[Results of a randomized double blind parallel study on the efficacy and safety of tolpersione in patients with acute nonspecific low back pain]. / Rezul'taty randomizirovannogo dvoinogo slepogo parallel'nogo issledovaniia éffektivnosti i bezopasnosti primeneniia tolperizona u patsientov s ostroi nespetsificheskoi bol'iu v nizhnei chasti spiny.

AIM: To evaluate the efficacy and safety of tolpersione injection and oral formulations combined with NSAID over NSAID monotherapy in acute non-specific low back pain. MATERIAL AND METHODS: In this randomized double blind study 239 patients were included in the per protocol analysis. The first 5 days of treatment, patients received tolpersione or placebo injection which was followed by per os administration of tolpersione/placebo tablet up to 14 days. NSAID diclofenac tablet was used in both groups through the study. Functionality assessed by the Roland Morris Disability Questionnaire (RMDQ) at day 5 was the primary endpoint. Secondary endpoints were RMDQ at other time points, pain level change at rest and on movement assessed by the Visual Analogue Scale (VAS), the Clinical Global Impression of Improvement/Patient Global Impression of Improvement (CGI-I and PGI-I), change in the range of motion assessed by the distance from the fingertips to the floor, period of disability days, relative (%) changes in the daily dose of diclofenac from the 7th to the 14th day of therapy. RESULTS AND CONCLUSION: The primary and secondary endpoints clearly demonstrated the significant superiority of tolpersione added to NSAID monotherapy over NSAID monotherapy. The safety assessment revealed no statistically significant differences between the two groups. Based on the results, tolpersione injection and per os formulations can be considered an effective and safe drugs in the combined therapy for patients with acute nonspecific back pain.

[Molecular markers of endothelial damage in patients with Parkinson's disease].

A comparative analysis of clinical, instrumental and laboratory data in groups of patients with Parkinson's disease and chronic brain ischemia (stages I-II) was carried out. The information obtained in the groups showed significant differences in clinical and instrumental data that indicated the presence of chronic brain ischemia. A significant increase in molecular markers of endothelial damage comparable with the group of chronic cerebral ischemia was identified in patients with Parkinson's disease. The increase in indicators including monocyte chemoattractant protein-1, vascular endothelial growth factor and endothelin-1 is important for the verification of the disease before the appearance of symptoms of chronic cerebral ischemia in the examined groups of patients.

Describing two-photon absorptivity of fluorescent proteins with a new vibronic coupling mechanism.

Fluorescent proteins (FPs) are widely used in two-photon microscopy as genetically encoded probes. Understanding the physical basics of their two-photon absorption (2PA) properties is therefore crucial for creation of two-photon brighter mutants. On the other hand, it can give us better insight into molecular interactions of the FP chromophore with a complex protein environment. It is known that, compared to the one-photon absorption spectrum, where the pure electronic transition is the strongest, the 2PA spectrum of a number of FPs is dominated by a vibronic transition. The physical mechanism of such intensity redistribution is not understood. Here, we present a new physical model that explains this effect through the "Herzberg-Teller"-type vibronic coupling of the difference between the permanent dipole moments in the ground and excited states (Δµ) to the bond-length-alternating coordinate. This model also enables us to quantitatively describe a large variability of the 2PA peak intensity in a series of red FPs with the same chromophore through the interference between the "Herzberg-Teller" and Franck-Condon terms.

Absolute two-photon absorption spectra and two-photon brightness of orange and red fluorescent proteins.

Fluorescent proteins with long emission wavelengths are particularly attractive for deep tissue two-photon microscopy. Surprisingly, little is known about their two-photon absorption (2PA) properties. We present absolute 2PA spectra of a number of orange and red fluorescent proteins, including DsRed2, mRFP, TagRFP, and several mFruit proteins, in a wide range of excitation wavelengths (640-1400 nm). To evaluate 2PA cross section (sigma(2)), we use a new method relying only on the optical properties of the intact mature chromophore. In the tuning range of a mode-locked Ti:sapphire laser, 700-1000 nm, TagRFP possesses the highest two-photon cross section, sigma(2) = 315 GM, and brightness, sigma(2)phi = 130 GM, where phi is the fluorescence quantum yield. At longer wavelengths, 1000-1100 nm, tdTomato has the largest values, sigma(2) = 216 GM and sigma(2)phi = 120 GM, per protein chain. Compared to the benchmark EGFP, these proteins present 3-4 times improvement in two-photon brightness.

Resonance enhancement of two-photon absorption in fluorescent proteins.

We measure two-photon absorption (2PA) spectra of wild-type green fluorescent protein, cyan fluorescent protein, and monomeric red fluorescent protein in absolute cross section values in a wide spectral range (lambda2PA = 550 - 1300 nm), and find, for the first time to our knowledge, a new S0 --> Sn 2PA transition in all three proteins in the short-wavelength region. This transition is strongly resonantly enhanced, showing 2PA cross section values of approximately 20-160 GM, which are at least 2-4 times higher than those measured in the lowest energy (S0 --> S1) transition of corresponding proteins. We also show that the change of permanent dipole moment upon S0 --> S1 excitation (|Deltamu10|) can be deduced from 2PA cross section, providing a new tool for fast evaluation of |Deltamu10| in physiological conditions.

Near-infrared two-photon absorption in phthalocyanines: enhancement of lowest gerade-gerade transition by symmetrical electron-accepting substitution.

This paper presents, to the best of our knowledge, the first study of two-photon absorption (2PA) spectra of a number of symmetrically substituted phthalocyanines in the excitation wavelength region from lambda(ex)=800 to 1600 nm. The selected molecules vary by position of substitution (alpha or beta), number of substituent groups (4, 8, or 16), and presence or absence of metal (Zn or Al) in the center. For all phthalocyanines we find a moderately strong (sigma(2) approximately 100-200 GM), pure electronic, gerade-gerade (g-g) 2PA transition, which shows up as a well-resolved relatively narrow peak in the energy region between Q and B bands (lambda(ex)=870-1100 nm). In metallophthalocyanines (MPcs) this lowest g-g transition is followed by the onset of other higher-frequency 2PA transitions. In some metal-free phthalocyanines (H(2)Pcs) we also reveal a second, broader 2PA transition at slightly higher frequency. In both MPcs and H(2)Pcs, we find a strong monotonic increase of integrated strength of the lowest g-g transition as a function of electron-accepting ability of peripheral substituents, expressed as their aggregated Hammett constant. By using few essential states models (three states for MPcs and four states for H(2)Pcs) we demonstrate the primary role of excited-state transition dipole moment in this effect.