ФАРМАКОДИНАМИЧЕСКАЯ ЭКВИВАЛЕНТНОСТЬ ПРИМЕНЕНИЯ3-МЕСЯЧНОЙ И 28-ДНЕВНОЙ ФОРМЫ ДЕКАПЕПТИЛА ДЕПО МЕДЛЕННОГО ВЫСВОБОЖДЕНИЯ У ПАЦИЕНТОВ С РАСПРОСТРАНЕННЫМ РАКОМ ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ

Objective: to evaluate the pharmacodynamic equivalence of 3-month and 28-day formulations of tryptoreline, a sustained-release luteininghormone (LH)-releasing hormone analogue.Subjects and methods. The patients who had a verified diagnosis of locally advanced or metastatic prostate cancer were randomized intogroups to have either one injection of a 3-month dosage form (n = 63) or 3 injections of a 28-day formulation at 28-day intervals (n = 68).The onset rate of drug-induced castration, which was defined as a percentage of the patients achieving a plasma testosterone level of ≤0.5ng/ml, was compared on day 84 (i.e. thrice every 28 days). The plasma profiles of testosterone, LH, and tryptoreline, as well as the changesin the plasma concentration of prostate-specific antigen (PCA) from the baseline values were estimated within 3 months (from the initiationof therapy to day 91).Results. In the 3-month and 28-day groups, the onset rate of drug-induced castration was 98 and 96%, respectively (at confidenceintervals (94.2% bilaterally) in [-8.1%; 9.6%]. The median time for drug-induced castration was 18.8 and 18.5 days, respective-ly (p = 0.86; log-rank test). The ratios of the mean peak plasma concentrations to AUC91 of the two formulations for testosteroneand LH were within 0.80; 1.25 equivalence interval. By day 91, the mean PSA level was decreased by 91.0 and 91.7%, respec-tively (p = 0.73).Conclusion. The use of the two formulations during 3 months is pharmacologically equal.  Фармакодинамическая эквивалентность применения3-месячной и 28-дневной формы Декапептила депо медленного высвобождения у пациентов с распространенным раком предстательной железы

PHARMACODYNAMIC EQUIVALENCE OF USING 3-MONTH AND 28-DAY SUSTAINED-RELEASE DECAPEPTYL DEPOT FORMULATIONS IN PATIENTS WITH ADVANCED PROSTATE CANCER

Objective: to evaluate the pharmacodynamic equivalence of 3-month and 28-day formulations of tryptoreline, a sustained-release luteininghormone (LH)-releasing hormone analogue.Subjects and methods. The patients who had a verified diagnosis of locally advanced or metastatic prostate cancer were randomized intogroups to have either one injection of a 3-month dosage form (n = 63) or 3 injections of a 28-day formulation at 28-day intervals (n = 68).The onset rate of drug-induced castration, which was defined as a percentage of the patients achieving a plasma testosterone level of ≤0.5ng/ml, was compared on day 84 (i.e. thrice every 28 days). The plasma profiles of testosterone, LH, and tryptoreline, as well as the changesin the plasma concentration of prostate-specific antigen (PCA) from the baseline values were estimated within 3 months (from the initiationof therapy to day 91).Results. In the 3-month and 28-day groups, the onset rate of drug-induced castration was 98 and 96%, respectively (at confidenceintervals (94.2% bilaterally) in [-8.1%; 9.6%]. The median time for drug-induced castration was 18.8 and 18.5 days, respective-ly (p = 0.86; log-rank test). The ratios of the mean peak plasma concentrations to AUC91 of the two formulations for testosteroneand LH were within 0.80; 1.25 equivalence interval. By day 91, the mean PSA level was decreased by 91.0 and 91.7%, respec-tively (p = 0.73).Conclusion. The use of the two formulations during 3 months is pharmacologically equal

Plume-induced dynamic instabilities near cratonic blocks: Implications for P-T-t paths and metallogeny

Plume head - lithosphere interactions around cratonic blocks result in thermo-mechanical disturbances that lead to heating and burial phases of crustal rocks. We present results from numerical models of plume head - cratonic blocks interactions where a free upper surface condition and realistic rheologies are accounted for. These models include distinct cratonic blocks embedded within a continental lithosphere and separated by several hundreds of kilometres. Surface topography, thermal field and effective viscosity values are tracked for 20 Myr of interactions. The modelled dynamic interaction of a plume head around cratonic blocks results in two main types of instabilities, each of them resulting in a distinct P-T-t path. The "slab-like" instability, focused on cratonic edges when plume head is away from the craton centre, shows a near-isothermal burial phase, while the "drip-like" instability occurring above plume head material results in a near-isobaric heating phase. Consequently, both clockwise and counterclockwise P-T-t paths can be expected around cratons, as actually observed around the Tanzanian craton and other cratonic areas. Metallogenic data from gemstone-bearing rocks in south-east Africa and data from ultrahigh temperature and ultrahigh pressure metamorphism are compatible with our model. It appears that vertical mantle dynamics around cratons may also explain thermobarometric signatures that are often attributed to horizontal tectonic

Prognostic value of energy loss index in patients with low gradient severe aortic stenosis and preserved ejection fraction

Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Paris, FRANCE, AUG 31-SEP 04, 2019International audienc

Geochemistry of Gold ores Mined During celtic times from the north- Western french Massif central

International audienceThe Celtic culture of Western Europe left magnificent gold objects, such as jewellery and weapons from nobility graves and hoarded coins, as well as field evidence of pre-Roman gold mining and metallurgical workshops that attest to the mining of local ores. This is the case of Central France where many precious metallic ores have been mined throughout the ages from the Prehistoric times onwards. One of the lingering problems in assessing the provenance of gold artefacts and coins is the lack of relevant data on the isotope geochemistry and mineralogy of ore sources. Forty gold ores samples were collected and studied from Limousin (French Massif Central), a very significant gold mining district from the Celtic times. Their Pb isotope compositions clearly show a local dichotomy i.e. two distinct groups of ores, one of Late proterozoic to early paleozoic pb model age and another associated to Variscan ages and consistent with field relationships, mineralogy and elemental analyses. The use of Cu and Ag isotopes, and their coupling with Pb isotopes, will refine the tracing of future metal provenance studies, but also highlight some metallurgical practices like deliberate metal additions to gold artefact or debasement of gold coins. The newly acquired Pb, Ag, and Cu isotopic data on gold ores improves our understanding of ore deposits geology and provide clarifications on the provenance of Celtic gold from this area and its economic importance