Thesis (Ph. D.)--University of Wisconsin--Madison, 1969. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of California, San Diego, 1982. / Vita. Includes bibliographical references (leaves 94-98).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1998. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1951. / Parts I.B., C., D., F., and II. A. reprinted from Journal of biological chemistry: Part I.B.: vol. 185, no. 2 (Aug. 1950), p. 741-747 ; Part I.C.: vol. 187, no. 2 (Dec. 1950), p. 597-604 ; Part I.D.: vol. 189, no. 2 (Apr. 1951), p. 659-663 ; Part I.F.: vol. 189, no. 1 (Mar. 1951), p. 361-369 ; Part II. A.: vol. 185, no. 2 (Aug. 1950), p. 887-893. Remainder typescript. Vita. Includes bibliographical references.

Niacin has been in clinical use for over 50 years and was the first drug shown in a randomized trial to improve outcomes after MI, but substantial uncertainty remains about its efficacy and safety in the context of current standard medical therapy. This thesis explores the biochemical efficacy, tolerability and safety of extended release (ER) niacin/laropiprant in the large, randomized HPS2-THRIVE trial. Laropiprant is a prostaglandin D₂ receptor (DP1) antagonist which reduces the main adverse effect of niacin, namely “flushing” (an unpleasant cutaneous vasodilation) that makes a large trial of niacin practicable. ER niacin/laropiprant increases high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1, and reduces low density lipoprotein cholesterol (LDL-C), apolipoprotein B, triglycerides and lipoprotein (a), consistent with previous studies of ER niacin. The reasons for stopping ER niacin/laropiprant reflected the known adverse effect profile of ER niacin, although unlike previous trials flushing was not the most frequent reason for stopping. Skin (pruritus and rash), gastrointestinal (nausea, pain and diarrhoea) and diabetes-related (hyperglycaemia) adverse events were the most common reasons for stopping ER niacin/laropiprant during 3.9 years’ follow-up. The analyses presented here identified three major previously unknown hazards of ER niacin. ER niacin/laropiprant increased the risk of statin-related myopathy almost five-fold, and this effect was greater among participants in China than Europe. ER niacin/laropiprant also increased the risk of bleeding (intracranial, gastrointestinal and other sites) and infection. Compared to placebo there was an absolute excess of 3.1% of serious adverse events (excluding cancer and major vascular events [MVEs]) among participants assigned ER niacin/laropiprant. ER niacin/laropiprant did not significantly reduce MVEs. These findings suggest that the use of niacin to reduce vascular risk should now be reconsidered.

<p>Cilj ove disertacije je da se ispita uticaj aplikacije niacina na metabolizam lipida u peripartalnom periodu, da se utvrdi dali aplikacija niacina utiče na insulinsku rezistenciju, vezu između metaboličkih parametara i lipolize i ketogeneze i uticaj aplikacije niacina na koncetracije NAD i NADP. NAD i NADP predstavljaju adekvatne pokazatelje statusa niacina kod krava u ranoj laktaciji, a njihova vrednost je značajno vi&scaron;a kod krava koje su primale ovaj vitamin. NED i NADP pokazuju pozitivnu korelaciju. Pored ovoga izvedene vrednosti kao &scaron;to je NAD:NADP indeks i povr&scaron;ina ispod krive koju prave ovi vitameri posle teljnja zavise od aplikacije niacina. Aplikacija niacina dovodi do smanjenja koncentracije NEFA, BHB i MDA, a do povećanja koncentracije triglicerida i holesterola u krvi krava. Aplikacija niacina dovodi do porasta koncentracije insulina i glukoze kod krava posle teljenja. Uticaj niacina na insulinsku rezistenciju se mora dvojako posmatrati. Krave koje primaju niacin imaju nižu vrednost indeksa glukoza:insulin, &scaron;to znači da se po jedinici insulina neutrali&scaron;e manje glukoze. Ovakvo stanje nastaje jer sa porastom koncentracije insulina opada njegova efikasnost i životinje ulaze u insulinsku rezustenciju. Međutim, RQUICKIBHB indeks insulinske rezistencije je pokazao da su krave koje su primale niacin mnogo osetljivije na insulin, &scaron;to se može pripisati povećanoj insulinskoj senzitivnosti masnog tkiva. Kod krava koje su primale niacin nađena je niža koncentracija bilirubina i aktivnost AST, ALP i GGT. Nađena je vi&scaron;a koncentracija albumina i vi&scaron;a koncentracija uree i niža koncentracija fosfora. Rezultati pokazuju da aplikacija niacina pozitivno utiče na status hepatocita, a može uticati i na metabolizam proteina u organizmu zbog promena u vrednosti uree. Promena metaboličkih parametara posle teljenja i&scaron;la je u istom pravcu u oglednoj i kontrolnog grupu, samo se menjao intenzitet promena u funkciji aplikacije niacina. Parcijalna korelacija pokazuje da vitameri niacina mogu objasniti određeni deo korelacije koji postoji između lipolize, ketogeneze i metaboličkim parametrima. Stopa promene veze između<br />142<br />&nbsp;<br />metaboličkih parametara sa NEFA i BHB zavisi od stope promene statusa niacina u organizmu krava u ranoj laktaciji. Naknadnim istraživanjima treba odrediti kauzalnu prirodu ovih veza. Krave koje su primale niacina pokazivale su tendenciju povećane proizvodnje mleka do 30. dana laktacije. Ovakav uticaj niacina se izgubio prilikom merenja u 60. danu laktacije. Krave sa boljim statusom niacina (vi&scaron;a vrednost NAD i NADP) pokazuju manji stepen zama&scaron;ćenja i bolju vitalnost hepatocita, a nađen je i veći dijametar adipocita u potkožnom&nbsp; masnom&nbsp; tkivu, &scaron;to se može pripisati antilipoliznom efektu niacina.</p> / <p>AB&nbsp;<br />The aim of this dissertation is to examine the effect of niacin on lipid metabolism in perpaturient period, to determine does application of niacin have effects on insulin resistance, relationship between metabolic parameters and lipolysis and ketogenesis and effects of application of niacin on NAD and NADP concentration in plasma. NAD and NADP present the adequate indicator of the status of niacin in cows in early lactation, and concentration of NAD and NADP is significant increase in cows that were treated with niacin. NAD and NADP demonstrate positive correlation. Despite this, the derived values like NAD:NADP ratio and area under the curve depends of the application of niacin. Application of niacin leads to decreased NEFA, BHB and MDA plasma concentration, and increased triglyceride and cholesterol concentration in plasma in cows. Application of niacin leads to increased concentration of insulin and glucose in plasma after partum. The effect of niacin on insulin resistance may have two sides. Cows that received niacin had lower value of&nbsp; glucose:insulin ratio, that means that one unit of insulin metabolized less glucose. This state became because with increased insulin concentration decreased its efficiency and animals obtained insulin resistance. On the other hand index RQUICKIBHB for insulin resistance showed that cows that received niacin were much more sensitive to insulin, and that may be as a result of increased insulin sensitivity in adipose tissue.&nbsp; Cows that have received niacin bilirubin concentration and activity of AST, ALP and GGT were decrease. Albumin concentration was increased, urea and phosphor concentration was decreased in group that had received niacin. Results indicate that application of niacin have positive impact on status hepatocytes, and may have influence on protein metabolism in organism because of alteration on value in urea. In control and niacin group alteration on metabolic parameters after partum went on the same direction, but intensity of changing was in function of application of niacin. Partial correlation indicates that niacin vitamers may explain certain part of correlation that exists between lipolysis, ketogenesis, and metabolic parameters.&nbsp; Rate changes of the relationship between metabolic parameters with NEFA&nbsp; and BHB depends of the rate changes of the niacin status in cows in early lactation. Subsequent research should determinate the causal nature of this relationship. Cows that have received niacin were demonstrating tendency of increased milk production until 30.day lactation. This impact of niacin was lost in 60.day of lactation. Cows with better status niacin (greater value of NAD and NADP) manifest smaller grade of hepatic lipidosis and better vitality of hepatocytes, and was found bigger<br />145<br />&nbsp;<br />diameter on subcutaneous adipocytes, which can be as a result of antilipolitic effects of niacin.</p>

No description available.

The maintenance and regulation of cellular NAD(P)(H) content and its influence on cell function involves in many metabolic pathways which are poorly understood. Niacin deficiency in humans, which leads to low NAD status, causes sun sensitivity in skin, indicative of DNA repair deficiencies. Animal models of niacin deficiency demonstrate genomic instability and increased cancer development in sensitive tissues including skin. Therefore, we have developed a cell culture model that allows assessment of pathways regulated by NAD(P) content as a way to identify NAD-dependent signaling events that may be critical in early skin carcinogenesis. Using our model, we showed that niacin restriction, and consequent NAD depletion, reversibly alters NAD(P)(H) pools, increases apoptosis, induces G2/M cell cycle arrest, and decreases DNA stability. These alterations are affected by increased expression and activity of NOX leading to an accumulation of ROS, which may provide a survival mechanism as has been shown in cancer cells. Our data also support the hypothesis that glutamine is a likely alternative energy source during niacin deficiency. Here, we also identified the expression of all seven NAD-dependent deacetylase (SIRT) family members in skin cells. We showed that in response to photodamage, the expression of several SIRTs is altered in keratinocytes. Furthermore, we showed that SIRTs responses to photodamage differ between normal and immortalized keratinocytes, which may be indicative of alterations potentially important in skin carcinogenesis. In addition, we have shown that NAD-depleted HaCaT keratinocytes are more sensitive to photodamage. We observed that both poly(ADP-ribose) polymerases (PARPs) and SIRTs are inhibited by the unavailability of their substrate, NAD+, leading to unrepaired DNA damage upon photodamage and subsequent increase in cell death. Our data demonstrate that both SIRTs and PARPs are critical following DNA damage and identify which SIRTs are essential. Finally, we identified for the first time the expression of the nicotinic acid receptor in human skin keratinocytes, mainly in the differentiating keratinocytes of the stratum corneum in the epidermis. This study identifies new roles for niacin as a potential skin cancer prevention agent and demonstrates that niacin status is a critical resistance factor for UV damaged skin cells.

Two strategies to reduce impact of heat stress on high producing dairy cows were examined. The first was to recalculate the temperature-humidity index (THI) using high producing dairy cows under diurnal summer conditions. This re-evaluation confirmed that current THI values underestimate the severity of heat stress levels. Therefore, cooling of dairy cattle during warm summer months should begin at a THI of 68. Previously, a THI equal to or greater than 72 has been used to define onset of heat stress. This study demonstrated that a THI greater than or equal to 68 is sufficient to increase body heat storage, respiration rate, skin evaporative heat loss, declines in feed intake and milk yield. A second objective involved three studies carried out to evaluate use of niacin in dairy cow rations to improve evaporative heat loss and resistance to heat stress. Niacin is known to cause intense vasodilation in human and lab species. We hypothesized that increasing vasodilation would improve evaporative heat loss in dairy cows. In the first niacin study, supplementation of lactating dairy cows with an encapsulated rumen by-pass form of niacin (NIASHURE™; Balchem Corporation, New Hampton, NY) at a dose of 12 g/d proved effective in alleviating some affects of heat stress during mild thermal stress. We hypothesized that encapsulated niacin would induce vasodilation effects documented in humans and lab animals increasing evaporative heat loss. Past research demonstrated that the possible mechanism for vasodilation affects seen by niacin were most likely due to prostaglandin D secretions. Niacin may act through increased prostaglandin D and E production and secretion by Langerhans cells which then act upon vascular endothelial prostaglandin D receptors to increase vasodilation. No studies have evaluated impact of encapsulated niacin on milk yield and composition during periods of thermal stress under commercial dairy conditions. The objective of the last study was to examine the effects of encapsulated niacin during heat stress on milk production and composition as well as core body temperatures under commercial conditions.

Thesis (M.S.)--Auburn University, 2008. / Abstract. Vita. Includes bibliographical references (p. 100-116).