Synthesis of Novel Indane-1,3-dione Derivatives and Their Biological Evaluation as Anticoagulant Agents

2-Substituted derivatives of indane-1,3-dione 3a–f , 5a–g, 6a–g were synthesized and investigated as anticoagulant agents. 2-Arylindane-1,3-diones (3) were obtained in the reaction of phthalide with appropriate arylaldehydes. 2-Arylmethyleneindane-1,3-diones (5) were prepared by condensation of indane-1,3-dione with the corresponding arylaldehydes. The compounds 5 were converted into their methyl analogues 6 by reduction with sodium tetrahydroborate. All of the compounds studied were screened for the anticoagulant activity. The highest prothrombin time was established for 2-[4-(methyl-sulfanyl)phenyl]indane-1,3-dione (3c) (PT = 33.71(±26.01) s), which was very close to PT of the drug anisindione (PT = 36.0(±26.42) s). </p

Recreational Development at Pelican Lake, Minnesota: An Analysis of Factors Affecting Site Selection

In order to better predict those areas whicd\u27 have the po tential to be developed more rapidly than others, research concerning physical land use character isti ;s which determine current lakeshore patterns needs to be implemented. This study is designed to assess which physics . land use/cover characteristics have affected lake home development at Peli can Lake in north central Minnesota. Analysis involves the interpretation of aerial photo graphs from the years 1939, I960, 1969, and 1978 which were used to map location and extent of land use/cover change in the Pelican Lake area. Archival data is utilized in order to determine number and location of recreational homes ex isting on the shoreline of Pelican Lake. Finally, correla tion and regression techniques are used in order to ascer tain relationships between the physical parameters of the watershed and location of lakeshore homes. Length of shoreline is found to be the leading indicator in number of homes in each section bordering Pelican Lake. Distance to nearest improved road also proves to be a sig nificant factor. Of the land use/cover data obtained from aerial photographs, only acres of that land covered by water and.acres in Pelican. Lake are determined to be of signifi cance in location of lakeshore homes

Wpływ dodatków biowęglowych na właściwości funkcjonalne smarów plastycznych

The article presents the results of tests on tribological and physicochemical properties of plastic greases, in which the dispersing phase was highly refined mineral oil and the dispersed phase (thickener) lithium stearate. The functional additives were biocarbon, which were obtained in the pyrolysis process of waste of natural origin, i.e. stems with corn leaves, wheat straw, flax straw, and cherry stones. The compositions containing 5% m/m biocarbon were prepared. Their evaluated on the functional properties of plastic greases was assessed. Tribological characteristics of the greases compositions were determined using the T-02 tester in accordance with the requirements of the subject standards. The effect of biocarbon used on anti-wear (Goz) and anti-seizing (Pt, poz) plastic greases was determined. An assessment was also made of the effect of plant biocarbon on changes in basic physicochemical properties of the composition of plastic greases, i.e. penetration, dropping temperature, and thermo-oxidative stability. It was found that some of the biocarbon significantly improve the tribological properties of plastic greases without significantly affecting the change of key physicochemical parameters. The most beneficial impact of the tested additives on the operational properties of plastic greases was observed when using biocarbon from wheat straw. In some cases, a lower oxidative resistance of biocarbon grease is observed compared to grease without the addition of biocarbon.W artykule przedstawiono wyniki badań właściwości tribologicznych i fizykochemicznych smarów plastycznych, w których fazą dyspergującą był wysokorafinowany olej mineralny, a fazą zdyspergowaną (zagęszczaczem) stearynian litu, dodatkami funkcyjnymi były biowęgle otrzymane w procesie pirolizy odpadów pochodzenia naturalnego tj. łodyg wraz z liśćmi kukurydzy, słomy pszenicznej, paździerzy lnianych i pestek wiśni. Sporządzono kompozycje zawierające 5% m/m biowęgli i oceniono ich wpływ na właściwości funkcjonalne otrzymanych smarów plastycznych. Charakterystyki tribologiczne kompozycji smarowych wyznaczono z wykorzystaniem testera T-02 zgodnie z wymaganiami norm przedmiotowych. Określono wpływ zastosowanych biowęgli na właściwości przeciwzużyciowe (Goz) i przeciwzatarciowe (Pt, poz) opracowanych smarów plastycznych. Dokonano także oceny wpływu biowęgli pochodzenia roślinnego na zmiany podstawowych właściwości fizykochemicznych kompozycji smarów plastycznych, tj. penentrację, temperaturę kroplenia i stabilność termooksydacyjną. Stwierdzono, że niektóre z biowęgli zdecydowanie poprawiają właściwości tribologiczne smarów plastycznych, nie wpływając istotnie na zmianę kluczowych parametrów fizykochemicznych. Najkorzystniejszy wpływ badanych dodatków na właściwości eksploatacyjne smarów plastycznych zaobserwowano w przypadku zastosowania biowegli ze słomy pszenicznej. W niektórych przypadkach obserwuje się niższą odporność oksydacyjną smarów biowęglowych w porównaniu ze smarem bez dodatku biowęgla

Wpływ rodzaju biowęgla na charakterystyki tribologiczne smarów wytworzonych na bazie oleju roślinnego i syntetycznego

The article presents the tribological characteristics of plastic greases in which the dispersing phase was vegetable (rapeseed) oil or synthetic ester oil (Priolube). The lithium stearate was used as a thickener in an amount sufficient to obtain a composition in the second consistency class, and the functional additives were biocarbon produced in the process of pyrolysis of the following plant waste: flax straw, wheat straw, corn leaves and stalks, and cherry stones. The compositions containing 5% m/m of biocarbon were prepared and the influence of the type of biocarbon on the tribological properties of the obtained plastic greases was assessed. The tribological characteristics of the grease compositions were determined using the T-02 tester in accordance with the requirements of the relevant standards. The influence of the applied biocarbon on the anti-wear (Goz) and anti-seize (Pt, poz) properties of plastic greases made with vegetable and synthetic basis was determined. It was found that some of the biocarbon, especially those derived from the pyrolysis of corn waste, significantly improve the tribological properties of plastic greases, both those based on plant and synthetic sources.W artykule przedstawiono charakterystyki tribologiczne smarów plastycznych, w których fazą dyspergującą był olej roślinny (rzepakowy) lub syntetyczny olej estrowy (Priolube). Jako zagęszczacz zastosowano stearynian litu w ilości pozwalającej na uzyskanie kompozycji w drugiej klasie konsrystencji, a dodatkami funkcyjnymi były biowęgle wytwarzane w procesie pirolizy następujących odpadów roślinnych: paździerze lniane, słoma pszeniczna, liście i łodygi kukurydzy oraz pestki wiśni. Sporządzono kompozycje zawierające, do których wprowadzano 5% m/m biowęgli i oceniono wpływ rodzaju biowęgla na właściwości tribologiczne otrzymanych smarów plastycznych. Charakterystyki tribologiczne kompozycji smarowych wyznaczono z wykorzystaniem testera T-02 zgodnie z wymaganiami norm przedmiotowych. Określono wpływ zastosowanych biowęgli na właściwości przeciwzużyciowe (Goz) i przeciwzatarciowe (Pt, poz) smarów plastycznych wytworzonych na bazie roślinnej i syntetycznej. Stwierdzono, że niektóre z biowęgli, szczególnie te pochodzące z pirolizy odpadów kukurydzy, zdecydowanie poprawiają właściwości tribologiczne smarów plastycznych zarówno tych na bazie roślinnej, jak i syntetycznej

In vitro/In vivo translation of synergistic combination of MDM2 and MEK inhibitors in melanoma using PBPK/PD modelling : part I

Translation of the synergy between the Siremadlin (MDM2 inhibitor) and Trametinib (MEK inhibitor) combination observed in vitro into in vivo synergistic efficacy in melanoma requires estimation of the interaction between these molecules at the pharmacokinetic (PK) and pharmacodynamic (PD) levels. The cytotoxicity of the Siremadlin and Trametinib combination was evaluated in vitro in melanoma A375 cells with MTS and RealTime-Glo assays. Analysis of the drug combination matrix was performed using Synergy and Synergyfinder packages. Calculated drug interaction metrics showed high synergy between Siremadlin and Trametinib: 23.12%, or a 7.48% increase of combined drug efficacy (concentration-independent parameter β from Synergy package analysis and concentration-dependent δ parameter from Synergyfinder analysis, respectively). In order to select the optimal PD interaction parameter which may translate observed in vitro synergy metrics into the in vivo setting, further PK/PD studies on cancer xenograft animal models coupled with PBPK/PD modelling are needed

Thermoplastic elastomers containing 2D nanofillers: montmorillonite, graphene nanoplatelets and oxidized graphene platelets

This paper presents a comparative study on which type of platelets nanofiller, organic or inorganic, will affect the properties of thermoplastic elastomer matrix in the stronger manner. Therefore, poly(trimethylene terephthalate-block-poly(tetramethylene oxide) copolymer (PTT-PTMO) based nanocomposites with 0.5 wt.% of clay (MMT), graphene nanoplatelets (GNP) and graphene oxide (GO) have been prepared by in situ polymerization. The structure of the nanocomposites was characterized by transmission electron microscopy (TEM) in order to present good dispersion without large aggregates. It was indicated that PTT-PTMO/GNP composite shows the highest crystallization temperature. Unlike the addition of GNP and GO, the introduction of MMT does not have great effect on the glass transition temperature of PTMO-rich soft phase. An addition of all three types of nanoplatelets in the nanocomposites caused the enhancement in tensile modulus and yield stress. Additionally, the cyclic tensile tests showed that prepared nanocomposites have values of permanent set slightly higher than neat PTT-PTMO

In vitro/in vivo translation of synergistic combination of MDM2 and MEK inhibitors in melanoma using PBPK/PD modelling : part II

The development of in vitro/in vivo translational methods for synergistically acting drug combinations is needed to identify the most effective therapeutic strategies. We performed PBPK/PD modelling for siremadlin, trametinib, and their combination at various dose levels and dosing schedules in an A375 xenografted mouse model (melanoma cells). In this study, we built models based on in vitro ADME and in vivo PK/PD data determined from the literature or estimated by the Simcyp Animal simulator (V21). The developed PBPK/PD models allowed us to account for the interactions between siremadlin and trametinib at PK and PD levels. The interaction at the PK level was described by an interplay between absorption and tumour disposition levels, whereas the PD interaction was based on the in vitro results. This approach allowed us to reasonably estimate the most synergistic and efficacious dosing schedules and dose levels for combinations of siremadlin and trametinib in mice. PBPK/PD modelling is a powerful tool that allows researchers to properly estimate the in vivo efficacy of the anticancer drug combination based on the results of in vitro studies. Such an approach based on in vitro and in vivo extrapolation may help researchers determine the most efficacious dosing strategies and will allow for the extrapolation of animal PBPK/PD models into clinical settings

Failures in total HIP arthroplasty connected with polyethylene

Polietylen jest obecnie powszechnie stosowanym matariałem Implantacyjnym w chirurgii ortopedycznej. Pojawiające się ostatnio coraz liczniej doniesienia przedstawiające problemy związane z jego diugotrwafą implantacją świadczą o tym, że materiał ten obok swych niewątpliwych zalet nie jest również pozbawiony wad. Do tych ostatnich należą: nadmiernie szybkie zużycie niektórych panewek polietylenowych, odwarstwienia i złuszczenia powierzchni nośnej panewek, złamania i rozkawałkowania panewek polietylenowych oraz wywoływanie niekorzystnych reakcji biologicznych ustroju wokół impłantowanych endoprotez siewów biodrowych. Niestabilność struktury wewnętrznej polietylenu i wzrost stopnia krystaliczności panewek polietylenowych mogą powodować zmianę ich właściwości mechanicznych i stanowić źródło powikłań po alloplastykach stawów biodrowych.Polyethylene is commonly used as a component in the majority of hip joint prostheses. Growing number of information regarding failures of the polyethylene due to its long-term implantation shows that this material, besides obvious advantages, has also many disadvantages. The latter are undoubtedly: excessive wear of some polyethylene cups, delamination and peeling of the bearing surfaces of the cups, fracture and fragmentation of the cups and ability to cause harmful biological reactions. Unstable internal structure of the polyethylene and varying crystallinity of the polyethylene cups may cause changes in the mechanical properties of the cups with consequent failure of the hip arthroplasty

Electron beam treatment of simulated marine diesel exhaust gases

The exhaust gases from marine diesel engines contain high SO2 and NOx concentration. The applicability of the electron beam flue gas treatment technology for purification of marine diesel exhaust gases containing high SO2 and NOx concentration gases was the main goal of this paper. The study was performed in the laboratory plant with NOx concentration up to 1700 ppmv and SO2 concentration up to 1000 ppmv. Such high NOx and SO2 concentrations were observed in the exhaust gases from marine high-power diesel engines fuelled with different heavy fuel oils. In the first part of study the simulated exhaust gases were irradiated by the electron beam from accelerator. The simultaneous removal of SO2 and NOx were obtained and their removal efficiencies strongly depend on irradiation dose and inlet NOx concentration. For NOx concentrations above 800 ppmv low removal efficiencies were obtained even if applied high doses. In the second part of study the irradiated gases were directed to the seawater scrubber for further purification. The scrubbing process enhances removal efficiencies of both pollutants. The SO2 removal efficiencies above 98.5% were obtained with irradiation dose greater than 5.3 kGy. For inlet NOx concentrations of 1700 ppmv the NOx removal efficiency about 51% was obtained with dose greater than 8.8 kGy. Methods for further increase of NOx removal efficiency are presented in the paper