Concentration of purine compounds in the cerebrospinal fluid of infants suffering from sepsis, convulsions and hydrocephalus

Abstract

Catabolites of purine nucleotides were measured in the cerebrospinal fluid (CSF) of newborn infants with sepsis, seizures and hydrocephalus using isocratic reversed-phase HPLC. The inosine levels in the CSF of the infants with any of the illnesses were significantly higher when compared with the controls. There was a tendency for hypoxanthine levels to be higher in the group of children with hydrocephalus. No significant differences in the concentrations of xanthine, adenine and uric acid were found. The inosine concentration in the CSF is proposed to be a more sensitive indicator of brain injury than the levels of other CSF purines. The levels of all purine metabolites measured in the CSF showed large individual variations. The ratio between hypoxanthine (as an indicator of ATP breakdown) and uric acid (as a scavenger of oxygen free radicals) concentration is proposed as a new criterion to be used in the evaluation of brain injury.

Inosine Inhibits Inflammatory Cytokine Production by a Posttranscriptional Mechanism and Protects Against Endotoxin-Induced Shock

“…Although the ␤-adrenoceptor agonist isoproterenol caused a substantial increase in cAMP, inosine failed to exhibit such an effect (vehicle, 0.28 Ϯ 0.03 pmol/ml (n ϭ 3); isoproterenol, 1.25 Ϯ 0.14 pmol/ml (n ϭ 3); inosine, 0.25 Ϯ 0.09 pmol/ml (n ϭ 3)). The lack of involvement of cAMP in the effect of inosine was confirmed in an experiment, in which cAMP-dependent protein kinase inhibitor (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) failed to reverse the inhibition of TNF-␣ production by inosine (not shown).…”

“…The selective A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), A 2 antagonist 3,7-dimethyl-1-propargylxanthine (DMPX), 3-isobutyl-1-methylxanthine, protein kinase inhibitor (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), dipyridamole, and S-(4-nitrobenzyl)-6-thioinosine (NBTI) were obtained from Research Biochemicals (Natick, MA). RPMI 1640, FCS, and penicillin-streptomycin were obtained from Life Technologies (Grand Island, NY).…”

Differential requirement for A2a and A3 adenosine receptors for the protective effect of inosine in vivo

“…Indeed, while normal interstitial concentrations of inosine have been reported to be in the micromolar range, concentrations of more than 1 mM in ischemic tissues and in patients with sepsis have been documented. [14][15][16][17][18] Inosine is now known to exert wideranging anti-inflammatory effects that include inhibition of proinflammatory cytokine and chemokine production, enhancement of anti-inflammatory cytokine interleukin-10 (IL-10) production, and protection from endotoxin-induced inflammation and lung tissue damage [19][20][21][22] as well as skeletal muscle reperfusion injury 23 in mice. In humans, inosine has shown promise as a therapeutic agent against multiple sclerosis (MS) 24 and Tourette syndrome, 25 perhaps by indirectly increasing uric acid levels and acting as a dopamine agonist, respectively.…”

Adenosine A2A Receptor Inactivation Increases Survival in Polymicrobial Sepsis

“…Because sepsis can be associated with any of these metabolically stressful conditions, it is not surprising that systemic adenosine levels reach high concentrations in patients with sepsis and septic shock (12)(13)(14). Adenosine interacts with one or more of four G-protein-coupled receptors (A 1 , A 2A , A 2B , and A 3 ) through which it can exert substantial anti-inflammatory and immunosuppressive effects (15)(16)(17)(18)(19)(20)(21)(22).…”