Volume 26, Issue 4

The electronic structures of the five radicals resulting from homolytic elimination of one of the hydrogen atoms from the most stable tautomeric form of neutral pterin were investigated in gas phase as well as in aqueous solution. Molecular wave functions obtained by density functional theory were analysed by quantum theory of atoms in molecules and electron localisation functions (ELF). Spin densities of the radicals as well as electrostatic potential functions were analysed. Radicals resulting from elimination of N-bonded hydrogen atoms are more stable in comparison with radicals obtained after abstraction of C-bonded hydrogen atoms. N-centred radicals show strong delocalisation of spin density over both heteroaromatic rings; in C-centred radicals delocalisation does not occur. ELF analyses showed that in N-derived radicals particularly the lone electron pair at N 2 ′ is strongly involved into the bicyclic heteroaromatic π-electron system. Thereby, bonding geometry at N 2 ′ in these radicals changes from pyramidal to planar. Transition from gas phase to solution phase (water) generally leads to increased polarity of the structures. Pterin-derived free radicals have been implicated in several biologically important reactions; so this investigation provides first insights into the detailed electronic structures of such molecular systems.

Cold water immersion is thought to reduce the inflammatory response to injury. Using cultured mononuclear cells and human subjects in a mixed martial arts (MMA) contest, we examined the effect of cryotherapy on 7,8-dihydroneopterin and neopterin generation. Urine was collected from 10 elite male mixed martial artists before, immediately post and 1, 2, 24 and 48 h following a contest. Myoglobin was analysed by reverse-phase high performance liquid chromatography, and urinary neopterin and total neopterin (neopterin+7,8-dihydroneopterin) were measured by strong cation exchange high-performance liquid chromatography. Cold water immersion and passive recovery were compared using changes in these markers, while cryotherapy tested total neopterin production in γ-interferon and phorbol myristate acetate (PMA)-stimulated blood-derived mononuclear cells (monocytes/T cells). Myoglobin significantly increased (p<0.05) at 1 h post-contest, neopterin significantly increased at 1 and 24 h (p<0.05), total neopterin significantly increased (p<0.05) at 1 h post for the passive group only, and significant individual variation was observed for all markers (p<0.01). Cold water immersion attenuated total neopterin production (p<0.05), while cryotherapy significantly reduced total neopterin production in PMA-stimulated mononuclear cells (p<0.01). Cryotherapy attenuates the post-exercise inflammatory response following an MMA contest. The evidence also suggests that the mechanisms responsible for this may be related to direct immune cell suppression.

Neopterin, cortisol and immunoglobulin A were measured to determine what effect a professional rugby competition has on the immunity, inflammatory and psychophysiological stress response. Urine and saliva were collected from 37 professional players at regular intervals throughout a 20 week professional competition. Total neopterin, cortisol and secretory immunoglobulin A were analysed using enzyme linked immunosorbant assay (ELISA) and high performance liquid chromatography (HPLC). All markers did not change significantly when analysed as a group during the course of the season compared to baseline (p>0.05), although long-distance travel had a minor effect on cortisol and secretory immunoglobulin A concentrations (p<0.05). More importantly, a large inter-individual variation for all markers was observed (p<0.001). These results indicate this competition of professional rugby does not cause significant changes in psychophysiological stress. Some players however, may become more susceptible to fatigue and infection during the course of a season as a result of suppressed immunity and sustained activation of the inflammatory response.

The aim of the present study was to evaluate the correlations of peripheral blood cell count (PBC)-derived ratios with neopterin concentration and biomarkers of atherosclerosis risk in patients with history of breast cancer. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) were calculated in three cohorts of patients with a history of breast cancer and in controls. Significant differences were observed between PBC-derived ratios obtained from automated and manual counts. NLR and PLR were significantly higher and LMR was significantly lower in patients. NLR and PLR correlated positively with each other and negatively with LMR. NLR exhibited a significant correlation with age, glucose and C-reactive protein (CRP) concentrations, whereas LMR correlated negatively with CRP. With the exception of a correlation between LMR and urinary or serum neopterin concentrations in controls, no other correlation between neopterin concentrations and PBC-derived ratios was observed. NLR ≥3 was a significant predictor of poor survival, but neither urinary neopterin ≥205 μmol/mol creatinine, NLR ≥150 nor LMR ≥4.25 was significantly associated with survival. In conclusion, no consistent correlation was observed between urinary and serum neopterin concentrations and any of the PBC-derived ratios. In a cohort of breast cancer patients, a higher NLR predicted poor survival.