science.gov (United States)

    Barkin, Robert L

    2013-07-01

    Pain management of patients continues to pose challenges to clinicians. Given the multiple dimensions of pain--whether acute or chronic, mild, moderate, or severe, nociceptive or neuropathic--a multimodal approach may be needed. Fortunately, clinicians have an array of nonpharmacologic and pharmacologic treatment choices; however, each modality must be chosen carefully, because some often used oral agents are associated with safety and tolerability issues that restrict their use in certain patients. In particular, orally administered nonsteroidal antiinflammatory drugs, opioids, antidepressants, and anticonvulsants are known to cause systemic adverse effects in some patients. To address this problem, a number of topical therapies in various therapeutic classes have been developed to reduce systemic exposure and minimize the risks of patients developing adverse events. For example, topical nonsteroidal anti-inflammatory drug formulations produce a site-specific effect (ie, cyclo-oxygenase inhibition) while decreasing the systemic exposure that may lead to undesired effects in patients. Similarly, derivatives of acetylsalicylic acid (ie, salicylates) are used in topical analgesic formulations that do not significantly enter the patient's systemic circulation. Salicylates, along with capsaicin, menthol, and camphor, compose the counterirritant class of topical analgesics, which produce analgesia by activating and then desensitizing epidermal nociceptors. Additionally, patches and creams that contain the local anesthetic lidocaine, alone or co-formulated with other local anesthetics, are also used to manage patients with select acute and chronic pain states. Perhaps the most common topical analgesic modality is the cautious application of cutaneous cold and heat. Such treatments may decrease pain not by reaching the target tissue through systemic distribution, but by acting more directly on the affected tissue. Despite the tolerability benefits associated with avoiding

  17. Analyzing Nicotinamide Adenine Dinucleotide Phosphate Oxidase Activation in Aging and Vascular Amyloid Pathology

    Directory of Open Access Journals (Sweden)

    Helena Radbruch

    2017-07-01

    Full Text Available In aging individuals, both protective as well as regulatory immune functions are declining, resulting in an increased susceptibility to infections as well as to autoimmunity. Nicotinamide adenine dinucleotide phosphate (NADPH oxidase 2-deficiency in immune cell subsets has been shown to be associated with aging. Using intravital marker-free NAD(PH-fluorescence lifetime imaging, we have previously identified microglia/myeloid cells and astrocytes as main cellular sources of NADPH oxidase (NOX activity in the CNS during neuroinflammation, due to an overactivation of NOX. The overactivated NOX enzymes catalyze the massive production of the highly reactive O2−, which initiates in a chain reaction the overproduction of diverse reactive oxygen species (ROS. Age-dependent oxidative distress levels in the brain and their cellular sources are not known. Furthermore, it is unclear whether in age-dependent diseases oxidative distress is initiated by overproduction of ROS or by a decrease in antioxidant capacity, subsequently leading to neurodegeneration in the CNS. Here, we compare the activation level of NOX enzymes in the cerebral cortex of young and aged mice as well as in a model of vascular amyloid pathology. Despite the fact that a striking change in the morphology of microglia can be detected between young and aged individuals, we find comparable low-level NOX activation both in young and old mice. In contrast, aged mice with the human APPE693Q mutation, a model for cerebral amyloid angiopathy (CAA, displayed increased focal NOX overactivation in the brain cortex, especially in tissue areas around the vessels. Despite activated morphology in microglia, NOX overactivation was detected only in a small fraction of these cells, in contrast to other pathologies with overt inflammation as experimental autoimmune encephalomyelitis (EAE or glioblastoma. Similar to these pathologies, the astrocytes majorly contribute to the NOX overactivation in the brain

  18. Antidiabetic Activity of Polyherbal Formulation in Streptozotocin – Nicotinamide Induced Diabetic Wistar Rats

    Directory of Open Access Journals (Sweden)

    Rajendran Ramesh Petchi

    2014-04-01

    Full Text Available Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known plants available throughout India and they are commonly used for the treatment of various diseases including diabetes mellitus. The antidiabetic activity of the individual plant parts is well known, but the synergistic or combined effects are unclear. The concept of polyherbalism has been highlighted in Sharangdhar Samhita, an Ayurvedic literature dating back to 1300 AD. Polyherbal formulations enhance the therapeutic action and reduce the concentrations of single herbs, thereby reducing adverse events. The aim of the present study is to formulate a polyherbal formulation and evaluate its antidiabetic potential in animals. The polyherbal formulation was formulated using the ethanol extracts of the stem bark of G. pentaphylla, whole plant of T. procumbens, and leaves of M. indica. The polyherbal formulation contains the ethanol extracts of G. pentaphylla, T. procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished product was evaluated as per the World Health Organization’s guidelines for the quality control of herbal materials. The quality testing parameters of the polyherbal formulation were within the limits. Fingerprint analysis of the polyherbal formulation showed effective separation at 366 nm, and it revealed that the active compound present in the polyherbal formulation and the active compounds present in all the three extracts were the same. The acute toxicity studies of the polyherbal formulation did not show any toxic symptoms in doses up to 2000 mg/kg over 14 days. The oral antidiabetic activity of the polyherbal formulation (250 and 500 mg/kg was screened against streptozotocin (50 mg/kg; i.p.+nicotinamide (120 mg/kg; i.p. induced diabetes mellitus in rats. The investigational drug was administered for 21 consecutive days, and the effect of the polyherbal formulation on blood glucose levels was studied at regular intervals. At

  19. Nicotinamide impairs entry into and exit from meiosis I in mouse oocytes.

    Directory of Open Access Journals (Sweden)

    Angelique Riepsamen

    Full Text Available Following exit from meiosis I, mammalian oocytes immediately enter meiosis II without an intervening interphase, accompanied by rapid reassembly of a bipolar spindle that maintains condensed chromosomes in a metaphase configuration (metaphase II arrest. Here we study the effect of nicotinamide (NAM, a non-competitive pan-sirtuin inhibitor, during meiotic maturation in mouse oocytes. Sirtuins are a family of seven NAD+-dependent deacetylases (Sirt1-7, which are involved in multiple cellular processes and are emerging as important regulators in oocytes and embryos. We found that NAM significantly delayed entry into meiosis I associated with delayed accumulation of the Cdk1 co-activator, cyclin B1. GVBD was also inhibited by the Sirt2-specific inhibitor, AGK2, and in a very similar pattern to NAM, supporting the notion that as in somatic cells, NAM inhibits sirtuins in oocytes. NAM did not affect subsequent spindle assembly, chromosome alignment or the timing of first polar body extrusion (PBE. Unexpectedly, however, in the majority of oocytes with a polar body, chromatin was decondensed and a nuclear structure was present. An identical phenotype was observed when flavopiridol was used to induce Cdk1 inactivation during late meiosis I prior to PBE, but not if Cdk1 was inactivated after PBE when metaphase II arrest was already established, altogether indicating that NAM impaired establishment rather than maintenance of metaphase II arrest. During meiosis I exit in NAM-treated medium, we found that cyclin B1 levels were lower and inhibitory Cdk1 phosphorylation was increased compared with controls. Although activation of the anaphase-promoting complex-Cdc20 (APC-Cdc20 occurred on-time in NAM-treated oocytes, Cdc20 levels were higher in very late meiosis I, pointing to exaggerated APC-Cdc20-mediated proteolysis as a reason for lower cyclin B1 levels. Collectively, therefore, our data indicate that by disrupting Cdk1 regulation, NAM impairs entry into

  20. Pharmacokinetics of pirfenidone after topical administration in rabbit eye

    OpenAIRE

    Sun, Guoying; Lin, Xianchai; Zhong, Hua; Yang, Yangfan; Qiu, Xuan; Ye, Chengtian; Wu, Kaili; Yu, Minbin

    2011-01-01

    Purpose Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) is a new, broad-spectrum agent that has an inhibition effect on the proliferation, migration, and collagen contraction of human Tenon’s fibroblasts, and thus modulating the wound healing process of glaucoma filtering surgical site. This study investigated the pharmacokinetics of topically administered pirfenidone (0.5%) in rabbit eyes. Methods Pirfenidone solution (50 μl) was instilled into the rabbit’s conjunctival sac. The rabbits were...

  1. Special topics in infrared interferometry. [Michelson interferometer development

    Science.gov (United States)

    Hanel, R. A.

    1985-01-01

    Topics in IR interferometry related to the development of a Michelson interferometer are treated. The selection and reading of the signal from the detector to the analog to digital converter is explained. The requirements for the Michelson interferometer advance speed are deduced. The effects of intensity modulation on the interferogram are discussed. Wavelength and intensity calibration of the interferometer are explained. Noise sources (Nyquist or Johnson noise, phonon noise), definitions of measuring methods of noise, and noise measurements are presented.

  2. Pnc1p-mediated nicotinamide clearance modifies the epigenetic properties of rDNA silencing in Saccharomyces cerevisiae.

    Science.gov (United States)

    McClure, Julie M; Gallo, Christopher M; Smith, Daniel L; Matecic, Mirela; Hontz, Robert D; Buck, Stephen W; Racette, Frances G; Smith, Jeffrey S

    2008-10-01

    The histone deacetylase activity of Sir2p is dependent on NAD(+) and inhibited by nicotinamide (NAM). As a result, Sir2p-regulated processes in Saccharomyces cerevisiae such as silencing and replicative aging are susceptible to alterations in cellular NAD(+) and NAM levels. We have determined that high concentrations of NAM in the growth medium elevate the intracellular NAD(+) concentration through a mechanism that is partially dependent on NPT1, an important gene in the Preiss-Handler NAD(+) salvage pathway. Overexpression of the nicotinamidase, Pnc1p, prevents inhibition of Sir2p by the excess NAM while maintaining the elevated NAD(+) concentration. This growth condition alters the epigenetics of rDNA silencing, such that repression of a URA3 reporter gene located at the rDNA induces growth on media that either lacks uracil or contains 5-fluoroorotic acid (5-FOA), an unusual dual phenotype that is reminiscent of telomeric silencing (TPE) of URA3. Despite the similarities to TPE, the modified rDNA silencing phenotype does not require the SIR complex. Instead, it retains key characteristics of typical rDNA silencing, including RENT and Pol I dependence, as well as a requirement for the Preiss-Handler NAD(+) salvage pathway. Exogenous nicotinamide can therefore have negative or positive impacts on rDNA silencing, depending on the PNC1 expression level.

  3. Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss.

    Science.gov (United States)

    Brown, Kevin D; Maqsood, Sadia; Huang, Jing-Yi; Pan, Yong; Harkcom, William; Li, Wei; Sauve, Anthony; Verdin, Eric; Jaffrey, Samie R

    2014-12-02

    Intense noise exposure causes hearing loss by inducing degeneration of spiral ganglia neurites that innervate cochlear hair cells. Nicotinamide adenine dinucleotide (NAD(+)) exhibits axon-protective effects in cultured neurons; however, its ability to block degeneration in vivo has been difficult to establish due to its poor cell permeability and serum instability. Here, we describe a strategy to increase cochlear NAD(+) levels in mice by administering nicotinamide riboside (NR), a recently described NAD(+) precursor. We find that administration of NR, even after noise exposure, prevents noise-induced hearing loss (NIHL) and spiral ganglia neurite degeneration. These effects are mediated by the NAD(+)-dependent mitochondrial sirtuin, SIRT3, since SIRT3-overexpressing mice are resistant to NIHL and SIRT3 deletion abrogates the protective effects of NR and expression of NAD(+) biosynthetic enzymes. These findings reveal that administration of NR activates a NAD(+)-SIRT3 pathway that reduces neurite degeneration caused by noise exposure. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Coupling of NAD+ biosynthesis and nicotinamide ribosyl transport: characterization of NadR ribonucleotide kinase mutants of Haemophilus influenzae.

    Science.gov (United States)

    Merdanovic, Melisa; Sauer, Elizabeta; Reidl, Joachim

    2005-07-01

    Previously, we characterized a pathway necessary for the processing of NAD+ and for uptake of nicotinamide riboside (NR) in Haemophilus influenzae. Here we report on the role of NadR, which is essential for NAD+ utilization in this organism. Different NadR variants with a deleted ribonucleotide kinase domain or with a single amino acid change were characterized in vitro and in vivo with respect to cell viability, ribonucleotide kinase activity, and NR transport. The ribonucleotide kinase mutants were viable only in a nadV+ (nicotinamide phosphoribosyltransferase) background, indicating that the ribonucleotide kinase domain is essential for cell viability in H. influenzae. Mutations located in the Walker A and B motifs and the LID region resulted in deficiencies in both NR phosphorylation and NR uptake. The ribonucleotide kinase function of NadR was found to be feedback controlled by NAD+ under in vitro conditions and by NAD+ utilization in vivo. Taken together, our data demonstrate that the NR phosphorylation step is essential for both NR uptake across the inner membrane and NAD+ synthesis and is also involved in controlling the NAD+ biosynthesis rate.

  5. Hydrotropic solubilization of lipophilic drugs for oral delivery: The effects of urea and nicotinamide on carbamazepine solubility-permeability interplay

    Directory of Open Access Journals (Sweden)

    Avital Beig

    2016-10-01

    Full Text Available Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs' permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility-permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility-permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ~30-fold. A concomitant permeability decrease was evident both in-vitro and in-vivo (~17-fold for nicotinamide and ~9-fold for urea, revealing a solubility-permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility-permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility-permeability balance may promote the overall goal of the formulation to maximize oral drug exposure.

  6. Kinetic and thermodynamic study of the reaction catalyzed by glucose-6-phosphate dehydrogenase with nicotinamide adenine dinucleotide

    International Nuclear Information System (INIS)

    Martin del Campo, Julia S.; Patino, Rodrigo

    2011-01-01

    Research highlights: → The reaction catalyzed by one enzyme of the pentose phosphate pathway was studied. → A spectrophotometric method is proposed for kinetic and thermodynamic analysis. → The pH and the temperature influences are reported on physical chemical properties. → Relative concentrations of substrates are also important in the catalytic process. - Abstract: The enzyme glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) from Leuconostoc mesenteroides has a dual coenzyme specificity with oxidized nicotinamide adenine dinucleotide (NAD ox ) and oxidized nicotinamide adenine dinucleotide phosphate as electron acceptors. The G6PD coenzyme selection is determined by the metabolic cellular prevailing conditions. In this study a kinetic and thermodynamic analysis is presented for the reaction catalyzed by G6PD from L. mesenteroides with NAD ox as coenzyme in phosphate buffer. For this work, an in situ spectrophotometric technique was employed based on the detection of one product of the reaction. Substrate and coenzyme concentrations as well as temperature and pH effects were evaluated. The apparent equilibrium constant, the Michaelis constant, and the turnover number were determined as a function of each experimental condition. The standard transformed Gibbs energy of reaction was determined from equilibrium constants at different initial conditions. For the product 6-phospho-D-glucono-1,5-lactone, a value of the standard Gibbs energy of formation is proposed, Δ f G o = -1784 ± 5 kJ mol -1 .

  7. Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD.

    Directory of Open Access Journals (Sweden)

    Nathalie Busso

    Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT, also known as visfatin, is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide. Since its expression is upregulated during inflammation, NAMPT represents a novel clinical biomarker in acute lung injury, rheumatoid arthritis, and Crohn's disease. However, its role in disease progression remains unknown. We report here that NAMPT is a key player in inflammatory arthritis. Increased expression of NAMPT was confirmed in mice with collagen-induced arthritis, both in serum and in the arthritic paw. Importantly, a specific competitive inhibitor of NAMPT effectively reduced arthritis severity with comparable activity to etanercept, and decreased pro-inflammatory cytokine secretion in affected joints. Moreover, NAMPT inhibition reduced intracellular NAD concentration in inflammatory cells and circulating TNFalpha levels during endotoxemia in mice. In vitro pharmacological inhibition of NAMPT reduced the intracellular concentration of NAD and pro-inflammatory cytokine secretion by inflammatory cells. Thus, NAMPT links NAD metabolism to inflammatory cytokine secretion by leukocytes, and its inhibition might therefore have therapeutic efficacy in immune-mediated inflammatory disorders.

  8. Hydrotropic Solubilization of Lipophilic Drugs for Oral Delivery: The Effects of Urea and Nicotinamide on Carbamazepine Solubility–Permeability Interplay

    Science.gov (United States)

    Beig, Avital; Lindley, David; Miller, Jonathan M.; Agbaria, Riad; Dahan, Arik

    2016-01-01

    Hydrotropy refers to increasing the water solubility of otherwise poorly soluble compound by the presence of small organic molecules. While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs’ permeation through the intestinal membrane has not been studied. The purpose of this work was to investigate the solubility–permeability interplay when using hydrotropic drug solubilization. The concentration-dependent effects of the commonly used hydrotropes urea and nicotinamide, on the solubility and the permeability of the lipophilic antiepileptic drug carbamazepine were studied. Then, the solubility–permeability interplay was mathematically modeled, and was compared to the experimental data. Both hydrotropes allowed significant concentration-dependent carbamazepine solubility increase (up to ∼30-fold). A concomitant permeability decrease was evident both in vitro and in vivo (∼17-fold for nicotinamide and ∼9-fold for urea), revealing a solubility–permeability tradeoff when using hydrotropic drug solubilization. A relatively simplified simulation approach based on proportional opposite correlation between the solubility increase and the permeability decrease at a given hydrotrope concentration allowed excellent prediction of the overall solubility–permeability tradeoff. In conclusion, when using hydrotropic drug solubilization it is prudent to not focus solely on solubility, but to account for the permeability as well; achieving optimal solubility–permeability balance may promote the overall goal of the formulation to maximize oral drug exposure. PMID:27826241

  9. Optimization of SERS scattering by Ag-NPs-coated filter paper for quantification of nicotinamide in a cosmetic formulation.

    Science.gov (United States)

    Sallum, Loriz Francisco; Soares, Frederico Luis Felipe; Ardila, Jorge Armando; Carneiro, Renato Lajarim

    2014-01-01

    Supported silver nanoparticles on filter paper were synthesized using Tollens' reagent. Experimental designs were performed to obtain the highest SERS enhancement factor by study of the influence of the parameters: filter paper pretreatment, type of filter paper, reactants concentration, reaction time and temperature. To this end, fractional factorial and central composite designs were used in order to optimize the synthesis for quantification of nicotinamide in the presence of excipients in a commercial sample of cosmetic. The values achieved for the optimal condition were 150 mM of ammonium hydroxide, 50 mM of silver nitrate, 500 mM of glucose, 8 min for the reaction time, 45 °C temperature, pretreatment with ammonium hydroxide and quantitative filter paper (1-2 µm). Despite the variation of SERS intensity, it was possible to use an adapted method of internal standard to obtain a calibration curve with good precision. The coefficient of determination of the linear fit was 0.97. The method proposed in this work was capable of quantifying nicotinamide on a commercial cosmetic gel, at low concentration levels, with a relative error of 1.06% compared to the HPLC. SERS spectroscopy presents faster analyses than HPLC, also complex sample preparation and large amount of reactants are not necessary. © 2013 Published by Elsevier B.V.

  10. Pharmacokinetics of pirfenidone after topical administration in rabbit eye.

    Science.gov (United States)

    Sun, Guoying; Lin, Xianchai; Zhong, Hua; Yang, Yangfan; Qiu, Xuan; Ye, Chengtian; Wu, Kaili; Yu, Minbin

    2011-01-01

    Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) is a new, broad-spectrum agent that has an inhibition effect on the proliferation, migration, and collagen contraction of human Tenon's fibroblasts, and thus modulating the wound healing process of glaucoma filtering surgical site. This study investigated the pharmacokinetics of topically administered pirfenidone (0.5%) in rabbit eyes. Pirfenidone solution (50 μl) was instilled into the rabbit's conjunctival sac. The rabbits were quickly sacrificed at 2, 5, 8, 10, 15, 20, 30, 60, 90, and 120 min after the administration and ocular tissues were obtained. The concentrations of pirfenidone in conjunctiva, sclera, cornea, aqueous humor, and vitreous were determined by high performance liquid chromatography. After topical administration, there was wide distribution and fast clearance of pirfenidone among the various ocular tissues. The mean maximum concentrations (C(max)) of pirfenidone in cornea, conjunctiva, sclera, aqueous humor, and vitreous were 9.64 mg/g, 9.62 mg/g, 2.13 mg/g, 34.88 mg/l and 0.52 mg/l, respectively. The half-life for these tissues was 18.26, 34.16, 15.71, 70.91, and 39.48 min, respectively. Measurable concentrations of pirfenidone are achieved in ocular tissues after topical application in rabbit model. Topical administration of pirfenidone may be an effective approach for modulation of wound healing responses in glaucoma filtration surgical site.

  11. Do scientists trace hot topics?

    Science.gov (United States)

    Wei, Tian; Li, Menghui; Wu, Chensheng; Yan, Xiao-Yong; Fan, Ying; di, Zengru; Wu, Jinshan

    2013-07-01

    Do scientists follow hot topics in their scientific investigations? In this paper, by performing analysis to papers published in the American Physical Society (APS) Physical Review journals, it is found that papers are more likely to be attracted by hot fields, where the hotness of a field is measured by the number of papers belonging to the field. This indicates that scientists generally do follow hot topics. However, there are qualitative differences among scientists from various countries, among research works regarding different number of authors, different number of affiliations and different number of references. These observations could be valuable for policy makers when deciding research funding and also for individual researchers when searching for scientific projects.

  12. Retapamulin: A newer topical antibiotic

    Directory of Open Access Journals (Sweden)

    D Dhingra

    2013-01-01

    Full Text Available Impetigo is a common childhood skin infection. There are reports of increasing drug resistance to the currently used topical antibiotics including fusidic acid and mupirocin. Retapamulin is a newer topical agent of pleuromutilin class approved by the Food and Drug Administration for treatment of impetigo in children and has been recently made available in the Indian market. It has been demonstrated to have low potential for the development of antibacterial resistance and a high degree of potency against poly drug resistant Gram-positive bacteria found in skin infections including Staphylococcus aureus strains. The drug is safe owing to low systemic absorption and has only minimal side-effect of local irritation at the site of application.

  13. Hot topics in functional neuroradiology.

    Science.gov (United States)

    Faro, S H; Mohamed, F B; Helpern, J A; Jensen, J H; Thulborn, K R; Atkinson, I C; Sair, H I; Mikulis, D J

    2013-12-01

    Functional neuroradiology represents a relatively new and ever-growing subspecialty in the field of neuroradiology. Neuroradiology has evolved beyond anatomy and basic tissue signal characteristics and strives to understand the underlying physiologic processes of central nervous system disease. The American Society of Functional Neuroradiology sponsors a yearly educational and scientific meeting, and the educational committee was asked to suggest a few cutting-edge functional neuroradiology techniques (hot topics). The following is a review of several of these topics and includes "Diffusion Tensor Imaging of the Pediatric Spinal Cord"; "Diffusional Kurtosis Imaging"; "From Standardization to Quantification: Beyond Biomarkers toward Bioscales as Neuro MR Imaging Surrogates of Clinical End Points"; Resting-State Functional MR Imaging"; and "Current Use of Cerebrovascular Reserve Imaging."

  14. Stochastic Analysis and Related Topics

    CERN Document Server

    Ustunel, Ali

    1988-01-01

    The Silvri Workshop was divided into a short summer school and a working conference, producing lectures and research papers on recent developments in stochastic analysis on Wiener space. The topics treated in the lectures relate to the Malliavin calculus, the Skorohod integral and nonlinear functionals of white noise. Most of the research papers are applications of these subjects. This volume addresses researchers and graduate students in stochastic processes and theoretical physics.

  15. Topics in clinical oncology. 15

    International Nuclear Information System (INIS)

    Cepcek, P.

    1987-12-01

    The monograph comprising primarily papers on topical subjects of oncology and cancer research, contains also a selection of papers presented at the 2. Congress of the Czechoslovak Society of Nuclear Medicine and Radiation Hygiene. Seven papers were selected on behalf of their subject related to clinical oncology. All of them were iputted in INIS; five of them deal with the scintiscanning of the skeleton of cancer patients, one with radioimmunodetection of tumors, and one with radionuclide lymphography. (A.K.)

  16. [Topical anesthesia in flexible nasofibrolaryngoscopy].

    Science.gov (United States)

    Chiesa Estomba, Carlos Miguel; Ossa Echeverri, Carla Cristina; Araujo da Costa, Ana Sofía; Rivera Schmitz, Teresa; Castro Ruiz, Pilar; Santidrián Hidalgo, Carmelo

    2015-01-01

    The emergence of flexible nasofibrolaryngoscopy in recent decades has facilitated the development of Otolaryngology and the nasofibrolaryngoscope has become an essential diagnostic tool for the otolaryngologist. However, its use is not without discomfort for the patient, which is why various options for topical anaesthesia have been proposed during the development of the technique. This was a prospective, double blind, crossover study in patients with no history of nasal disease, through which we compared the use of topical anaesthetic (Lidocaine) + epinephrine, oxymetazoline and placebo. Using a visual analogue scale, the degree of discomfort was assessed during each scan. We evaluated 18 patients, 10 women (55.6%) and 8 men (44.4%), with a mean age of 28±4 years. The degree of disturbance generated by the scan with the application of lidocaine-epinephrine was 1.94; with oxymetazoline it was 3.78, and with placebo, 4.61. When the lidocaine-epinephrine solution was compared with oxymetazoline, there was a statistical significance in favour of lidocaine-epinephrine (P<0.05). When we compared the use of lidocaine-epinephrine with the placebo, the result was also statistically significant in favour of lidocaine-epinephrine (P<0.05). In this study we demonstrated that using lidocaine associated with epinephrine as a topical anaesthetic prior to flexible nasofibrolaryngoscopy decreases pain and feeling of discomfort for the patient. Consequently, we can recommend the use of topical nasal anaesthesia when performing this exploration. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

  17. Probabilistic analysis and related topics

    CERN Document Server

    Bharucha-Reid, A T

    1983-01-01

    Probabilistic Analysis and Related Topics, Volume 3 focuses on the continuity, integrability, and differentiability of random functions, including operator theory, measure theory, and functional and numerical analysis. The selection first offers information on the qualitative theory of stochastic systems and Langevin equations with multiplicative noise. Discussions focus on phase-space evolution via direct integration, phase-space evolution, linear and nonlinear systems, linearization, and generalizations. The text then ponders on the stability theory of stochastic difference systems and Marko

  18. Topical glycopyrrolate reduces axillary hyperhidrosis.

    Science.gov (United States)

    Baker, D M

    2016-12-01

    Oral anti-cholinergic medications reduce generalized hyperhidrosis, but the effectiveness of topical anticholinergic solutions on axillary hyperhidrosis is unclear. This study determines the initial effectiveness of 1% and 2% topical glycopyrrolate spray and compares this with Botulinum toxin type A injections for the management of axillary hyperhidrosis. In a non-randomized, consecutive patient, prospective questionnaire, treatment comparison study, 40 patients with axillary hyperhidrosis were allocated to one of four study groups (10 patients to each group): (a) 1% glycopyrrolate spray, (b) 2% glycopyrrolate spray, (c) subcutaneous Botulinum toxin type A injections, (d) no treatment. Clinical outcomes were measured by comparing a prospectively administered questionnaire, completed both pre-treatment and 6 weeks after starting treatment. Forty healthy volunteers without axillary hyperhidrosis completed the same questionnaire. The three treatment groups showed a significant (P hyperhidrosis scores following treatment. The degree of improvement was less for the 1% glycopyrrolate group when compared with the Botulinum toxin type A group (P hyperhidrosis to a level similar to those without hyperhidrosis. Patients in both, the 2% glycopyrrolate and Botulinum toxin type A groups reported a significant improvement in axillary hyperhidrosis symptoms. These included reduction in psychologically precipitating factors (e.g. public speaking) and axillary hyperhidrosis-specific physical effects (e.g. limitation of clothing choice). Topical glycopyrrolate spray could provide a further treatment modality to manage axillary hyperhidrosis. © 2016 European Academy of Dermatology and Venereology.

  19. Induced modules over group algebras

    CERN Document Server

    Karpilovsky, Gregory

    1990-01-01

    In 1898 Frobenius discovered a construction which, in present terminology, associates with every module of a subgroup the induced module of a group. This construction proved to be of fundamental importance and is one of the basic tools in the entire theory of group representations.This monograph is designed for research mathematicians and advanced graduate students and gives a picture of the general theory of induced modules as it exists at present. Much of the material has until now been available only in research articles. The approach is not intended to be encyclopedic, rather each topic is

  20. Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolic flexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet

    NARCIS (Netherlands)

    Shi, W.; Hegeman, M.A.; Dartel, van D.A.M.; Tang, J.; Suarez, M.; Swarts, H.; Hee, van der B.; Arola, L.; Keijer, J.

    2017-01-01

    Scope: Metabolic flexibility is the ability to switch metabolism between carbohydrate oxidation (CHO) and fatty acid oxidation (FAO) and is a biomarker for metabolic health. The effect on metabolic health of nicotinamide riboside (NR) as an exclusive source of vitamin B3 is unknown and is examined

  1. Meat Intake and the Dose of Vitamin B – Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

    Directory of Open Access Journals (Sweden)

    Lisa J Hill

    2017-05-01

    Full Text Available Meat and vitamin B 3 – nicotinamide – intake was high during hunter-gatherer times. Intake then fell and variances increased during and after the Neolithic agricultural revolution. Health, height, and IQ deteriorated. Low dietary doses are buffered by ‘welcoming’ gut symbionts and tuberculosis that can supply nicotinamide, but this co-evolved homeostatic metagenomic strategy risks dysbioses and impaired resistance to pathogens. Vitamin B 3 deficiency may now be common among the poor billions on a low-meat diet. Disease transitions to non-communicable inflammatory disorders (but longer lives may be driven by positive ‘meat transitions’. High doses of nicotinamide lead to reduced regulatory T cells and immune intolerance. Loss of no longer needed symbiotic ‘old friends’ compounds immunological over-reactivity to cause allergic and auto-immune diseases. Inhibition of nicotinamide adenine dinucleotide consumers and loss of methyl groups or production of toxins may cause cancers, metabolic toxicity, or neurodegeneration. An optimal dosage of vitamin B 3 could lead to better health, but such a preventive approach needs more equitable meat distribution. Some people may require personalised doses depending on genetic make-up or, temporarily, when under stress.

  2. Prognostic value of the proliferation marker Ki-67 in laryngeal carcinoma : Results of the Accelerated Radiotherapy with Carbogen Breathing and Nicotinamide phase III randomized trial

    NARCIS (Netherlands)

    Rademakers, Saskia E.; Hoogsteen, Ilse J.; Rijken, Paul F.; Terhaard, Chris H.; Doornaert, Patricia A.; Langendijk, Johannes A.; van den Ende, Piet; van der Kogel, Albert J.; Bussink, Johan; Kaanders, Johannes H.

    BackgroundThe prognostic and predictive value of the proliferation marker Ki-67 was investigated in a randomized trial comparing accelerated radiotherapy with carbogen breathing and nicotinamide (ARCON) to accelerated radiotherapy in laryngeal carcinoma. MethodsLabeling index of Ki-67 (Li Ki-67) in

  3. Prognostic value of the proliferation marker Ki-67 in laryngeal carcinoma : Results of the Accelerated Radiotherapy with Carbogen Breathing and Nicotinamide phase III randomized trial

    NARCIS (Netherlands)

    Rademakers, Saskia E.; Hoogsteen, Ilse J.; Rijken, Paul F.; Terhaard, Chris H.; Doornaert, Patricia A.; Langendijk, Johannes A.; Van Den Ende, Piet; Van Der Kogel, Albert J.; Bussink, Johan; Kaanders, Johannes H.

    2015-01-01

    Background The prognostic and predictive value of the proliferation marker Ki-67 was investigated in a randomized trial comparing accelerated radiotherapy with carbogen breathing and nicotinamide (ARCON) to accelerated radiotherapy in laryngeal carcinoma. Methods Labeling index of Ki-67 (Li Ki-67)

  4. The Chainstitch Machine. Module 18.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the chainstitch machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers one topic: performing special operations on the chainstitch machine. These components are provided: an introduction, directions, an objective, learning activities, student information, a student self-check, and…

  5. Diaquabis(2-hydroxybenzoato-κO1bis(nicotinamide-κN1cadmium–diaquabis(2-hydroxybenzoato-κ2O1,O1′(nicotinamide-κNcadmium–water (1/2/4

    Directory of Open Access Journals (Sweden)

    Nagihan Çaylak Delibaş

    2013-04-01

    Full Text Available The crystal structure of the title compound, [Cd(C7H5O32(C6H6NO2(H2O2]·2[Cd(C7H5O32(C6H6NO(H2O2]·4H2O, consists of two kinds of CdII complexes (A and B and lattice water molecules. In complex A, [Cd(C7H5O32(C6H6NO2(H2O2], the CdII cation is located on an inversion center and is coordinated by two salicylate anions, two nicotinamide (NA ligands and two water molecules in a slightly distorted octahedral geometry. In complex B, [Cd(C7H5O32(C6H6NO(H2O2], the CdII cation is coordinated by two salicylate anions, one nicotinamide (NA ligand and two water molecules in an irregular seven-coordinate geometry. There are extensive intramolecular O—H...O and weak C—H...O hydrogen bonds as well as extensive intermolecular O—H...O and N—H...O hydrogen bonding in the crystal structure. π–π stacking between the pyridine and benzene rings, between the benzene rings, between the benzene and pyridine rings and between the pyridine rings [centroid–centroid distances = 3.5989 (10, 3.6005 (10, 3.5800 (9 and 3.5205 (10 Å, respectively] further stabilize the crystal structure. A weak N—H...π interaction also occurs. One of the lattice water molecules is disordered over two positions with an occupancy ratio of 0.70:0.30.

  6. Topic extraction from adverbial clauses

    Directory of Open Access Journals (Sweden)

    Carlos Rubio Alcalá

    2016-06-01

    Full Text Available This paper offers new data to support findings about Topic extraction from adverbial clauses. Since such clauses are strong islands, they should not allow extraction of any kind, but we show here that if the appropriate conditions are met, Topics of the CLLD kind in Romance can move out of them. We propose that two conditions must be met for such movement to be possible: the first is that the adverbial clause must have undergone topicalisation in the first place; the second is that the adverbial clause is inherently topical from a semantic viewpoint. Contrast with other language families (Germanic, Quechua and Japanese is provided and the semantic implications of the proposal are briefly discussed. Keywords: topicalisation; Clitic Left Dislocation; syntactic islands; adverbial clauses Este artículo ofrece nuevos datos sobre la extracción de Tópicos desde oraciones subordinadas adverbiales. Dado que dichas oraciones son islas fuertes, no deberían permitir extracción de ningún tipo, pero mostramos que si se dan las condiciones apropiadas, los Tópicos del tipo CLLD en lenguas románicas pueden desplazarse fuera de ellas. Proponemos que se deben cumplir dos condiciones para que ese movimiento sea posible: la primera es que la propia subordinada adverbial se haya topicalizado en primer lugar; la segunda es que la subordinada adverbial sea inherentemente un Tópico desde el punto de vista semántico. Proporcionamos también algunos contrastes con otras familias lingüísticas (germánica, quechua y japonés y se discuten brevemente las implicaciones semánticas de la propuesta. Palabras clave: topicalización; dislocación a la izquierda con clítico; islas sintácticas; oraciones adverbiales

  7. Tactile friction of topical formulations.

    Science.gov (United States)

    Skedung, L; Buraczewska-Norin, I; Dawood, N; Rutland, M W; Ringstad, L

    2016-02-01

    The tactile perception is essential for all types of topical formulations (cosmetic, pharmaceutical, medical device) and the possibility to predict the sensorial response by using instrumental methods instead of sensory testing would save time and cost at an early stage product development. Here, we report on an instrumental evaluation method using tactile friction measurements to estimate perceptual attributes of topical formulations. Friction was measured between an index finger and an artificial skin substrate after application of formulations using a force sensor. Both model formulations of liquid crystalline phase structures with significantly different tactile properties, as well as commercial pharmaceutical moisturizing creams being more tactile-similar, were investigated. Friction coefficients were calculated as the ratio of the friction force to the applied load. The structures of the model formulations and phase transitions as a result of water evaporation were identified using optical microscopy. The friction device could distinguish friction coefficients between the phase structures, as well as the commercial creams after spreading and absorption into the substrate. In addition, phase transitions resulting in alterations in the feel of the formulations could be detected. A correlation was established between skin hydration and friction coefficient, where hydrated skin gave rise to higher friction. Also a link between skin smoothening and finger friction was established for the commercial moisturizing creams, although further investigations are needed to analyse this and correlations with other sensorial attributes in more detail. The present investigation shows that tactile friction measurements have potential as an alternative or complement in the evaluation of perception of topical formulations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Topics in atomic collision theory

    CERN Document Server

    Geltman, Sydney; Brueckner, Keith A

    1969-01-01

    Topics in Atomic Collision Theory originated in a course of graduate lectures given at the University of Colorado and at University College in London. It is recommended for students in physics and related fields who are interested in the application of quantum scattering theory to low-energy atomic collision phenomena. No attention is given to the electromagnetic, nuclear, or elementary particle domains. The book is organized into three parts: static field scattering, electron-atom collisions, and atom-atom collisions. These are in the order of increasing physical complexity and hence necessar

  9. Influence of Sodium Lauryl Sulfate and Tween 80 on Carbamazepine–Nicotinamide Cocrystal Solubility and Dissolution Behaviour

    Directory of Open Access Journals (Sweden)

    Ke Wang

    2013-10-01

    Full Text Available The influence of the surfactants of sodium lauryl sulfate (SLS and Tween 80 on carbamazepine–nicotinamide (CBZ–NIC cocrystal solubility and dissolution behaviour has been studied in this work. The solubility of the CBZ–NIC cocrystal was determined by measuring the eutectic concentrations of the drug and the coformer. Evolution of the intrinsic dissolution rate (IDR of the CBZ–NIC cocrystal was monitored by the UV imaging dissolution system during dissolution. Experimental results indicated that SLS and Tween 80 had little influence upon the solubility of the CBZ–NIC cocrystal but they had totally opposite effects on the IDR of the CBZ–NIC cocrystal during dissolution. SLS significantly increased the IDR of the CBZ–NIC cocrystal while Tween 80 decreased its IDR.

  10. Function of Ubiquinone in Electron Transport from Reduced Nicotinamide Adenine Dinucleotide to Nitrate and Oxygen in Aerobacter aerogenes

    Science.gov (United States)

    Knook, D. L.; Planta, R. J.

    1971-01-01

    The possible role of quinones in the electron transport system of Aerobacter aerogenes was investigated. The only quinone found in measurable amounts in bacteria grown in minimal media under both aerobic and anaerobic conditions was ubiquinone-8. Membrane-bound ubiquinone-8 could be removed by extraction with pentane, or destroyed by ultraviolet irradiation, with a concomitant loss of both reduced nicotinamide adenine dinucleotide (NADH) oxidase and NADH-linked respiratory nitrate reductase activity. In the extracted membrane preparations, these enzymatic activities could be restored, both to the same degree, by incorporation of ubiquinone-6, -8, or -10, but not by incorporation of menaquinones. The NADH oxidation and the nitrate reduction were sensitive to the respiratory inhibitors dicoumarol, lapachol, and cyanide. The results obtained indicate that ubiquinone-8 mediates the electron transport between NADH and oxygen as well as between NADH and nitrate. Branching of the electron transport chain to oxygen and nitrate occurs after an initial common pathway. PMID:4100202

  11. Recent developments in topical thrombins.

    Science.gov (United States)

    Kessler, Craig M; Ortel, Thomas L

    2009-07-01

    Managing blood loss is part of the surgeon's responsibility during surgical procedures, and a variety of therapeutic strategies are available to help accomplish this. Topical haemostatic agents are among the agents used to control surgical bleeding and locally arrest blood flow. Bovine thrombin is a commonly used topical haemostatic agent; however, its use has been associated with potential risks, including well-documented cases of antibody-mediated coagulopathy. This coagulopathy develops as a consequence of antibody formation directed against bovine thrombin, other bovine coagulation proteins, and their human orthologs. The fact that a coagulopathy can result in association with the use of bovine plasma-derived thrombin preparations prompted the FDA to require pharmaceutical companies to place a black-box warning in their prescribing information for products containing bovine plasma-derived thrombin. Recently, human plasma-derived thrombin and recombinant human thrombin have been approved by the FDA with the expectation that they will be less immunogenic than the bovine-derived product. In clinical studies, purified human plasma-derived thrombin and recombinant thrombin have demonstrated equivalent efficacy and safety, with improved immunogenicity profiles compared with bovine-derived thrombin agents. Well-designed and adequately powered clinical trials should be conducted to indicate whether human thrombin products would improve the risk-benefit and cost-benefit profiles for surgeries complicated by excessive bleeding.

  12. Satellite DNA: An Evolving Topic.

    Science.gov (United States)

    Garrido-Ramos, Manuel A

    2017-09-18

    Satellite DNA represents one of the most fascinating parts of the repetitive fraction of the eukaryotic genome. Since the discovery of highly repetitive tandem DNA in the 1960s, a lot of literature has extensively covered various topics related to the structure, organization, function, and evolution of such sequences. Today, with the advent of genomic tools, the study of satellite DNA has regained a great interest. Thus, Next-Generation Sequencing (NGS), together with high-throughput in silico analysis of the information contained in NGS reads, has revolutionized the analysis of the repetitive fraction of the eukaryotic genomes. The whole of the historical and current approaches to the topic gives us a broad view of the function and evolution of satellite DNA and its role in chromosomal evolution. Currently, we have extensive information on the molecular, chromosomal, biological, and population factors that affect the evolutionary fate of satellite DNA, knowledge that gives rise to a series of hypotheses that get on well with each other about the origin, spreading, and evolution of satellite DNA. In this paper, I review these hypotheses from a methodological, conceptual, and historical perspective and frame them in the context of chromosomal organization and evolution.

  13. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice.

    Science.gov (United States)

    Gariani, Karim; Menzies, Keir J; Ryu, Dongryeol; Wegner, Casey J; Wang, Xu; Ropelle, Eduardo R; Moullan, Norman; Zhang, Hongbo; Perino, Alessia; Lemos, Vera; Kim, Bohkyung; Park, Young-Ki; Piersigilli, Alessandra; Pham, Tho X; Yang, Yue; Ku, Chai Siah; Koo, Sung I; Fomitchova, Anna; Cantó, Carlos; Schoonjans, Kristina; Sauve, Anthony A; Lee, Ji-Young; Auwerx, Johan

    2016-04-01

    With no approved pharmacological treatment, nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in Western countries and its worldwide prevalence continues to increase along with the growing obesity epidemic. Here, we show that a high-fat high-sucrose (HFHS) diet, eliciting chronic hepatosteatosis resembling human fatty liver, lowers hepatic nicotinamide adenine dinucleotide (NAD(+) ) levels driving reductions in hepatic mitochondrial content, function, and adenosine triphosphate (ATP) levels, in conjunction with robust increases in hepatic weight, lipid content, and peroxidation in C57BL/6J mice. To assess the effect of NAD(+) repletion on the development of steatosis in mice, nicotinamide riboside, a precursor of NAD(+) biosynthesis, was added to the HFHS diet, either as a preventive strategy or as a therapeutic intervention. We demonstrate that NR prevents and reverts NAFLD by inducing a sirtuin (SIRT)1- and SIRT3-dependent mitochondrial unfolded protein response, triggering an adaptive mitohormetic pathway to increase hepatic β-oxidation and mitochondrial complex content and activity. The cell-autonomous beneficial component of NR treatment was revealed in liver-specific Sirt1 knockout mice (Sirt1(hep-/-) ), whereas apolipoprotein E-deficient mice (Apoe(-/-) ) challenged with a high-fat high-cholesterol diet affirmed the use of NR in other independent models of NAFLD. Our data warrant the future evaluation of NAD(+) boosting strategies to manage the development or progression of NAFLD. © 2015 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

  14. Identification of nicotinamide mononucleotide deamidase of the bacterial pyridine nucleotide cycle reveals a novel broadly conserved amidohydrolase family.

    Science.gov (United States)

    Galeazzi, Luca; Bocci, Paola; Amici, Adolfo; Brunetti, Lucia; Ruggieri, Silverio; Romine, Margaret; Reed, Samantha; Osterman, Andrei L; Rodionov, Dmitry A; Sorci, Leonardo; Raffaelli, Nadia

    2011-11-18

    The pyridine nucleotide cycle is a network of salvage and recycling routes maintaining homeostasis of NAD(P) cofactor pool in the cell. Nicotinamide mononucleotide (NMN) deamidase (EC 3.5.1.42), one of the key enzymes of the bacterial pyridine nucleotide cycle, was originally described in Enterobacteria, but the corresponding gene eluded identification for over 30 years. A genomics-based reconstruction of NAD metabolism across hundreds of bacterial species suggested that NMN deamidase reaction is the only possible way of nicotinamide salvage in the marine bacterium Shewanella oneidensis. This prediction was verified via purification of native NMN deamidase from S. oneidensis followed by the identification of the respective gene, termed pncC. Enzymatic characterization of the PncC protein, as well as phenotype analysis of deletion mutants, confirmed its proposed biochemical and physiological function in S. oneidensis. Of the three PncC homologs present in Escherichia coli, NMN deamidase activity was confirmed only for the recombinant purified product of the ygaD gene. A comparative analysis at the level of sequence and three-dimensional structure, which is available for one of the PncC family member, shows no homology with any previously described amidohydrolases. Multiple alignment analysis of functional and nonfunctional PncC homologs, together with NMN docking experiments, allowed us to tentatively identify the active site area and conserved residues therein. An observed broad phylogenomic distribution of predicted functional PncCs in the bacterial kingdom is consistent with a possible role in detoxification of NMN, resulting from NAD utilization by DNA ligase.

  15. Effects of cavities at the nicotinamide binding site of liver alcohol dehydrogenase on structure, dynamics and catalysis.

    Science.gov (United States)

    Yahashiri, Atsushi; Rubach, Jon K; Plapp, Bryce V

    2014-02-11

    A role for protein dynamics in enzymatic catalysis of hydrogen transfer has received substantial scientific support, but the connections between protein structure and catalysis remain to be established. Valine residues 203 and 207 are at the binding site for the nicotinamide ring of the coenzyme in liver alcohol dehydrogenase and have been suggested to facilitate catalysis with "protein-promoting vibrations" (PPV). We find that the V207A substitution has small effects on steady-state kinetic constants and the rate of hydrogen transfer; the introduced cavity is empty and is tolerated with minimal effects on structure (determined at 1.2 Å for the complex with NAD(+) and 2,3,4,5,6-pentafluorobenzyl alcohol). Thus, no evidence is found to support a role for Val-207 in the dynamics of catalysis. The protein structures and ligand geometries (including donor-acceptor distances) in the V203A enzyme complexed with NAD(+) and 2,3,4,5,6-pentafluorobenzyl alcohol or 2,2,2-trifluoroethanol (determined at 1.1 Å) are very similar to those for the wild-type enzyme, except that the introduced cavity accommodates a new water molecule that contacts the nicotinamide ring. The structures of the V203A enzyme complexes suggest, in contrast to previous studies, that the diminished tunneling and decreased rate of hydride transfer (16-fold, relative to that of the wild-type enzyme) are not due to differences in ground-state ligand geometries. The V203A substitution may alter the PPV and the reorganization energy for hydrogen transfer, but the protein scaffold and equilibrium thermal motions within the Michaelis complex may be more significant for enzyme catalysis.

  16. The sodium phosphate cotransporter family and nicotinamide phosphoribosyltransferase contribute to the daily oscillation of plasma inorganic phosphate concentration.

    Science.gov (United States)

    Miyagawa, Atsumi; Tatsumi, Sawako; Takahama, Wako; Fujii, Osamu; Nagamoto, Kenta; Kinoshita, Emi; Nomura, Kengo; Ikuta, Kayo; Fujii, Toru; Hanazaki, Ai; Kaneko, Ichiro; Segawa, Hiroko; Miyamoto, Ken-Ichi

    2018-02-01

    Circulating inorganic phosphate exhibits a remarkable daily oscillation based on food intake. In humans and rodents, the daily oscillation in response to food intake may be coordinated to control the intestinal absorption, renal excretion, cellular shifts, and extracellular concentration of inorganic phosphate. However, mechanisms regulating the resulting oscillation are unknown. Here we investigated the roles of the sodium phosphate cotransporter SLC34 (Npt2) family and nicotinamide phosphoribosyltransferase (Nampt) in the daily oscillation of plasma inorganic phosphate levels. First, it is roughly linked to urinary inorganic phosphate excretion. Second, expression of renal Npt2a and Npt2c, and intestinal Npt2b proteins also exhibit a dynamic daily oscillation. Analyses of Npt2a, Npt2b, and Npt2c knockout mice revealed the importance of renal inorganic phosphate reabsorption and cellular inorganic phosphate shifts in the daily oscillation. Third, experiments in which nicotinamide and a specific Nampt inhibitor (FK866) were administered in the active and rest phases revealed that the Nampt/NAD + system is involved in renal inorganic phosphate excretion. Additionally, for cellular shifts, liver-specific Nampt deletion disturbed the daily oscillation of plasma phosphate during the rest but not the active phase. In systemic Nampt +/- mice, NAD levels were significantly reduced in the liver, kidney, and intestine, and the daily oscillation (active and rest phases) of the plasma phosphate concentration was attenuated. Thus, the Nampt/NAD + system for Npt2 regulation and cellular shifts to tissues such as the liver play an important role in generating daily oscillation of plasma inorganic phosphate levels. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  17. Nicotinamide starvation and inhibition of poly(ADP-Ribose) synthesis enhance the induced mutation in Chinese hamster V79 cells

    International Nuclear Information System (INIS)

    Okada, Gensaku; Kaneko, Ichiro; Mitsui, Hideki.

    1987-01-01

    The effects of nicotinamide (NA) deficiency and added NA and 3-aminobenzamide (3AB) on the cytotoxicity and the induction of mutations in Chinese hamster V79-14 cells were investigated. In NA deficiency the addition of NA (up to 4 mM) and 3AB (up to 7.5 mM) was not cytotoxic. The presence of NA prior to exposure to mitomycin C (MMC) or γ-rays produced a dose-dependent increase in the relative cloning ability of DNA-damaged cells. The lethality of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was significantly potentiated by pre-treatment with 5 mM 3AB, but no potentiation by 3AB was observed for MMC, ultraviolet (UV)-B light, or γ-rays. Among cells pre-cultured in NA-free medium there were increased frequencies of mutations at both the hypoxanthineguanine phosphoribosyltransferase (HGPRT) and the adenine phosphoribosyltransferase (APRT) loci following DNA damage. The enhancing effect by NA deficiency was time-dependent. Incubation with NA prior to DNA damage produced a significant reduction in the frequency of mutations. The addition of 3AB to the nicotinamide adenine dinucleotide (NAD + )-depleted cell cultures before or after the DNA damage also strongly increased the frequency of induced mutations, with increasing concentrations of 3AB up to 5 mM, but the frequency was reduced at higher concentrations. The interaction between NA deficiency and the addition of 3AB appears to act synergistically on mutation induction. A correlation was observed between the potential of inhibiting poly (ADP-ribose) polymerase and the enhancement of mutation frequency. (author)

  18. Topics in strong Langmuir turbulence

    International Nuclear Information System (INIS)

    Skoric, M.M.

    1981-01-01

    This thesis discusses certain aspects of the turbulence of a fully ionised non-isothermal plasma dominated by the Langmuir mode. Some of the basic properties of strongly turbulent plasmas are reviewed. In particular, interest is focused on the state of Langmuir turbulence, that is the turbulence of a simple externally unmagnetized plasma. The problem of the existence and dynamics of Langmuir collapse is discussed, often met as a non-linear stage of the modulational instability in the framework of the Zakharov equations (i.e. simple time-averaged dynamical equations). Possible macroscopic consequences of such dynamical turbulent models are investigated. In order to study highly non-linear collapse dynamics in its advanced stage, a set of generalized Zakharov equations are derived. Going beyond the original approximation, the author includes the effects of higher electron non-linearities and a breakdown of slow-timescale quasi-neutrality. He investigates how these corrections may influence the collapse stabilisation. Recently, it has been realised that the modulational instability in a Langmuir plasma will be accompanied by the collisionless-generation of a slow-timescale magnetic field. Accordingly, a novel physical situation has emerged which is investigated in detail. The stability of monochromatic Langmuir waves in a self-magnetized Langmuir plasma, is discussed, and the existence of a novel magneto-modulational instability shown. The wave collapse dynamics is investigated and a physical interpretation of the basic results is given. A problem of the transient analysis of an interaction of time-dependent electromagnetic pulses with linear cold plasma media is investigated. (Auth.)

  19. Antibiotic Resistance: MedlinePlus Health Topic

    Science.gov (United States)

    ... GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Health Topics → Antibiotic Resistance URL of this page: https://medlineplus.gov/antibioticresistance. ...

  20. Child Safety: MedlinePlus Health Topic

    Science.gov (United States)

    ... safety (Medical Encyclopedia) Also in Spanish Preventing head injuries in children (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus ... Safety Seats Cribs and crib safety Preventing head injuries in children Related Health Topics Infant and Newborn Care Internet ...

  1. Diets: MedlinePlus Health Topic

    Science.gov (United States)

    ... Claims? (Mayo Foundation for Medical Education and Research) DASH Diet: MedlinePlus Health Topic (National Library of Medicine) Also ... foods Mediterranean diet Related Health Topics Child Nutrition DASH Eating Plan Diabetic Diet Nutrition Nutrition for Seniors Vegetarian Diet ...

  2. Human-competitive automatic topic indexing

    CERN Document Server

    Medelyan, Olena

    2009-01-01

    Topic indexing is the task of identifying the main topics covered by a document. These are useful for many purposes: as subject headings in libraries, as keywords in academic publications and as tags on the web. Knowing a document’s topics helps people judge its relevance quickly. However, assigning topics manually is labor intensive. This thesis shows how to generate them automatically in a way that competes with human performance. Three kinds of indexing are investigated: term assignment, a task commonly performed by librarians, who select topics from a controlled vocabulary; tagging, a popular activity of web users, who choose topics freely; and a new method of keyphrase extraction, where topics are equated to Wikipedia article names. A general two-stage algorithm is introduced that first selects candidate topics and then ranks them by significance based on their properties. These properties draw on statistical, semantic, domain-specific and encyclopedic knowledge. They are combined using a machine learn...

  3. Teaching the Middle East: Topics and Resources.

    Science.gov (United States)

    Albright, Charlotte F.

    1982-01-01

    Topics and resources for a discussion of the Middle East in a secondary social studies classroom are presented. The topics include geography and world resources, ethnic groups, religions, and case studies of specific countries. (AM)

  4. KEY TOPICS IN SPORTS MEDICINE

    Directory of Open Access Journals (Sweden)

    Amir Ali Narvani

    2006-12-01

    Full Text Available Key Topics in Sports Medicine is a single quick reference source for sports and exercise medicine. It presents the essential information from across relevant topic areas, and includes both the core and emerging issues in this rapidly developing field. It covers: 1 Sports injuries, rehabilitation and injury prevention, 2 Exercise physiology, fitness testing and training, 3 Drugs in sport, 4 Exercise and health promotion, 5 Sport and exercise for special and clinical populations, 6 The psychology of performance and injury. PURPOSE The Key Topics format provides extensive, concise information in an accessible, easy-to-follow manner. AUDIENCE The book is targeted the students and specialists in sports medicine and rehabilitation, athletic training, physiotherapy and orthopaedic surgery. The editors are authorities in their respective fields and this handbook depends on their extensive experience and knowledge accumulated over the years. FEATURES The book contains the information for clinical guidance, rapid access to concise details and facts. It is composed of 99 topics which present the information in an order that is considered logical and progressive as in most texts. Chapter headings are: 1. Functional Anatomy, 2. Training Principles / Development of Strength and Power, 3. Biomechanical Principles, 4. Biomechanical Analysis, 5. Physiology of Training, 6. Monitoring of Training Progress, 7. Nutrition, 8. Hot and Cold Climates, 9. Altitude, 10. Sport and Travelling, 11. Principles of Sport Injury Diagnosis, 12. Principles of Sport and Soft Tissue Management, 13. Principles of Physical Therapy and Rehabilitation, 14. Principles of Sport Injury Prevention, 15. Sports Psychology, 16. Team Sports, 17. Psychological Aspects of Injury in Sport, 18. Injury Repair Process, 19. Basic Biomechanics of Tissue Injury, 20. Plain Film Radiography in Sport, 21. Nuclear Medicine, 22. Diagnostic Ultrasound, 23. MRI Scan, 24. Other Imaging, 5. Head Injury, 26. Eye

  5. [Regulatory requirements for topical preparations].

    Science.gov (United States)

    Wohlrab, J; Klauck, D; Savtcheva, E

    2014-03-01

    Professional use of topical treatment in dermatological practice requires not only knowledge about the pharmacological properties, efficacy, safety and pharmaceutical quality of a preparation, but also about its regulatory classification. The latter essentially determines the physician's prescription practice and therapeutic freedom. The regulatory framework with which one is confronted unfortunately lacks transparency. It regulates not only the prescribability and reimbursability of proprietary medicinal products and extemporaneous preparations, but also the obligation to give information as well as the details of liability of both the prescriber (physician) and the manufacturer (pharmaceutical company or pharmacist). The prescriber needs to be aware of to what extent the pharmacist has the possibility and even obligation to change the prescribed preparation. In some cases this can directly affect the therapeutic concept of the physician and even impair the effectiveness and safety of the chosen therapy.

  6. Topics in Banach space theory

    CERN Document Server

    Albiac, Fernando

    2016-01-01

    This text provides the reader with the necessary technical tools and background to reach the frontiers of research without the introduction of too many extraneous concepts. Detailed and accessible proofs are included, as are a variety of exercises and problems. The two new chapters in this second edition are devoted to two topics of much current interest amongst functional analysts: Greedy approximation with respect to bases in Banach spaces and nonlinear geometry of Banach spaces. This new material is intended to present these two directions of research for their intrinsic importance within Banach space theory, and to motivate graduate students interested in learning more about them. This textbook assumes only a basic knowledge of functional analysis, giving the reader a self-contained overview of the ideas and techniques in the development of modern Banach space theory. Special emphasis is placed on the study of the classical Lebesgue spaces Lp (and their sequence space analogues) and spaces of continuous f...

  7. Synergetics introduction and advanced topics

    CERN Document Server

    Haken, Hermann

    2004-01-01

    This book is an often-requested reprint of two classic texts by H. Haken: "Synergetics. An Introduction" and "Advanced Synergetics". Synergetics, an interdisciplinary research program initiated by H. Haken in 1969, deals with the systematic and methodological approach to the rapidly growing field of complexity. Going well beyond qualitative analogies between complex systems in fields as diverse as physics, chemistry, biology, sociology and economics, Synergetics uses tools from theoretical physics and mathematics to construct an unifying framework within which quantitative descriptions of complex, self-organizing systems can be made. This may well explain the timelessness of H. Haken's original texts on this topic, which are now recognized as landmarks in the field of complex systems. They provide both the beginning graduate student and the seasoned researcher with solid knowledge of the basic concepts and mathematical tools. Moreover, they admirably convey the spirit of the pioneering work by the founder of ...

  8. Neutron transport simulation (selected topics)

    Science.gov (United States)

    Vaz, P.

    2009-10-01

    Neutron transport simulation is usually performed for criticality, power distribution, activation, scattering, dosimetry and shielding problems, among others. During the last fifteen years, innovative technological applications have been proposed (Accelerator Driven Systems, Energy Amplifiers, Spallation Neutron Sources, etc.), involving the utilization of intermediate energies (hundreds of MeV) and high-intensity (tens of mA) proton accelerators impinging in targets of high Z elements. Additionally, the use of protons, neutrons and light ions for medical applications (hadrontherapy) impose requirements on neutron dosimetry-related quantities (such as kerma factors) for biologically relevant materials, in the energy range starting at several tens of MeV. Shielding and activation related problems associated to the operation of high-energy proton accelerators, emerging space-related applications and aircrew dosimetry-related topics are also fields of intense activity requiring as accurate as possible medium- and high-energy neutron (and other hadrons) transport simulation. These applications impose specific requirements on cross-section data for structural materials, targets, actinides and biologically relevant materials. Emerging nuclear energy systems and next generation nuclear reactors also impose requirements on accurate neutron transport calculations and on cross-section data needs for structural materials, coolants and nuclear fuel materials, aiming at improved safety and detailed thermal-hydraulics and radiation damage studies. In this review paper, the state-of-the-art in the computational tools and methodologies available to perform neutron transport simulation is presented. Proton- and neutron-induced cross-section data needs and requirements are discussed. Hot topics are pinpointed, prospective views are provided and future trends identified.

  9. Topic supervised non-negative matrix factorization

    OpenAIRE

    MacMillan, Kelsey; Wilson, James D.

    2017-01-01

    Topic models have been extensively used to organize and interpret the contents of large, unstructured corpora of text documents. Although topic models often perform well on traditional training vs. test set evaluations, it is often the case that the results of a topic model do not align with human interpretation. This interpretability fallacy is largely due to the unsupervised nature of topic models, which prohibits any user guidance on the results of a model. In this paper, we introduce a se...

  10. Shielded Metal Arc Welding. Welding Module 4. Instructor's Guide.

    Science.gov (United States)

    Missouri Univ., Columbia. Instructional Materials Lab.

    This guide is intended to assist vocational educators in teaching an eight-unit module in shielded metal arc welding. The module is part of a welding curriculum that has been designed to be totally integrated with Missouri's Vocational Instruction Management System. The following topics are covered in the module: safety; theory, power sources, and…

  11. Gas Metal Arc Welding. Welding Module 5. Instructor's Guide.

    Science.gov (United States)

    Missouri Univ., Columbia. Instructional Materials Lab.

    This guide is intended to assist vocational educators in teaching an eight-unit module in gas metal arc welding. The module is part of a welding curriculum that has been designed to be totally integrated with Missouri's Vocational Instruction Management System. The following topics are covered in the module: safety and testing, gas metal arc…

  12. Place Value. Fundamentals of Occupational Mathematics. Module 1.

    Science.gov (United States)

    Engelbrecht, Nancy; And Others

    This module is the first in a series of 12 learning modules designed to teach occupational mathematics. Designed for improving machine shop technology skills, this module begins with an introduction to the topic. Blocks of informative material and rules are followed by examples and practice problems. The solutions to the practice problems are…

  13. Credibility improves topical blog post retrieval

    NARCIS (Netherlands)

    Weerkamp, W.; de Rijke, M.

    2008-01-01

    Topical blog post retrieval is the task of ranking blog posts with respect to their relevance for a given topic. To improve topical blog post retrieval we incorporate textual credibility indicators in the retrieval process. We consider two groups of indicators: post level (determined using

  14. Topical report review status: Volume 10

    International Nuclear Information System (INIS)

    1996-03-01

    This report provides industry with procedures for submitting topical reports, guidance on how the U.S. Nuclear Regulatory Commission (NRC) processes and responds to topical report submittals, and an accounting, with review schedules, of all topical reports currently accepted for review by the NRC. This report is published annually

  15. Topical treatments for cutaneous warts.

    Science.gov (United States)

    Kwok, Chun Shing; Gibbs, Sam; Bennett, Cathy; Holland, Richard; Abbott, Rachel

    2012-09-12

    Viral warts are a common skin condition, which can range in severity from a minor nuisance that resolve spontaneously to a troublesome, chronic condition. Many different topical treatments are available. To evaluate the efficacy of local treatments for cutaneous non-genital warts in healthy, immunocompetent adults and children. We updated our searches of the following databases to May 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), AMED (from 1985), LILACS (from 1982), and CINAHL (from 1981). We searched reference lists of articles and online trials registries for ongoing trials. Randomised controlled trials (RCTs) of topical treatments for cutaneous non-genital warts. Two authors independently selected trials and extracted data; a third author resolved any disagreements. We included 85 trials involving a total of 8815 randomised participants (26 new studies were included in this update). There was a wide range of different treatments and a variety of trial designs. Many of the studies were judged to be at high risk of bias in one or more areas of trial design.Trials of salicylic acid (SA) versus placebo showed that the former significantly increased the chance of clearance of warts at all sites (RR (risk ratio) 1.56, 95% CI (confidence interval) 1.20 to 2.03). Subgroup analysis for different sites, hands (RR 2.67, 95% CI 1.43 to 5.01) and feet (RR 1.29, 95% CI 1.07 to 1.55), suggested it might be more effective for hands than feet.A meta-analysis of cryotherapy versus placebo for warts at all sites favoured neither intervention nor control (RR 1.45, 95% CI 0.65 to 3.23). Subgroup analysis for different sites, hands (RR 2.63, 95% CI 0.43 to 15.94) and feet (RR 0.90, 95% CI 0.26 to 3.07), again suggested better outcomes for hands than feet. One trial showed cryotherapy to be better than both placebo and SA, but only for hand warts.There was no significant difference in cure rates between

  16. Tazarotene as alternative topical treatment for onychomycosis

    Directory of Open Access Journals (Sweden)

    Campione E

    2015-02-01

    Full Text Available Elena Campione,1 Evelin Jasmine Paternò,2 Gaetana Costanza,2,3 Laura Diluvio,1 Isabella Carboni,1 Daniele Marino,4 Cartesio Favalli,4 Sergio Chimenti,1 Luca Bianchi,1 Augusto Orlandi2,3 1Department of Dermatology, 2Department of Biomedicine and Prevention, 3Department of Anatomic Pathology, Policlinic Tor Vergata, 4Department of Microbiology, University of Rome Tor Vergata, Rome, Italy Background: Distal and lateral onychomycoses are the most frequent forms of onychomycosis, causing subungual hyperkeratosis that usually limits local penetration of antimycotic drugs. Tazarotene exerts anti-inflammatory and immune-modulating activities toward both infective agents and damaged keratinocytes. Given the well-documented efficacy of tazarotene on hyperkeratotic nail psoriasis, we investigated its therapeutic use in onychomycosis. Patients and methods: We designed a preliminary open clinical trial in patients affected by distal and lateral subungual onychomycosis of the toenails and verified the fungistatic activity of tazarotene in vitro. Fifteen patients were treated with topical tazarotene 0.1% gel once per day for 12 weeks. Mycological cultures and potassium hydroxide stains of nail samples were performed at the beginning and at the end of the study. Treatment was considered effective when clinical healing and negative mycological culture were obtained. Onycholysis, nail bed discoloration, and subungual hyperkeratosis were measured using standardized methodologies and analyzed by means of Mann–Whitney test and analysis of variance. Fungistatic activity of tazarotene was evaluated by disk diffusion assay. Results: Six patients (40% reached a mycological cure on target nail samples already after 4 weeks of treatment. Complete clinical healing and negative cultures were reached in all patients at week 12, with a significant improvement of all clinical parameters of the infected nails. Disk diffusion assay after 48 hours of incubation with

  17. Topic Space: Rapid Prototyping a Mobile Augmented Reality Recommendation App

    Directory of Open Access Journals (Sweden)

    Jim Hahn

    2015-10-01

    Full Text Available With funding from an Institute of Museum and Library Services (IMLS Sparks! Ignition Grant, researchers from the University of Illinois Library designed and tested a mobile recommender app with augmented reality features. By embedding open source optical character recognition software into a “Topic Space” module, the augmented reality app can recognize call numbers on a book in the library and suggest relevant items that are not shelved nearby. Topic Space can also show users items that are normally shelved in the starting location but that are currently checked out. Using formative UX methods, grant staff shaped app interface and functionality through early user testing. This paper reports results of UX testing; a redesigned mobile interface, and provides considerations on the future development of personalized recommendation functionality.

  18. Affirmative Action. Module Number 16. Work Experience Program Modules. Coordination Techniques Series.

    Science.gov (United States)

    Shawhan, Carl; Morley, Ray

    This self-instructional module, the last in a series of 16 on techniques for coordinating work experience programs, deals with affirmative action. Addressed in the module are the following topics: the nature of affirmative action legislation and regulations, the role of the teacher-coordinator as a resource person for affirmative action…

  19. Topical tacrolimus for atopic dermatitis.

    Science.gov (United States)

    Cury Martins, Jade; Martins, Ciro; Aoki, Valeria; Gois, Aecio F T; Ishii, Henrique A; da Silva, Edina M K

    2015-07-01

    Atopic dermatitis (AD) (or atopic eczema) is a chronic inflammatory skin condition that affects children and adults and has an important impact on quality of life. Topical corticosteroids (TCS) are the first-line therapy for this condition; however, they can be associated with significant adverse effects when used chronically. Tacrolimus ointment (in its 2 manufactured strengths of 0.1% and 0.03%) might be an alternative treatment. Tacrolimus, together with pimecrolimus, are drugs called topical calcineurin inhibitors (TCIs). To assess the efficacy and safety of topical tacrolimus for moderate and severe atopic dermatitis compared with other active treatments. We searched the following databases up to 3 June 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 5, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), and the Global Resource of Eczema Trials (GREAT database). We searched six trials registers and checked the bibliographies of included studies for further references to relevant trials. We contacted specialists in the field for unpublished data.A separate search for adverse effects of topical tacrolimus was undertaken in MEDLINE and EMBASE on 30 July 2013. We also scrutinised the U.S. Food and Drug Administration (FDA) websites for adverse effects information. All randomised controlled trials (RCTs) of participants with moderate to severe atopic dermatitis (both children and adults) using topical tacrolimus at any dose, course duration, and follow-up time compared with other active treatments. Two authors independently screened and examined the full text of selected studies for compliance with eligibility criteria, risk of bias, and data extraction. Our three prespecified primary outcomes were physician's assessment, participant's self-assessment of improvement, and adverse effects. Our secondary outcomes included assessment of improvement of the disease by validated or objective measures, such as

  20. Main technical topics in 1999

    International Nuclear Information System (INIS)

    2000-01-01

    This Safety Authority annual report strives to present current organizational provisions and future trends in nuclear safety supervision in France and to describe the most outstanding occurrences during the past year. A first part presents nine documents concerning the main topics of 1999: aging of nuclear installations, the Offsite Emergency Plans (PPI), the impact of nuclear activities on man and the environment, the criticality hazards, EDF in 1999, the EPR project, the Andra in 1999, the transport incidents, the nuclear safety in eastern Europe. The second part presents the missions and actions of the Nuclear Installations Safety in the domains of the liabilities, the organization of the nuclear safety control, the regulations of the INB, the public information, the international relations, the crisis management, the radioactive materials transportation, the radioactive wastes. The equipment, the radiation protection and the exploitation of the pressurized water reactors are also treated just as the experimental reactors, the fuel cycle installations and the the nuclear installations dismantling. (A.L.B.)

  1. Topics in theoretical surface science

    Energy Technology Data Exchange (ETDEWEB)

    Todd, R.

    1991-10-25

    The energetics and structures of clean and adsorbate covered surfaces are investigated in this dissertation. First, the formalism, within the Corrected Effective Medium (CEM) method, for calculating the surface energy of a clean surface is derived. The surface energies for many different metals and their low index surfaces are presented. The minimization of the surface energy is then used to predict the multilayer relaxation of the Al(111), (100), Ni(100), (110) and Fe(100) surfaces. Extensions of the surface CEM formalism to calculate the binding energies of ordered adsorbates on metals surfaces are also derived. The minimization of the binding energy allowed determination of the binding heights, sites and the extent of induced multilayer relaxation for H and N atoms on the Fe(110), (100) and W(110) surfaces. The last topic deals with the dynamics of the epitaxial growth of metals on metal surfaces. The CEM method was first modified by making approximations to enable faster evaluations of the potential and its corresponding forces for molecular dynamics simulations. The goal of these simulations was to identify the important steps in the formation of equilibrium epitaxial structures. 180 refs., 31 figs., 18 tabs.

  2. Topical absorption and systemic toxicity.

    Science.gov (United States)

    Alikhan, Fatima Sasha; Maibach, Howard

    2011-09-01

    Dermal absorption of some chemicals and drugs can cause systemic toxicity. We evaluated several case reports from the past decade, which discuss the dermal absorption of a specific chemical and potential local and systemic effects. We focused on herbicide and pesticide exposure along with exposure to cutaneous medication, occupational contact, and cosmeceutical exposure. Although causality cannot be established in most cases, it is critical to be aware of the possible effects of topical absorption that may not be immediately apparent. We recommended further studies on specific chemicals to ascertain causality and determine the highest exposure level with no observed adverse affect level (NOAEL) and the reference dose (RfD). Post-marketing epidemiology data in most geographical areas are markedly limited. A weak link in public health resides in the inadequate reporting and workup of alleged chemically related adverse effects. This arena mandates a re-thinking of how to increase this reporting, and workup, as a backup to our preclinical and clinical studies. Public awareness and funding will be rewarded by increased evidence to backup pre-approval pre-marketing studies.

  3. Decision Point 1 Topical Report

    Energy Technology Data Exchange (ETDEWEB)

    Yablonsky, Al; Barsoumian, Shant; Legere, David

    2013-05-01

    This Topical Report addresses accomplishments achieved during Phase 2a of the SkyMine® Carbon Mineralization Pilot Project. The primary objectives of this project are to design, construct, and operate a system to capture CO2 from a slipstream of flue gas from a commercial coal-fired cement kiln, convert that CO2 to products having commercial value (i.e., beneficial use), show the economic viability of the CO2 capture and conversion process, and thereby advance the technology to the point of readiness for commercial scale demonstration and proliferation. The overall process is carbon negative, resulting in mineralization of CO2 that would otherwise be released into the atmosphere. The project will also substantiate market opportunities for the technology by sales of chemicals into existing markets, and identify opportunities to improve technology performance and reduce costs at the commercial scale. The project is being conducted in two phases. The primary objectives of Phase 1 were to elaborate proven SkyMine® process chemistry to commercial pilot-scale operation and complete the preliminary design for the pilot plant to be built and operated in Phase 2, complete a NEPA evaluation, and develop a comprehensive carbon life cycle analysis. The objective of the current Phase (2a) is to complete the detailed design of the pilot plant to be built in Phase 2b.

  4. The Virtual Robotics Laboratory; TOPICAL

    International Nuclear Information System (INIS)

    Kress, R.L.; Love, L.J.

    1999-01-01

    The growth of the Internet has provided a unique opportunity to expand research collaborations between industry, universities, and the national laboratories. The Virtual Robotics Laboratory (VRL) is an innovative program at Oak Ridge National Laboratory (ORNL) that is focusing on the issues related to collaborative research through controlled access of laboratory equipment using the World Wide Web. The VRL will provide different levels of access to selected ORNL laboratory secondary education programs. In the past, the ORNL Robotics and Process Systems Division has developed state-of-the-art robotic systems for the Army, NASA, Department of Energy, Department of Defense, as well as many other clients. After proof of concept, many of these systems sit dormant in the laboratories. This is not out of completion of all possible research topics. but from completion of contracts and generation of new programs. In the past, a number of visiting professors have used this equipment for their own research. However, this requires that the professor, and possibly his/her students, spend extended periods at the laboratory facility. In addition, only a very exclusive group of faculty can gain access to the laboratory and hardware. The VRL is a tool that enables extended collaborative efforts without regard to geographic limitations

  5. Topics in Number Theory Conference

    CERN Document Server

    Andrews, George; Ono, Ken

    1999-01-01

    From July 31 through August 3,1997, the Pennsylvania State University hosted the Topics in Number Theory Conference. The conference was organized by Ken Ono and myself. By writing the preface, I am afforded the opportunity to express my gratitude to Ken for beng the inspiring and driving force behind the whole conference. Without his energy, enthusiasm and skill the entire event would never have occurred. We are extremely grateful to the sponsors of the conference: The National Sci­ ence Foundation, The Penn State Conference Center and the Penn State Depart­ ment of Mathematics. The object in this conference was to provide a variety of presentations giving a current picture of recent, significant work in number theory. There were eight plenary lectures: H. Darmon (McGill University), "Non-vanishing of L-functions and their derivatives modulo p. " A. Granville (University of Georgia), "Mean values of multiplicative functions. " C. Pomerance (University of Georgia), "Recent results in primality testing. " C. ...

  6. Identifying Topics in Microblogs Using Wikipedia.

    Directory of Open Access Journals (Sweden)

    Ahmet Yıldırım

    Full Text Available Twitter is an extremely high volume platform for user generated contributions regarding any topic. The wealth of content created at real-time in massive quantities calls for automated approaches to identify the topics of the contributions. Such topics can be utilized in numerous ways, such as public opinion mining, marketing, entertainment, and disaster management. Towards this end, approaches to relate single or partial posts to knowledge base items have been proposed. However, in microblogging systems like Twitter, topics emerge from the culmination of a large number of contributions. Therefore, identifying topics based on collections of posts, where individual posts contribute to some aspect of the greater topic is necessary. Models, such as Latent Dirichlet Allocation (LDA, propose algorithms for relating collections of posts to sets of keywords that represent underlying topics. In these approaches, figuring out what the specific topic(s the keyword sets represent remains as a separate task. Another issue in topic detection is the scope, which is often limited to specific domain, such as health. This work proposes an approach for identifying domain-independent specific topics related to sets of posts. In this approach, individual posts are processed and then aggregated to identify key tokens, which are then mapped to specific topics. Wikipedia article titles are selected to represent topics, since they are up to date, user-generated, sophisticated articles that span topics of human interest. This paper describes the proposed approach, a prototype implementation, and a case study based on data gathered during the heavily contributed periods corresponding to the four US election debates in 2012. The manually evaluated results (0.96 precision and other observations from the study are discussed in detail.

  7. Identifying Topics in Microblogs Using Wikipedia.

    Science.gov (United States)

    Yıldırım, Ahmet; Üsküdarlı, Suzan; Özgür, Arzucan

    2016-01-01

    Twitter is an extremely high volume platform for user generated contributions regarding any topic. The wealth of content created at real-time in massive quantities calls for automated approaches to identify the topics of the contributions. Such topics can be utilized in numerous ways, such as public opinion mining, marketing, entertainment, and disaster management. Towards this end, approaches to relate single or partial posts to knowledge base items have been proposed. However, in microblogging systems like Twitter, topics emerge from the culmination of a large number of contributions. Therefore, identifying topics based on collections of posts, where individual posts contribute to some aspect of the greater topic is necessary. Models, such as Latent Dirichlet Allocation (LDA), propose algorithms for relating collections of posts to sets of keywords that represent underlying topics. In these approaches, figuring out what the specific topic(s) the keyword sets represent remains as a separate task. Another issue in topic detection is the scope, which is often limited to specific domain, such as health. This work proposes an approach for identifying domain-independent specific topics related to sets of posts. In this approach, individual posts are processed and then aggregated to identify key tokens, which are then mapped to specific topics. Wikipedia article titles are selected to represent topics, since they are up to date, user-generated, sophisticated articles that span topics of human interest. This paper describes the proposed approach, a prototype implementation, and a case study based on data gathered during the heavily contributed periods corresponding to the four US election debates in 2012. The manually evaluated results (0.96 precision) and other observations from the study are discussed in detail.

  8. Selected topics of fluid mechanics

    Science.gov (United States)

    Kindsvater, Carl E.

    1958-01-01

    the Euler, Froude, Reynolds, Weber, and Cauchy numbers are defined as essential tools for interpreting and using experimental data. The derivations of the energy and momentum equations are treated in detail. One-dimensional equations for steady nonuniform flow are developed, and the restrictions applicable to the equations are emphasized. Conditions of uniform and gradually varied flow are discussed, and the origin of the Chezy equation is examined in relation to both the energy and the momentum equations. The inadequacy of all uniform-flow equations as a means of describing gradually varied flow is explained. Thus, one of the definitive problems of river hydraulics is analyzed in the light of present knowledge. This report is the outgrowth of a series of short schools conducted during the spring and summer of 1953 for engineers of the Surface Water Branch, Water Resources Division, U. S. Geological Survey. The topics considered are essentially the same as the topics selected for inclusion in the schools. However, in order that they might serve better as a guide and outline for informal study, the arrangement of the writer's original lecture notes has been considerably altered. The purpose of the report, like the purpose of the schools which inspired it, is to build a simple but strong framework of the fundamentals of fluid mechanics. It is believed that this framework is capable of supporting a detailed analysis of most of the practical problems met by the engineers of the Geological Survey. It is hoped that the least accomplishment of this work will be to inspire the reader with the confidence and desire to read more of the recent and current technical literature of modern fluid mechanics.

  9. Topical clonidine for neuropathic pain.

    Science.gov (United States)

    Wrzosek, Anna; Woron, Jaroslaw; Dobrogowski, Jan; Jakowicka-Wordliczek, Joanna; Wordliczek, Jerzy

    2015-08-31

    Clonidine is a presynaptic alpha-2-adrenergic receptor agonist used for many years to treat hypertension and other conditions, including chronic pain. Adverse events associated with systemic use of the drug have limited its application. Topical use of drugs is currently gaining interest, as it may limit adverse events without loss of analgesic efficacy. Topical clonidine (TC) formulations have been investigated recently in clinical trials. The objectives of this review were to assess the analgesic efficacy of TC for chronic neuropathic pain in adults and to assess the frequency of adverse events associated with clinical use of TC for chronic neuropathic pain. We searched the Cochrane Register of Studies (CRS) Online (Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE and EMBASE databases, reference lists of retrieved papers and trial registries, and we contacted experts in the field. We performed the most recent search on 17 September 2014. We included randomised, double-blind studies of at least two weeks' duration comparing TC versus placebo or other active treatment in patients with chronic neuropathic pain. Two review authors extracted data from the studies and assessed bias. We planned three tiers of evidence analysis. The first tier was designed to analyse data meeting current best standards, by which studies reported the outcome of at least 50% pain intensity reduction over baseline (or its equivalent) without use of the last observation carried forward or other imputation method for dropouts, reported an intention-to-treat (ITT) analysis, lasted eight weeks or longer, had a parallel-group design and included at least 200 participants (preferably at least 400) in the comparison. The second tier was designed to use data from at least 200 participants but in cases in which one of the above conditions was not met. The third tier of evidence was assumed in other situations. We included two studies in the review, with a total of 344 participants

  10. Recent Advances In Topical Therapy In Dermatology

    Directory of Open Access Journals (Sweden)

    Mohan Thappa Devinder

    2003-01-01

    Full Text Available With changing times various newer topical agents are introduced in the field of dermatology. Tacrolimus and pimecrolimus are immunisuppressants, which are effective topically and are tried in the management of atopic dermatitis as well as other disorders including allergic contact dermatitis, atrophic lichen planus, pyoderma gangrenosum. Imiquimod, an immune response modifier, is presently in use for genital warts but has potentials as anti- tumour agent and in various other dermatological conditions when used topically. Tazarotene is a newer addition to the list of topical reginoids, which is effective in psoriasis and has better effect in combination with calcipotriene, phototherapy and topical costicosteroids. Tazarotene and adapelene are also effective in inflammatory acne. Calcipotriol, a vitamin D analogue has been introduced as a topical agent in the treatment of psoriasis. Steroid components are also developed recently which will be devoid of the side effects but having adequate anti-inflammatory effect. Topical photodynamic therapy has also a wide range of use in dermatology. Newer topical agents including cidofovir, capsaicin, topical sensitizers, topical antifungal agents for onychomycosis are also of use in clinical practice. Other promising developments include skin substitutes and growth factors for wound care.

  11. Dense module enumeration in biological networks

    International Nuclear Information System (INIS)

    Tsuda, Koji; Georgii, Elisabeth

    2009-01-01

    Analysis of large networks is a central topic in various research fields including biology, sociology, and web mining. Detection of dense modules (a.k.a. clusters) is an important step to analyze the networks. Though numerous methods have been proposed to this aim, they often lack mathematical rigorousness. Namely, there is no guarantee that all dense modules are detected. Here, we present a novel reverse-search-based method for enumerating all dense modules. Furthermore, constraints from additional data sources such as gene expression profiles or customer profiles can be integrated, so that we can systematically detect dense modules with interesting profiles. We report successful applications in human protein interaction network analyses.

  12. Transportation life cycle assessment (LCA) synthesis : life cycle assessment learning module series.

    Science.gov (United States)

    2015-03-12

    The Life Cycle Assessment Learning Module Series is a set of narrated, self-advancing slideshows on : various topics related to environmental life cycle assessment (LCA). This research project produced the first 27 of such modules, which : are freely...

  13. Validation of an RPHPTLC-Densitometric Method Using Silica Gel 60 RP18WF254 for Simultaneous Determination of Nicotinamide in Selected Pharmaceutical Formulations

    Directory of Open Access Journals (Sweden)

    Małgorzata Dołowy

    2015-01-01

    Full Text Available This research study describes the applicability of silica gel 60 RPW18F254 plates for the development and validation of new, simple, economic, accurate, and precise RPHPTLC-densitometric method suitable for the quantification of nicotinamide (as Vitamin PP in three marketed preparations. The mobile phase used was methanol-water in volume composition 3 : 7. Detection wavelength was 200 nm. The proposed method was validated according to ICH guidelines and also based on Ferenczi-Fodor and Konieczka reports. Results were found to be linear over a range of 1.00 to 2.00 μg/spot. Limit of detection (LOD and limit of quantification (LOQ were 0.15 μg/spot and 0.45 μg/spot, respectively. The percent content of nicotinamide in the investigated preparations was found to be 99.2% (Product 1, 99.3% (Product 2, and 99.4% (Product 3. Developed method is accurate and precise (CV<3% and may be successfully applied for the quality control of pharmaceutical formulations containing nicotinamide in the presence of its derivatives, such as N,N-diethylnicotinamide, N-methylnicotinamide, and nicotinic acid.

  14. Affinity chromatography and binding studies on immobilized 5'-monophosphate and adenosine 2',5'-bisphosphate of nicotinamide nucleotide transhydrogenase from Pseudomonas aeruginosa.

    Science.gov (United States)

    Höjeberg, B; Brodelius, P; Rydström, J; Mosbach, K

    1976-07-15

    1. Nicotinamide nucleotide transhydrogenase from Pseudomonas aeruginosa was purified to apparent homogeneity with an improved method employing affinity chromatography on N6-(6aminohexyl)-adenosine 2', 5'-bisphosphate-Sepharose 4B. 2. Polyacrylamide gel electrophoresis of the purified transhydrogenase carried out in the presence of sodium dodecyl sulphate, indicated a minimal molecular weight of 55000 +/- 2000. 3. The kinetic and regulatory properties of the purified transhydrogenase resembled those of the crude enzyme, i.e., NADPH, adenosine 2'-monophosphate and Ca2+ were activators whereas NADP+ was inhibitory. 4. Nicotinamide nucleotide-specific release of binding of the transhydrogenase to N6-(6-aminohexyl)-adenosine-2',5'-bisphosphate-Sepharose and N6-(-aminohexyl)-adenosine-5'-monophosphate-Sepharose suggests the presence of at least two separate binding sites for nicotinamide nucleotides, one that is specific for NADP(H) and one that binds both NAD(H) and NADP(H). 5. Binding of transhydrogenase to N6-)6-aminohexyl)-adenosine-2',5'-bisphosphate-Sepharose and activation of the enzyme by adenosine-2',5'-bisphophate showed a marked pH dependence. In contrast, inhibition of the Ca2+-activated enzyme by adenosine 2',5'-bisphosphate was virtually constant at various pH values. This descrepancy was interpreted to indicate the existence of separate nucleotide-binding effector and active sites.

  15. Multimedia Activities in L2 Course Websites--A Case Study of a Site Dedicated to Cultural Topics of Portuguese-Speaking Countries

    Science.gov (United States)

    Vasconcelos, Ricardo

    2012-01-01

    This study examines student preferences and behavior when navigating online multimedia modules dedicated to teaching cultural aspects associated with an L2, and the contribution of the online multimedia format of the modules to raising interest in these cultural topics. It focuses on student options regarding reading texts on the modules' main…

  16. Topics in Extended Dynamical Systems

    Science.gov (United States)

    Bhagavatula, Ravi S.

    This thesis consists of three chapters. Each chapter is self-contained and is devoted to the investigation of a particular topic in extended dynamical systems. In the first chapter, an approach based on Langevin equations is implemented to understand the non-Gaussian nature of the probability distribution function (PDF) of local diffusive variables in extended dynamical systems, e.g., a passive scalar advected by turbulent velocity fluctuations. Two mechanisms are proposed for the origin of non-Gaussian tails: One relies on the nature of temporal correlations of the fluctuations that couple additively to the diffusive field, leading to exponential and stretched exponential tails in the PDF; the other depends on multiplicative coupling between the diffusive field and the fluctuations, producing algebraic tails in the PDF. The mechanisms are illustrated using models for a passive scalar and also a current driven Josephson junction array. This study indicates that shapes of local PDFs in turbulent states are non-universal and crucially depend on local couplings and time scales. The second chapter establishes the existence of a class of locally conserving chaotic (deterministic) systems that exhibit Generic Scale Invariance--algebraic decay of spatial and temporal correlations without tuning parameters. This study also reveals the similarity between noise and chaos in extended systems as far as long-wavelength and long -time behavior is concerned. Specifically, a two dimensional coupled-map lattice model with a conserved density is numerically shown to exhibit, in agreement with heuristic arguments, algebraic decay of spatio-temporal correlations in chaotic states with simple predictable exponents. The third chapter investigates scaling behavior of earthquakes in seismic zone models in which an earthquake is modeled by a quasi-static description that ignores short -time dynamics during an earthquake. The models incorporate the essential feature of long-ranged stress

  17. Topics in elementary particle physics

    Science.gov (United States)

    Jin, Xiang

    The author of this thesis discusses two topics in elementary particle physics: n-ary algebras and their applications to M-theory (Part I), and functional evolution and Renormalization Group flows (Part II). In part I, Lie algebra is extended to four different n-ary algebraic structure: generalized Lie algebra, Filippov algebra, Nambu algebra and Nambu-Poisson tensor; though there are still many other n-ary algebras. A natural property of Generalized Lie algebras — the Bremner identity, is studied, and proved with a totally different method from its original version. We extend Bremner identity to n-bracket cases, where n is an arbitrary odd integer. Filippov algebras do not focus on associativity, and are defined by the Fundamental identity. We add associativity to Filippov algebras, and give examples of how to construct Filippov algebras from su(2), bosonic oscillator, Virasoro algebra. We try to include fermionic charges into the ternary Virasoro-Witt algebra, but the attempt fails because fermionic charges keep generating new charges that make the algebra not closed. We also study the Bremner identity restriction on Nambu algebras and Nambu-Poisson tensors. So far, the only example 3-algebra being used in physics is the BLG model with 3-algebra A4, describing two M2-branes interactions. Its extension with Nambu algebra, BLG-NB model, is believed to describe infinite M2-branes condensation. Also, there is another propose for M2-brane interactions, the ABJM model, which is constructed by ordinary Lie algebra. We compare the symmetry properties between them, and discuss the possible approaches to include these three models into a grand unification theory. In Part II, we give an approximate solution for Schroeder's equations, based on series and conjugation methods. We use the logistic map as an example, and demonstrate that this approximate solution converges to known analytical solutions around the fixed point, around which the approximate solution is constructed

  18. Ensemble Topic Modeling via Matrix Factorization

    OpenAIRE

    Belford, Mark; MacNamee, Brian; Greene, Derek

    2016-01-01

    Topic models can provide us with an insight into the underlying latent structure of a large corpus of documents, facilitating knowledge discovery and information summarization. A range of methods have been proposed in the literature, including probabilistic topic models and techniques based on matrix factorization. However, these methods tend to have stochastic elements in their initialization, which can lead to their output being unstable. That is, if a topic modeling algorithm is applied to...

  19. Topic Signatures in Political Campaign Speeches

    OpenAIRE

    Gautrais , Clément; Cellier , Peggy; Quiniou , René; Termier , Alexandre

    2017-01-01

    International audience; Highlighting the recurrence of topics usage in candidates speeches is a key feature to identify the main ideas of each candidate during a political campaign. In this paper, we present a method combining standard topic modeling with signature mining for analyzing topic recurrence in speeches of Clinton and Trump during the 2016 American presidential campaign. The results show that the method extracts automatically the main ideas of each candidate and, in addition, provi...

  20. Tracking topic birth and death in LDA.

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Andrew T.; Robinson, David Gerald

    2011-09-01

    Most topic modeling algorithms that address the evolution of documents over time use the same number of topics at all times. This obscures the common occurrence in the data where new subjects arise and old ones diminish or disappear entirely. We propose an algorithm to model the birth and death of topics within an LDA-like framework. The user selects an initial number of topics, after which new topics are created and retired without further supervision. Our approach also accommodates many of the acceleration and parallelization schemes developed in recent years for standard LDA. In recent years, topic modeling algorithms such as latent semantic analysis (LSA)[17], latent Dirichlet allocation (LDA)[10] and their descendants have offered a powerful way to explore and interrogate corpora far too large for any human to grasp without assistance. Using such algorithms we are able to search for similar documents, model and track the volume of topics over time, search for correlated topics or model them with a hierarchy. Most of these algorithms are intended for use with static corpora where the number of documents and the size of the vocabulary are known in advance. Moreover, almost all current topic modeling algorithms fix the number of topics as one of the input parameters and keep it fixed across the entire corpus. While this is appropriate for static corpora, it becomes a serious handicap when analyzing time-varying data sets where topics come and go as a matter of course. This is doubly true for online algorithms that may not have the option of revising earlier results in light of new data. To be sure, these algorithms will account for changing data one way or another, but without the ability to adapt to structural changes such as entirely new topics they may do so in counterintuitive ways.

  1. Health Screening: MedlinePlus Health Topic

    Science.gov (United States)

    ... for You (Mayo Foundation for Medical Education and Research) TB Screening Tests (American Association for Clinical Chemistry) Genetics Genetic Testing: MedlinePlus Health Topic (National Library ...

  2. Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide

    Science.gov (United States)

    Harmayani, Eni; Sunarti

    2015-01-01

    The study aimed to evaluate the effect of kefir combination from goat milk and soy milk on lipid profile, plasma glucose, glutathione peroxidase (GPx) activity and the improvement of pancreatic β-cell in diabetic rats. Male rats were divided into five treatments: normal control, diabetic control, goat milk kefir, combination of goat milk-soy milk kefir and soy milk kefir. All rats were induced by streptooztocin-nicotinamide (STZ-NA), except for normal control. After 35 d experiment, the rats were sampled for blood, sacrificed and sampled for pancreatic tissues. Results showed that diabetic rats fed kefir combination had higher (pmilk or soy milk kefir. Decreasing of plasma glucose in diabetic rats fed kefir combination was higher (p<0.05) than rats fed goat millk kefir. The activity of GPx in diabetic rats fed three kinds of kefir were higher (p<0.01) than untreated diabetic rats. The average number of Langerhans and β-cells in diabetic rats fed kefir combination was the same as the normal control, but it was higher than diabetic control. It was concluded that kefir combination can be used as antidiabetic through maintaining in serum triglyceride, decreasing in plasma glucose, increasing in GPx activity and improving in pancreatic β-cells. PMID:26877646

  3. Nicotinamide-NAD sequence: redox process and related behavior, behavior and properties of intermediate and final products

    International Nuclear Information System (INIS)

    Elving, P.J.; Schmakel, C.O.; Santhanam, K.S.V.

    1976-01-01

    Illustrations of the application of analytical chemical techniques to the study of chemical phenomena are given. In particular, electrochemical techniques and methodology and, to a lesser extent, spectrophotometry were used to investigate the solution behavior, adsorption, redox processes including coupled chemical reactions, and allied aspects of biologically significant compounds and of their intermediate and final redox products, e.g., the behavior of the free radicals produced by initial one-electron processes. This approach is illustrated by the consideration of the behavior in aqueous and nonaqueous media of a sequence of compounds ranging from nicotinamide (3-carbamoylpyridine) to NAD + and NADP + ; the latter compounds function as coenzymes for the pyridinoproteins which are principal components in the Krebs citric acid cycle and in the electron transport chain in biological redox reactions. The discussion is presented under the following section headings: interpretation of electrochemical behavior; mechanistic patterns; kinetic aspects of charge-transfer and chemical reactions; correlation with theoretically calculated parameters; and, mechanisms of biological oxidation-reduction reactions. The use of pulse radiolysis, chronopotentiometric, and cyclic voltammetric methods in studies on free radical dimerization rates is reviewed in the discussion of the kinetic aspects of charge-transfer and chemical reactions. (188 references)

  4. Effect of a mixture of caffeine and nicotinamide on the solubility of vitamin (B2) in aqueous solution.

    Science.gov (United States)

    Evstigneev, M P; Evstigneev, V P; Santiago, A A Hernandez; Davies, D B

    2006-05-01

    The effect of caffeine (CAF) and nicotinamide (NMD) on the solubility of a vitamin B2 derivative (FMN) has been evaluated for mixtures containing either a single hydrotrope (CAF or NMD) or the two hydrotropes simultaneously. A model for analysis of ternary systems, which takes into account all possible complexes between the molecules, has been developed and tested with experimental NMR data on the three-component mixture FMN-CAF-NMD. The results indicate that special attention should be given to the concentration of a hydrotropic agent used to enhance the solubility of a particular drug. A decrease in the efficacy of solubility of the vitamin on addition of large amounts of hydrotropic agent is expected in the two-component systems due to the increased proportion of self-association of the hydrotrope. It is found that a mixture of two hydrotropic agents leads to an increase in the solubility of the vitamin in three-component compared to the two-component system. Rather than using just one hydrotropic agent, it is proposed that a strategy for optimising the solubility of aromatic drugs is to use a mixture of hydrotropic agents.

  5. Photosensitized oxidation of nicotinamide adenine dinucleotide by diethoxyphosphorus(V)tetraphenylporphyrin and its fluorinated derivative: Possibility of chain reaction

    Science.gov (United States)

    Hirakawa, Kazutaka; Murata, Atsushi

    2018-01-01

    Water-soluble porphyrins, diethoxyphosphorus(V)tetraphenylporphyrin (EtP(V)TPP) and its fluorinated analogue (FEtP(V)TPP), decreased the typical absorption around 340 nm of nicotinamide adenine dinucleotide (NADH) under visible light irradiation, indicating oxidative decomposition. A singlet oxygen quencher, sodium azide, and a triplet quencher, potassium iodide, slightly inhibited photosensitized NADH oxidation. However, these inhibitory effects were very small. Furthermore, the fluorescence lifetime of these P(V)porphyrins was decreased by NADH, suggesting the contribution of electron transfer to the singlet excited (S1) state of P(V)porphyrin. The redox potential measurement supports the electron transfer-mediated oxidation of NADH. The quantum yields of NADH photodecomposition by P(V)porphyrins could be estimated from the kinetic data and the effect of these quenchers on NADH oxidation. The obtained values suggest that the electron accepting by the S1 states of P(V)porphyrins triggers a chain reaction of NADH oxidation. This photosensitized reaction may play an important role in the photocytotoxicity of P(V)porphyrins. The axial ligand fluorination of P(V)porphyrins improved electron accepting ability. However, fluorination slightly suppressed static interaction with NADH, resulting in decreased oxidation quantum yield.

  6. Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation.

    Science.gov (United States)

    Lozoya, Oswaldo A; Martinez-Reyes, Inmaculada; Wang, Tianyuan; Grenet, Dagoberto; Bushel, Pierre; Li, Jianying; Chandel, Navdeep; Woychik, Richard P; Santos, Janine H

    2018-04-18

    Mitochondrial function affects many aspects of cellular physiology, and, most recently, its role in epigenetics has been reported. Mechanistically, how mitochondrial function alters DNA methylation patterns in the nucleus remains ill defined. Using a cell culture model of induced mitochondrial DNA (mtDNA) depletion, in this study we show that progressive mitochondrial dysfunction leads to an early transcriptional and metabolic program centered on the metabolism of various amino acids, including those involved in the methionine cycle. We find that this program also increases DNA methylation, which occurs primarily in the genes that are differentially expressed. Maintenance of mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation in the context of mtDNA loss rescues methionine salvage and polyamine synthesis and prevents changes in DNA methylation and gene expression but does not affect serine/folate metabolism or transsulfuration. This work provides a novel mechanistic link between mitochondrial function and epigenetic regulation of gene expression that involves polyamine and methionine metabolism responding to changes in the tricarboxylic acid (TCA) cycle. Given the implications of these findings, future studies across different physiological contexts and in vivo are warranted.

  7. Cofactor balance by nicotinamide nucleotide transhydrogenase (NNT) coordinates reductive carboxylation and glucose catabolism in the tricarboxylic acid (TCA) cycle.

    Science.gov (United States)

    Gameiro, Paulo A; Laviolette, Laura A; Kelleher, Joanne K; Iliopoulos, Othon; Stephanopoulos, Gregory

    2013-05-03

    Cancer and proliferating cells exhibit an increased demand for glutamine-derived carbons to support anabolic processes. In addition, reductive carboxylation of α-ketoglutarate by isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) was recently shown to be a major source of citrate synthesis from glutamine. The role of NAD(P)H/NAD(P)(+) cofactors in coordinating glucose and glutamine utilization in the tricarboxylic acid (TCA) cycle is not well understood, with the source(s) of NADPH for the reductive carboxylation reaction remaining unexplored. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial enzyme that transfers reducing equivalents from NADH to NADPH. Here, we show that knockdown of NNT inhibits the contribution of glutamine to the TCA cycle and activates glucose catabolism in SkMel5 melanoma cells. The increase in glucose oxidation partially occurred through pyruvate carboxylase and rendered NNT knockdown cells more sensitive to glucose deprivation. Importantly, knocking down NNT inhibits reductive carboxylation in SkMel5 and 786-O renal carcinoma cells. Overexpression of NNT is sufficient to stimulate glutamine oxidation and reductive carboxylation, whereas it inhibits glucose catabolism in the TCA cycle. These observations are supported by an impairment of the NAD(P)H/NAD(P)(+) ratios. Our findings underscore the role of NNT in regulating central carbon metabolism via redox balance, calling for other mechanisms that coordinate substrate preference to maintain a functional TCA cycle.

  8. Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide.

    Science.gov (United States)

    Nurliyani; Harmayani, Eni; Sunarti

    2015-01-01

    The study aimed to evaluate the effect of kefir combination from goat milk and soy milk on lipid profile, plasma glucose, glutathione peroxidase (GPx) activity and the improvement of pancreatic β-cell in diabetic rats. Male rats were divided into five treatments: normal control, diabetic control, goat milk kefir, combination of goat milk-soy milk kefir and soy milk kefir. All rats were induced by streptooztocin-nicotinamide (STZ-NA), except for normal control. After 35 d experiment, the rats were sampled for blood, sacrificed and sampled for pancreatic tissues. Results showed that diabetic rats fed kefir combination had higher (pkefir. Decreasing of plasma glucose in diabetic rats fed kefir combination was higher (pkefir. The activity of GPx in diabetic rats fed three kinds of kefir were higher (pkefir combination was the same as the normal control, but it was higher than diabetic control. It was concluded that kefir combination can be used as antidiabetic through maintaining in serum triglyceride, decreasing in plasma glucose, increasing in GPx activity and improving in pancreatic β-cells.

  9. Design and production of various fusion proteins of the nicotinamide/nicotinate mononucleotide adenilil transferase (NMNAT of Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Carlos Alfonso Nieto Clavijo

    2017-09-01

    Full Text Available Recombinant proteins have become useful tools in biochemistry research. During their production, however, inclusion bodies (IB appear, on the one hand, due to the high expression rate from the recombinant plasmids, which have high efficiency promoters, and, on the other hand, intrinsic characteristics of the expressed protein. Furhtermore, the nicotinamide/nicotinate mononucleotide adenilyl transferase (NMNAT is a central protein in NAD(H+ biosynthesis, an essential cofactor in cell metabolism, and in protozoon parasite has been studied. To study the NMNAT protein of these parasites, their recombinant version in E. coli has been expressed, getting a great quantity of IB as a by-product. To increase the solubility of the protein, the coding sequence of the NMNAT enzyme of Plasmodium falciparum was cloned in different expression plasmids which were subsequently transformed into E. coli BL21(DE3 expression strain. The solubility of the recombinant proteins was assessed and the one with the highest presence in the soluble fraction was subsequently purified and its enzyme activity was determined. The recombinant protein with a MBP (maltose-binding protein tag showed an increased solubility and purity.

  10. Deficiency of Nicotinamide Mononucleotide Adenylyltransferase 3 (Nmnat3) Causes Hemolytic Anemia by Altering the Glycolytic Flow in Mature Erythrocytes*

    Science.gov (United States)

    Hikosaka, Keisuke; Ikutani, Masashi; Shito, Masayuki; Kazuma, Kohei; Gulshan, Maryam; Nagai, Yoshinori; Takatsu, Kiyoshi; Konno, Katsuhiro; Tobe, Kazuyuki; Kanno, Hitoshi; Nakagawa, Takashi

    2014-01-01

    NAD biosynthesis is of substantial interest because of its important roles in regulating various biological processes. Nicotinamide mononucleotide adenylyltransferase 3 (Nmnat3) is considered a mitochondria-localized NAD synthesis enzyme involved in de novo and salvage pathways. Although the biochemical properties of Nmnat3 are well documented, its physiological function in vivo remains unclear. In this study, we demonstrated that Nmnat3 was localized in the cytoplasm of mature erythrocytes and critically regulated their NAD pool. Deficiency of Nmnat3 in mice caused splenomegaly and hemolytic anemia, which was associated with the findings that Nmnat3-deficient erythrocytes had markedly lower ATP levels and shortened lifespans. However, the NAD level in other tissues were not apparently affected by the deficiency of Nmnat3. LC-MS/MS-based metabolomics revealed that the glycolysis pathway in Nmnat3-deficient erythrocytes was blocked at a glyceraldehyde 3-phosphate dehydrogenase (GAPDH) step because of the shortage of the coenzyme NAD. Stable isotope tracer analysis further demonstrated that deficiency of Nmnat3 resulted in glycolysis stall and a shift to the pentose phosphate pathway. Our findings indicate the critical roles of Nmnat3 in maintenance of the NAD pool in mature erythrocytes and the physiological impacts at its absence in mice. PMID:24739386

  11. Converting NADH to NAD+ by nicotinamide nucleotide transhydrogenase as a novel strategy against mitochondrial pathologies during aging.

    Science.gov (United States)

    Olgun, Abdullah

    2009-08-01

    Mitochondrial DNA defects are involved supposedly via free radicals in many pathologies including aging and cancer. But, interestingly, free radical production was not found increased in prematurely aging mice having higher mutation rate in mtDNA. Therefore, some other mechanisms like the increase of mitochondrial NADH/NAD(+) and ubiquinol/ubiquinone ratios, can be in action in respiratory chain defects. NADH/NAD(+) ratio can be normalized by the activation or overexpression of nicotinamide nucleotide transhydrogenase (NNT), a mitochondrial enzyme catalyzing the following very important reaction: NADH + NADP(+ ) NADPH + NAD(+). The products NAD(+) and NADPH are required in many critical biological processes, e.g., NAD(+) is used by histone deacetylase Sir2 which regulates longevity in different species. NADPH is used in a number of biosynthesis reactions (e.g., reduced glutathione synthesis), and processes like apoptosis. Increased ubiquinol/ubiquinone ratio interferes the function of dihydroorotate dehydrogenase, the only mitochondrial enzyme involved in ubiquinone mediated de novo pyrimidine synthesis. Uridine and its prodrug triacetyluridine are used to compensate pyrimidine deficiency but their bioavailability is limited. Therefore, the normalization of the ubiquinol/ubiquinone ratio can be accomplished by allotopic expression of alternative oxidase, a mitochondrial ubiquinol oxidase which converts ubiquinol to ubiquinone.

  12. Red algae (Gelidium amansii reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide

    Directory of Open Access Journals (Sweden)

    Tsung-Han Yang

    2015-12-01

    Full Text Available Gelidium amansii (GA is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1 rats without diabetes fed a high-fat diet (control group; (2 rats with diabetes fed a high-fat diet; (3 rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4 rats with diabetes fed a high-fat diet and GA. The experimental diet and drinking water were available ad libitum for 11 weeks. After the 11-week feeding study, plasma glucose, triglyceride, and cholesterol concentrations were lower in rats with diabetes fed the GA diet than in animals with diabetes fed the control diet. In addition, cholesterol and triglyceride excretion were significantly higher in rats with diabetes fed the GA diet. Moreover, GA feeding induced lipolysis in both paraepididymal and perirenal adipose tissues. Adipose tissue (paraepididymal and perirenal weight and triglyceride contents were lower after GA treatment. Plasma adipocytokines including tumor necrosis factor-alpha, interleukin-6, and plasminogen activator inhibitor-1 were reduced by GA feeding in rats with diabetes. The results of the current study suggest that GA feeding may regulate plasma glucose and lipid levels and prevent adipose tissue accumulation in rats with diabetes.

  13. Topical cholesterol in clofazimine induced ichthyosis

    Directory of Open Access Journals (Sweden)

    Pandey S

    1994-01-01

    Full Text Available Topical application of 10% cholesterol in petrolatum significantly (P< 0.05 controlled the development of ichthyosis in 62 patients taking 100 mg clofazimine daily for a period of 3 months. However, topical cholesterol application did not affect the lowering of serum cholesterol induced by oral clofazimine. Probable mechanism of action is being discussed.

  14. Aerodynamics of wind turbines emerging topics

    CERN Document Server

    Amano, R S

    2014-01-01

    Focusing on Aerodynamics of Wind Turbines with topics ranging from Fundamental to Application of horizontal axis wind turbines, this book presents advanced topics including: Basic Theory for Wind turbine Blade Aerodynamics, Computational Methods, and Special Structural Reinforcement Technique for Wind Turbine Blades.

  15. Topical silver for treating infected wounds

    NARCIS (Netherlands)

    Vermeulen, H.; van Hattem, J. M.; Storm-Versloot, M. N.; Ubbink, D. T.

    2007-01-01

    BACKGROUND: Topical silver treatments and silver dressings are increasingly used for the local treatment of contaminated or infected wounds, however, there is a lack of clarity regarding the evidence for their effectiveness. OBJECTIVES: To evaluate the effects on wound healing of topical silver and

  16. Topical treatment options for allergic conjunctivitis

    African Journals Online (AJOL)

    of topical dual-acting agents which have mast cell stabilising properties and act as antihistamines. Although corticosteroids are among the most effective agents in the treatment of .... diclofenac, has been shown to reduce ocular inflammation in VKC, and to reduce topical steroid use in these patients.9. Although ketorolac ...

  17. Anesthesia: A Topic for Interdisciplinary Study.

    Science.gov (United States)

    Labianca, Dominick A.; Reeves, William J.

    1977-01-01

    Describes an interdisciplinary approach for teaching the topic of anesthesia as one aspect of a chemistry-oriented course for nonscience majors which focuses on timely topics such as the energy crisis and drugs. Historical treatment with the examination of literature is emphasized in teaching. (HM)

  18. Croup: MedlinePlus Health Topic

    Science.gov (United States)

    ... Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Health Topics → Croup URL of this page: https://medlineplus.gov/croup.html Croup Also called: Spasmodic croup, Viral croup Summary Croup is an inflammation of the ...

  19. Behavior Analysis of Elderly using Topic Models

    NARCIS (Netherlands)

    Rieping, K.; Englebienne, G.; Kröse, B.

    2014-01-01

    This paper describes two new topic models for the analysis of human behavior in homes that are equipped with sensor networks. The models are based on Latent Dirichlet Allocation (LDA) topic models and can detect patterns in sensor data in an unsupervised manner. LDA-Gaussian, the first variation of

  20. Fostering Topic Knowledge: Essential for Academic Writing

    Science.gov (United States)

    Proske, Antje; Kapp, Felix

    2013-01-01

    Several researchers emphasize the role of the writer's topic knowledge for writing. In academic writing topic knowledge is often constructed by studying source texts. One possibility to support that essential phase of the writing process is to provide interactive learning questions which facilitate the construction of an adequate situation…

  1. Exploring Topic Structure: Coherence, Diversity and Relatedness

    NARCIS (Netherlands)

    J. He (Jiyin)

    2011-01-01

    htmlabstractThe use of topical information has long been studied in the context of information retrieval. For example, grouping search results into topical categories enables more effective information presentation to users, while grouping documents in a collection can lead to efficient information

  2. Corneal staining after treatment with topical tetracycline

    NARCIS (Netherlands)

    Lapid-Gortzak, Ruth; Nieuwendaal, Carla P.; Slomovic, Allan R.; Spanjaard, Lodewijk

    2006-01-01

    PURPOSE: The purpose of this paper is to report a case of corneal staining after treatment with topical tetracycline. METHODS: A patient with crystalline keratopathy caused by Streptococcus viridans after corneal transplantation was treated topically with tetracycline eye drops, based on results of

  3. Topic Time Series Analysis of Microblogs

    Science.gov (United States)

    2014-10-01

    of residence. Topic 158, Distance: 3.7809 Top words: 1. tracking 2. graffiti 3. station 4. plaza 5. mariachi Analysis: This topic describes Tweets by a... graffiti tracking service hired by the LA Metro Link. On the righthand side are the locations of the Metro Link stations in the area, which

  4. Infantile generalized hypertrichosis caused by topical minoxidil.

    Science.gov (United States)

    Rampon, Greice; Henkin, Caroline; de Souza, Paulo Ricardo Martins; Almeida, Hiram Larangeira de

    2016-01-01

    Rare cases of hypertrichosis have been associated with topically applied minoxidil. We present the first reported case in the Brazilian literature of generalized hypertrichosis affecting a 5-year-old child, following use of minoxidil 5%, 20 drops a day, for hair loss. The laboratory investigation excluded hyperandrogenism and thyroid dysfunction. Topical minoxidil should be used with caution in children.

  5. Infantile generalized hypertrichosis caused by topical minoxidil*

    Science.gov (United States)

    Rampon, Greice; Henkin, Caroline; de Souza, Paulo Ricardo Martins; de Almeida Jr, Hiram Larangeira

    2016-01-01

    Rare cases of hypertrichosis have been associated with topically applied minoxidil. We present the first reported case in the Brazilian literature of generalized hypertrichosis affecting a 5-year-old child, following use of minoxidil 5%, 20 drops a day, for hair loss. The laboratory investigation excluded hyperandrogenism and thyroid dysfunction. Topical minoxidil should be used with caution in children. PMID:26982785

  6. Correlated Topic Vector for Scene Classification.

    Science.gov (United States)

    Wei, Pengxu; Qin, Fei; Wan, Fang; Zhu, Yi; Jiao, Jianbin; Ye, Qixiang

    2017-07-01

    Scene images usually involve semantic correlations, particularly when considering large-scale image data sets. This paper proposes a novel generative image representation, correlated topic vector, to model such semantic correlations. Oriented from the correlated topic model, correlated topic vector intends to naturally utilize the correlations among topics, which are seldom considered in the conventional feature encoding, e.g., Fisher vector, but do exist in scene images. It is expected that the involvement of correlations can increase the discriminative capability of the learned generative model and consequently improve the recognition accuracy. Incorporated with the Fisher kernel method, correlated topic vector inherits the advantages of Fisher vector. The contributions to the topics of visual words have been further employed by incorporating the Fisher kernel framework to indicate the differences among scenes. Combined with the deep convolutional neural network (CNN) features and Gibbs sampling solution, correlated topic vector shows great potential when processing large-scale and complex scene image data sets. Experiments on two scene image data sets demonstrate that correlated topic vector improves significantly the deep CNN features, and outperforms existing Fisher kernel-based features.

  7. Atopic dermatitis: skin care and topical therapies.

    Science.gov (United States)

    Fleischer, David M; Udkoff, Jeremy; Borok, Jenna; Friedman, Adam; Nicol, Noreen; Bienstock, Jeffrey; Lio, Peter; Tollefson, Megha M; Eichenfield, Lawrence F

    2017-09-01

    Atopic dermatitis (AD) pathogenesis is strongly influenced by Type 2 innate lymphoid cell and T-helper cell type 2 lymphocyte-driven inflammation and skin barrier dysfunction. AD therapies attempt to correct this pathology, and guidelines suggest suggest basics of AD therapy, which include repair of the skin barrier through bathing practices and moisturizers, infection control, and further lifestyle modifications to avoid and reduce AD triggers.While some patients' AD may be controlled using these measures, inflammatory eczema including acute flares and maintenance therapy in more severe patients are treated with topical pharmacologic agents such as topical corticosteroids, topical calcineurin inhibitors, and, more recently, topical PDE-4 inhibitors. This model of basic skin therapy and, as needed, topical pharmacologic agents may be used to treat the vast majority of patients with AD and remains the staple of AD therapy. ©2017 Frontline Medical Communications.

  8. Topics on Electricity Transmission Pricing

    Energy Technology Data Exchange (ETDEWEB)

    Bjoerndal, Mette

    2000-02-01

    Directorate (NVE). To prevent cross-subsidization, the largest state-owned firm was split to form Statkraft SF, Norway's largest generation company, and Statnett SF, the major transmission company. Statnett is also the system operator of the entire Norwegian power system. Many distribution companies, usually publicly owned, are still part of vertically integrated companies, but there is strict separation of the financial accounts for transmission/distribution and generation/marketing. Trading is accomplished through several channels. The largest organized market is the common Norwegian-Swedish pool, NordPool. NordPool ASA is owned by Statnett Marked (which is a subsidiary of Statnett) and the Swedish grid-company, Svenska Kraftnaet. NordPool also supports the Finnish and Danish markets, thus through cooperation with the grid-companies of Denmark (Eltra) and Finland (Fingrid), locational markets are provided in these countries as well. Unlike England and Wales, only part of actual production is traded on this market. In addition, independent brokers offer various energy-contracts and facilitate bilateral contracts. In 1998 22% of the energy was traded on the hourly day-ahead (spot) market of NordPool. NordPool also organizes a forward and futures market and settles contracts from the regulation market organized by Statnett. The regulation market is a realtime market used to settle imbalances in real time. In total, close to 30% of the energy traded is organized through NordPool, and this share is increasing year by year. The efficiency of the market is heavily affected by the operation and pricing of the transmission system, and the topic of this thesis concerns the interaction of the transmission network and the energy markets. Throughout, the findings are illustrated by means of simple examples. This is to enhance readability and intuition. Chapter 2 is devoted to power flow models, whereas chapter 3 provides an overview of models developed to efficiently coordinate the

  9. Topics on Electricity Transmission Pricing

    International Nuclear Information System (INIS)

    Bjoerndal, Mette

    2000-02-01

    -subsidization, the largest state-owned firm was split to form Statkraft SF, Norway's largest generation company, and Statnett SF, the major transmission company. Statnett is also the system operator of the entire Norwegian power system. Many distribution companies, usually publicly owned, are still part of vertically integrated companies, but there is strict separation of the financial accounts for transmission/distribution and generation/marketing. Trading is accomplished through several channels. The largest organized market is the common Norwegian-Swedish pool, NordPool. NordPool ASA is owned by Statnett Marked (which is a subsidiary of Statnett) and the Swedish grid-company, Svenska Kraftnaet. NordPool also supports the Finnish and Danish markets, thus through cooperation with the grid-companies of Denmark (Eltra) and Finland (Fingrid), locational markets are provided in these countries as well. Unlike England and Wales, only part of actual production is traded on this market. In addition, independent brokers offer various energy-contracts and facilitate bilateral contracts. In 1998 22% of the energy was traded on the hourly day-ahead (spot) market of NordPool. NordPool also organizes a forward and futures market and settles contracts from the regulation market organized by Statnett. The regulation market is a realtime market used to settle imbalances in real time. In total, close to 30% of the energy traded is organized through NordPool, and this share is increasing year by year. The efficiency of the market is heavily affected by the operation and pricing of the transmission system, and the topic of this thesis concerns the interaction of the transmission network and the energy markets. Throughout, the findings are illustrated by means of simple examples. This is to enhance readability and intuition. To start with, chapter 2 is devoted to power flow models, whereas chapter 3 provides an overview of models developed to efficiently coordinate the allocation of transmission

  10. Topics in Electricity Transmission Pricing

    Energy Technology Data Exchange (ETDEWEB)

    Bjoerndal, Mette

    2000-02-01

    Directorate (NVE). To prevent cross-subsidization, the largest state-owned firm was split to form Statkraft SF, Norway's largest generation company, and Statnett SF, the major transmission company. Statnett is also the system operator of the entire Norwegian power system. Many distribution companies, usually publicly owned, are still part of vertically integrated companies, but there is strict separation of the financial accounts for transmission/distribution and generation/marketing. Trading is accomplished through several channels. The largest organized market is the common Norwegian-Swedish pool, NordPool. NordPool ASA is owned by Statnett Marked (which is a subsidiary of Statnett) and the Swedish grid-company, Svenska Kraftnaet. NordPool also supports the Finnish and Danish markets, thus through cooperation with the grid-companies of Denmark (Eltra) and Finland (Fingrid), locational markets are provided in these countries as well. Unlike England and Wales, only part of actual production is traded on this market. In addition, independent brokers offer various energy-contracts and facilitate bilateral contracts. In 1998 22% of the energy was traded on the hourly day-ahead (spot) market of NordPool. NordPool also organizes a forward and futures market and settles contracts from the regulation market organized by Statnett. The regulation market is a realtime market used to settle imbalances in real time. In total, close to 30% of the energy traded is organized through NordPool, and this share is increasing year by year. The efficiency of the market is heavily affected by the operation and pricing of the transmission system, and the topic of this thesis concerns the interaction of the transmission network and the energy markets. Throughout, the findings are illustrated by means of simple examples. This is to enhance readability and intuition. To start with, chapter 2 is devoted to power flow models, whereas chapter 3 provides an overview of models developed to efficiently

  11. 76 FR 81806 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

    Science.gov (United States)

    2011-12-29

    .... FDA-2011-N-0003] Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution... solution of ivermectin. DATES: This rule is effective December 29, 2011. FOR FURTHER INFORMATION CONTACT... ANADA 200-318 for [[Page 81807

  12. What Patients Can Tell Us: Topic Analysis for Social Media on Breast Cancer.

    Science.gov (United States)

    Tapi Nzali, Mike Donald; Bringay, Sandra; Lavergne, Christian; Mollevi, Caroline; Opitz, Thomas

    2017-07-31

    Social media dedicated to health are increasingly used by patients and health professionals. They are rich textual resources with content generated through free exchange between patients. We are proposing a method to tackle the problem of retrieving clinically relevant information from such social media in order to analyze the quality of life of patients with breast cancer. Our aim was to detect the different topics discussed by patients on social media and to relate them to functional and symptomatic dimensions assessed in the internationally standardized self-administered questionnaires used in cancer clinical trials (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Core 30 [QLQ-C30] and breast cancer module [QLQ-BR23]). First, we applied a classic text mining technique, latent Dirichlet allocation (LDA), to detect the different topics discussed on social media dealing with breast cancer. We applied the LDA model to 2 datasets composed of messages extracted from public Facebook groups and from a public health forum (cancerdusein.org, a French breast cancer forum) with relevant preprocessing. Second, we applied a customized Jaccard coefficient to automatically compute similarity distance between the topics detected with LDA and the questions in the self-administered questionnaires used to study quality of life. Among the 23 topics present in the self-administered questionnaires, 22 matched with the topics discussed by patients on social media. Interestingly, these topics corresponded to 95% (22/23) of the forum and 86% (20/23) of the Facebook group topics. These figures underline that topics related to quality of life are an important concern for patients. However, 5 social media topics had no corresponding topic in the questionnaires, which do not cover all of the patients' concerns. Of these 5 topics, 2 could potentially be used in the questionnaires, and these 2 topics corresponded to a total of 3.10% (523

  13. The B vitamins nicotinamide (B3) and riboflavin (B2) stimulate metamorphosis in larvae of the deposit-feeding polychaete Capitella teleta: implications for a sensory ligand-gated ion channel.

    Science.gov (United States)

    Burns, Robert T; Pechenik, Jan A; Biggers, William J; Scavo, Gia; Lehman, Christopher

    2014-01-01

    Marine sediments can contain B vitamins, presumably incorporated from settled, decaying phytoplankton and microorganisms associated with decomposition. Because B vitamins may be advantageous for the energetically intensive processes of metamorphosis, post-metamorphic growth, and reproduction, we tested several B vitamins to determine if they would stimulate larvae of the deposit-feeding polychaete Capitella teleta to settle and metamorphose. Nicotinamide and riboflavin individually stimulated larvae of C. teleta to settle and metamorphose, generally within 1-2 hours at nicotinamide concentrations as low as 3 µM and riboflavin concentrations as low as 50 µM. More than 80% of the larvae metamorphosed within 30 minutes at a nicotinamide concentration of 7 µM. The pyridine channel agonist pyrazinecarboxamide also stimulated metamorphosis at very low concentrations. In contrast, neither lumichrome, thiamine HCl, pyridoxine HCl, nor vitamin B12 stimulated larvae of C. teleta to metamorphose at concentrations as high as 500 µM. Larvae also did not metamorphose in response to either nicotinamide or pyrazinecarboxamide in calcium-free seawater or with the addition of 4-acetylpyridine, a competitive inhibitor of the pyridine receptor. Together, these results suggest that larvae of C. teleta are responding to nicotinamide and riboflavin via a chemosensory pyridine receptor similar to that previously reported to be present on crayfish chela and involved with food recognition. Our data are the first to implicate B vitamins as possible natural chemical settlement cues for marine invertebrate larvae.

  14. Characterization and mutational analysis of a nicotinamide mononucleotide deamidase from Agrobacterium tumefaciens showing high thermal stability and catalytic efficiency.

    Directory of Open Access Journals (Sweden)

    Ana Belén Martínez-Moñino

    Full Text Available NAD+ has emerged as a crucial element in both bioenergetic and signaling pathways since it acts as a key regulator of cellular and organismal homeostasis. Among the enzymes involved in its recycling, nicotinamide mononucleotide (NMN deamidase is one of the key players in the bacterial pyridine nucleotide cycle, where it catalyzes the conversion of NMN into nicotinic acid mononucleotide (NaMN, which is later converted to NAD+ in the Preiss-Handler pathway. The biochemical characteristics of bacterial NMN deamidases have been poorly studied, although they have been investigated in some firmicutes, gamma-proteobacteria and actinobacteria. In this study, we present the first characterization of an NMN deamidase from an alphaproteobacterium, Agrobacterium tumefaciens (AtCinA. The enzyme was active over a broad pH range, with an optimum at pH 7.5. Moreover, the enzyme was quite stable at neutral pH, maintaining 55% of its activity after 14 days. Surprisingly, AtCinA showed the highest optimal (80°C and melting (85°C temperatures described for an NMN deamidase. The above described characteristics, together with its high catalytic efficiency, make AtCinA a promising biocatalyst for the production of pure NaMN. In addition, six mutants (C32A, S48A, Y58F, Y58A, T105A and R145A were designed to study their involvement in substrate binding, and two (S31A and K63A to determine their contribution to the catalysis. However, only four mutants (C32A, S48A Y58F and T105A showed activity, although with reduced catalytic efficiency. These results, combined with a thermal and structural analysis, reinforce the Ser/Lys catalytic dyad mechanism as the most plausible among those proposed.

  15. Quercetin ameliorates oxidative stress, inflammation and apoptosis in the heart of streptozotocin-nicotinamide-induced adult male diabetic rats.

    Science.gov (United States)

    Roslan, Josef; Giribabu, Nelli; Karim, Kamarulzaman; Salleh, Naguib

    2017-02-01

    Quercetin is known to possess beneficial effects in ameliorating diabetic complications, however the mechanisms underlying cardioprotective effect of this compound in diabetes is not fully revealed. In this study, quercetin effect on oxidative stress, inflammation and apoptosis in the heart in diabetes were investigated. Normal and streptozotocin-nicotinamide induced adult male diabetic rats received quercetin (10, 25 and 50mg/kg/bw) orally for 28days were anesthetized and hemodynamic parameters i.e. systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured. Blood was collected for analyses of fasting glucose (FBG), insulin and cardiac injury marker levels (troponin-C, CK-MB and LDH). Following sacrificed, heart was harvested and histopathological changes were observed. Heart was subjected for analyses of oxidative stress marker i.e. lipid peroxidation and activity and expression levels of anti-oxidative enzymes i.e. SOD, CAT and GPx. Levels of inflammation in the heart were determined by measuring nuclear factor (p65-NF-κB), tumor necrosis factor (TNF-α), interleukins (IL)-1β and IL-6 levels by using enzyme-linked immunoassay (ELISA). Distribution and expression levels of TNF-α and Ikk-β (inflammatory markers), caspase-3, caspase-9, Blc-2 and Bax (apoptosis markers) in the heart were identified by immunohistochemistry and Western blotting respectively. Administration of quercetin to diabetic rats caused significant decrease in FBG and cardiac injury marker levels with increased in insulin levels. In diabetic rat heart, lesser histopathological changes were observed with oxidative stress, inflammation and apoptosis levels markedly decreased. Quercetin could potentially be used to ameliorate myocardial damage due to oxidative stress, inflammation and apoptosis in diabetes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  16. Nicotinamide treatment induces behavioral recovery when administered up to 4 hours following cortical contusion injury in the rat.

    Science.gov (United States)

    Hoane, M R; Pierce, J L; Holland, M A; Anderson, G D

    2008-06-26

    Recent studies have demonstrated nicotinamide (NAM), a soluble B-group vitamin, to be an effective treatment in experimental models of traumatic brain injury (TBI). However, research on this compound has been limited to administration regimens starting shortly after injury. This study was conducted to establish the window of opportunity for NAM administration following controlled cortical impact (CCI) injury to the frontal cortex. Groups of rats were assigned to NAM (50 mg/kg), saline (1 ml/kg), or sham conditions and received contusion injuries or sham procedures. Injections of NAM or saline were administered at 15 min, 4 h, or 8 h post-injury, followed by five boosters at 24 h intervals. Following the last injection, blood was taken for serum NAM analysis. Animals were tested on a variety of tasks to assess somatosensory performance (bilateral tactile adhesive removal and vibrissae-forelimb placement) and cognitive performance (reference and working memory) in the Morris water maze. The results of the serum NAM analysis showed that NAM levels were significantly elevated in treated animals. Behavioral analysis on the tactile removal test showed that all NAM-treated groups facilitated recovery of function compared with saline treatment. On the vibrissae-forelimb placing test all NAM-treated groups also were significantly different from the saline-treated group. However, the acquisition of reference memory was only significantly improved in the 15-min and 4-h groups. In the working memory task both the 15-min and 4-h groups also improved working memory compared with saline treatment. The window of opportunity for NAM treatment is task-dependent and extends to 8 h for the sensorimotor tests but only extends to 4 h post-injury in the cognitive tests. These results suggest that a 50 mg/kg treatment regimen starting at the clinically relevant time point of 4 h may result in attenuated injury severity in the human TBI population.

  17. Signal-enhanced electrochemiluminescence immunosensor based on synergistic catalysis of nicotinamide adenine dinucleotide hydride and silver nanoparticles.

    Science.gov (United States)

    Wang, Guangjie; Jin, Feng; Dai, Nan; Zhong, Zhaoyang; Qing, Yi; Li, Mengxia; Yuan, Ruo; Wang, Dong

    2012-03-01

    A new metal-organic nanocomposite with synergistic catalysis function was prepared and developed to construct an electrochemiluminescence (ECL) immunosensor for ultrasensitive detection of tumor biomarker CA125. Silver nanoparticles (AgNPs) and nicotinamide adenine dinucleotide hydride (NADH) that can participate and catalyze the ECL reaction of Ru(bpy)(3)(2+) were employed as the metal component and the organic component to synthesize the metal-organic nanocomposite of NADH-AgNPs (NA). The novel ECL immunosensor was assembled via Ru(bpy)(3)(2+)-doped silica nanoparticles (Ru-SiO(2)) modified electrode with the NA as immune labels. First, the chitosan-suspended Ru-SiO(2) nanoparticles were cast on the gold electrode surface to immobilize the ECL probes of Ru(bpy)(3)(2+) and link gold nanoparticles. Then, the primary antibodies were loaded onto the modified electrode via the gold sulfhydryl covalent binding. After immunobinding the analytes of antigen, NA-attached secondary antibodies could be captured as a sandwich type on the electrode. Finally, based on the circularly synergistic catalysis by the silver and NADH for the solid-phase ECL of Ru(bpy)(3)(2+), the proposed immunosensor sensed the concentration of antigen. The synergistic ECL catalysis of metal-organic nanocomposite amplified response signal and pushed the detection limit down to 0.03 U ml(-1), which initiated a new ECL labeling field and has great significance for ECL immunoassays. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Effect of nicotinamide on amino acids content in bone collagen depending on biological availability of vitamins in diabetic rats.

    Science.gov (United States)

    Guzyk, M M; Sergiichuk, Iu T; Dyakun, K O; Yanitska, L V; Kuchmerovska, T M

    2014-01-01

    Connective tissue is highly susceptible to imbalances induced by diabetes. Diabetes-related osteopenia, decreased bone strength etc. may be associated with altered metabolism of various collagens: Although it is assumed that alterations in collagen amino acids (AA) may strongly affect protein properties andphysiological functions, however, very limited evidences are present at the moment regarding AA composition of bone type I collagen and its relevance to abnormal availability of vitamins which are necessary for collagen synthesis in diabetes. We have tested whether nicotinamide (NAm) can influence type Icollagen formation and AA composition as well as vitamins availability in diabetes. After 4 weeks of STZ-induced diabetes (60 mg/ kg) male Wistar rats were injected for 2 weeks with/without NAm (200 mg/kg b. w). Acid extraction of type I collagen from the bones was performed with following stepwise salting out. The content of type I collagen after its acid extraction from the bones was estimated by the amounts of hydroxyproline. Amino acids were assayed by cation exchange chromatography Diabetes-associated changes in AA composition of type I collagen mainly affect those amino acids which are known to be involved in helix formation and cross-linking of the molecules. Diabetes was found to significantly reduce bone collagen contents of o-Pro, Gly, Ala, o-Lys and Pro, whereas Lys, His, Arg, Glu, Thr, Leu, Phe contents were elevated (P vitamin C and B3 contents were shown to be significantly lowered, whereas a-tocopherol was slightly increased compared with control (P vitamin C and B3 was observed. The data demonstrate the close relationship between the diabetes-associated decrease in type I collagen deposition, altered amino acids metabolism and impaired availability of vitamins, which are necessary for collagen synthesis. Thus, NAm might be a useful agent for treatment of bone failures related to diabetes.

  19. Morphological features, distribution and compartmental organization of the nicotinamide adenine dinucleotide phosphate reduced-diaphorase interneurons in the human striatum.

    Science.gov (United States)

    Bernácer, Javier; Prensa, Lucía; Giménez-Amaya, José Manuel

    2005-08-29

    Striatal nicotinamide adenine dinucleotide phosphate reduced-diaphorase (NADPH-d)-positive (+) cells are one of the major classes of striatal interneurons. The present study analyzes their somatodendritic morphology, distribution pattern, and compartmental organization in the caudate nucleus (CN) and putamen (Put) of nine normal human brains. The following striatal territories are examined: 1) the precommissural head of the CN; 2) the postcommissural head of the CN; 3) the body of the CN; 4) the gyrus of the CN; 5) the tail of the CN; 6) the precommissural Put; and 7) the postcommissural Put. Three morphologically distinct types of NADPH-d+ neurons were found in each of these territories. The two most common NADPH-d+ neurons displayed an ovoid or triangular perikaryon from which several thick primary dendrites emerged, although much less numerous, bipolar-shaped NADPH-d+ cells were also observed. The highest density of NADPH-d+ neurons was found in the gyrus of the CN, followed by the body of the CN, tail of the CN, postcommissural head of the CN, postcommissural Put, precommissural head of the CN, and precommissural Put. The matrix was the striatal compartment with the densest NADPH-d+ neuronal population. Some of these cells also occurred in the center and peripheral regions of the striosomes located in the head of the CN and in the Put. In the body and gyrus of the CN, the striosomes were largely devoid of these striatal interneurons. Knowledge of the density and distribution of these interneurons should advance our understanding of the organization of the normal human striatum and help to evaluate the effects of neurodegenerative processes on cell density. (c) 2005 Wiley-Liss, Inc.

  20. An ecofriendly green liquid chromatographic method for simultaneous determination of nicotinamide and clindamycin phosphate in pharmaceutical gel for acne treatment

    Directory of Open Access Journals (Sweden)

    Fawzia Ibrahim

    2017-07-01

    Full Text Available A new green micellar liquid chromatographic method was developed and validated for the quantitative estimation of nicotinamide (NICO and clindamycin phosphate (CLD in bulk and pharmaceutical gel formulation. The analytes are well resolved in less than 6.0 minutes using micellar mobile phase consisting of 0.10M sodium dodecyl sulfate (SDS, 0.3% triethylamine, and 10% 2-propanol in 0.02M orthophosphoric acid at pH 3.0, running through an Eclipse XDB-C8 column (150 mm×4.6 mm, 5 μm particle size with flow rate 1.0 mL/min. The effluent was monitored with diode array detection at 210 nm. The retention times of NICO and CLD were 3.8 minutes and 5.6 minutes, respectively. The method was validated according to the International Conference on Harmonisation (ICH guidelines in terms of linearity, limit of detection, limit of quantification, accuracy, precision, robustness, and specificity to prove its reliability. Linear correlation was achieved by plotting the peak area of each drug against its concentration. It was found to be rectilinear in the ranges of 1.0–40.0 μg/mL and 0.5–15.0 μg/mL with limits of detection of 0.06 μg/mL and 0.03 μg/mL and limits of quantification of 0.19 μg/mL and 0.09 μg/mL for NICO and CLD, respectively. The method was successfully implemented for the simultaneous determination of the analytes in their bulk powder and combined gel formulation with high % recoveries. The ease of sample treatment facilitates and greatly expedites the treatment with reduced cost and improved accuracy of the procedure.

  1. Hypoglycemic and hypolipidemic effects of Bersama engleriana leaves in nicotinamide/streptozotocin-induced type 2 diabetic rats

    Directory of Open Access Journals (Sweden)

    Pierre Watcho

    2012-12-01

    Full Text Available Abstract Background The present investigation was aimed at evaluating the hypoglycemic and hypolipidemic properties of the aqueous and methanolic extracts from Bersama engleriana leaves in streptozotocin/nicotinamide (STZ-NA-induced type 2 diabetic rats. Methods Animals were orally treated for 4 consecutive weeks with Bersama engleriana extracts at doses of 300 or 600 mg/kg. The anti-diabetic effect was examined by measuring blood glucose (BG at 0, 1, 14 and 28 days after STZ-NA treatment and, total cholesterol (TC, high density lipoprotein cholesterol (HDL-C, low density lipoprotein cholesterol (LDL-C and triglycerides (TG levels at sacrifice (day 29. Glibenclamide (0.25 mg/kg was used for comparison. Results STZ-NA-induced diabetic rats showed moderate to significant increases in the levels of BG, TG, TC, LDL-C while body weight, HDL-C levels and relative weights of liver and pancreas were decreased compared to controls (non diabetic rats. Administration of the plant extracts to STZ-NA diabetic rats resulted in a significant decrease in BG, TG, TC and LDL-C and the dose 600 mg/kg of the methanolic extract was the most effective; HDL-C level was markedly increased after four weeks compared to untreated diabetic rats. A dose-dependent increase in the relative weights of the diabetogenic organs was observed in the Bersama engleriana groups. It can be also noticed that the methanolic extract, especially the dose 600 mg/kg (p Conclusion Results of the present study showed that Bersama engleriana extracts and especially its methanolic extract possess antidiabetogenic properties and beneficial effects on diabetic hyperlipidemia. All these effects could be due to the bioactive components revealed in the Bersama engleriana extracts such as triterpenes and phenols and which could justify its ethnomedical use.

  2. Digital Social Network Mining for Topic Discovery

    Science.gov (United States)

    Moradianzadeh, Pooya; Mohi, Maryam; Sadighi Moshkenani, Mohsen

    Networked computers are expanding more and more around the world, and digital social networks becoming of great importance for many people's work and leisure. This paper mainly focused on discovering the topic of exchanging information in digital social network. In brief, our method is to use a hierarchical dictionary of related topics and words that mapped to a graph. Then, with comparing the extracted keywords from the context of social network with graph nodes, probability of relation between context and desired topics will be computed. This model can be used in many applications such as advertising, viral marketing and high-risk group detection.

  3. Module descriptor

    DEFF Research Database (Denmark)

    Vincenti, Gordon; Klausen, Bodil; Kjær Jensen, Jesper

    2016-01-01

    The Module Descriptor including a Teacher’s Guide explains and describes how to work innovatively and co-creatively with wicked problems and young people. The descriptor shows how interested educators and lecturers in Europe can copy the lessons of the Erasmus+ project HIP when teaching their own...

  4. Memory Modulation

    NARCIS (Netherlands)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive

  5. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR and its effects on blood NAD+ levels in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Sophia E Airhart

    Full Text Available The co-primary objectives of this study were to determine the human pharmacokinetics (PK of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+ levels.Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR, improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials.In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed.Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss were observed for both NR (p = 0.03 and NAD+ (p = 0.001; the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008.Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.

  6. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers.

    Science.gov (United States)

    Airhart, Sophia E; Shireman, Laura M; Risler, Linda J; Anderson, Gail D; Nagana Gowda, G A; Raftery, Daniel; Tian, Rong; Shen, Danny D; O'Brien, Kevin D

    2017-01-01

    The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels. Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR), improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials. In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed. Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss) were observed for both NR (p = 0.03) and NAD+ (p = 0.001); the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008). Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.

  7. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Janssens, Geert O., E-mail: g.janssens@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Terhaard, Chris H. [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Doornaert, Patricia A. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Bijl, Hendrik P. [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands); Ende, Piet van den [Department of Radiation Oncology, Maastricht University Medical Centre, Maastricht (Netherlands); Chin, Alim [Department of Clinical Oncology, Leiden University Medical Centre, Leiden (Netherlands); Pop, Lucas A.; Kaanders, Johannes H. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-02-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  8. Effects of garlic extract on TNF-α expression and oxidative stress status in the kidneys of rats with STZ + nicotinamide-induced diabetes.

    Science.gov (United States)

    Ziamajidi, Nasrin; Nasiri, Abolfazl; Abbasalipourkabir, Roghayeh; Sadeghi Moheb, Somayeh

    2017-12-01

    Allium sativum L. (Liliaceae) (garlic) is a medicinal plant that is widely used in herbal medicine. Nephropathy is a complication of diabetes that is induced by long-term hyperglycaemia. The effects of aqueous extract of garlic (AGE) on the expression of tumour necrosis factor-alpha (TNF-α) and oxidative stress status were studied in the kidneys of rats with streptozotocin (STZ) + nicotinamide-induced diabetes. Twenty-four Wistar rats were divided into four groups: control rats, rats with STZ + nicotinamide-induced diabetes that received a single dose of STZ (65 mg/kg) and nicotinamide (110 mg/kg) intraperitoneally, diabetic rats that were treated with garlic (2 g/kg/d, gavage), and normal rats that received garlic (2 g/kg/d, gavage). The glucose level was determined in the start of study, 7 d after induction of diabetes and 33 d after treatment with garlic. At the end of the treatment period, urea, uric acid and creatinine levels were estimated in sera. Malondialdehyde (MDA), total oxidant status (TOS), nitric oxide (NO) levels and TNF-α gene and protein expression were measured in the renal tissues of the rats. The glucose, uric acid, and urea levels increased in the serum of diabetic rats compared with control rats, and decreased in garlic-treated diabetic rats compared with diabetic rats (p garlic-treated diabetic rats compared with diabetic rats (p garlic, it was close to the normal level (p garlic extract has hypoglycaemic, antioxidant and anti-inflammatory properties; therefore, it can be useful for the alleviation of diabetic complications.

  9. Nicotinamide Phosphoribosyltransferase in Smooth Muscle Cells Maintains Genome Integrity, Resists Aortic Medial Degeneration, and Is Suppressed in Human Thoracic Aortic Aneurysm Disease.

    Science.gov (United States)

    Watson, Alanna; Nong, Zengxuan; Yin, Hao; O'Neil, Caroline; Fox, Stephanie; Balint, Brittany; Guo, Linrui; Leo, Oberdan; Chu, Michael W A; Gros, Robert; Pickering, J Geoffrey

    2017-06-09

    The thoracic aortic wall can degenerate over time with catastrophic consequences. Vascular smooth muscle cells (SMCs) can resist and repair artery damage, but their capacities decline with age and stress. Recently, cellular production of nicotinamide adenine dinucleotide (NAD + ) via nicotinamide phosphoribosyltransferase (Nampt) has emerged as a mediator of cell vitality. However, a role for Nampt in aortic SMCs in vivo is unknown. To determine whether a Nampt-NAD + control system exists within the aortic media and is required for aortic health. Ascending aortas from patients with dilated aortopathy were immunostained for NAMPT, revealing an inverse relationship between SMC NAMPT content and aortic diameter. To determine whether a Nampt-NAD + control system in SMCs impacts aortic integrity, mice with Nampt -deficient SMCs were generated. SMC- Nampt knockout mice were viable but with mildly dilated aortas that had a 43% reduction in NAD + in the media. Infusion of angiotensin II led to aortic medial hemorrhage and dissection. SMCs were not apoptotic but displayed senescence associated-ß-galactosidase activity and upregulated p16, indicating premature senescence. Furthermore, there was evidence for oxidized DNA lesions, double-strand DNA strand breaks, and pronounced susceptibility to single-strand breakage. This was linked to suppressed poly(ADP-ribose) polymerase-1 activity and was reversible on resupplying NAD + with nicotinamide riboside. Remarkably, we discovered unrepaired DNA strand breaks in SMCs within the human ascending aorta, which were specifically enriched in SMCs with low NAMPT. NAMPT promoter analysis revealed CpG hypermethylation within the dilated human thoracic aorta and in SMCs cultured from these tissues, which inversely correlated with NAMPT expression. The aortic media depends on an intrinsic NAD + fueling system to protect against DNA damage and premature SMC senescence, with relevance to human thoracic aortopathy. © 2017 American Heart

  10. Web Enabled DROLS Verity TopicSets

    National Research Council Canada - National Science Library

    Tong, Richard

    1999-01-01

    The focus of this effort has been the design and development of automatically generated TopicSets and HTML pages that provide the basis of the required search and browsing capability for DTIC's Web Enabled DROLS System...

  11. Heroin: MedlinePlus Health Topic

    Science.gov (United States)

    ... overdose (Medical Encyclopedia) Also in Spanish Opiate and opioid withdrawal (Medical Encyclopedia) Also in Spanish Tips for Teens: ... this? GO MEDICAL ENCYCLOPEDIA Heroin overdose Opiate and opioid withdrawal Opioid intoxication Related Health Topics Drug Abuse Opioid ...

  12. Emerging topics in translation: Audio description

    OpenAIRE

    Perego, Elisa

    2012-01-01

    The volume deals with several aspects of audio description for the blind and sight impaired which came to the surface during the AD session of the conference Emerging topics in translation and interpreting held at the Department of Language, Translation and Interpreting Studies of the University of Trieste, 16-18 June 2010. The topics dealt with in the volume range from the more established (linguistic analysis of ADs in various languages, strategies to overcome possible obs...

  13. Selected topics in e+e- physics

    International Nuclear Information System (INIS)

    Sau Lan Wu

    1981-01-01

    Selected topics of recent experimental results from the high-energy electron-positron storage rings are presented. The topics include some of the tau and charm physics from SPEAR, the upsilon physics from DORIS and CESR, and the γγ physics and quark and gluon physics from the PLUTO and TASSO Collaborations at PETRA. Related data from the JADE and MARK J Collaborations at PETRA are discussed in separated papers at this school. (orig.)

  14. Systemic side-effects of topical corticosteroids

    Directory of Open Access Journals (Sweden)

    Sandipan Dhar

    2014-01-01

    Full Text Available With the introduction of topical corticosteroids, a milestone has been achieved in dermatologic therapy; owing to its potent anti-inflammatory and ant proliferative effects, it became possible to treat some hitherto resistant dermatoses. But this magic drug can cause enough mischief if used inappropriately. Children are more susceptible to the systemic adverse effects because of enhanced percutaneous absorption through their tender skin. So, systemic side effects should be kept in mind while prescribing this therapeutically valuable topical medicament.

  15. [18F]FLT and [18F]FDG PET for non-invasive treatment monitoring of the nicotinamide phosphoribosyltransferase inhibitor APO866 in human xenografts

    DEFF Research Database (Denmark)

    Erichsen, Kamille Dumong; Johnbeck, Camilla Bardram; Björkling, Fredrik

    2013-01-01

    APO866 is a new anti-tumor compound inhibiting nicotinamide phosphoribosyltransferase (NAMPT). APO866 has an anti-tumor effect in several pre-clinical tumor models and is currently in several clinical phase II studies. 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) is a tracer used to assess cell...... proliferation in vivo. The aim of this study was non-invasively to study effect of APO866 treatment on [18F]FLT and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake....

  16. N-methyl-2-pyridone-5-carboxamide (2PY—Major Metabolite of Nicotinamide: An Update on an Old Uremic Toxin

    Directory of Open Access Journals (Sweden)

    Aurélie Lenglet

    2016-11-01

    Full Text Available N-methyl-2-pyridone-5-carboxamide (2PY, a major metabolite of nicotinamide, NAM was recently identified as a uremic toxin. Recent interventional trials using NAM to treat high levels of phosphorus in end-stage renal disease have highlighted new potential uremic toxicities of 2PY. In the context of uremia, the accumulation of 2PY could be harmful—perhaps by inhibiting poly (ADP-ribose polymerase-1 activity. Here, we review recently published data on 2PY’s metabolism and toxicological profile.

  17. Plumbing. Building Maintenance. Module III. Instructor's Guide.

    Science.gov (United States)

    Brunk, Art

    This curriculum guide, one of six modules keyed to the building maintenance competency profile developed by industry and education professionals, provides materials for a plumbing procedures unit of seven lessons. Lesson topics are: safety procedures, joining pipes, water systems, fixtures and appliances, maintenance and repair, drainage systems,…

  18. The Button Sew Machine. Module 12.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the button sew machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers one topic: performing special operations on the button sew machine. These components are provided: an introduction, direction, an objective, learning activities, student information, a student self-check, and a…

  19. The Zig Zag Machine. Module 14.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the zig zag machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers one topic: performing special operations on the zig zag machine. These components are provided: an introduction, directions, an objective, learning activities, student information, a student self-check, and a…

  20. The Bar Tack Machine. Module 16.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on the bar tack machine, one in a series dealing with industrial sewing machines, their attachments, and operation, covers one topic: performing special operations on the bar tack machine. These components are provided: an introduction, directions, an objective, learning activities, student information, a student self-check, and a…

  1. Topical steroid addiction in atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Fukaya M

    2014-10-01

    Full Text Available Mototsugu Fukaya,1 Kenji Sato,2 Mitsuko Sato,3 Hajime Kimata,4 Shigeki Fujisawa,5 Haruhiko Dozono,6 Jun Yoshizawa,7 Satoko Minaguchi8 1Tsurumai Kouen Clinic, Nagoya, 2Department of Dermatology, Hannan Chuo Hospital, Osaka, 3Sato Pediatric Clinic, Osaka, 4Kimata Hajime Clinic, Osaka, 5Fujisawa Dermatology Clinic, Tokyo, 6Dozono Medical House, Kagoshima, 7Yoshizawa Dermatology Clinic, Yokohama, 8Department of Dermatology, Kounosu Kyousei Hospital, Saitama, Japan Abstract: The American Academy of Dermatology published a new guideline regarding topical therapy in atopic dermatitis in May 2014. Although topical steroid addiction or red burning skin syndrome had been mentioned as possible side effects of topical steroids in a 2006 review article in the Journal of the American Academy of Dermatology, no statement was made regarding this illness in the new guidelines. This suggests that there are still controversies regarding this illness. Here, we describe the clinical features of topical steroid addiction or red burning skin syndrome, based on the treatment of many cases of the illness. Because there have been few articles in the medical literature regarding this illness, the description in this article will be of some benefit to better understand the illness and to spur discussion regarding topical steroid addiction or red burning skin syndrome. Keywords: topical steroid addiction, atopic dermatitis, red burning skin syndrome, rebound, corticosteroid, eczema

  2. Online Video Modules for Improvement in Student Learning

    Science.gov (United States)

    Lancellotti, Matthew; Thomas, Sunil; Kohli, Chiranjeev

    2016-01-01

    The objective of this teaching innovation was to incorporate a comprehensive set of short online video modules covering key topics from the undergraduate principles of marketing class, and to evaluate its effectiveness in improving student learning. A quasiexperimental design was used to compare students who had access to video modules with a…

  3. Incorporating Topic Assignment Constraint and Topic Correlation Limitation into Clinical Goal Discovering for Clinical Pathway Mining

    Directory of Open Access Journals (Sweden)

    Xiao Xu

    2017-01-01

    Full Text Available Clinical pathways are widely used around the world for providing quality medical treatment and controlling healthcare cost. However, the expert-designed clinical pathways can hardly deal with the variances among hospitals and patients. It calls for more dynamic and adaptive process, which is derived from various clinical data. Topic-based clinical pathway mining is an effective approach to discover a concise process model. Through this approach, the latent topics found by latent Dirichlet allocation (LDA represent the clinical goals. And process mining methods are used to extract the temporal relations between these topics. However, the topic quality is usually not desirable due to the low performance of the LDA in clinical data. In this paper, we incorporate topic assignment constraint and topic correlation limitation into the LDA to enhance the ability of discovering high-quality topics. Two real-world datasets are used to evaluate the proposed method. The results show that the topics discovered by our method are with higher coherence, informativeness, and coverage than the original LDA. These quality topics are suitable to represent the clinical goals. Also, we illustrate that our method is effective in generating a comprehensive topic-based clinical pathway model.

  4. THE EFFECTS OF READING TOPIC AND TOPIC PREFERENCE ON READING COMPREHENSION

    Directory of Open Access Journals (Sweden)

    Hesty Widiastuty

    2011-09-01

    Full Text Available This study is aimed at investigating the interaction effect of reading topic and topic preference, the effect of reading topic, and the effect of topic preference on Physics score, Biology score, and Chemistry score of single cause-multiple effects text. The population of this study was the eleventh grade of IPA students of SMA Negeri 2 Kuala Kapuas in Academic Year 2008/2009. There were 64 students of two classes (XI IA1 and IX IA2 as the sample of this study chosen by using cluster random sampling. It was used experimental research with factorial experimental design. The data were processed and analyzed through these steps: taking the data, coding scoring, tabulating, analyzing the data by using statistic technique of ANOVA processed by using SPSS 15 and taking the conclusion based on the statistical result. The results show that: (1 there was significant interaction effect among reading topic and topic preference on Physics score, Biology score, and Chemistry score of single cause-multiple effects text, (2 there was no significance effect of reading topic of single cause-multiple effects text, and (3 there was no significance effect of topic preference on Physics score, Biology score, and Chemistry score of single cause-multiple effects text. Keywords: reading topic, topic preference, reading comprehension

  5. Osmolarity as a contributing factor in topical drug delivery

    Science.gov (United States)

    Funke, Claire; Szeri, Andrew J.

    2017-11-01

    Gels and dissolvable solids are drug delivery platforms being evaluated for application of active pharmaceutical ingredients, termed microbicides, which act topically against infection by sexually transmitted HIV. In previous work, we have investigated how dilution by naturally produced fluid from the vaginal mucosa affects drug transport into the vaginal wall. We expand on this work by no longer assuming a constant flux and instead developing a relation for fluid transport based on osmolarity - thus allowing fluid to pass both into and out of epithelial cells. This relation shows that varying the osmolarity of the applied solution can have a significant effect on the amount of drug delivered to its target while holding the applied amount constant. This effect is modulated by a dimensionless group that relates the rates of solute and solvent transport. Ultimately, our goal is to develop a tool to understand better how to manipulate solution osmolarity in order to improve drug delivery within safety parameters for mucosal tissue.

  6. Assess Student Performance: Skills. Second Edition. Module D-4 of Category D--Instructional Evaluation. Professional Teacher Education Module Series.

    Science.gov (United States)

    Ohio State Univ., Columbus. National Center for Research in Vocational Education.

    This module, one of a series of 127 performance-based teacher education learning packages focusing upon specific professional competencies of vocational education teachers, deals with assessing student performance of psychomotor skills. Included in the module are learning experiences that address the following topics: important considerations…

  7. Association of Nicotinamide Phosphoribosyltransferase (NAMPT Gene Polymorphisms and of Serum NAMPT Levels with Dilated Cardiomyopathy in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Qingyu Dou

    2015-09-01

    Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT has crucial roles for myocardial development, cardiomyocyte energy metabolism and cell death/survival by regulating NAD+-dependent sirtuin-1 (SIRT1 deacetylase. This study aimed to determine if the single nucleotide polymorphisms (SNPs of the NAMPT gene may affect the susceptibility and prognosis for patients with dilated cardiomyopathy (DCM and to describe the association of serum NAMPT levels with clinical features of DCM. Three SNPs (rs61330082, rs2505568, and rs9034 were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method in a case-control study of 394 DCM patients and 395 controls from China. Serum NAMPT levels were measured by enzyme-linked immunosorbent assay kits. The homozygote for the minor allele at rs2505568 and rs9034 could not be detected in this study. Rs9034 T allele and CT genotype were associated with increased DCM risk (OR: 1.63, 95% CI = 1.16–2.27, p = 0.005 and OR: 1.72, 95% CI = 1.20–2.50, p = 0.0027, respectively. Nominally significant decreased DCM risk was found to be associated with the A allele and AT genotype of rs2505568 (OR: 0.48, 95% CI = 0.35–0.67, p < 0.0001 and OR: 0.44, 95% CI = 0.31–0.62, p < 0.0001, respectively, but it should be interpreted with caution because of Hardy-Weinberg disequilibrium in the control group. Of five haplotypes constructed, TAC (rs61330082-rs2505568-rs9034 was a protective haplotype to DCM (OR: 0.22, 95% CI = 0.13–0.39, p = 1.84 × 10−8. The Cox multivariate survival analysis indicated that the rs9034 CT genotype (hazard ratio (HR: 0.59, 95% CI = 0.37–0.96, p = 0.03 was an independently multivariate predictor for longer overall survival in DCM patients. Serum NAMPT levels were significantly higher in the DCM group than controls (p < 0.0001 and gradually increased with the increase of New York Heart Association grade in DCM patients. However, there was a lack of association of the three

  8. Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 Regulates LPS-Induced Inflammation and Alveolar Remodeling in the Developing Lung

    Science.gov (United States)

    Menden, Heather L.; Xia, Sheng; Mabry, Sherry M.; Navarro, Angels; Nyp, Michael F.

    2016-01-01

    In premature infants, sepsis is associated with alveolar simplification manifesting as bronchopulmonary dysplasia. The redox-dependent mechanisms underlying sepsis-induced inflammation and alveolar remodeling in the immature lung remain unclear. We developed a neonatal mouse model of sepsis-induced lung injury to investigate whether nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) regulates Toll-like receptor (TLR)–mediated inflammation and alveolar remodeling. Six-day-old NOX2+/+ and NOX2−/− mice were injected with intraperitoneal LPS to induce sepsis. Lung inflammation and canonical TLR signaling were assessed 24 hours after LPS. Alveolar development was examined in 15-day-old mice after LPS on Day 6. The in vivo efficacy of a NOX2 inhibitor (NOX2-I) on NOX2 complex assembly and sepsis-induced lung inflammation were examined. Lung cytokine expression and neutrophil influx induced with sepsis in NOX2+/+ mice was decreased by >50% in NOX2−/− mice. LPS-induced TLR4 signaling evident by inhibitor of NF-κB kinase-β and mitogen-activated protein kinase phosphorylation, and nuclear factor-κB/AP-1 translocation were attenuated in NOX2−/− mice. LPS increased matrix metalloproteinase 9 while decreasing elastin and keratinocyte growth factor levels in NOX2+/+ mice. An LPS-induced increase in matrix metalloproteinase 9 and decrease in fibroblast growth factor 7 and elastin were not evident in NOX2−/− mice. An LPS-induced reduction in radial alveolar counts and increased mean linear intercepts were attenuated in NOX2−/− mice. LPS-induced NOX2 assembly evident by p67phox/gp91phox coimmunoprecipitation was disrupted with NOX2-I. NOX2-I also mitigated LPS-induced cytokine expression, TLR pathway signaling, and alveolar simplification. In a mouse model of neonatal sepsis, NOX2 regulates proinflammatory TLR signaling and alveolar remodeling induced by a single dose of LPS. Our results provide mechanistic insight into the regulation of sepsis

  9. Topical electrophilic nitro-fatty acids potentiate cutaneous inflammation.

    Science.gov (United States)

    Mathers, Alicia R; Carey, Cara D; Killeen, Meaghan E; Salvatore, Sonia R; Ferris, Laura K; Freeman, Bruce A; Schopfer, Francisco J; Falo, Louis D

    2018-02-01

    Endogenous electrophilic fatty acids mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction and gene expression. Nitro-fatty acids and other electrophilic fatty acids may thus be useful for the prevention and treatment of immune-mediated diseases, including inflammatory skin disorders. In this regard, subcutaneous (SC) injections of nitro oleic acid (OA-NO 2 ), an exemplary nitro-fatty acid, inhibit skin inflammation in a model of allergic contact dermatitis (ACD). Given the nitration of unsaturated fatty acids during metabolic and inflammatory processes and the growing use of fatty acids in topical formulations, we sought to further study the effect of nitro-fatty acids on cutaneous inflammation. To accomplish this, the effect of topically applied OA-NO 2 on skin inflammation was evaluated using established murine models of contact hypersensitivity (CHS). In contrast to the effects of subcutaneously injected OA-NO 2 , topical OA-NO 2 potentiated hapten-dependent inflammation inducing a sustained neutrophil-dependent inflammatory response characterized by psoriasiform histological features, increased angiogenesis, and an inflammatory infiltrate that included neutrophils, inflammatory monocytes, and γδ T cells. Consistent with these results, HPLC-MS/MS analysis of skin from psoriasis patients displayed a 56% increase in nitro-conjugated linoleic acid (CLA-NO 2 ) levels in lesional skin compared to non-lesional skin. These results suggest that nitro-fatty acids in the skin microenvironment are products of cutaneous inflammatory responses and, in high local concentrations, may exacerbate inflammatory skin diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Development and Evaluation of Topical Gabapentin Formulations

    Directory of Open Access Journals (Sweden)

    Christopher J. Martin

    2017-08-01

    Full Text Available Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w gabapentin 0.75% (w/w Carbopol® hydrogels containing 5% (w/w DMSO or 70% (w/w ethanol and a compounded 10% (w/w gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations.

  11. Development and Evaluation of Topical Gabapentin Formulations

    Science.gov (United States)

    Alcock, Natalie; Hiom, Sarah; Birchall, James C.

    2017-01-01

    Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w) gabapentin 0.75% (w/w) Carbopol® hydrogels containing 5% (w/w) DMSO or 70% (w/w) ethanol and a compounded 10% (w/w) gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations. PMID:28867811

  12. Tissue-specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding.

    Science.gov (United States)

    Drew, Janice E; Farquharson, Andrew J; Horgan, Graham W; Williams, Lynda M

    2016-11-01

    The sirtuin (SIRT)/nicotinamide adenine dinucleotide (NAD) system is implicated in development of type 2 diabetes (T2D) and diet-induced obesity, a major risk factor for T2D. Mechanistic links have not yet been defined. SIRT/NAD system gene expression and NAD/NADH levels were measured in liver, white adipose tissue (WAT) and skeletal muscle from mice fed either a low-fat diet or high-fat diet (HFD) for 3 days up to 16 weeks. An in-house custom-designed multiplex gene expression assay assessed all 7 mouse SIRTs (SIRT1-7) and 16 enzymes involved in conversion of tryptophan, niacin, nicotinamide riboside and metabolic precursors to NAD. Significantly altered transcription was correlated with body weight, fat mass, plasma lipids and hormones. Regulation of the SIRT/NAD system was associated with early (SIRT4, SIRT7, NAPRT1 and NMNAT2) and late phases (NMNAT3, NMRK2, ABCA1 and CD38) of glucose intolerance. TDO2 and NNMT were identified as markers of HFD consumption. Altered regulation of the SIRT/NAD system in response to HFD was prominent in liver compared with WAT or muscle. Multiple components of the SIRTs and NAD biosynthetic enzymes network respond to consumption of dietary fat. Novel molecular targets identified above could direct strategies for dietary/therapeutic interventions to limit metabolic dysfunction and development of T2D. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Dellinger, Ryan W; Santos, Santiago Roel; Morris, Mark; Evans, Mal; Alminana, Dan; Guarente, Leonard; Marcotulli, Eric

    2017-01-01

    NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD +) precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. Here, we report this first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (commercially known as Basis). NRPT was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X). All subjects took their blinded supplement daily for eight weeks. Analysis of NAD + in whole blood demonstrated that NRPT significantly increases the concentration of NAD + in a dose-dependent manner. NAD + levels increased by approximately 40% in the NRPT 1X group and approximately 90% in the NRPT 2X group after 4 weeks as compared to placebo and baseline. Furthermore, this significant increase in NAD + levels was sustained throughout the entire 8-week trial. NAD + levels did not increase for the placebo group during the trial. No serious adverse events were reported in this study. This study shows that a repeat dose of NRPT is a safe and effective way to increase NAD + levels sustainably.

  14. Changes in phosphorylation of adenosine phosphate and redox state of nicotinamide-adenine dinucleotide (phosphate) in Geobacter sulfurreducens in response to electron acceptor and anode potential variation

    KAUST Repository

    Rose, Nicholas D.

    2015-12-01

    © 2015 Elsevier B.V. Geobacter sulfurreducens is one of the dominant bacterial species found in biofilms growing on anodes in bioelectrochemical systems. The intracellular concentrations of reduced and oxidized forms of nicotinamide-adenine dinucleotide (NADH and NAD+, respectively) and nicotinamide-adenine dinucleotide phosphate (NADPH and NADP+, respectively) as well as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were measured in G. sulfurreducens using fumarate, Fe(III)-citrate, or anodes poised at different potentials (110, 10, -90, and -190mV (vs. SHE)) as the electron acceptor. The ratios of CNADH/CNAD+ (0.088±0.022) and CNADPH/CNADP+ (0.268±0.098) were similar under all anode potentials tested and with Fe(III)-citrate (reduced extracellularly). Both ratios significantly increased with fumarate as the electron acceptor (0.331±0.094 for NAD and 1.96±0.37 for NADP). The adenylate energy charge (the fraction of phosphorylation in intracellular adenosine phosphates) was maintained near 0.47 under almost all conditions. Anode-growing biofilms demonstrated a significantly higher molar ratio of ATP/ADP relative to suspended cultures grown on fumarate or Fe(III)-citrate. These results provide evidence that the cellular location of reduction and not the redox potential of the electron acceptor controls the intracellular redox potential in G. sulfurreducens and that biofilm growth alters adenylate phosphorylation.

  15. Analyses of Research Topics in the Field of Informetrics Based on the Method of Topic Modeling

    Directory of Open Access Journals (Sweden)

    Sung-Chien Lin

    2014-07-01

    Full Text Available In this study, we used the approach of topic modeling to uncover the possible structure of research topics in the field of Informetrics, to explore the distribution of the topics over years, and to compare the core journals. In order to infer the structure of the topics in the field, the data of the papers published in the Journal of Informetricsand Scientometrics during 2007 to 2013 are retrieved from the database of the Web of Science as input of the approach of topic modeling. The results of this study show that when the number of topics was set to 10, the topic model has the smallest perplexity. Although data scopes and analysis methodsare different to previous studies, the generating topics of this study are consistent with those results produced by analyses of experts. Empirical case studies and measurements of bibliometric indicators were concerned important in every year during the whole analytic period, and the field was increasing stability. Both the two core journals broadly paid more attention to all of the topics in the field of Informetrics. The Journal of Informetricsput particular emphasis on construction and applications ofbibliometric indicators and Scientometrics focused on the evaluation and the factors of productivity of countries, institutions, domains, and journals.

  16. The human heart and the circulatory system as an interesting interdisciplinary topic in lessons of physics and biology

    International Nuclear Information System (INIS)

    Volná, M; Látal, F; Kubínek, R; Richterek, L

    2014-01-01

    Many topics which are closely related can be found in the national curriculum of the Czech Republic for physics and biology. One of them is the heart and the circulatory system in the human body. This topic was examined cross curriculum, a teaching module was created and the topic was chosen for our research. The task was to determine if the students of bachelor study are aware of connections between physics and biology within this topic and whether we can help them effectively to describe the corresponding physics phenomena in the human body connected, for example, with a heart attack or with the measurement of blood pressure. In this paper, the heart and the circulatory system are presented as suitable topics for an interdisciplinary teaching module which includes both theoretical and experimental parts. The module was evaluated by a group of first-year undergraduate students of physics at the Faculty of Science, Palacký University. The acquired knowledge was compared with another control group through a test. The highest efficiency of the module was evaluated on the basis of questions that covered the calculation problems. (paper)

  17. Lecture Notes on Topics in Accelerator Physics

    Energy Technology Data Exchange (ETDEWEB)

    Chao, Alex W.

    2002-11-15

    These are lecture notes that cover a selection of topics, some of them under current research, in accelerator physics. I try to derive the results from first principles, although the students are assumed to have an introductory knowledge of the basics. The topics covered are: (1) Panofsky-Wenzel and Planar Wake Theorems; (2) Echo Effect; (3) Crystalline Beam; (4) Fast Ion Instability; (5) Lawson-Woodward Theorem and Laser Acceleration in Free Space; (6) Spin Dynamics and Siberian Snakes; (7) Symplectic Approximation of Maps; (8) Truncated Power Series Algebra; and (9) Lie Algebra Technique for nonlinear Dynamics. The purpose of these lectures is not to elaborate, but to prepare the students so that they can do their own research. Each topic can be read independently of the others.

  18. Topical thrombin-related corneal calcification.

    Science.gov (United States)

    Kiratli, Hayyam; Irkeç, Murat; Alaçal, Sibel; Söylemezoğlu, Figen

    2006-09-01

    To report a highly unusual case of corneal calcification after brief intraoperative use of topical thrombin. A 44-year-old man underwent sclerouvectomy for ciliochoroidal leiomyoma, during which 35 UNIH/mL lyophilized bovine thrombin mixed with 9 mL of diluent containing 1500 mmol/mL calcium chloride was used. From the first postoperative day, corneal and anterior lenticular capsule calcifications developed, and corneal involvement slightly enlarged thereafter. A year later, 2 corneal punch biopsies confirmed calcification mainly in the Bowman layer. Topical treatment with 1.5% ethylenediaminetetraacetic acid significantly restored corneal clarity. Six months later, a standard extracapsular cataract extraction with intraocular lens placement improved visual acuity to 20/60. This case suggests that topical thrombin drops with elevated calcium concentrations may cause acute corneal calcification in Bowman layer and on the anterior lens capsule.

  19. Getting Started with Topic Modeling and MALLET

    Directory of Open Access Journals (Sweden)

    Shawn Graham

    2012-09-01

    Full Text Available In this lesson you will first learn what topic modeling is and why you might want to employ it in your research. You will then learn how to install and work with the MALLET natural language processing toolkit to do so. MALLET involves modifying an environment variable (essentially, setting up a short-cut so that your computer always knows where to find the MALLET program and working with the command line (ie, by typing in commands manually, rather than clicking on icons or menus. We will run the topic modeller on some example files, and look at the kinds of outputs that MALLET installed. This will give us a good idea of how it can be used on a corpus of texts to identify topics found in the documents without reading them individually.

  20. Topical minoxidil: cardiac effects in bald man.

    Science.gov (United States)

    Leenen, F H; Smith, D L; Unger, W P

    1988-01-01

    Systemic cardiovascular effects during chronic treatment with topical minoxidil vs placebo were evaluated using a double-blind, randomized design for two parallel groups (n = 20 for minoxidil, n = 15 for placebo). During 6 months of follow-up, blood pressure did not change, whereas minoxidil increased heart rate by 3-5 beats min-1. Compared with placebo, topical minoxidil caused significant increases in LV end-diastolic volume, in cardiac output (by 0.751 min-1) and in LV mass (by 5 g m-2). We conclude that in healthy subjects short-term use of topical minoxidil is likely not to be detrimental. However, safety needs to be established regarding ischaemic symptoms in patients with coronary artery disease as well as for the possible development of LV hypertrophy in healthy subjects during years of therapy. PMID:3191000

  1. Topical antimicrobial agents in ophthalmology. A review

    Directory of Open Access Journals (Sweden)

    E. V. Dovgan’

    2014-01-01

    Full Text Available The data on different antimicrobial agents (fluoroquinolones, minoglycosides, macrolides, fusidic acid, chloramphenicol and their activity against various microorganisms are reviewed. The findings from different researchers are analyzed. Considerable attention is devoted to the problem of antimicrobial resistance in ophthalmology. Pharmacokinetics of topical antimicrobial agents applied in ophthalmology, their safety and tolerability are described. The indications for topical antimicrobial agents use in ophthalmology approved in Russian Federation are presented. With regard for pharmacokinetics and pharmacodynamics, safety profile and good tolerability, it is concluded that fluoroquinolones are medication of choice for empirical antimicrobial treatment in ophthalmology.

  2. Applied atomic and collision physics special topics

    CERN Document Server

    Massey, H S W; Bederson, Benjamin

    1982-01-01

    Applied Atomic Collision Physics, Volume 5: Special Topics deals with topics on applications of atomic collisions that were not covered in the first four volumes of the treatise. The book opens with a chapter on ultrasensitive chemical detectors. This is followed by separate chapters on lighting, magnetohydrodynamic electrical power generation, gas breakdown and high voltage insulating gases, thermionic energy converters, and charged particle detectors. Subsequent chapters deal with the operation of multiwire drift and proportional chambers and streamer chambers and their use in high energy p

  3. Topics in current aerosol research (part2)

    CERN Document Server

    Hidy, G M

    1972-01-01

    Topics in Current Aerosol Research, Part 2 contains some selected articles in the field of aerosol study. The chosen topics deal extensively with the theory of diffusiophoresis and thermophoresis. Also covered in the book is the mathematical treatment of integrodifferential equations originating from the theory of aerosol coagulation. The book is the third volume of the series entitled International Reviews in Aerosol Physics and Chemistry. The text offers significant understanding of the methods employed to develop a theory for thermophoretic and diffusiophoretic forces acting on spheres in t

  4. Conference on Stochastic Analysis and Related Topics

    CERN Document Server

    Peterson, Jonathon

    2017-01-01

    The articles in this collection are a sampling of some of the research presented during the conference “Stochastic Analysis and Related Topics”, held in May of 2015 at Purdue University in honor of the 60th birthday of Rodrigo Bañuelos. A wide variety of topics in probability theory is covered in these proceedings, including heat kernel estimates, Malliavin calculus, rough paths differential equations, Lévy processes, Brownian motion on manifolds, and spin glasses, among other topics.

  5. Importance of Sex Education Topics: Correlates with Teacher Characteristics and Inclusion of Topics in Instruction.

    Science.gov (United States)

    Yarber, William L.; McCabe, George P., Jr.

    1984-01-01

    This article examines school sex educators' views toward selected topics and their importance to the sex education curriculum. Findings indicate that teachers feel the topics were necessary, with biological aspects and sexual health care being most important. Details of the methodology used in the study are discussed. (DF)

  6. Measurement Conversions: English and Metric Systems. Fundamentals of Occupational Mathematics. Module 9.

    Science.gov (United States)

    Engelbrecht, Nancy; And Others

    This module is the ninth in a series of 12 learning modules designed to teach occupational mathematics. Blocks of informative material and rules are followed by examples and practice problems. The solutions to the practice problems are found at the end of the module. Specific topics covered include measurement conversions, the English system of…

  7. Stationary Engineers Apprenticeship. Related Training Modules. 12.1-12.9. Boilers.

    Science.gov (United States)

    Lane Community Coll., Eugene, OR.

    This learning module, one in a series of 20 related training modules for apprentice stationary engineers, deals with boilers. Addressed in the individual instructional packages included in the module are the following topics: firetube and watertube boilers; boiler construction; procedures for operating and cleaning boilers; and boiler fittings,…

  8. Senior Science Enrichment Modules. S.S.T.A. Research Centre Report No. 58.

    Science.gov (United States)

    Fedorak, Allen; And Others

    Presented is a set of learning modules intended for teaching science to students in grades eleven and twelve. Each module incorporates problem solving using the scientific viewpoint and emphasizing the interface between science and society. The fifteen modules presented include the following topics: group dynamics; the value of science; a puzzle…

  9. 77 FR 35691 - Update to Electronic Common Technical Document Module 1

    Science.gov (United States)

    2012-06-14

    ... HUMAN SERVICES Food and Drug Administration Update to Electronic Common Technical Document Module 1... (FDA) is announcing the following meeting: Update to Electronic Common Technical Document Module 1. The topic to be discussed is final documentation of the Electronic Common Technical Document (eCTD) Module 1...

  10. Getting Down to Business: Travel Agency, Module 9. [Student Guide]. Entrepreneurship Training Components.

    Science.gov (United States)

    Rassen, Rachel L.

    This module on owning and operating a travel agency is one of 36 modules in a series on entrepreneurship. The introduction tells the student what topics will be covered and suggests other modules to read in related occupations. Each unit includes student goals, a case study, and a discussion of the unit subject matter. Learning activities are…

  11. Millwright Apprenticeship. Related Training Modules. 8.1-8.5 Turbines.

    Science.gov (United States)

    Lane Community Coll., Eugene, OR.

    This packet, part of the instructional materials for the Oregon apprenticeship program for millwright training, contains five modules covering turbines. The modules provide information on the following topics: types, components, and auxiliaries of steam turbines; operation and maintenance of steam turbines; and gas turbines. Each module consists…

  12. Stationary Engineers Apprenticeship. Related Training Modules. 15.1-15.5 Turbines.

    Science.gov (United States)

    Lane Community Coll., Eugene, OR.

    This learning module, one in a series of 20 related training modules for apprentice stationary engineers, deals with turbines. addressed in the individual instructional packages included in the module are the following topics: types and components of steam turbines, steam turbine auxiliaries, operation and maintenance of steam turbines, and gas…

  13. CLIC Quadrupole Module final report

    CERN Document Server

    Artoos, K; Mainaud-Durand, H

    2013-01-01

    Future Linear colliders will need particle beam sizes in the nanometre range. The beam also needs to be stable all along the beam line. The CLIC Main Beam Quadrupole (MBQ) module has been defined and studied. It is meant as a test stand for stabilisation and pre-alignment with a MB Quadrupole. The main topic that has been tackled concerns the Quadrupole magnet stabilisation to 1nm at 1Hz. This is needed to obtain the desired CLIC luminosity of 2.1034 cm-2m-1. The deliverable was demonstrated by procuring a MBQ and by stabilising a powered and cooled CLIC MBQ quadrupole. In addition, the stabilisation system has to be compatible with the pre-alignment procedures. Pre-alignment movement resolution has been demonstrated to 1m. The last step is the combined test of stability with a quadrupole on a CLIC Module with the pre-alignment.

  14. Integrating STEM education through Project-Based Inquiry Learning (PIL) in topic space among year one pupils

    Science.gov (United States)

    Ng, Chee Hoe; Adnan, M.

    2018-01-01

    This research aims to investigate the effect of integrating STEM education through Project-based Inquiry Learning (PIL) and the users of the STEM modules which consists of five projects on topic Space in Year One Mathematics Syllabus in Kurikulum Standard Sekolah Rendah (KSSR) of Malaysia. STEM education in primary school focuses on the introduces and awareness of students about the importance of STEM education. The projects in STEM modules are covering the different ethnic cultures in Malaysia. The modules are designed using the four phases in PIL. Concepts and the explanation of STEM education on each project are emphasized and provided in the modules so the teachers able to carry out the projects by using the modules. By using the modules in primary Mathematics, the students and teachers will be more understanding on how to integrate the Mathematics’ concepts in STEM education.

  15. Atopic dermatitis: tacrolimus vs. topical corticosteroid use

    African Journals Online (AJOL)

    However, concerns over adverse drug reactions associated with their long-term application limit their use. Tacrolimus, on the other hand, has been shown to be effective in stabilising the symptoms of AD in the long-term setting, without the side-effects that hamper the use of topical corticosteroids. Long-term safety data up to ...

  16. Dexmedetomidine premedication in cataract surgery under topical ...

    African Journals Online (AJOL)

    Keywords: cataract surgery, dexmedetomidine, intraocular pressure, patient and surgeon satisfaction, topical anesthesia. Introduction. Traditionally, cataract surgeries are performed under regional anaesthesia with either a peribulbar or retrobulbar block. With the anaesthesia has also evolved from painful regional blocks to ...

  17. Topics in cement and concrete research

    NARCIS (Netherlands)

    Brouwers, Jos; Russel, M.I.; Basheer, P.A.M.

    2007-01-01

    The present paper addresses several topics in regard to the sustainable design and use of concrete. First, major features concerning the sustainable aspects of the material concrete are summarised. Then the major constituent, from an environmental point of view, cement is discussed in detail,

  18. Colorimetric analysis of hexachlorophene in topical formulations.

    Science.gov (United States)

    French, W N; Matsui, F; Smith, S J; Wood, R J

    1975-01-01

    The commonly used 4-aminoantipyrine dye formation procedure for hexachlorophene analysis in topical formulations was modified to overcome interference due to other components. Bar soaps and nonemulsion formulations are analyzed directly, employing a chloroform back-extraction stage of the dye prior to quantitation. Hexachlorophene in emulsions and liquid soaps is determined using a TLC separation prior to dye formation.

  19. Common Core: Teaching Optimum Topic Exploration (TOTE)

    Science.gov (United States)

    Karge, Belinda Dunnick; Moore, Roxane Kushner

    2015-01-01

    The Common Core has become a household term and yet many educators do not understand what it means. This article explains the historical perspectives of the Common Core and gives guidance to teachers in application of Teaching Optimum Topic Exploration (TOTE) necessary for full implementation of the Common Core State Standards. An effective…

  20. Chlorhexidine allergy due to topical application

    Directory of Open Access Journals (Sweden)

    Nandita N Keni

    2012-01-01

    Full Text Available Chlorhexidine is commonly used in dentistry in various forms. Allergic reactions to chlorhexidine of both immediate and delayed type have been reported. Although the incidence is low there may be severe manifestations in some patients. This report presents a case of allergy to chlorhexidine following topical application.

  1. Topics in the Nez Perce Verb

    Science.gov (United States)

    Deal, Amy Rose

    2010-01-01

    This dissertation investigates several topics in the morphology, syntax and semantics of the Nez Perce verb and verbal clause. The first part of the dissertation focuses on the morphological segmentation of the Nez Perce verb and on the semantic description of the verb and clause. Chapter 1 provides a grammar sketch. Chapter 2 discusses the…

  2. Hot topics in flavor physics at CDF

    Energy Technology Data Exchange (ETDEWEB)

    Jun, Soon Yung; /Carnegie Mellon U.

    2005-01-01

    Hot topics in flavor physics at CDF are reviewed. Selected results of top, beauty, charm physics and exotic states in about 200 pb{sup -1} data collected by the CDF II detector in p{bar p} collisions at {radical}s = 1.96 TeV at the Fermilab Tevatron are presented.

  3. Shock wave dynamics derivatives and related topics

    CERN Document Server

    Emanuel, George

    2012-01-01

    "...this monograph develops an esoteric niche within shock wave theory. …treats shock waves from an analytical approach assuming perfect gas. Emanuel has made significant contributions to the theory of shock waves and has selected a number of topics that reflect those contributions."-Shock Waves, 2013.

  4. Pain Relievers: MedlinePlus Health Topic

    Science.gov (United States)

    ... Health) ClinicalTrials.gov: Narcotics (National Institutes of Health) Journal Articles References and abstracts from MEDLINE/PubMed (National ... Concentration Before Giving Acetaminophen to Infants (Food and Drug Administration) ... Related Health Topics Chronic Pain Medicines Opioid Abuse and Addiction Over-the-Counter Medicines Pain Other ...

  5. Topical Treatment: Basic Rules and Absorbtion

    Directory of Open Access Journals (Sweden)

    Ertuğrul H. Aydemir

    2012-09-01

    Full Text Available Topical treatment, is applied as putting the medicines just on the problemmatic area of the skin. It is useful for avoiding the systemic side effects, decreasing the cost and it also works like an occupying treatment. Absorbtion of active ingredient is a passive process and amount of absorption of active ingredient is affected by the properties of skin area applied and topical medicine itself. Absorption is more thinner, warmer and wetter areas of the skin.. Absorption is much more than needed, in the areas which are eroded and damaged. But, entrance of the topical medicine to the circulation is not useful and may cause systemic effects. Active ingredient in the topical medicine might have a high concentration, lipophilic nature and higher affinity to the skin than the affinity to the vehicle for a better absorbtion. Stages of absorbtion: Adsorbtion, absorbtion (penetration, permeation, resorbtion. Vehicles can be classified as liquids, semi solides and solides, but the classification as monophasic, biphasic and poliphasic is better (basicly mixtures of water-oils-powders.

  6. Topical Metered-dosing Dispenser Performance Evaluation.

    Science.gov (United States)

    Liu, Qiang; Kupiec, Thomas C; Vu, Nicole T

    2016-01-01

    Topical metered-dosing dispensers are designed for dosing accuracy and ease-of-use by the patients while protecting the packaged products from environmental exposure and contamination. The objective of this study was to evaluate the accuracy, precision, and residual of available topical metered-dosing dispensers with different types of topical cream for practical application. Triplicate samples of five different dispensers were tested. This test was completed using three types of commercial topical cream-bases of dissimilar Total Active Pharmaceutical Ingredient Load Percentages, Transdermal Penetration Percentages, and Specific Gravities. The dispensers were evaluated according to specified dose-uniformity criteria for a total dispensing capacity of 30 mL at 0.5 mL per dose for 60 doses. The study shows Topi-CLICK performed with the best precision and accuracy of dosing in comparison to the airless-pump type dispensers. While the dispensing was highly variable with airless pumps and may require calibration for each packaged product, remarkably the performance of Topi-CLICK was not affected by different types of cream-bases and does not require additional metering calibration. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  7. [Oral hairy leukoplakia induced by topical steroids].

    Science.gov (United States)

    Vigarios, E; Fricain, J-C; Projetti, F; Boulanger, M; Sibaud, V

    2015-10-01

    Oral hairy leukoplakia (OHL) is an EBV-associated condition of the oral mucosa, which is often painless. It is found predominantly in HIV-positive patients and is considered a clinical indicator of immunosuppression. OHL has rarely been described in HIV-negative patients, being found most often in association with iatrogenic immunosuppression. OHL induced by topical steroids remains extremely rare. An 81-year-old HIV-negative woman, treated for 3 months with topical steroids for oral lichen planus, developed an asymptomatic white, corrugated, non-removable plaque with vertical folds on the lateral edge of the tongue. Associated oral candidiasis was noted. Based upon histological findings and in situ hybridisation showing numerous EBV-infected epithelial cells, a diagnosis of oral hairy leucoplakia was made. To our knowledge, we report herein only the second recorded case of OHL induced strictly by topical steroids. Self-medication and poor adherence to dosage recommendations were noted in the patient's medical history. Physicians must be aware of the rare but nevertheless possible adverse events associated with topical steroid use, particularly when such medication is prescribed over a long period for inflammatory diseases of the oral mucosa. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Gender and Topicality in Onwueme's Plays

    African Journals Online (AJOL)

    User

    2011-04-19

    Apr 19, 2011 ... century Nigerian social reality. This, one figures, is one of the preoccupations of Onwueme's plays What Mama said and No Vacancy. A second concern is to underscore the sensitivity of the playwright to topical issues of both national and global hue and colour and draw conclusions on her perspective and ...

  9. Special topics in the theory of piezoelectricity

    CERN Document Server

    Yang, Jiashi

    2009-01-01

    Piezoelectricity has been a steadily growing field, with recent advances made by researchers from applied physics, acoustics, materials science, and engineering. This collective work presents a comprehensive treatment of selected advanced topics in the subject. The book is written for an intermediate graduate level and is intended for researchers, mechanical engineers, and applied mathematicians interested in the advances and new applications in piezoelectricity.

  10. Interview "Problems" as Topics for Analysis

    Science.gov (United States)

    Roulston, Kathryn

    2011-01-01

    In this article the author argues that interactional difficulties and questioning practices identified in the methodological literature on qualitative interviewing as "problems" provide topics of analysis. Methodological examinations of interview data drawing on conversation analysis also explicate how interview "problems" may be conceptualized in…

  11. Topical morphine for oral mucositis in children

    DEFF Research Database (Denmark)

    Nielsen, Bettina Nygaard; Aagaard, Gitte; Henneberg, Steen W

    2012-01-01

    Systemic opioids for painful chemotherapy-induced oral mucositis in children often result in unsatisfactory pain relief and a high frequency of side effects. Opioids applied topically can produce analgesia by binding to opioid receptors on peripheral terminals of sensory neurons. These receptors...

  12. Qualitative content analysis of complementary topical therapies ...

    African Journals Online (AJOL)

    In order to alleviate diabetic foot problems, patients sometimes seek complementary therapies outside the professional context. This paper describes the use of complementary remedies as a topical treatment for diabetic foot ulcers among Jordanians. Qualitative content analysis was used to analyse written responses of 68 ...

  13. Spectral Learning for Supervised Topic Models.

    Science.gov (United States)

    Ren, Yong; Wang, Yining; Zhu, Jun

    2018-03-01

    Supervised topic models simultaneously model the latent topic structure of large collections of documents and a response variable associated with each document. Existing inference methods are based on variational approximation or Monte Carlo sampling, which often suffers from the local minimum defect. Spectral methods have been applied to learn unsupervised topic models, such as latent Dirichlet allocation (LDA), with provable guarantees. This paper investigates the possibility of applying spectral methods to recover the parameters of supervised LDA (sLDA). We first present a two-stage spectral method, which recovers the parameters of LDA followed by a power update method to recover the regression model parameters. Then, we further present a single-phase spectral algorithm to jointly recover the topic distribution matrix as well as the regression weights. Our spectral algorithms are provably correct and computationally efficient. We prove a sample complexity bound for each algorithm and subsequently derive a sufficient condition for the identifiability of sLDA. Thorough experiments on synthetic and real-world datasets verify the theory and demonstrate the practical effectiveness of the spectral algorithms. In fact, our results on a large-scale review rating dataset demonstrate that our single-phase spectral algorithm alone gets comparable or even better performance than state-of-the-art methods, while previous work on spectral methods has rarely reported such promising performance.

  14. Topical Antibacterials and Global Challenges on Resistance ...

    African Journals Online (AJOL)

    ingredient or are in combination with other antibiotics or corticosteroids. Community pharmacy have a variety of topical antibacterial agents which are available for potential use in; acne vulgaris, pyoderma including impetigo, folliculitis, rosacea, infected eczema, secondarily infected traumatic skin lesions, prevention of.

  15. Selected papers on analysis and related topics

    CERN Document Server

    2008-01-01

    This volume contains translations of papers that originally appeared in the Japanese journal Sūgaku. The papers range over a variety of topics, including operator algebras, analysis, and statistics. This volume is suitable for graduate students and research mathematicians interested in analysis and its applications.

  16. Genetic Counseling: MedlinePlus Health Topic

    Science.gov (United States)

    ... it if you Have a personal or family history of a genetic condition or birth defect Are pregnant or planning to be pregnant ... GO MEDICAL ENCYCLOPEDIA Genetic counseling Related Health Topics Birth Defects Family History Genetic Disorders Genetic Testing Prenatal Testing National Institutes ...

  17. Effects of Hydro-alcoholic Extract from Arctium lappa L. (Burdock) Root on Gonadotropins, Testosterone, and Sperm Count and Viability in Male Mice with Nicotinamide/ Streptozotocin-Induced Type 2 Diabetes

    OpenAIRE

    AHANGARPOUR, Akram; OROOJAN, Ali Akbar; HEIDARI, Hamid; GHAEDI, Ehsan; TAHERKHANI, Reza

    2015-01-01

    Background: Reproductive dysfunction is a complication of diabetes. Arctium lappa (burdock) root has hypoglycemic and antioxidative properties, which are traditionally used for treatment of impotence and sterility. Therefore, the aim of this study is to investigate the effects of its hydro alcoholic extract on gonadotropin, testosterone, and sperm parameters in nicotinamide/ streptozotocin-induced diabetic mice.

  18. MEMORY MODULATION

    Science.gov (United States)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

  19. The kinetic analysis of the N-methylation of 4-phenylpyridine by nicotinamide N-methyltransferase: Evidence for a novel mechanism of substrate inhibition.

    Science.gov (United States)

    van Haren, Matthijs J; Thomas, Martin G; Sartini, Davide; Barlow, David J; Ramsden, David B; Emanuelli, Monica; Klamt, Fábio; Martin, Nathaniel I; Parsons, Richard B

    2018-03-13

    The N-methylation of 4-phenylpyridine produces the neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+). We investigated the kinetics of 4-phenylpyridine N-methylation by nicotinamide N-methyltransferase (NNMT) and its effect upon 4-phenylpyridine toxicity in vitro. Human recombinant NNMT possessed 4-phenylpyridine N-methyltransferase activity, with a specific activity of 1.7 ± 0.03 nmol MPP+ produced/h/mg NNMT. Although the K m for 4-phenylpyridine was similar to that reported for nicotinamide, its k cat of 9.3 × 10 -5  ± 2 × 10 -5  s -1 and specificity constant, k cat /K m , of 0.8 ± 0.8 s -1  M -1 were less than 0.15% of the respective values for nicotinamide, demonstrating that 4-phenylpyridine is a poor substrate for NNMT. At low (N-methylation was competitively inhibited by dimethylsulphoxide, with a K i of 34 ± 8 mM. At high (>2.5 mM) substrate concentration, enzyme activity followed substrate inhibition kinetics, with a K i of 4 ± 1 mM. In silico molecular docking suggested that 4-phenylpyridine binds to the active site of NNMT in two non-redundant poses, one a substrate binding mode and the other an inhibitory mode. Finally, the expression of NNMT in the SH-SY5Y cell-line had no effect cell death, viability, ATP content or mitochondrial membrane potential. These data demonstrate that 4-phenylpyridine N-methylation by NNMT is unlikely to serve as a source of MPP+. The possibility for competitive inhibition by dimethylsulphoxide should be considered in NNMT-based drug discovery studies. The potential for 4-phenylpyridine to bind to the active site in two binding orientations using the same active site residues is a novel mechanism of substrate inhibition. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. A comparison between topical Griseofulvin and topical Clotrimazole in Tinea Versicolor

    Directory of Open Access Journals (Sweden)

    Mansoori P

    1998-05-01

    Full Text Available Griseofulvin is a well-known, effective, systemic antifungal agent which has not been used topically in the current clinical practice. In order to treat the common superficial fungal infection of tinea versicolor, a new topical formulation of griseofulvin (1% was tried in 105 patients during a double blind study and its efficacy compared with placebo (its vehicle and clotrimazol (1% solutions. As a result, 17.9% of patients treated by griseofulvin, 38.9% of patients on clotrimazole and 3.3% of patients receiving placebo were completely cured. This study suggests that in proper solvent, topical griseofulvin might show its antifungal action.