The cytoplasmic enzyme, NAD⁺ kinase (ATP: NAD⁺ 2-phosphotransferase, [E.C. 2.7.1.23}) has been characterized and purified from yeast. A continuous fluorescence assay was developed. A purification procedure was developed utilizing NAD⁺-Agarose affinity column chromatography.

Dans le cadre des recherches menées au sein du laboratoire de Physiologie Animale le gène codant pour la nicotinamide phosphorybosyltransférase (NAmPT) à été identifié et cloné. Au cours de ce travail, nous avons étudié le rôle de cette enzyme du métabolisme du Nicotinamide Adénine Dinucléotide ainsi que celui des enzymes dépendantes du NAD (PARP et sirtuines) dans le contrôle de la réponse inflammatoire.

The clinical relevance of vitamin B3, nicotinamide (NAm), has been demonstrated in a variety of injury models to exert a number of therapeutic benefits in the protection against and treatment of traumatic brain injury (TBI). This study investigated its efficacy on recovery from TBI in animals of differing ages (6- and 10-months old) that were injured using the controlled cortical impact model and tested for motor and cognitive recovery following injury. Injured animals were treated with NAm or saline following injury and sham-injured animals were included as a control group. It was hypothesized that increasing age reduces the potentiality of recovery from injury as well as a decreased therapeutic benefit derived from the post-injury administration of NAm. The results found that neither the 6- nor 10-month old animals treated with NAm demonstrated improved functional recovery, indicating that age is an important factor in the vitamin's efficacy. These results indicate that the success of possible treatments for TBI needs to also consider the effects of an individual's age on the drug's effectiveness.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 1981 / Includes bibliographical references. / by Ze'ev Shaked. / Ph. D. / Ph.D. Massachusetts Institute of Technology, Department of Chemistry

Le nicotinamide est un des deux constituants de la vitamine B3. C’est aussi un agent pharmacologique qui a été testé dans le traitement du HIV chez l’homme, et comme traitement contre diverses pathologies. Il présente également des capacités cytoprotectrices dans plusieurs modèles de stress cellulaire et est considéré comme un agent pharmacologique prometteur dans le traitement des maladies de dégénérescence cérébrale d’origine vasculaire. Il module la réponse innée en inhibant notamment la synthèse de molécules pro-inflammatoires. Toutefois, son influence sur la réponse adaptative n’a pas encore été analysée. <p>Le nicotinamide intervient dans la biosynthèse du NAD comme précurseur dans la voie de « sauvetage ». Le rôle du NAD comme coenzyme dans de nombreuses réactions enzymatiques du métabolisme de la cellule est bien connu. De plus, le NAD peut être dégradé par différentes enzymes impliquées dans différentes modifications post-traductionnelles de protéines (PARPs, Sirtuines et MARTs). Le nicotinamide est un produit de la dégradation du NAD mais également un inhibiteur de ces enzymes et constitue donc un outil permettant d’étudier le rôle de ces enzymes dans la transduction de signaux intracellulaires. <p>Nous avons utilisé le nicotinamide comme un inhibiteur non toxique des différentes enzymes impliquées dans les réactions d’ADP-ribosylation et étudié son effet sur l’activation des lymphocytes B. Le nicotinamide inhibe la prolifération et la différentiation de ces cellules. Il ne module pas les étapes précoces du BCR mais inhibe l’activation des MAPKs et de la kinase Akt. L’inhibition des MAPKs Erk est corrélée avec une réduction de l’expression de la cycline D2 et du marqueur d’activation CD69. L’utilisation d’un inhibiteur des PARPs ne nous a pas permis de reproduire les effets du NAm sur la voie MAPK Erk et CD69. Par contre, le MIBG, un inhibiteur des MARTs inhibe bien la surexpression du CD69 ainsi que la phosphorylation des kinases Erk. Bien que le nicotinamide soit capable d’inhiber l’expression du CD69 in vivo, nos expériences ne nous ont pas permis de moduler la réponse immune adaptative in vivo. <p>Ceci suggère dès lors que l’utilisation de fortes doses de nicotinamide comme traitement pharmacologique de certaines affections chez l’homme ne devrait pas poser de problème au niveau de la réponse adaptative. De plus, notre mise en évidence des MARTs dans le contrôle de l’activation des lymphocytes B ouvre des perspectives encourageantes pour de nouveaux traitements modulant la réponse adaptative. Cette réponse étant particulièrement impliquée dans certaines maladies auto-immunes, il est potentiellement intéressant de trouver des inhibiteurs de ces enzymes plus puissants que le nicotinamide afin de moduler la réponse immune adaptative in vivo<p> / Doctorat en sciences, Spécialisation biologie moléculaire / info:eu-repo/semantics/nonPublished

Dans le cadre des recherches menées au sein du laboratoire de Physiologie Animale le gène codant pour la nicotinamide phosphorybosyltransférase (NAmPT) à été identifié et cloné. Au cours de ce travail, nous avons étudié le rôle de cette enzyme du métabolisme du Nicotinamide Adénine Dinucléotide ainsi que celui des enzymes dépendantes du NAD (PARP et sirtuines) dans le contrôle de la réponse inflammatoire. / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

No description available.

The purpose of this study is to investigate an animal model of distress (conditioned suppression) to assess the effects of magnesium (MAG) and nicotinamide (B3) administration on recovery of anxiety-like behavior following traumatic brain injury (TBI). Post-traumatic stress disorder (PTSD) is comorbid with TBI and both affects a victim’s ability to maintain daily activities and have a good quality of life. Administration of MAG decreases swelling of the brain considerably and lessens cell death. B3 is a neuroprotective precursor to NAD+ and enhances energy levels as well has help reduce free radicals after TBI. A conditioned suppression procedure is an established method for generating disruptive fearful anxiety-like responses in animals and these treatments may help to reduce anxiety responses.

Acne is an extremely common condition, affecting almost 80% of adolescents and young adults. It is an inflammatory disease, characterised by comedones, papules, pustules and sometimes cysts. Factors causing acne include enhanced sebum excretion, hypercornification of the sebaceous duct, ductal coloniazation with Propionibacterium acnes and production of inflammation (Gollnick & Cunliffe, 2003:1). Because of the widespread use of topically applied antimicrobial agents in the treatment of inflammatory acne, resistance of disease-related micro-organisms developed. Therefore new strategies for the treatment of moderate inflammatory acne are necessary. Nicotinamide is a new approach to topical treatment of moderate inflammatory acne without the development of resistant micro-organisms (Otte et al., 2005:257). Using the skin as an alternative route for the administration of nicotinamide for the treatment of acne, may be beneficial. When nicotinamide permeates through the skin, it is directly delivered to the dermis, the place where action is needed and better results can thus be expected after the treatment has started. Another benefit is that smaller amounts of the drug are absorbed systemically with decreased adverse reactions. Unfortunately, using the skin as an alternative route for administering drugs (transdermal drug delivery), has numerous limitations. One of these limitations is the barrier function of the skin (Naik et al., 2000:319). Because of the skin's outstanding ability to protect the body against unwanted substances from its surroundings, it is necessary to use methods to enhance drug penetration through the skin. A new technology, named Pheroid™ technology, was used in this study to enhance penetration through the skin. This technology is based on the use of vesicular structures with no phospholipids or cholesterol to enhance penetration (Grobler et al., 2008:283). The aim of this study was to formulate four different semi-solid formulations with nicotinamide as the active ingredient, and to determine which of the formulations deliver nicotinamide best to the target site. Stability tests over a six months period were also performed on the different formulations. A 3% nicotinamide cream, with and without Pheroid™ vesicles, and a 3% nicotinamide gel, with and without Pheroid™ vesicles, were formulated. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

Acne is an extremely common condition, affecting almost 80% of adolescents and young adults. It is an inflammatory disease, characterised by comedones, papules, pustules and sometimes cysts. Factors causing acne include enhanced sebum excretion, hypercornification of the sebaceous duct, ductal coloniazation with Propionibacterium acnes and production of inflammation (Gollnick & Cunliffe, 2003:1). Because of the widespread use of topically applied antimicrobial agents in the treatment of inflammatory acne, resistance of disease-related micro-organisms developed. Therefore new strategies for the treatment of moderate inflammatory acne are necessary. Nicotinamide is a new approach to topical treatment of moderate inflammatory acne without the development of resistant micro-organisms (Otte et al., 2005:257). Using the skin as an alternative route for the administration of nicotinamide for the treatment of acne, may be beneficial. When nicotinamide permeates through the skin, it is directly delivered to the dermis, the place where action is needed and better results can thus be expected after the treatment has started. Another benefit is that smaller amounts of the drug are absorbed systemically with decreased adverse reactions. Unfortunately, using the skin as an alternative route for administering drugs (transdermal drug delivery), has numerous limitations. One of these limitations is the barrier function of the skin (Naik et al., 2000:319). Because of the skin's outstanding ability to protect the body against unwanted substances from its surroundings, it is necessary to use methods to enhance drug penetration through the skin. A new technology, named Pheroid™ technology, was used in this study to enhance penetration through the skin. This technology is based on the use of vesicular structures with no phospholipids or cholesterol to enhance penetration (Grobler et al., 2008:283). The aim of this study was to formulate four different semi-solid formulations with nicotinamide as the active ingredient, and to determine which of the formulations deliver nicotinamide best to the target site. Stability tests over a six months period were also performed on the different formulations. A 3% nicotinamide cream, with and without Pheroid™ vesicles, and a 3% nicotinamide gel, with and without Pheroid™ vesicles, were formulated. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.