Unraveling Water Solvation Effects with Quantum Mechanics/Molecular Mechanics Semiclassical Vibrational Spectroscopy: The Case of Thymidine.

We introduce a quantum mechanics/molecular mechanics semiclassical method for studying the solvation process of molecules in water at the nuclear quantum mechanical level with atomistic detail. We employ it in vibrational spectroscopy calculations because this is a tool that is very sensitive to the molecular environment. Specifically, we look at the vibrational spectroscopy of thymidine in liquid water. We find that the C═O frequency red shift and the C═C frequency blue shift, experienced by thymidyne upon solvation, are mainly due to reciprocal polarization effects, that the molecule and the water solvent exert on each other, and nuclear zero-point energy effects. In general, this work provides an accurate and practical tool to study quantum vibrational spectroscopy in solution and condensed phase, incorporating high-level and computationally affordable descriptions of both electronic and nuclear problems.

Vibrational spectroscopy simulation of solvation effects on a G-quadruplex.

It is commonly believed that solvation effects on the vibrational properties of a solute are easily accounted for by simple rules of thumbs, that is, solvating a polar molecule in a polar medium has the only effect of red shifting all its spectroscopical features and, similarly, solvating a polar molecule in a nonpolar medium has the opposite effect. In this work, we use theoretical vibrational spectroscopy at quasi-classical and quantum approximate semiclassical level to gain atomistic insights about solvent-solute interactions for 2'-deoxyguanosine and the G-quadruplex. We employ the quasi-classical trajectory method to include full anharmonicity into our calculated spectra, and then introduce quantum nuclear effects by means of divide-and-conquer semiclassical spectroscopy calculations. Solvation is treated explicitly leading to a good reproducibility of the available experimental data and reliable predictions when an experimental reference is missing.Communicated by Ramaswamy H. Sarma.

Osmophobia as an early marker of migraine: a follow-up study in juvenile patients.

BACKGROUND: Osmophobia is frequent in children with migraine (20-35%) but can also occur in up to 14% of cases with tension-type headache (TTH). So far, the prognostic role of this symptom in children with primary headaches has never been evaluated. METHODS: A longitudinal prospective study was conducted on 90 young patients with TTH (37 with osmophobia, 53 without osmophobia). We evaluated whether osmophobia could predict the diagnosis transformation from TTH to migraine after a 3-year follow-up. RESULTS AND DISCUSSION: In our cases the rate of diagnosis change was significantly greater in cases with osmophobia (62%) than in those without (23%). Osmophobia persisted at a 3-year follow-up in the majority of our cases (85%) and it was found to be one of the major predictors for the development of migraine; other predictors of evolution to migraine were phonophobia, a probable rather than certain diagnosis of TTH and olfactory triggers (p < 0.05). CONCLUSION: Our data confirm that osmophobia has an important diagnostic and prognostic role in children with primary headaches and should be systematically investigated at diagnosis and during follow-up.

Frovatriptan versus almotriptan for acute treatment of menstrual migraine: analysis of a double-blind, randomized, cross-over, multicenter, Italian, comparative study.

The objective of the study was to compare the efficacy and safety of frovatriptan and almotriptan in women with menstrually related migraine (IHS Classification of Headache disorders) enrolled in a multicenter, randomized, double-blind, cross-over study. Patients received frovatriptan 2.5 mg or almotriptan 12.5 mg in a randomized sequence: after treating 3 episodes of migraine in no more than 3 months with the first treatment, the patient was switched to the other treatment. 67 of the 96 female patients of the intention-to-treat population of the main study had regular menstrual cycles and were thus included in this subgroup analysis. 77 migraine attacks classified as related to menses were treated with frovatriptan and 78 with almotriptan. Rate of pain relief at 2 and 4 h was 36 and 53 % for frovatriptan and 41 and 50 % for almotriptan (p = NS between treatments). Rate of pain free at 2 and 4 h was 19 and 47 % with frovatriptan and 29 and 54 % for almotriptan (p = NS). At 24 h, 62 % of frovatriptan-treated and 67 % of almotriptan-treated patients had pain relief, while 60 versus 67 % were pain free (p = NS). Recurrence at 24 h was significantly (p < 0.05) lower with frovatriptan (8 vs. 21 % almotriptan). This was the case also at 48 h (9 vs. 24 %, p < 0.05). Frovatriptan was as effective as almotriptan in the immediate treatment of menstrually related migraine attacks. However, it showed a more favorable sustained effect, as shown by a lower rate of migraine recurrence.

A double-blind, randomized, multicenter, Italian study of frovatriptan versus almotriptan for the acute treatment of migraine.

The objective of this study was to evaluate patients' satisfaction with acute treatment of migraine with frovatriptan or almotriptan by preference questionnaire. One hundred and thirty three subjects with a history of migraine with or without aura (IHS 2004 criteria), with at least one migraine attack in the preceding 6 months, were enrolled and randomized to frovatriptan 2.5 mg or almotriptan 12.5 mg, treating 1-3 attacks. The study had a multicenter, randomized, double blind, cross-over design, with treatment periods lasting <3 months. At study end patients assigned preference to one of the treatments using a questionnaire with a score from 0 to 5 (primary endpoint). Secondary endpoints were pain free and pain relief episodes at 2 and 4 h, and recurrent and sustained pain free episodes within 48 h. Of the 133 patients (86%, intention-to-treat population) 114 of them expressed a preference for a triptan. The average preference score was not significantly different between frovatriptan (3.1 ± 1.3) and almotriptan (3.4 ± 1.3). The rates of pain free (30% frovatriptan vs. 32% almotriptan) and pain relief (54% vs. 56%) episodes at 2 h did not significantly differ between treatments. This was the case also at 4 h (pain free: 56% vs. 59%; pain relief: 75% vs. 72%). Recurrent episodes were significantly (P < 0.05) less frequent under frovatriptan (30% vs. 44%), also for the attacks treated within 30 min. No significant differences were observed in sustained pain free episodes (21% vs. 18%). The tolerability profile was similar between the two drugs. In conclusion, our study suggests that frovatriptan has a similar efficacy of almotriptan in the short-term, while some advantages are observed during long-term treatment.

Post-traumatic headache from moderate head injury.

The onset of post-traumatic headache occurs frequently in children, where it is often caused by severe head injuries, therefore, it is part of a post-traumatic syndrome, rather than of an independent headache and in this case no cause is clearly evident. The problem, conversely, arises in post-traumatic headache after a light trauma, since it is difficult to establish the cause-effect link. We have studied PTH incidence for one year in the patients of the emergency ward of the Saint Charles of Nancy Hospital, compared to the activity of 4 Italian headache centres. At the Saint Charles of Nancy Hospital of 98 patients with PTH after a moderate head trauma, 18 had acute and 26 chronic PTH, the majority ceased after six months. In the Italian headache centres 1,656 patients were examined, of these 3.2% suffered from PTH: 25 acute, 29 chronic. These data confirm the poor evidence of PTH after a light trauma and lead to doubt of the existence of this nosological entity.