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PubMed1982

Effects of niceritrol (pentaerythritol tetranicotinate) on plasma lipoprotein concentration: increment of high density lipoprotein(HDL) cholesterol and HDL-cholesterol/low density lipoprotein cholesterol ratio in hypo-high density lipoproteinemia.

The purpose of the present study was to investigate the effects of niceritrol on HDL metabolism. In study (A), niceritrol, 750 mg/day was given for initial period of 12 weeks and 1,500 mg/day was prescribed for an additional 12 weeks to 12 subjects. In six of them, the HDL cholesterol (Ch) levels were less than 45 mg/100 ml with normal plasma cholesterol levels and with plasma triglyceride levels of less than 250 mg/100 ml. In the remaining six subjects, HDL-Ch, plasma cholesterol and triglyceride levels were all within normal limits except in one subject having a higher triglyceride level, 213 mg/100 ml. Plasma lipoproteins were fractionated by sequential ultracentrifugation and analyzed for cholesterol, triglyceride (TG), phospholipid(PL), apolipoprotein(Apo) B and Apo A-I, every 4 weeks. Niceritrol decreased plasma-Ch, VLDL-Ch, LDL-Ch, plasma-TG, VLDL-TG, plasma-PL, VLDL-PL and LDL-PL. Niceritrol increased HDL-Ch and the HDL-Ch/LDL-Ch ratio. These effects were more significant for the dose of 1,500 mg/day than 750 mg/day and were more marked in the patients with lower pretreatment HDL-Ch levels. Apo B level at 20 weeks was significantly lower than that before treatment. Initial plasma Apo A-I levels of the patients were approximately one-half of the control plasma. After treatment with niceritrol, Apo A-I concentration tended to increase. In study (B), changes of lipids concentration in HDL2 and HDL3 fraction were investigated in 5 patients during treatment with niceritrol, 1,500 mg/day for 8 weeks. Lipoproteins were analyzed every 2 weeks. HDL2-Ch levels tended to increase without significant changes of HDL3-Ch levels and HDL2-Ch/HDL3-Ch ratio showed a tendency to increase. A significantly but weakly inverse correlation between changes of VLDL-TG and HDL-Ch was observed, suggesting that the increment of HDL might be due partly to promoted lipolysis of TG-rich lipoproteins. However, it was suggested that the effects of niceritrol on lipoprotein synthesis in the liver and HDL catabolism should be considered.

Aged↗
PubMed2003

Adenosine-5'-O-phosphorylated and adenosine-5'-O-phosphorothioylated polyols as strong inhibitors of (symmetrical) and (asymmetrical) dinucleoside tetraphosphatases.

Dinucleoside 5',5"'- P (1), P ( n )-polyphosphates, and particularly the diadenosine compounds, have been implicated in extracellular purinergic signalling and in various intracellular processes, including DNA metabolism, tumour suppression and stress responses. If permitted to accumulate, they may also be toxic. One approach to understanding their function is through the various specific degradative enzymes that regulate their levels. Eight adenosine-5'- O -phosphorylated polyols (derivatives of glycerol, erythritol and pentaerythritol) and 11 adenosine-5'- O -phosphorothioylated polyols (derivatives of glycerol, erythritol, pentaerythritol, butanediol and pentanediol) have been tested as inhibitors of specific diadenosine tetraphosphate (Ap(4)A) hydrolases. Of these two groups of novel nucleotides, the adenosine-5'- O -phosphorothioylated polyols were generally stronger inhibitors than their adenosine-5'- O -phosphorylated counterparts. 1,4-Di(adenosine-5'- O -phosphorothio) erythritol appeared to be the strongest inhibitor of ( asymmetrical ) Ap(4)A hydrolases (EC 3.6.1.17) from both lupin and human, with K (i) values of 0.15 microM and 1.5 microM respectively. Of eight adenosine-5'- O -phosphorylated polyols, 1,4-di(adenosine-5'- O -phospho) erythritol was the only compound that inhibited the lupin enzyme. Two derivatives of pentaerythritol, di(adenosine-5'- O -phosphorothio)-di(phosphorothio) pentaerythritol and tri(adenosine-5'- O -phosphorothio)-phosphorothio-pentaerythritol, proved to be the strongest inhibitors of the prokaryotic ( symmetrical ) Ap(4)A hydrolase (EC 3.6.1.41) so far reported. The estimated K (i) values were 0.04 microM and 0.08 microM respectively. All of these inhibitors were competitive with respect to Ap(4)A. These new selectively acting Ap(4)A analogues should prove to be valuable tools for further studies of Ap(4)A function and of the enzymes involved in its metabolism.

Acid Anhydride Hydrolases↗
PubMed2005

[Comparison of the effect of nitroglycerine and pentaerithritol compositum on exercise time restricted by anginal pain or objective parameters of ischaemia in patients with stable angina].

Short acting nitrates are commonly used to prevent the anginal pain. The purpose of the study was to compare antianginal efficacy of Pentaerythritol compositum (20 mg of pentaerythritol tetranitrate and 0.5 mg of nitroglicerine) and 0,5 mg of nitroglycerine. Twenty patients aged 45-75 years with stable angina were enrolled. Antianginal effectiveness was evaluated during treadmill test. Time to ischemic pain and/or electrocardiographic parameters of ischemia were measured. It was found that Pentaerythritol compositum was superior to nitroglycerine in preventing angina with the difference disappearing 60 minutes after drug administration. Both drugs were well tolerated. Achieved results show that Pentaerythritol compositum can be effective as antianginal drug in patients with stable angina.

Aged↗
PubMed2002

A versatile linker for nontoxic polyamine-mediated DNA transfection.

Low levels of transfection efficacy and lipid-associated cytotoxicity have complicated the use of cationic lipids to facilitate transfer of exogenous DNA to eukaryotic cells. To address these issues, we synthesized a panel of six tetraester polyamines that were designed to minimize cytotoxicity by using pentaerythritol to link the hydrophobic and the DNA-binding domains. We conducted this study to probe the effects of structural modifications around pentaerythritol as a linker on transfection activity and cell viability. We compared polyamines against commercial lipid reagents using luciferase and green fluorescent protein transfection assays in both CHO and NIH3T3 cells. Measurement of transfection activity and cytotoxicity using flow cytometry showed that the more active polyamine analogs exhibited activities comparable to LipofectAMINE PLUS and TransFast. Flow cytometry analyses revealed that all the pentaerythritol-based polyamines were uniformly nontoxic, whereas transfection activity was dependent on headgroup and sidechain composition. These results demonstrate that pentaerythritol is a useful core material for the development of active, nontoxic transfection agents.

3T3 Cells↗
PubMed2002

Liquid photocurable biodegradable copolymers: in vivo degradation of photocured poly(epsilon-caprolactone-co-trimethylene carbonate).

Liquid photoreactive poly(epsilon-caprolactone-co-trimethylene carbonate)s endcapped with a coumarin group [coumarinated poly(CL/TMC)s] were prepared using tetra-functional hydroxylated substances such as pentaerythritol or four-branched poly(ethylene glycol), b-PEG. These coumarinated copolymers are tetra-branched and exist as a viscous liquid (MW 5 x10(3) approximately 7 x 10(3)). They were photocured by ultraviolet (UV) light irradiation to obtain a swelling or nonswelling solid under water, depending on the type of initiator used. The resultant films were implanted into the subcutaneous tissues of rats for up to 5 months. The photocured b-PEG-based copolymer was completely degraded and sorbed within a 1 month. On the other hand, surface-eroding degradation of pentaerythritol-based, coumarinated poly(CL/TMC) progressed with implantation time, and minimal recruitment of neutrophils, macrophages, and multinucleated giant cells was observed over the implantation period. Among the pentaerythritol-based copolymers, the fastest surface erosion was observed for the copolymer with the highest epsilon-caprolactone content. Microfabricated films with microarrays in which photoconstructs were stereolithographically prepared, using three different coumarinated copolymers at different regions, showed that upon implantation there was regionally differentiated biodegradation of microarrays, and the degree of region-specific biodegradation depended on the type of photocured copolymer. The observed tendency for biodegradation was in good agreement with that observed during implantation of individual films in vivo. This study also demonstrates that the use of multi-material-arrayed films enables the determination of different responses in vivo using only one sample.

Absorbable Implants↗