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Nicotinamide
Terms modified by Nicotinamide Selected AbstractsNicotinamide , biologic actions of an emerging cosmetic ingredientINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2005N. Otte Synopsis Nicotinamide, the water-soluble amide of nicotinic acid, is a component of the two most important coenzymes , nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate. Thus nicotinamide is involved in numerous oxidation,reduction reactions in mammalian biological systems. Nicotinamide essentially acts as an antioxidant. Most effects are exerted via poly-adenosine diphosphate-ribose polymerase inhibition. Thus nicotinamide increasingly gains interest in the prevention and treatment of several skin diseases. It is well established in the systemic therapy of pellagra, a deficiency disease linked to nicotinic acid, but with respect to topical use there is still a need for further evidence with respect to its manifold potential uses. Currently, its local use is established in the care of acne-prone skin. Résumé Le nicotinamide, l,amide hydrosoluble de l'acide nicotinique est un composant des deux plus importants co-enzymes NAD et NADP. Le nicotinamide est impliqué dans de nombreuses réactions d'oxydo-réduction dans les systèmes biologiques des mammifères. Le nicotinamide agit essentiellement en tant qu'anti-oxydant. La plupart des effets sont exercés via l'inhibition de la poly (ADP-ribose) polymerase (PARP). Ainsi, l'intérêt du nicotinamide croît dans la prévention et le traitement de nombreuses maladies cutanées. Son rôle est bien établi dans la thérapie systémique de la pellagre, une maladie déficiente liée à l'acide nicotinique, mais en ce qui concerne son utilisation topique, du fait de ses multiples applications potentielles, il est encore nécessaire d'accumuler davantage de preuves. Son utilisation locale est couramment admise dans le traitement des peaux sujettes à l'acné. [source] Nicotinamide in dermatology: a capsule summaryINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2007Mohammad R. Namazi MD No abstract is available for this article. [source] Activation of Sirt1 Decreases Adipocyte Formation During Osteoblast Differentiation of Mesenchymal Stem Cells,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2006Carl-Magnus Bäckesjö PhD Abstract In vitro, mesenchymal stem cells differentiate to osteoblasts when exposed to bone-inducing medium. However, adipocytes are also formed. We showed that activation of the nuclear protein deacetylase Sirt1 reduces adipocyte formation and promotes osteoblast differentiation. Introduction: Mesenchymal stem cells (MSCs) can differentiate into osteoblasts, adipocytes, chondrocytes, and myoblasts. It has been suggested that a reciprocal relationship exists between the differentiation of MSCs into osteoblasts and adipocytes. Peroxisome proliferator-activated receptor ,2 (PPAR,2) is a key element for the differentiation into adipocytes. Activation of Sirt1 has recently been shown to decrease adipocyte development from preadipocytes through inhibition of PPAR,2. Materials and Methods: We used the mouse mesenchymal cell line C3H10T1/2 and primary rat bone marrow cells cultured in osteoblast differentiation medium with or without reagents affecting Sirt1 activity. Adipocyte levels were analyzed by light microscopy and flow cytometry (FACS) after staining with Oil red O and Nile red, respectively. Osteoblast and adipocyte markers were studied with quantitative real-time PCR. Mineralization in cultures of primary rat bone marrow stromal cells was studied by von Kossa and alizarin red staining. Results: We found that Sirt1 is expressed in the mesenchymal cell line C3H10T1/2. Treatment with the plant polyphenol resveratrol as well as isonicotinamide, both of which activate Sirt1, blocked adipocyte development and increased the expression of osteoblast markers. Nicotinamide, which inhibits Sirt1, increased adipocyte number and increased expression of adipocyte markers. Furthermore, activation of Sirt1 prevented the increase in adipocytes caused by the PPAR,-agonist troglitazone. Finally, activation of Sirt1 in rat primary bone marrow stromal cells increased expression of osteoblast markers and also mineralization. Conclusions: In this study, we targeted Sirt1 to control adipocyte development during differentiation of MSCs into osteoblasts. The finding that resveratrol and isonicotinamide markedly inhibited adipocyte and promoted osteoblast differentiation may be relevant in the search for new treatment regimens of osteoporosis but also important for the evolving field of cell-based tissue engineering. [source] Nicotinamide enhances mitochondria quality through autophagy activation in human cellsAGING CELL, Issue 4 2009Hyun Tae Kang Summary Nicotinamide (NAM) treatment causes a decrease in mitochondrial respiration and reactive oxygen species production in primary human fibroblasts and extends their replicative lifespan. In the current study, it is reported that NAM treatment induces a decrease in mitochondrial mass and an increase in membrane potential (,,m) by accelerating autophagic degradation of mitochondria. In the NAM-treated cells, the level of LC3-II as well as the number of LC3 puncta and lysosomes co-localizing with mitochondria substantially increased. Furthermore, in the NAM-treated cells, the levels of Fis1, Drp1, and Mfn1, proteins that regulate mitochondrial fission and fusion, increased and mitochondria experienced dramatic changes in structure from filaments to dots or rings. This structural change is required for the decrease of mitochondrial mass indicating that NAM accelerates mitochondrial autophagy, at least in part, by inducing mitochondrial fragmentation. The decrease in mitochondria mass was attenuated by treatment with cyclosporine A, which prevents the loss of mitochondrial membrane potential by blocking the mitochondrial permeability transition, suggesting autophagic degradation selective for mitochondria with low ,,m. All these changes were accompanied by and dependent on an increase in the levels of GAPDH, and are blocked by inhibition of the cellular conversion of NAM to NAD+. Taken together with our previous findings, these results suggest that up-regulation of GAPDH activity may prolong healthy lifespan of human cells through autophagy-mediated mitochondria quality maintenance. [source] Micronutrients and the Risk of Type 1 Diabetes: Vitamin D, Vitamin E, and NicotinamideNUTRITION REVIEWS, Issue 9 2004Elina Hypponen Ph.D., M.P.H., M.Sc. Evidence from animal experiments and human observational studies suggests that some dietary micronutrients may protect against the development of type 1 diabetes. The most promising data so far have been obtained for a beneficial role of vitamin D. Beneficial effects of vitamin E (or other antioxidants) in diabetes development remain hypothetical. Despite plausible theoretical background evidence from animal experiments and supportive data from pilot studies, randomized, controlled trials using nicotinamide have not provided any evidence for a beneficial effect. [source] ChemInform Abstract: Synthesis of Nicotinamide and Isonicotinamide Derivatives via Multicomponent Reaction of Alkyl Isocyanides and Acetylenic Compounds in the Presence of Nicotinic or Isonicotinic Acid.CHEMINFORM, Issue 2 2008Abdolali Alizadeh Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] The efficacy of nicotinamide gel 4% as an adjuvant therapy in the treatment of cutaneous erosions of pemphigus vulgarisDERMATOLOGIC THERAPY, Issue 3 2010Fariba Iraji ABSTRACT The high rate of morbidity and mortality resulting from long-term use of corticosteroids in pemphigus vulgaris (PV) warrants discovery of a new treatment strategy. Based on the pathophysiology of PV, nicotinamide can block the process of blister formation through its anti-inflammatory properties. This study was conducted to evaluate the clinical effectiveness of nicotinamide gel in the treatment of skin lesions of PV. In a double-blind, placebo-controlled study, eight PV patients with a total of 60 skin lesions were treated by either nicotinamide or placebo gel. After 30 days of treatment, epithelialization index of the two groups was compared. The mean of the epithelialization index in skin lesions that received nicotinamide was significantly higher than that of the placebo group (26 vs. ,5.8, p < 0.001). Our results were suggestive that nicotinamide gel can effectively be used as an adjunctive treatment for PV lesions. [source] Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulationDIABETES OBESITY & METABOLISM, Issue 11 2008R. R Ortiz-Andrade Aim:, The present investigation was designed to determine the in vivo antidiabetic effect of naringenin (NG) in normoglycaemic and diabetic rat models through blood glucose (GLU) measurements following acute and subchronic time periods. Possible modes of action of NG were investigated and its acute toxicity determined. Methods:, Normoglycaemic and non-insulin-dependent diabetes mellitus (NIDDM) rat models were treated for acute and subchronic (5 days) time periods with 50 mg/kg/day of NG. Blood biochemical profiles were determined after 5 days of the treatment in normoglycaemic and NIDDM rats using commercial kits for GLU, triglycerides (TG), total cholesterol (CHOL) and high-density lipoprotein (HDL). In order to elucidate its antidiabetic mode of action, NG was administered intragastrically and an oral glucose tolerance test performed using GLU and sucrose (2 g/kg) as substrates. The inhibitory effect of a single concentration of NG (10 ,M) on 11,-hydroxysteroid dehydrogenase type 1 (11,-HSD1) activity in vitro was determined. Finally, the preclinical safety and tolerability of NG was determined by toxicological evaluation in mice and rats using Organization for Economic Cooperation and Development (OECD) protocols. Results:, Intragastrically administered NG (50 mg/kg) induced a significant decrease in plasma GLU in normoglycaemic and NIDDM rat models (p < 0.05) following acute and subchronic time periods. After 5 days of administration, NG produced significant diminished blood GLU and TG levels in streptozotocin,nicotinamide,induced diabetic rats. The administration of NG to normal rats significantly increased the levels of TG, CHOL and HDL (p < 0.05). NG (5 and 50 mg/kg) induced a total suppression in the increase of plasma GLU levels after administration of substrates (p < 0.01), but NG did not produce inhibition of ,-glucosidase activity in vitro. However, NG (10 ,M) was shown to inhibit 11,-HSD1 activity by 39.49% in a cellular enzyme assay. Finally, NG showed a Medium Lethal Dose LD50 > 5000 mg/kg and ranking at level five based on OECD protocols. Conclusion:, Our findings suggest that NG may exert its antidiabetic effect by extra-pancreatic action and by suppressing carbohydrate absorption from intestine, thereby reducing the postprandial increase in blood GLU levels. [source] Assay of vitamin B in urine by capillary electrochromatography with methacrylate-based monolithic columnELECTROPHORESIS, Issue 19 2010Xiaoyi Wei Abstract A novel and simple method for the separation of major vitamin B analytes, such as thiamine, riboflavin, nicotinamide, vitamin B4, pyridoxine, has been developed by CEC using the monolithic column. It has been found that the baseline separation of the five analytes could be achieved with 5.0,mM phosphate buffer at pH 4.0. Compared with the open-tubular capillary and the bared capillary columns, the poly(butylmethacrylate-co-ethylene glycol dimethacrylate) monolithic capillary could exhibit the best resolution in the analysis. Then the method was validated and the linear calibration ranges were obtained with correlation coefficients more than 0.997. The precision and the recovery were also investigated and showed a good result. Furthermore, the proposed method was successfully applied to assay the concentration of vitamin B analytes and the metabolic situation in human urine samples. [source] Aminoguanidine prevents arterial stiffening in a new rat model of type 2 diabetesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2006K.-C. Chang Abstract Background, Formation of advanced glycation end-products (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study focused on investigating the role of aminoguanidine (AG), an inhibitor of AGE formation, in the prevention of noninsulin-dependent diabetes mellitus (NIDDM)-derived arterial stiffening and cardiac hypertrophy in rats. Materials and methods, The NIDDM was induced in male Wistar rats, which were administered intraperitoneally with 180 mg kg,1 nicotinamide (NA) 30 min before an intravenous injection of 50 mg kg,1 streptozotocin (STZ). After induction of diabetes mellitus type 2, animals receiving daily peritoneal injections with 50 mg kg,1 AG for 8 weeks were compared with the age-matched, untreated, diabetic controls. Results, After exposure to AG, the STZ-NA diabetic rats had improved aortic distensibility, as evidenced by 18·8% reduction of aortic characteristic impedance (P < 0·05). Treatment of the experimental syndrome with AG also resulted in a significant increase in wave transit time (+23·7%, P < 0·05) and a decrease in wave reflection factor (,26·6%, P < 0·05), suggesting that AG may prevent the NIDDM-induced augmentation in systolic load of the left ventricle. Also, the glycation-derived modification on aortic collagen was found to be retarded by AG. The diminished ratio of left ventricular weight to body weight suggested that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening. Conclusions, Long-term administration of AG to the STZ-NA diabetic rats imparts significant protection against the NIDDM-derived impairment in vascular dynamics, at least partly through inhibition of the AGE accumulation on collagen in the arterial wall. [source] Arterial stiffening and cardiac hypertrophy in a new rat model of type 2 diabetesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2006K.-C. Chang Abstract Background, We determined the effects of NIDDM on haemodynamic parameters describing arterial wall elasticity and cardiac hypertrophy in rats administered streptozotocin (STZ) and nicotinamide (NA), using the aortic impedance analysis. Methods, Male Wistar rats at 2 months were administered intraperitoneally 180 mg kg,1 of NA, 30 min before an intravenous injection of 50 mg kg,1 STZ, to induce type 2 diabetes. The STZ-NA rats were divided into two groups, 4 weeks and 8 weeks after induction of diabetes, and compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured by a high-fidelity pressure sensor and electromagnetic flow probe, respectively, and were then subjected to Fourier transformation for the analysis of aortic input impedance. Results, In each diabetic group, the experimental syndrome was characterized by a moderate and stable hyperglycaemia and a relative deficiency of insulin secretion. However, the 8-week but not the 4-week STZ-NA diabetic rats showed a decrease in cardiac output in the absence of any significant changes in mean aortic pressure, having increased total peripheral resistance. The diabetic syndrome at 8 weeks also contributed to an increase in aortic characteristic impedance, from 1·49 ± 0·33 (mean ± SD) to 1·95 ± 0·28 mmHg s mL,1 (P < 0·05), suggesting a detriment to the aortic distensibility in NIDDM. Meanwhile, the STZ-NA diabetic animals after 8 weeks had an increased wave reflection factor (0·46 ± 0·09 vs. 0·61 ± 0·13, P < 0·05) and decreased wave transit time (25·8 ± 3·8 vs. 20·6 ± 2·8 ms, P < 0·05). Ratio of the left ventricular weight to body weight was also enhanced in the 8-week STZ-NA diabetic rats. Conclusion, The heavy intensity with early return of the pulse wave reflection may augment systolic load of the left ventricle coupled to the arterial system, leading to cardiac hypertrophy in the rats at 8 weeks after following STZ and NA administration. [source] Serum or target deprivation-induced neuronal death causes oxidative neuronal accumulation of Zn2+ and loss of NAD+EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2010Christian T. Sheline Abstract Trophic deprivation-mediated neuronal death is important during development, after acute brain or nerve trauma, and in neurodegeneration. Serum deprivation (SD) approximates trophic deprivation in vitro, and an in vivo model is provided by neuronal death in the mouse dorsal lateral geniculate nucleus (LGNd) after ablation of the visual cortex (VCA). Oxidant-induced intracellular Zn2+ release ([Zn2+]i) from metallothionein-3 (MT-III), mitochondria or ,protein Zn2+', was implicated in trophic deprivation neurotoxicity. We have previously shown that neurotoxicity of extracellular Zn2+ required entry, increased [Zn2+]i, and reduction of NAD+ and ATP levels causing inhibition of glycolysis and cellular metabolism. Exogenous NAD+ and sirtuin inhibition attenuated Zn2+ neurotoxicity. Here we show that: (1) Zn2+ is released intracellularly after oxidant and SD injuries, and that sensitivity to these injuries is proportional to neuronal Zn2+ content; (2) NAD+ loss is involved , restoration of NAD+ using exogenous NAD+, pyruvate or nicotinamide attenuated these injuries, and potentiation of NAD+ loss potentiated injury; (3) neurons from genetically modified mouse strains which reduce intracellular Zn2+ content (MT-III knockout), reduce NAD+ catabolism (PARP-1 knockout) or increase expression of an NAD+ synthetic enzyme (Wlds) each had attenuated SD and oxidant neurotoxicities; (4) sirtuin inhibitors attenuated and sirtuin activators potentiated these neurotoxicities; (5) visual cortex ablation (VCA) induces Zn2+ staining and death only in ipsilateral LGNd neurons, and a 1 mg/kg Zn2+ diet attenuated injury; and finally (6) NAD+ synthesis and levels are involved given that LGNd neuronal death after VCA was dramatically reduced in Wlds animals, and by intraperitoneal pyr vate or nicotinamide. Zn2+ toxicity is involved in serum and trophic deprivation-induced neuronal death. [source] Restorable Type Conversion of Carbon Nanotube Transistor Using Pyrolytically Controlled Antioxidizing Photosynthesis CoenzymeADVANCED FUNCTIONAL MATERIALS, Issue 16 2009Bo Ram Kang Abstract Here, a pyrolytically controlled antioxidizing photosynthesis coenzyme, , -Nicotinamide adenine dinucleotide, reduced dipotassium salt (NADH) for a stable n-type dopant for carbon nanotube (CNT) transistors is proposed. A strong electron transfer from NADH, mainly nicotinamide, to CNTs takes place during pyrolysis so that not only the type conversion from p-type to n-type is realized with 100% of reproducibility but also the on/off ratio of the transistor is significantly improved by increasing on-current and/or decreasing off-current. The device was stable up to a few months with negligible current changes under ambient conditions. The n-type characteristics were completely recovered to an initial doping level after reheat treatment of the device. [source] Alcohol-induced alterations in hepatic microtubule dynamics can be explained by impaired histone deacetylase 6 function,HEPATOLOGY, Issue 5 2008Blythe D. Shepard We have been using polarized, hepatic WIF-B cells to examine ethanol-induced liver injury. These cells polarize in culture and maintain numerous liver-specific activities including the ability to metabolize alcohol. Previously, we found that microtubules were more highly acetylated and more stable in ethanol-treated WIF-B cells and that increased microtubule acetylation required ethanol metabolism and was likely mediated by acetaldehyde. This study was aimed at identifying the mechanism responsible for increased microtubule acetylation. We examined the expression of two known microtubule deacetylases, histone deacetylase 6 (HDAC6) and Sirtuin T2 (SirT2), in WIF-B cells. Immunoblotting, immunofluorescence microscopy, and assays using the SirT2 inhibitor nicotinamide revealed that WIF-B cells do not express SirT2. In contrast, HDAC6 was highly expressed in WIF-B cells. Addition of trichostatin A (TSA), an HDAC6 inhibitor, induced microtubule acetylation to the same extent as in ethanol-treated cells (approximately threefold). Although immunofluorescence labeling revealed that HDAC6 distribution did not change in ethanol-treated cells, immunoblotting showed HDAC6 protein levels slightly decreased. HDAC6 solubility was increased in nocodazole-treated cells, suggesting impaired microtubule binding. Direct microtubule binding assays confirmed this hypothesis. The decreased microtubule binding was partially prevented by 4-methyl pyrazole, indicating the effect was in part mediated by acetaldehyde. Interestingly, HDAC6 from ethanol-treated cells was able to bind and deacetylate exogenous tubulin to the same extent as control, suggesting that ethanol-induced tubulin modifications prevented HDAC6 binding to endogenous microtubules. Conclusion: We propose that lower HDAC6 levels combined with decreased microtubule binding lead to increased tubulin acetylation in ethanol-treated cells. (HEPATOLOGY 2008.) [source] Nicotinamide , biologic actions of an emerging cosmetic ingredientINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2005N. Otte Synopsis Nicotinamide, the water-soluble amide of nicotinic acid, is a component of the two most important coenzymes , nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate. Thus nicotinamide is involved in numerous oxidation,reduction reactions in mammalian biological systems. Nicotinamide essentially acts as an antioxidant. Most effects are exerted via poly-adenosine diphosphate-ribose polymerase inhibition. Thus nicotinamide increasingly gains interest in the prevention and treatment of several skin diseases. It is well established in the systemic therapy of pellagra, a deficiency disease linked to nicotinic acid, but with respect to topical use there is still a need for further evidence with respect to its manifold potential uses. Currently, its local use is established in the care of acne-prone skin. Résumé Le nicotinamide, l,amide hydrosoluble de l'acide nicotinique est un composant des deux plus importants co-enzymes NAD et NADP. Le nicotinamide est impliqué dans de nombreuses réactions d'oxydo-réduction dans les systèmes biologiques des mammifères. Le nicotinamide agit essentiellement en tant qu'anti-oxydant. La plupart des effets sont exercés via l'inhibition de la poly (ADP-ribose) polymerase (PARP). Ainsi, l'intérêt du nicotinamide croît dans la prévention et le traitement de nombreuses maladies cutanées. Son rôle est bien établi dans la thérapie systémique de la pellagre, une maladie déficiente liée à l'acide nicotinique, mais en ce qui concerne son utilisation topique, du fait de ses multiples applications potentielles, il est encore nécessaire d'accumuler davantage de preuves. Son utilisation locale est couramment admise dans le traitement des peaux sujettes à l'acné. [source] Nicotinamide phosphoribosyltransferase/sirtuin 1 pathway is involved in human immunodeficiency virus type 1 Tat-mediated long terminal repeat transactivationJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2010Hong-Sheng Zhang Abstract Tat is a multifunctional transactivator encoded by human immunodeficiency virus type 1 (HIV-1). Tat transactivating activity is controlled by nicotinamide adenine nucleotide+ (NAD+)-dependent deacetylase sirtuin 1 (SIRT1). Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the conversion of nicotinamide into NAD+, which is crucial for SIRT1 activation. Thus, the effect of Nampt on Tat-regulated SIRT activity was studied in Hela-CD4-,-gal (MAGI) cells. We demonstrated that Tat caused NAD+ depletion and inhibited Nampt mRNA and protein expression in MAGI cells. Resveratrol reversed Tat-induced NAD+ depletion and inhibition of Nampt mRNA and protein expression. Further investigation revealed that Tat-induced inhibition of SIRT1 activity was potentiated in Nampt-knockdown by Nampt siRNA compared to treatment with Tat alone. Nampt siRNA potentiated Tat-induced HIV-1 transactivation in MAGI cells. Altogether, these results indicate that Nampt is critical in the regulation of Tat-induced inhibition of SIRT1 activity and long terminal repeat (LTR) transactivation. Nampt/SIRT1 pathway could be a novel therapeutic tool for the treatment of HIV-1 infection. J. Cell. Biochem. 110: 1464,1470, 2010. © 2010 Wiley-Liss, Inc. [source] Induction of oxidative stress by homocyst(e)ine impairs endothelial function,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2001Vibhas S. Mujumdar Abstract Previous studies have demonstrated a relationship between hyperhomocysteinemia and endothelial dysfunction, reduced bioavailability of nitric oxide, elastinolysis and, vascular muscle cell proliferation. In vivo decreased nitric oxide production is associated with increased matrix metalloproteinase (MMP) activity and formation of nitrotyrosine. To test the hypothesis that homocysteine neutralizes vascular endothelial nitric oxide, activates metalloproteinase, causes elastinolysis and vascular hypertrophy, we isolated aortas from normotensive Wistar rats and cultured them in medium containing homocysteine, and calf serum for 14 days. Homocysteine-mediated impairment of endothelial-dependent vasodilatation was reversed by co-incubation of homocysteine with nicotinamide (an inhibitor of peroxinitrite and nitrotyrosine), suggesting a role of homocysteine in redox-mediating endothelial dysfunction and nitrotyrosine formation. The Western blot analysis, using anti-nitrotyrosine antibody, on aortic tissue homogeneates demonstrated decreased nitrotyrosine in hyperhomocysteinemic vessels treated with nicotinamide. Zymographic analysis revealed increased elastinolytic gelatinase A and B (MMP-2, -9) in homocysteine treated vessels and the treatment with nicotinamide decreases the homocysteine-induced MMP activation. Morphometric analyses revealed significant medial hypertrophic thickening (1.4,±,0.2-fold of control, P,=,0.03) and elastin disruption in homocysteine-treated vessels as compared to control. To determine whether homocysteine causes endothelial cell injury, cross-sections of aortas were analyzed for caspase activity by incubating with Ac-YVAD-AMC (substrate for apoptotic enzyme, caspase). The endothelium of homocysteine treated vessels, and endothelial cells treated with homocysteine, showed marked labeling for caspase. The length-tension relationship of homocysteine treated aortas was shifted to the left as compared to untreated aortas, indicating reduced vascular elastic compliance in homocysteine-treated vessels. Co-incubation of homocysteine and inhibitors of MMP, tissue inhibitor of metalloproteinase-4 (TIMP-4), and caspase, YVAD-CHO, improved vascular function. The results suggest that alteration in vascular elastin/collagen ratio and activation of MMP-2 are associated with decreased NO production in hyperhomocysteinemia. J. Cell. Biochem. 82:491,500, 2001. © 2001 Wiley-Liss, Inc. [source] How to overcome (and exploit) tumor hypoxia for targeted gene therapyJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2003Olga Greco Tumor hypoxia has long been recognized as a critical issue in oncology. Resistance of hypoxic areas has been shown to affect treatment outcome after radiation, chemotherapy, and surgery in a number of tumor sites. Two main strategies to overcome tumor hypoxia are to increase the delivery of oxygen (or oxygen-mimetic drugs), and exploiting this unique environmental condition of solid tumors for targeted therapy. The first strategy includes hyperbaric oxygen breathing, the administration of carbogen and nicotinamide, and the delivery of chemical radiosensitizers. In contrast, bioreductive drugs and hypoxia-targeted suicide gene therapy aim at activating cytotoxic agents at the tumor site, while sparing normal tissue from damage. The cellular machinery responds to hypoxia by activating the expression of genes involved in angiogenesis, anaerobic metabolism, vascular permeability, and inflammation. In most cases, transcription is initiated by the binding of the transcription factor hypoxia-inducible factor (HIF) to hypoxia responsive elements (HREs). Hypoxia-targeting for gene therapy has been achieved by utilizing promoters containing HREs, to induce selective and efficient transgene activation at the tumor site. Hypoxia-targeted delivery and prodrug activation may add additional levels of selectivity to the treatment. In this article, the latest developments of cancer gene therapy of the hypoxic environment are discussed, with particular attention to combined protocols with ionizing radiation. Ultimately, it is proposed that by adopting specific transgene activation and molecular amplification systems, resistant hypoxic tumor tissues may be effectively targeted with gene therapy. J. Cell. Physiol. 197: 312,325, 2003© 2003 Wiley-Liss, Inc. [source] Nicotinamide phosphoribosyltransferase imparts human endothelial cells with extended replicative lifespan and enhanced angiogenic capacity in a high glucose environmentAGING CELL, Issue 2 2009Nica M. Borradaile Summary Endothelial dysfunction is a characteristic of aging-related vascular disease and is worsened during diabetes. High glucose can impair endothelial cell (EC) function through cellular accumulation of reactive oxygen species, an insult that can also limit replicative lifespan. Nicotinamide phosphoribosyltransferase (Nampt), also known as PBEF and visfatin, is rate-limiting for NAD+ salvage from nicotinamide and confers resistance to oxidative stress via SIRT1. We therefore sought to determine if Nampt expression could resist the detrimental effects of high glucose and confer a survival advantage to human vascular EC in this pathologic environment. Human aortic EC were infected with retrovirus encoding eGFP or eGFP-Nampt, and FACS-selected to yield populations with similar, modest transgene expression. Using a chronic glucose exposure model we tracked EC populations to senescence, assessed cellular metabolism, and determined in vitro angiogenic function. Overexpression of Nampt increased proliferation and extended replicative lifespan, and did so preferentially during glucose overload. Nampt expression delayed markers of senescence and limited reactive oxygen species accumulation in high glucose through a modest increase in aerobic glycolysis. Furthermore, tube networks formed by Nampt-overexpressing EC were more extensive and glucose-resistant, in accordance with SIRT1-mediated repression of the anti-angiogenic transcription factor, FoxO1. We conclude that Nampt enables proliferating human EC to resist the oxidative stress of aging and of high glucose, and to productively use excess glucose to support replicative longevity and angiogenic activity. Enhancing endothelial Nampt activity may thus be beneficial in scenarios requiring EC-based vascular repair and regeneration during aging and hyperglycemia, such as atherosclerosis and diabetes-related vascular disease. [source] Capillary Zone Electrophoresis and Micellar Electrokinetic Capillary Chromatography for Determining Water-Soluble Vitamins in Commercial Capsules and TabletsJOURNAL OF FOOD SCIENCE, Issue 1 2001S-C. Su ABSTRACT: A rapid method was developed for simultaneously determining thiamine, riboflavin, pyridoxine, nicotinamide, nicotinic acid, and ascorbic acid. It was tested on 15 samples. The peaks of all components were cleanly separated with good resolution by capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MECC). CZE was performed with 0.02 M borate buffer, and MECC was performed with 4% acetonitrile in 0.02 M borate/phosphate buffer containing 0.1 M sodium dodecyl sulfate. Average recoveries for all components were 80.3% to 103.7% with coefficients of variation being less than 5%. Thiamine, nicotinic acid, and pyridoxine contents were consistent with those labeled on the packages, but nicotinamide, riboflavin, and ascorbic acid contents of some samples were less. [source] Response Surface Methodology for Reduction of Pinking in Cooked Turkey Breast Mince by Various Dairy Protein CombinationsJOURNAL OF FOOD SCIENCE, Issue 3 2000A.J. Slesinski ABSTRACT: Nonfat dry milk (NFDM), sodium caseinate (SC), whey protein concentrate (WPC), and combinations of each were evaluated for abilities to reduce pink color development in cooked, ground, uncured turkey breast. Protein treatments were also evaluated in the presence of pink-color-generating ligands (nicotinamide, 1%, sodium nitrite, 10 ppm, and sodium nitrate, 50 ppm) with and without ethylenedinitrilo-tetraacetic acid disodium salt (200 ppm). NFDM and WPC at levels as low as 1.5% were effective in reducing CIE a* values (P < 0.05) regardless of ligand treatment; SC was not. EDTA reduced pink color within all protein and ligand treatments. Poultry producers can reduce pink color development in further-processed products by selective addition of dairy proteins. [source] Preparation of 18O-labelled nicotinamideJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 12 2002Magdalena Ko, odziejska-Huben Abstract A method of preparing 18O-labelled nicotinamide, involving cyanopyridine, H218O, and 1,1,3,3,-tetramethylguanidine as a catalyst is described. The desired product is produced in 91% chemical yield and 97.5% isotopic incorporation. Copyright © 2002 John Wiley & Sons, Ltd. [source] Molecular dynamics simulations of hydrotropic solubilization and self-aggregation of nicotinamideJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2010Yong Cui Abstract Hydrotropy is a phenomenon where the presence of a large quantity of one solute enhances the solubility of another solute. The mechanism of this phenomenon remains elusive and a topic of debate. This study employed molecular dynamics simulation to investigate the hydrotropic mechanism of a model system consisting of a hydrotropic agent, nicotinamide (NA), a poorly water-soluble solute, PG-300995 (PG), and water. Our study demonstrates that NA and PG undergo significant aggregation in the aqueous solution, a result correlating closely to the self-aggregation of NA under the same conditions. The correlations are found both structurally and dynamically, suggesting that the self-aggregation of NA may be a prerequisite, or at least a major contributor, to its hydrotropic effects. The self-aggregation of NA allows the segregation of the hydrophobic solute from water, a key step to ease the energy increase to the system. Energetic evidences directly show that the hydrotropic solubilization is favored in the presence of NA aggregation. These results are in strong support of the molecular aggregation hypothesis for hydrotropic solubilization. Additionally, it is found that the restoration of water,water HBs from the interference of the NA and PG molecules plays an important role for the aggregation. The HBs between the solute and the hydrotrope may contribute, but is not vital, to the aggregation and hence the hydrotropic effects. The dynamic data confirm that the aggregates, while remain in liquid state, are much more active dynamically than a pure NA amorphous/liquid phase under the same temperature and pressure. By equilibrating an NA amorphous agglomerate with water, it is found that the aggregation state, rather than an NA,water two phase system, is the equilibrium state of the NA,+,water system. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3048,3059, 2010 [source] Ethyl-paraben and nicotinamide mixtures: Apparent solubility, thermal behavior and X-ray structure of the 1:1 co-crystal,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2008S. Nicoli Abstract This work aims at investigating the nicotinamide (NA),ethyl-paraben (EP) binary system both in solution and in the solid state. In particular, the apparent EP solubility in water was studied in the presence of different NA concentrations (between 0.28 and 1.64 M). It was found that the apparent EP solubility increase (nearly twofold) observed at the highest NA concentration tested can be ascribed to a change in the polarity of the solvent mixture, rather than to a direct effect of NA on EP. The effect of fusion and re-crystallization from water or ethanol solutions on EP and NA mixtures was investigated by means of differential scanning calorimetry, elemental analysis and X-ray diffraction both on powder and single crystal. It was discovered that EP and NA form a co-crystal having a 1:1 molar composition that can be easily crystallized from ethanol. Single crystal X-ray analysis of this species revealed that the NA and EP molecules form corrugated layers within which the two components are intimately associated by a dense network of hydrogen bonds. In the presence of an excess NA in solution, the EP-NA co-crystal has lower water solubility with respect to both the single co-crystal formers and precipitates in aqueous solutions at ambient temperature. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4830,4839, 2008 [source] Crystallization pathways and kinetics of carbamazepine,nicotinamide cocrystals from the amorphous state by in situ thermomicroscopy, spectroscopy, and calorimetry studiesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2007K. Seefeldt Abstract The work presented here was motivated by the premise that the amorphous state serves as a medium to study cocrystal formation. The molecular mobility inherent to amorphous phases can lead to molecular associations between different components such that a single crystalline phase of multiple components or cocrystal is formed. Cocrystallization pathways and kinetics were investigated from amorphous equimolar phases of carbamazepine and nicotinamide using hot-stage polarized microscopy (HSPM), hot-stage Raman microscopy (HSRM), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD). Nonisothermal studies revealed that amorphous phases generate cocrystals and that thermal history affects crystallization pathways in significant ways. Two different pathways to cocrystal formation from the amorphous phase were identified: (1) at low heating rates (3°C/min) a metastable cocrystalline phase initially nucleates and transforms to the more stable cocrystalline phase of CBZ,NCT, and (2) at higher heating rates (10°C/min) individual components crystallize, then melt and the stable cocrystalline phase nucleates and grows from the melt. Isothermal studies above the Tg of the amorphous equimolar phase also confirm the nucleation of a metastable cocrystalline phase from the amorphous state followed by a solid phase mediated transformation to the stable cocrystalline phase. Cocrystallization kinetics were measured by image analysis and by thermal analysis from small samples and are described by the Avrami,Erofeev model. These findings have important implications for the use of amorphous phases in the discovery of cocrystals and to determine the propensity of cocrystallization from process-induced amorphization. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1147,1158, 2007 [source] Antidiabetic properties of the alcoholic extract of Sphaeranthus indicus in streptozotocin-nicotinamide diabetic ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2008Kirti S. Prabhu We have investigated the possible antihyperglycaemic effects of Sphaeranthus indicus extract in rats rendered diabetic by nicotinamide (120 mgkg,1 i.p.) and streptozotocin (STZ) (60 mgkg,1 i.p). Fasting plasma glucose levels, serum insulin levels, serum lipid profiles, magnesium levels, glycosylated haemoglobin, changes in body weight and liver glycogen levels were evaluated in normal and diabetic rats. Oral administration of S. indicus for 15 days resulted in significant decrease in blood glucose levels and increases in hepatic glycogen and plasma insulin levels. Fasting normal rats treated with the alcoholic extract of S. indicus showed significant improvement in oral glucose tolerance test. Glibenclamide was used as a reference standard. The findings demonstrate that the alcoholic S. indicus extract may be useful in the treatment of diabetes. [source] Assimilation of NAD+ precursors in Candida glabrataMOLECULAR MICROBIOLOGY, Issue 1 2007Biao Ma Summary The yeast pathogen Candida glabrata is a nicotinamide adenine dinucleotide (NAD+) auxotroph and its growth depends on the environmental supply of vitamin precursors of NAD+. C. glabrata salvage pathways defined in this article allow NAD+ to be synthesized from three compounds , nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NA is salvaged through a functional Preiss,Handler pathway. NAM is first converted to NA by nicotinamidase and then salvaged by the Preiss,Handler pathway. Salvage of NR in C. glabrata occurs via two routes. The first, in which NR is phosphorylated by the NR kinase Nrk1, is independent of the Preiss,Handler pathway. The second is a novel pathway in which NR is degraded by the nucleosidases Pnp1 and Urh1, with a minor role for Meu1, and ultimately converted to NAD+ via the nicotinamidase Pnc1 and the Preiss,Handler pathway. Using C. glabrata mutants whose growth depends exclusively on the external NA or NR supply, we also show that C. glabrata utilizes NR and to a lesser extent NA as NAD+ sources during disseminated infection. [source] Micronutrients and the Risk of Type 1 Diabetes: Vitamin D, Vitamin E, and NicotinamideNUTRITION REVIEWS, Issue 9 2004Elina Hypponen Ph.D., M.P.H., M.Sc. Evidence from animal experiments and human observational studies suggests that some dietary micronutrients may protect against the development of type 1 diabetes. The most promising data so far have been obtained for a beneficial role of vitamin D. Beneficial effects of vitamin E (or other antioxidants) in diabetes development remain hypothetical. Despite plausible theoretical background evidence from animal experiments and supportive data from pilot studies, randomized, controlled trials using nicotinamide have not provided any evidence for a beneficial effect. [source] The cocrystal nicotinamide,succinic acid (2/1)ACTA CRYSTALLOGRAPHICA SECTION C, Issue 8 2010Laura J. Thompson In the asymmetric unit of the crystal structure of nicotinamide,succinic acid (2/1), 2C6H6N2O·C4H6O4, there are two independent nicotinamide molecules in general positions and two half succinic acid molecules which lie about inversion centres. The structure contains acid,pyridine and amide,amide synthons with nicotinamide molecules forming ladders of alternating R22(8) and R42(8) rings linked through succinic acid to generate a corrugated hydrogen-bonded sheet. This sheet is a common supramolecular unit found in other 2:1 nicotinamide,dicarboxylic acid cocrystals, but the presence of two crystallographically distinct nicotinamides with anti and syn conformations, forming two distinct sheets within the same structure, is a novel packing feature in this type of material. [source] Zero-, one- and two-dimensional hydrogen-bonded structures in the 1:1 proton-transfer compounds of 4,5-dichlorophthalic acid with the monocyclic heteroaromatic Lewis bases 2-aminopyrimidine, nicotinamide and isonicotinamideACTA CRYSTALLOGRAPHICA SECTION C, Issue 3 2009Graham Smith The structures of the anhydrous 1:1 proton-transfer compounds of 4,5-dichlorophthalic acid (DCPA) with the monocyclic heteroaromatic Lewis bases 2-aminopyrimidine, 3-(aminocarbonyl)pyridine (nicotinamide) and 4-(aminocarbonyl)pyridine (isonicotinamide), namely 2-aminopyrimidinium 2-carboxy-4,5-dichlorobenzoate, C4H6N3+·C8H3Cl2O4,, (I), 3-(aminocarbonyl)pyridinium 2-carboxy-4,5-dichlorobenzoate, C6H7N2O+·C8H3Cl2O4,, (II), and the unusual salt adduct 4-(aminocarbonyl)pyridinium 2-carboxy-4,5-dichlorobenzoate,methyl 2-carboxy-4,5-dichlorobenzoate (1/1), C6H7N2O+·C8H3Cl2O4,·C9H6Cl2O4, (III), have been determined at 130,K. Compound (I) forms discrete centrosymmetric hydrogen-bonded cyclic bis(cation,anion) units having both R22(8) and R12(4) N,H...O interactions. In (II), the primary N,H...O-linked cation,anion units are extended into a two-dimensional sheet structure via amide,carboxyl and amide,carbonyl N,H...O interactions. The structure of (III) reveals the presence of an unusual and unexpected self-synthesized methyl monoester of the acid as an adduct molecule, giving one-dimensional hydrogen-bonded chains. In all three structures, the hydrogen phthalate anions are essentially planar with short intramolecular carboxyl,carboxylate O,H...O hydrogen bonds [O...O = 2.393,(8),2.410,(2),Å]. This work provides examples of low-dimensional 1:1 hydrogen-bonded DCPA structure types, and includes the first example of a discrete cyclic `heterotetramer.' This low dimensionality in the structures of the 1:1 aromatic Lewis base salts of the parent acid is generally associated with the planar DCPA anion species. 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