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PubMed2000

A nucleoside-nucleotide mixture may reduce memory deterioration in old senescence-accelerated mice.

We investigated the effects of a mixture of dietary nucleosides and nucleotides (NS + NT) on memory in 1- and 7-mo-old senescence-accelerated mice (SAM). Memory retention was studied with passive avoidance (step-through) and active avoidance (shuttle) tests. For 14 wk, mice in the control groups were fed a 20 g of casein/100 g diet, whereas the NS + NT groups were fed this diet supplemented with a 0.5 g of NS + NT mixture/100 g. All mice were killed at wk 14, and we studied the brain histopathology. Lipofuscin, monovacuoles and multiple vacuoles of various brain regions were measured. Body weight, food intake and ambulatory activity did not differ between the control and NS + NT groups. In old mice, the time of passive avoidance was significantly higher in the NS + NT group than in the control group at d 1 and 7 (P: < 0.05). However, such an effect of NS + NT was not observed in young mice. In the active avoidance test, the incidence of successful avoidance in old mice was higher in the NS + NT group than in the control group at d 1 and 2 (P: < 0.05). The percentages of specific brain cells containing lipofuscin were lower in NS + NT groups than in the control groups in both young and old mice (P: < 0.05). The number of monovacuoles and multiple vacuoles in specific brain regions tended to be lower (P: = 0.1-0.25) in NS + NT than in control groups, with significant differences in the microvacuoles of the middle cortex of young mice and in the multiple vacuoles in the hind cortex of old mice (P: < 0. 05). These results suggest that increased dietary NS + NT may be associated with decreases in the age-induced deterioration of brain morphology and certain memory tasks.

Age Factors↗
PubMed2004

Immunosuppressive effect of nucleoside-nucleotide-free diet in rat allogeneic small intestinal transplantation.

BACKGROUND: We evaluated the effects of nucleosides (NS) and nucleotides (NT) on the rejection of rat allogeneic small intestinal transplants. METHODS: A 2-cm segment of jejunum from fetal Fischer rats (RT-1(lvl)) was transplanted at day 19 of gestation into the abdominal wall of 7-week-old Lewis rats (RT-1(l)) by a nonvascular technique. Two weeks before transplantation, recipient rats were separated into an NS-NT-free group and an NS-NT-supplemented group. At 2 days after transplantation, histologic study of the grafts was performed with hematoxylin-eosin staining and interleukin-2 (IL-2) production estimated in recipient blood using an ELISA method. The morphologic findings were graded in a blind fashion on a scale of 0 to 4, with 0 indicating an intact intestinal structure. RESULTS: Mean plasma IL-2 levels of the NS-NT-free group were significantly lower than those of the NS-NT-supplemented group. The mean rejection score of the NS-NT-free group was also significantly lower than that of the NS-NT-supplemented group. CONCLUSIONS: Administration of an NS-NT-free diet reduces acute rejection in rat small intestinal transplantations.

Animals↗
PubMed2000

Nucleosides, nucleotides and their biological applications--XIV International Roundtable. Recent Advances in Nucleosides Chemistry and Chemotherapy. 10-14 September 2000, San Francisco, CA, USA.

This satellite symposium honoring Dr Jack J Fox, provided a forum for reviewing recent advances in nucleoside research. The topics covered were: novel chemistries, applications to current problems in biology, antiviral and antitumor agents, and aspects of enzymology and mechanism of action of important nucleoside analogs.

Journal Article↗
PubMed1979

Axonal transport of nucleosides, nucleotides and 4S RNA in the neonatal rat visual system.

The axonal migration of RNA, the nucleoside uridine and its nucleotide derivates (NS/NT) were compared in neonatal and young adult rat optic axons. Tritiated uridine was injected into right eyes of developing (1- or 4-day-old) and young adult (40-day-old) rats which were sacrificed at times after injection ranging from 6 h to 20 days. Right and left lateral geniculates were removed and assayed for trichloroacetic acid soluble (NS/NT) and RNA radioactivity. Left minus right geniculate (L-RLG) radioactivity was used as an index of axonally migrating radioactivity. Results showed that uridine and its phosphorylated derivatives were transported along both neonatal and young adult rat optic axons. Greater than 90% of right geniculate (blood-borne) TCA soluble radioactivity was metabolized to volatile substances (probably 3H2O) by three days after injection, leaving approximately 3% of the neonatal and approximately 10% of the adult activity as [3H]NS/NT. In left geniculate fractions (containing transported material) approximately 15% and 40% of total TCA soluble radioactivity was present as [3H]NS/NT in neonates and adults, respectively. Thus, axonal NS/NT appears to be relatively protected from degradation when compared with blood-borne NS/NT. The amount of L-RLG [3H]RNA in the neonates was 10 times higher than in young adults. Peaks of neonatal [3H]RNA occurred at 5 and 10 days after birth, whether injections were made at 1 or 4 days of age indicating that this [3H]RNA may be linked to developmental events. Gel electrophoretic analysis of neonatal geniculate RNA indicated that a small portion of the [3H]RNA in the first peak represented axonally transported 4S RNA. The remainder of the L-RLG [3H]RNA in the neonates was probably due to a rapid and efficient incorporation of axonally transported [3H]NS/NT into extraaxonal geniculate RNA. In contrast, little or no axonal RNA transport could be demonstrated in the young adults.

Age Factors↗
PubMed1982

Molecular association between doxorubicin (adriamycin) and DNA-derived bases, nucleosides, nucleotides, other aromatic compounds, and proteins in aqueous solution.

Doxorubicin (adriamycin) forms molecular associations with other aromatic and planar molecules (hetero-association) and with other doxorubicin molecules (self-association) in aqueous solution. The ability of doxorubicin to form complexes was demonstrated in a nonbiological system by measuring the doxorubicin partition coefficient. A decreased apparent doxorubicin activity coefficient in the presence of complex formation was also demonstrated in a biological system by measuring the transmembranous doxorubicin transport and the doxorubicin distribution at equilibrium in human red blood cells and their suspending medium. Doxorubicin formed complexes in aqueous solution at 37 degrees (pH 7.3) with (a) DNA-derived bases, nucleosides, and nucleotides; (b) amino acids such as tryptophan; (c) proteins such as human serum albumin and hemoglobin; and (d) a broad range of biologically active compounds such as NAD, propanthelline, caffeine, chloroquine, imipramine, and propranolol. The apparent thermodynamic quantities of the complex formation with adenosine 5'-triphosphate were delta H0, -9.5 kcal . mole-1; delta S0, -19 eu . mole-1; and delta G0 (310 degrees K), -3.6 kcal . mole-1. The binding forces of the molecular associations were probably hydrophobic (short-range force), sometimes supported by electrostatic interaction (long-range force).

Chemical Phenomena↗
PubMed1996

Effects of dietary nucleoside-nucleotide mixture on memory in aged and young memory deficient mice.

Intestinal mucosa, bone marrow hematopoietic cells and brain have limited capacity for the de novo synthesis of nucleosides (NSs) and nucleotides (NTs). Whereas the role of dietary NS and NT in the former two tissues is known, it is not known in the brain. Therefore we studied the effect of dietary NS and NT mixture on memory in aged mice (Experiment 1) and young memory deficient mice (Experiment 2). Memory retention was studied by step-through type passive avoidance performance (maximum 180 seconds). In Experiment 1 aged (7 month old) senescence accelerated mice (SAM) were fed 20% casein diet (control) or this diet supplemented with 0.5% NS/NT mixture for 12 weeks. Memory was studied 1, 2 and 3 days after the electric shock (punishment). In Experiment 2, young (1 month old) memory deficient mice (Dull mice) and normal mice (ddY mice) were fed the same diets as those in Experiment 1 for 12 weeks. Memory retention was studied 1 and 3 days after the punishment. In the aged SAM the average time of avoidance and also the percentages of successful memory 2 and 3 days after the punishment were significantly higher in the NS/NT diet group than the control diet group (P < 0.05). In the Dull mice percentage of successful memory was higher in the NS/NT diet group than in the control group 3 days after the punishment, however, such an effect was not observed in the normal mice. These results suggest that insufficient endogenous supply of NSs and NTs may be responsible for the factor of memory deficiency with aging or of genetical memory deficiency, which can be improved by the dietary administration of NSs and NTs.

Aging↗
PubMed1988

Nucleotides, nucleosides, and oxypurines in human kidneys measured by use of reversed-phase high-performance liquid chromatography.

An HPLC technique is presented for determining adenine nucleotides and related substances in renal cortical tissue. Nineteen metabolic substances can be resolved in a single 25-min run, with use of a gradient-elution system. The mean intra-assay CV is 2.4%, the interassay CV 5%. The lower detection limit for substances commonly present in kidney tissue--such as ATP, ADP, AMP, GTP, GDP, GMP, IMP, inosine, adenosine, hypoxanthine, and xanthine--ranges from 0.6 to 3.6 mumol/L, corresponding to 18 and 107 pmol applied to the column. For reliable analysis, a specimen of renal cortex weighing at least 5 mg (wet weight), taken during donor nephrectomy, during cold storage of the kidney, and 1 h after the onset of reperfusion, can be used. The method presented provides a rapid, reproducible diagnostic tool for assessing the chemical energy status of human kidneys in renal surgery and transplantation.

Adenine Nucleotides↗
PubMed1976

Separation of nucleic acid hydrolysis products, purines, pyrimidines, nucleosides, nucleotides, ribonucleic acid hydrolyzates, and mixtures from nucleotide syntheses by column chromatography on amberlite XAD-4.

Amberlite XAD-4 resin has been studied as a support for liquid-solid column chromatography. By coating the resin with triethylammonium bicarbonate, a new and unique separation of nucleic acid components has been achieved. Separations are accomplished with a linear gradient of this buffer from 0.1 to 0.4 M. Separation occurs in the following order: inorganic phosphate, purine or pyrimidine bases, 5'-monophosphates, nucleosides and 5'-diphosphates or 5'-triphosphates; the 2'(3')-monophosphates are eluted after either the 5'mono-, di-or triphosphates. The bases and nucleosides are separated in the order: cytosine, uracil, guanine and adenine. Inorganic phosphate and the nucleotides are eluted in the order: inorganic phosphate 5'-mono, di- and tri-phosphates. Excellent separation of the 5'-monophosphates and the 2'(3')-monophosphates is now possible. In each series of 5'-mono-, di- and tri-phosphates or 2'(3')-monophosphates, the elution order is generally cytidine, uridine, guanosine and adenosine. By use of water instead of coating the resin with triethylammonium bicarbonate, the nucleotides and inorganic phosphate are found in the void volume; adenine is eluted very slowly, whereas adenosine is not eluted. Adenosine is eluted only with ethanol-water (1:3). The method is advantageous in that the recovery is quantitative, the buffer is easily removed, the capacity of the column is large (35 mugmoles pergram of resin), flow-rates are high, the time required is short and separations of combinations of inorganic phosphate, bases, nucleosides and nucleotides are now possible that previously could not be accomplished.

Buffers↗