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Results for “NICOTINIC ACID”

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At least 775 records · Page 43Linked to original sources
PubMed2005

Simultaneous determination of myristyl nicotinate, nicotinic acid, and nicotinamide in rabbit plasma by liquid chromatography-tandem mass spectrometry using methyl ethyl ketone as a deproteinization solvent.

Myristyl nicotinate (Nia-114) is an ester prodrug being developed for delivery of nicotinic acid (NIC) into the skin for prevention of actinic keratosis and its progression to skin cancer. To facilitate dermal studies of Nia-114, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using methyl ethyl ketone (MEK) as a deproteinization solvent was developed and validated for the simultaneous determination of Nia-114, NIC, and nicotinamide (NAM) in rabbit plasma. NAM is the principal metabolite of NIC, which is also expected to have chemopreventive properties. The analytes were chromatographically separated using a Spherisorb Cyano column under isocratic conditions, and detected by multiple reaction monitoring (MRM) in positive-ion electrospray ionization mode with a run time of 9 min. The method utilized a plasma sample volume of 0.2 ml and isotope-labeled D4 forms of each analyte as internal standards. The method was linear over the concentration range of 2-1000, 8-1000, and 75-1000 ng/ml, for Nia-114, NIC, and NAM, respectively. The intra- and inter-day assay accuracy and precision were within +/-15% for all analytes at low, medium, and high quality control standard levels. The relatively high value for the lower limit of quantitation (LLOQ) of NAM was demonstrated to be due to the high level of endogenous NAM in the rabbit plasma (about 350 ng/ml). Endogenous levels of NIC and NAM in human, dog, rat, and mouse plasma were also determined, and mean values ranged from <2 ng/ml NIC and 38.3 ng/ml NAM in human, to 233 ng/ml NIC and 622 ng/ml NAM in mouse. Nia-114 was generally unstable in rabbit plasma, as evidenced by loss of 44-50% at room temperature by 2 h, and loss of 64-70% upon storage at -20 degrees C for 1 week, whereas it was stable (<7% loss) upon storage at -80 degrees C for 1 month.

Animals↗
PubMed2006

The determination of nicotinic acid in plasma by mixed-mode liquid chromatography-tandem mass spectrometry following ion exchange solid phase extraction.

An assay for nicotinic acid in plasma samples has been developed using ion exchange solid phase extraction in 96-well format followed by mixed-mode ion exchange/reversed-phase liquid chromatography with positive ion tandem mass spectrometry detection. The assay avoids the need for time-consuming derivatisation procedures or involatile ion-pair chromatography reagents. The assay is linear over the wide range 0.05-20 microg/mL, based on a 100 microL sample (correlation coefficient>0.99). The assay is accurate and precise (bias and coefficient of variation<18%) over this calibration range.

Administration, Oral↗
PubMed2000

Gemfibrozil, nicotinic acid and combination therapy in patients with isolated hypoalphalipoproteinemia: a randomized, open-label, crossover study.

OBJECTIVES: To assess the effects of nicotinic acid (NA), gemfibrozil and combination therapy on the lipid profile of patients with clinical atherosclerotic disease and isolated hypoalphalipoproteinemia. BACKGROUND: Isolated hypoalphalipoproteinemia (low high density lipoprotein cholesterol [HDL-C] alone) accounts for a significant percentage of patients with premature atherosclerosis. However, it remains unclear whether currently available pharmacotherapy has the ability to favorably affect the lipid profile and therefore potentially reduce clinical events. METHODS: Twenty-three patients with clinically well-defined atherosclerosis and isolated hypoalphalipoproteinemia were prospectively randomized to receive gemfibrozil, NA or combination therapy in an open-label, crossover design trial to assess the effects on serum lipids. Lipid profiles and other relevant laboratory variables were monitored while the patients were on and off pharmacologic lipid-modulating therapy. RESULTS: In those 14 patients able to tolerate all forms of pharmacotherapy, HDL-C of 0.89 +/- 0.17 mmol/liter (34.5 +/- 6.5 mg/dl) increased by 15%, to 1.02 +/- 0.18 mmol/liter (39.7 +/- 7.1 mg/dl), while taking gemfibrozil (1,200 mg/day); by 35%, to 1.20 +/- 0.21 mmol/liter (46.5 +/- 8.1 mg/dl), while taking NA (mean dose 2,250 mg/day); and by 45%, to 1.29 +/- 0.19 mmol/liter (50.0 +/- 7.5 mg/dl), while taking combination therapy of gemfibrozil plus NA (p < 0.001 for all interventions as compared with baseline/washout; p < 0.005 NA vs. gemfibrozil; p < 0.001 combination therapy vs. gemfibrozil alone; p = 0.088 combination therapy vs. NA alone). Statistically significant favorable alterations were also observed with low density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C, non-HDL-C/HDL-C, apolipoprotein (Apo) B and Apo B/Apo A1. CONCLUSIONS: In the majority of patients with clinical atherosclerotic disease and isolated hypoalphalipoproteinemia, pharmacologic therapy to raise HDL-C is not only feasible but is also effective with currently available agents, particularly when used in combination.

Adult↗
PubMedDate not supplied

Anticonvulsant and acute neurotoxic characteristics of nicotinic acid benzylamide: a preclinical study.

The aim of this study was to evaluate time-course and dose-response relationships of nicotinic acid benzylamide (Nic-BZA) with regard to its anticonvulsant activity in the maximal electroshock (MES)-induced seizures and acute neurotoxic effects in terms of motor coordination impairment in the chimney test in mice. The experimental determination of both median effective dose (ED(50)) and median toxic dose (TD(50)) allowed for the calculation of protective index (PI) values characterizing a preclinical profile of Nic-BZA. Results indicated that Nic-BZA produced the time-dependent and clear-cut anticonvulsant activity in the MES test and its ED(50) values ranged between 35.7 and 84.0 mg/kg (after the ip administration of the agent at 5 and 60 min, respectively), and between 72.0 and 152.1 mg/kg (at 5 and 60 min, respectively, following the po administration of Nic-BZA). In the chimney test, the TD(50) values for Nic-BZA, after its ip administration ranged between 188.5 and 509.9 mg/kg, whereas following its po administration the TD(50) values for Nic-BZA were between 552 and 1222.1 mg/kg. The PI values for Nic-BZA, calculated at various times after its ip and po administrations (ranging between 3.56 and 17), revealed that the agent has a favorable profile, when considering its both anticonvulsant and acute neurotoxic effects in this preclinical study. Based on this study, one can conclude that Nic-BZA might occur advantageous as a potential antiepileptic drug for breaking seizure attacks in patients with epilepsy.

Administration, Oral↗
PubMed1994

[Induracin, prolonged-action nicotinic acid, in the treatment of atherogenic dyslipoproteinemia].

The author presents the results of a cross-over blind trial of induracin, prolonged nicotinic acid. The study covered 31 dyslipoproteinemic patients and lasted 6 months. The treatment gave rise to a significant fall in the total cholesterol, LDL cholesterol, triglycerides (by 11%, 17% and 19% respectively), HDL cholesterol levels went up by 14%, lipid transport proteins proportions changed for the better (AI apoprotein increased by 15% against lowering of apoprotein B by 29%). The drug was well tolerated.

Adult↗
PubMed1999

The NAD+ precursors, nicotinic acid and nicotinamide upregulate glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase mRNA in Jurkat cells.

To better understand the role of nicotinic acid and nicotinamide in the regulation of the oxidative stress response, we measured the levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glucose-6-phosphate dehydrogenase (G6PD) mRNA in Jurkat cells treated with these NAD+ precursors. We used a modified nonradioactive Northern blot method and detected the mRNA using 18-mer digoxigenin (DIG)-labeled oligonucleotides as probes. We observed increased levels of the mRNAs for the two enzymes in treated cells. Our findings suggest that the NAD+ precursors may protect against oxidative stress and DNA damage by up-regulating the stress response genes GAPDH and G6PD.

Gene Expression Regulation, Enzymologic↗
PubMed2000

Nicotinic acid adenine dinucleotide phosphate (NAADP(+)) is an essential regulator of T-lymphocyte Ca(2+)-signaling.

Microinjection of human Jurkat T-lymphocytes with nicotinic acid adenine dinucleotide phosphate (NAADP(+)) dose-dependently stimulated intracellular Ca(2+)-signaling. At a concentration of 10 nM NAADP(+) evoked repetitive and long-lasting Ca(2+)-oscillations of low amplitude, whereas at 50 and 100 nM, a rapid and high initial Ca(2+)-peak followed by trains of smaller Ca(2+)-oscillations was observed. Higher concentrations of NAADP(+) (1 and 10 microM) gradually reduced the initial Ca(2+)-peak, and a complete self-inactivation of Ca(2+)-signals was seen at 100 microM. The effect of NAADP(+) was specific as it was not observed with nicotinamide adenine dinucleotide phosphate. Both inositol 1,4, 5-trisphosphate- and cyclic adenosine diphosphoribose-mediated Ca(2+)-signaling were efficiently inhibited by coinjection of a self-inactivating concentration of NAADP(+). Most importantly, microinjection of a self-inactivating concentration of NAADP(+) completely abolished subsequent stimulation of Ca(2+)-signaling via the T cell receptor/CD3 complex, indicating that a functional NAADP(+) Ca(2+)-release system is essential for T-lymphocyte Ca(2+)-signaling.

Adenosine Diphosphate Ribose↗
PubMed1993

Effects of nicotinic acid on respiratory exchange ratio and substrate levels during exercise.

The purpose of this study was to investigate the effects of pharmacologic treatment with nicotinic acid (NA) (3 g NA.d-1) on fuel utilization during exercise and on total and HDL-cholesterol levels of trained runners. Eight experienced male runners performed four 30-min submaximal treadmill runs (SUB) at approximately 60% of aerobic capacity: the first served as the control condition, whereas SUBs 2, 3, and 4 were conducted at the onset, midpoint, and conclusion of the 3-wk NA treatment period. A 1-g NA dose was ingested 1 h prior to SUBs 2-4, which were conducted in the morning following a 12-h fast. The respiratory exchange ratio (RER) was significantly higher during SUBs 2, 3, and 4 (0.919 +/- 0.009, 0.898 +/- 0.007, and 0.896 +/- 0.009, respectively) than during SUB1 (0.871 +/- 0.008); and the RER during SUB2 was also significantly higher than that during SUB3 and SUB4 (P < 0.001). Serum free fatty acid (FFA) and glycerol levels were significantly lower during SUBs 2, 3, and 4 as compared with SUB1 (P < 0.001). Total cholesterol showed a significant decrease (from 195.3 +/- 9.2 to 174.5 +/- 9.2 mg.dl-1) and HDL cholesterol showed a significant elevation (from 56.2 +/- 2.9 to 63.0 +/- 3.9 mg.dl-1) during the NA treatment period (P < 0.05). The RER, FFA, and glycerol data demonstrate a persistent inhibition of fat utilization during submaximal exercise due to NA treatment. The 3-wk NA treatment period also proved to be sufficient to effect changes in total and HDL-cholesterol levels of these runners.

Adult↗