Structure and Function of Multidrug Resistance Protein 1.

This review considers one of the most clinically relevant representatives of the ABC transporters - multidrug resistance protein 1 (P-glycoprotein 1 or Pgp). Data on the primary, secondary, and tertiary structure of the protein, its synthesis and degradation, and roles of its fragments in transporter activity are presented. Particular attention is given to the mechanism of functioning of Pgp. In view of the absence of a generally recognized mechanism of action of Pgp, several existing models of the protein transport cycle are discussed. Epigenetic regulation of the ABCB1 gene and modulation of Pgp expression by microRNAs are discussed.

[A Case of Apical Hypertrophic Cardiomyopathy With Rare Anomaly of Coronary Arteries Origin].

A clinical case of apical hypertrophic cardiomyopathy (HCM) in 44­years old man is presented. In this patient exercise ECG testing and 24­hour ECG monitoring revealed exercise-induced ST depression in the angiographically confirmed absence of coronary atherosclerosis. The uncommonness of this observation was the combination of HCM with a rare anomaly of coronary arteries origin.

Morphology and dynamics of the upper cloud layer of Venus.

Venus is completely covered by a thick cloud layer, of which the upper part is composed of sulphuric acid and some unknown aerosols. The cloud tops are in fast retrograde rotation (super-rotation), but the factors responsible for this super-rotation are unknown. Here we report observations of Venus with the Venus Monitoring Camera on board the Venus Express spacecraft. We investigate both global and small-scale properties of the clouds, their temporal and latitudinal variations, and derive wind velocities. The southern polar region is highly variable and can change dramatically on timescales as short as one day, perhaps arising from the injection of SO2 into the mesosphere. The convective cells in the vicinity of the subsolar point are much smaller than previously inferred, which we interpret as indicating that they are confined to the upper cloud layer, contrary to previous conclusions, but consistent with more recent study.

A dynamic upper atmosphere of Venus as revealed by VIRTIS on Venus Express.

The upper atmosphere of a planet is a transition region in which energy is transferred between the deeper atmosphere and outer space. Molecular emissions from the upper atmosphere (90-120 km altitude) of Venus can be used to investigate the energetics and to trace the circulation of this hitherto little-studied region. Previous spacecraft and ground-based observations of infrared emission from CO2, O2 and NO have established that photochemical and dynamic activity controls the structure of the upper atmosphere of Venus. These data, however, have left unresolved the precise altitude of the emission owing to a lack of data and of an adequate observing geometry. Here we report measurements of day-side CO2 non-local thermodynamic equilibrium emission at 4.3 microm, extending from 90 to 120 km altitude, and of night-side O2 emission extending from 95 to 100 km. The CO2 emission peak occurs at approximately 115 km and varies with solar zenith angle over a range of approximately 10 km. This confirms previous modelling, and permits the beginning of a systematic study of the variability of the emission. The O2 peak emission happens at 96 km +/- 1 km, which is consistent with three-body recombination of oxygen atoms transported from the day side by a global thermospheric sub-solar to anti-solar circulation, as previously predicted.

South-polar features on Venus similar to those near the north pole.

Venus has no seasons, slow rotation and a very massive atmosphere, which is mainly carbon dioxide with clouds primarily of sulphuric acid droplets. Infrared observations by previous missions to Venus revealed a bright 'dipole' feature surrounded by a cold 'collar' at its north pole. The polar dipole is a 'double-eye' feature at the centre of a vast vortex that rotates around the pole, and is possibly associated with rapid downwelling. The polar cold collar is a wide, shallow river of cold air that circulates around the polar vortex. One outstanding question has been whether the global circulation was symmetric, such that a dipole feature existed at the south pole. Here we report observations of Venus' south-polar region, where we have seen clouds with morphology much like those around the north pole, but rotating somewhat faster than the northern dipole. The vortex may extend down to the lower cloud layers that lie at about 50 km height and perhaps deeper. The spectroscopic properties of the clouds around the south pole are compatible with a sulphuric acid composition.

A warm layer in Venus' cryosphere and high-altitude measurements of HF, HCl, H2O and HDO.

Venus has thick clouds of H2SO4 aerosol particles extending from altitudes of 40 to 60 km. The 60-100 km region (the mesosphere) is a transition region between the 4 day retrograde superrotation at the top of the thick clouds and the solar-antisolar circulation in the thermosphere (above 100 km), which has upwelling over the subsolar point and transport to the nightside. The mesosphere has a light haze of variable optical thickness, with CO, SO2, HCl, HF, H2O and HDO as the most important minor gaseous constituents, but the vertical distribution of the haze and molecules is poorly known because previous descent probes began their measurements at or below 60 km. Here we report the detection of an extensive layer of warm air at altitudes 90-120 km on the night side that we interpret as the result of adiabatic heating during air subsidence. Such a strong temperature inversion was not expected, because the night side of Venus was otherwise so cold that it was named the 'cryosphere' above 100 km. We also measured the mesospheric distributions of HF, HCl, H2O and HDO. HCl is less abundant than reported 40 years ago. HDO/H2O is enhanced by a factor of approximately 2.5 with respect to the lower atmosphere, and there is a general depletion of H2O around 80-90 km for which we have no explanation.

[Conjugates of cyclooligosaccharide scaffolds and carbohydrate ligands: methods of synthesis and interaction with lectins].

Main approaches to the preparation of mono- and oligodentate glycoconjugates based on cyclodextrin and cyclooligo-ß-(1 -> 6)-D-glucosamine scaffolds are surveyed in the review. The data on the biological activity of the glycoconjugates by the example of their interaction with lectins are discussed.

[Structural and functional reorganization of photosynthetic apparatus in cold adaptation of wheat plants].

The structural and functional characteristics of the photosynthetic apparatus (PSA) and the cold resistance of wheat seedlings were studied during low-temperature adaptation. It has been established that large chloroplasts with thylakoid system of "sun type" forme in the mesophyll cells in the early hours of plants hardening. At the same time the functional reorganization of the PSA in the leaves of wheat occurs: content of pigments changes, stabilization of the pigment-protein complexes is observed, non-photochemical quenching of excess energy increases. The stabilization of photosynthesis during cold adaptation occurs due to structural and functional reorganization of the PSA. It is assumed that the reorganization of the PSA is a prerequisite for formation of increased cold resistance of leaf cells, and this, along with other physiological and biochemical changes occurring in cells and tissues of plants, allows the plants to survive in chilling.

Phyllosilicates on Mars and implications for early martian climate.

The recent identification of large deposits of sulphates by remote sensing and in situ observations has been considered evidence of the past presence of liquid water on Mars. Here we report the unambiguous detection of diverse phyllosilicates, a family of aqueous alteration products, on the basis of observations by the OMEGA imaging spectrometer on board the Mars Express spacecraft. These minerals are mainly associated with Noachian outcrops, which is consistent with an early active hydrological system, sustaining the long-term contact of igneous minerals with liquid water. We infer that the two main families of hydrated alteration products detected-phyllosilicates and sulphates--result from different formation processes. These occurred during two distinct climatic episodes: an early Noachian Mars, resulting in the formation of hydrated silicates, followed by a more acidic environment, in which sulphates formed.

The phase composition, morphology and compressibility of graphene-zirconia composite nanostructured powder.

Nanostructured composite particles of nano- and submicron sizes were synthesized by a combination of sol-gel and sonochemical techniques. Their graphene content was 0.8-0.9 wt%. These layered particles consisted of graphene sheets in which zirconia nanocrystals were discretely incorporated. The synthesized powders were characterized using XRD, TEM, HRTEM, diffusion aerosol spectrometry and elemental analysis. A comparison of the compressibility modulus, limit values of linear section deformation and compressibility factor shows that the compressibility of the composite is difficult to achieve compared to that of pure zirconia, apparently, due to the low elasticity of graphene sheets.

Paclitaxel and cisplatin as salvage treatment in patients with non-seminomatous germ cell tumour who failed to achieve a complete remission on induction chemotherapy.

The purpose of this study was to evaluate the efficacy and toxicity of paclitaxel and cisplatin combination chemotherapy as salvage treatment in patients with non-seminomatous germ cell tumour. Sixteen patients with histologically proven germ cell tumour, measurable disease and/or elevated serum tumour markers were eligible for the protocol. All patients had previously not achieved a complete remission (CR) to platinum-based induction chemotherapy and cytoreductive surgery. The treatment consisted of paclitaxel 175-225 mg/m2 as a 3-hour infusion, followed by cisplatin 100 mg/m2, repeated every 3 weeks for up to four cycles. Seven patients achieved a marker-positive partial remission (PR) by the end of the cisplatin-based induction chemotherapy; the remainder had disease progression at the start of the paclitaxel plus cisplatin treatment. One (6%) CR and 3 (19%) PRs were achieved, with an overall response rate of 25% (90% confidence interval 7-43). The duration of the CR is currently 9+ months; two PRs lasted 2 months. One patient with a PR has been lost to follow-up. During a median follow-up of 8 months (range 1-11), 12 patients died from the disease progression. The median survival for the whole group was 7 months. Toxicity was moderate, with neutropenia grade 3 occurring in 29% of patients, thrombocytopenia grade 1-3 in 29%, creatinine > 130 mmol/l in 36%, peripheral neuropathy grade 1-2 in 50%, and nausea and vomiting in 43%. Paclitaxel plus cisplatin showed modest activity, with an overall response rate of 31% in patients with poor prognosis who had not achieved a CR on induction chemotherapy.

Drug dose delivery and treatment outcome relationship in standard bleomycin, etoposide and cisplatin combination chemotherapy in nonseminomatous germ cell tumor patients.

This study retrospectively evaluated the influence of drug dose delivery components (DDDC) of bleomycin, etoposide and cisplatin chemotherapy for metastatic nonseminomatous germ cell tumors on treatment outcome (NSGCT). Between December 1987 and January 1995, 75 NSGCT patients were treated with a median of 4 cycles (range 3-8) of cisplatin 120 mg/m2 on day 1, etoposide 100 mg/m2 on days 1 through 5 and bleomycin 30 U on days 1, 3, and 5 every 3 weeks. DDDC, such as cumulative dose, cumulative dose in mg/m2, dose intensity (DI), relative dose intensity (RDI), dose intensity products, and relative dose intensity products by drug, were calculated and tested as possible predictors of treatment outcome in patients classified according to Indiana University (IU), and International Germ Cell Cancer Cooperative Group (IGCCCG) classifications. Overall complete response (CR) rate was 64%, and 3-year progression-free survival (PFS) was 59%. By IU classification there were statistical differences in CR and survival between moderate (89-81%) and advanced disease (42-40%) (p < 0.005), while for patients classified according to IGCCCG criteria, statistical differences in CR and PFS there were not registered. DI (mg/m2/week) and RDI values for the entire group were: cisplatin 33-0.82; etoposide 133-0.80 and bleomycin 11-0.37. We did not observe a statistically significant difference in drug dose delivery components for treatment outcome between patients who achieved a CR and incomplete response when analyzed by either extent of disease or whole group. Extent of disease was the most important predictor of treatment outcome.

[The effect of a low dose of piracetam on the activity of the dopaminergic system in the rat striatum]. / Vliianie maloi dozy piratsetama na aktivnost' dofaminergicheskoi sistemy striatuma mozga krys.

The low-dose effect (100 mg/kg, intraperitoneally) of the nootropic drug pyracetam on some DA-ergic neurochemical parameters of the rat striatum, as well as on the locomotion activity of rats were studied using the "open-field" test. It was shown that pyracetam (l mM) in vitro increases the K(+)-stimulated (28 mM) DA release from the perfused isolated striatum to 148 +/- 14 pmole/mg tissue compared to the control animals: 101 +/- 10 pmole /mg (p < 0.05, Student's t-test). Pyracetam in a dose of 100 mg/kg increased the DA level and decreased the 5-HT level in the striatum homogenates: DA- to 121% and 5-HT-to 81% (p < 0.05), respectively. The content of DOPAC, HVA and 5-HIAA in the tissue remained the same. In addition to the mentioned effects pyracetam promoted the locomotion activity of rats in the "open field" -putative behavioral marker of the striatum DA-ergic function. Thus pyracetam is capable of modifying the DA-ergic activity of the rat striatum, thus stimulating the neuromediator release.

[The chemotherapy of nonseminomatous testicular tumors]. / Khimioterapiia neseminomnykh opukholei iaichka.

236 patients with nonseminomatous germ cell tumors have been treated for the last decade with VAB-6 combination and 188 ones with etoposide-containing regimens BEP and EP. Complete remissions were achieved in 97(41%) VAB-6 treated patients, 72(31%) patients were currently alive without evidence of the disease for 76 months of follow-up. Patients on BEP-EP presented better outcomes: 130(69%) of 188 patients achieved a complete remission and 119(63%) of them were free of symptoms within 47 months of follow-up. In spite of more pronounced toxicity, mainly myelosuppression, etoposide-containing combinations are more efficient than VAB-6 and should be considered as an induction chemotherapy in patients with nonseminomatous germ cell tumors.