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PubMed1989

Interrelationships between purine nucleotide degradation and radical formation during intestinal ischaemia and reperfusion: an application of ion-pair high-performance liquid chromatography of nucleotides, nucleosides and nucleobases.

There are peroxidative changes during the reperfusion of the rat small intestine following a 1h period of total ischaemia. That is demonstrated by the increases of the concentrations of glutathione disulphide and of thiobarbituric acid-reactive substances. An important source of the active oxygen species leading to peroxidations is the degradation of purine nucleotides. The nucleotides and their derivatives were measured by an ion-pair reversed-phase high-performance liquid chromatographic separation in a single analysis within 40 min. Modification of the elution gradient resulted in a high resolution of nucleosides and nucleobases, including allopurinol and oxypurinol. The decrease of the nucleoside triphosphate concentration and the increase of nucleoside monophosphate concentration, followed by accumulations of nucleosides and nucleobases in the course of the ischaemia were measured. During reperfusion the nucleotide pools are filled up. Restoration of adenosine triphosphate and guanosine triphosphate can be accelerated by application of the xanthine oxidoreductase inhibitor allopurinol. Pretreatment of the animals with allopurinol also diminished the formation of glutathione disulphide and thiobarbituric acid-reactive substances.

Animals↗
PubMed1985

A multicomponent self-diffusion NMR study of aggregation of nucleotides, nucleosides, nucleic acid bases and some derivatives in aqueous solution with divalent metal ions added.

The self-aggregation of the mononucleotides AMP, CMP, and UMP with Mg2+ added (nucleotide concentration = Mg2+ concentration) up to 0.4 molal or to their solubility limit in 2H2O has been monitored through self-diffusion measurements, using the Fourier transform NMR pulsed-gradient spin-echo multicomponent-self-diffusion technique. Also, purine, cytidine, uridine, purine with Mg2+ added and both cytidine and uridine with Mg2+, Zn2+ or Cd2+ added, were studied in the same way. The experimental data were fitted to two different aggregation models. For the mononucleotides with Mg2+ added a cooperative indefinite aggregation model, where the first (dimerization) aggregation constant is a magnitude lower than those for the higher aggregation step gives the best agreement between simulations and experiment. Typical values are 0.3 and 12 kg mol(-1), respectively. The latter value is about twice that found for the uncomplexed nucleotides. Also, purine and the nucleosides, cytidine and uridine, with divalent metal ions added fit best with this model. The degree of aggregation is increased upon metal ion addition, as previously shown for the mononucleotides. For purine, cytidine and uridine without metal ions added an 'isodesmic', indefinite aggregation model, with the aggregation constant for each step equal, fits the data as well. Here the application of the 'semi-isodesmic' model results in a higher first (dimerization) aggregation constant than is found for the nucleotides. The typical value is 2 kg mol(-1). In this case, the evaluated aggregation constants for the higher step become only about twice as large as those of the first step. The same measurements on isopropylcytidine, isopropyluridine and theophylline-7-acetic acid in water show that these three compounds aggregate to the same extent as the nucleosides, cytidine and uridine. Pyrimidine diffusion data reveal no aggregation at all; the application of either model results in essentially zero aggregation constants.

Journal Article↗
PubMed2004

Complexes of copper(II) with adenosine or guanosine nucleosides, nucleotides 5'-monophosphate, 2'-deoxynucleosides or 2'-deoxynucleotides 5'-monophosphate in aqueous solution.

In this paper copper(II) complex formation in aqueous solution with a series of nucleosides (adenosine or guanosine) or nucleotides 5'-monophosphate is studied by means of potentiometry, visible spectrophotometry and ultraviolet circular dichroism. A chemical model has been formulated for each binary system (at T= 25 degrees C and I = 0.1 M), with particular attention to the interaction in the basic field. A spectrum (both visible absorption and ultraviolet circular dichroism) for each complex with a significant percentage of formation (in the adopted experimental conditions) has been calculated, allowing structural details to be hypothesised. The interaction with deprotonated alcoholic group(s) of the ribose moiety has been found to be fundamental in determining the co-ordination chemistry of each ligand considered while cases of co-operation between the purine and ribose donor(s) were also considered. Confirmations were also obtained by an investigation on the corresponding 2'-deoxy compounds as ligands.

Adenosine↗
PubMed1975

Hydrolysis in 2'-chloro-2'-deoxy nucleosides, -nucleotides and -polynucleotides to arabinose-derivatives.

The rate of hydrolysis of 2'-chloro-2'-deoxycytidine and -uridine, and their 5'-phosphates, -diphosphates and polymers to the corresponding arabinocytidine and arabinouridine derivatives in the presence of Tris-HCL pH 8.9 is determined. This rate is highest for the nucleosides, less for the 5'-phosphates and 5'-diphosphates and even less for the polynucleotides. In the the 2'-chloro-2'-deoxyuridine series the O2, 2'-cyclonucleoside was formed in addition to the arabinonucleoside.

Alkaline Phosphatase↗
PubMed2005

The use of a triple nucleoside-nucleotide regimen for nonoccupational HIV post-exposure prophylaxis.

OBJECTIVES: Nonoccupational post-exposure prophylaxis (NPEP) for HIV is recommended after high-risk sexual exposure. Because of the high incidence of intolerable side effects observed with protease inhibitor- and zidovudine-based NPEP regimens, our unit changed standard NPEP treatment to 28 days of tenofovir-lamivudine-stavudine (TDF-3TC-d4T). The aim of this study was to compare side effects and numbers of individuals completing NPEP before and after this change. METHODS: Parameters were compared amongst individuals commencing the following NPEP regimens: zidovudine-lamivudine (ZDV-3TC), zidovudine-lamivudine-nelfinavir (ZDV-3TC-NFV) and TDF-3TC-d4T. RESULTS: A total of 385 individuals received ZDV-3TC (n = 36), ZDV-3TC-NFV (n = 225) or TDF-3TC-d4T (n = 137) as NPEP for the first time between June 1999 and November 2003. Noncompletion rates were 25%, 32% and 15%, respectively (P = 0.001), with odds ratios for noncompletion being 2.0 [95% confidence interval (CI) 0.8-4.8] and 2.7 (95% CI 1.6-4.8) in the first two groups compared with the TDF-3TC-d4T group (P = 0.008). Adverse events were less common in the TDF-3TC-d4T group, with significantly lower rates of nausea and headache, but significantly higher rates of peripheral neuropathy and asymptomatic raised transaminases. There was no HIV seroconversion in any group. CONCLUSIONS: TDF-3TC-d4T is significantly better tolerated than ZDV-3TC or ZDV-3TC-NFV as NPEP and results in greater numbers of individuals completing 28 days of treatment.

Adenine↗