90 research outputs found

    Π‘Π»ΠΎΠΆΠ½ΠΎΡΡ‚ΡŒ Π°Π»Π³ΠΎΡ€ΠΈΡ‚ΠΌΠΎΠ² криптографичСской систСмы Π­Π»ΡŒβ€“Π“Π°ΠΌΠ°Π»Ρ ΠΈ ΠΈΡ…ΡΡ„Ρ„Π΅ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒ

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    Objective. - Electrical remodeling as well as atrial contractile dysfunction after the conversion of atrial fibrillation (AF) to sinus rhythm (SR) are mainly caused by a reduction of the inward L-type Ca2+ current (ICaL). We investigated whether the expression of L-type Ca2+-channel subunits was reduced in atrial myocardium of AF patients. Methods. - Right atrial appendages were obtained from patients undergoing coronary artery bypass graft surgery (CAD, n = 35) or mitral valve surgery (MVD, n = 37). Seventeen of the CAD patients and 18 of the MVD patients were in chronic (>3 months) AF, whereas the others were in SR. The protein expression of the L-type Ca2+-channel subunits {alpha}1C and {beta}2 was quantified by western blot analysis. Furthermore, we measured the density of dihydropyridine (DHP)-binding sites of the L-type Ca2+ channel using 3H-PN220-100 as radioligand. Results. - Surprisingly, the {alpha}1C and the {beta}2-subunit expression was not altered in atrial myocardium of AF patients. Also, the DHP-binding site density was unchanged. Conclusion. - The protein expression of the L-type Ca2+-channel subunits {alpha}1C or {beta}2 is not reduced in atrial myocardium of AF patients. Therefore, the reduced ICaL might be due to downregulation of other accessory subunits ({alpha}2{delta}), expression of aberrant subunits, changes in channel trafficking or alterations in channel function

    Bitter gourd, Momordica charantia L., breeding lines differ in secondary metabolite content according to market type

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    Bitter gourd, Momordica charantia L., is an important commercial cucurbitaceous vegetable of enormous medicinal value in Asia because of its secondary metabolite content. We report here the characterization and evaluation of open-pollinated (OP) edible South Asian and Southeast Asian types of bitter gourd breeding lines, developed at the World Vegetable Center, for horticultural traits (11 OP) and secondary metabolites (10 OP) and their comparisons with commercial OP and F1 hybrid cultivars. Marketable yields of South Asian and Southeast Asian type breeding lines were comparable to the OP β€˜BARI Karella 1’ and the hybrid β€˜Benteng’, respectively.The bitter gourd cultivars and breeding lines included in this study exhibited specific patterns for five secondary metabolites (saponins, carotenoids, chlorophyll a and b, and vitamin C): in general the two cultivars and South Asian type breeding lines contained higher levels of secondary metabolites, e.g. carotenoids, than the Southeast Asian bitter gourd breeding lines.Some of these bitter gourd lines will be released to Asian home and school gardeners after conducting multi-location trials across Asia to improve vegetable consumption as a main task of bitter gourd breeding

    Aeolianite and barrier dune construction spanning the last two glacial-interglacial cycles from the southern Cape coast, South Africa

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    The southern Cape region of South Africa has extensive coastal aeolianites and barrier dunes. Whilst previously reported, limited knowledge of their age has precluded an understanding of their relationship with the climatic and sea-level fluctuations that have taken place during the Late Quaternary. Sedimentological and geomorphological studies combined with an optical dating programme reveal aeolianite development and barrier dune construction spanning at least the last two glacial–interglacial cycles. Aeolianite deposition has occurred on the southern Cape coast at ca 67–80, 88–90, 104–128, 160–189 and >200 ka before the present. Using this and other published data coupled with a better understanding of Late Quaternary sea-level fluctuations and palaeocoastline configurations, it is concluded that these depositional phases appear to be controlled by interglacial and subsequent interstadial sea-level high stands. These marine transgressions and regressions allowed onshore carbonate-rich sediment movement and subsequent aeolian reworking to occur at similar points in the landscape on a number of occasions. The lack of carbonates in more recent dunes (Oxygen Isotope Stages 1/2 and 4/5) is attributed not to leaching but to changes to carbonate production in the sediment source area caused by increased terrigenous material and/or changes in the balance between the warm Agulhas and nutrient-rich Benguela ocean current

    ЀлуоримСтричСская ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΈΠΊΠ° ΠΎΡ†Π΅Π½ΠΊΠΈ влияния доксорубицина Π½Π° ΠΆΠΈΠ·Π½Π΅ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡ‚ΡŒ Π»Π°ΠΊΡ‚ΠΎΠ±Π°ΠΊΡ‚Π΅Ρ€ΠΈΠΉ

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    ΠžΠ±ΡŠΠ΅ΠΊΡ‚Π°ΠΌΠΈ исслСдования ΡΠ²Π»ΡΡŽΡ‚ΡΡ лСкарствСнныС ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚Ρ‹ "Π›Π°ΠΊΡ‚ΠΎΠ±Π°ΠΊΡ‚Π΅Ρ€ΠΈΠ½" ΠΈ "Доксорубицин". ЦСль Ρ€Π°Π±ΠΎΡ‚Ρ‹ Π·Π°ΠΊΠ»ΡŽΡ‡Π°Π΅Ρ‚ΡΡ Π² Ρ€Π°Π·Ρ€Π°Π±ΠΎΡ‚ΠΊΠ΅ флуоримСтричСской ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΈΠΊΠΈ ΠΎΡ†Π΅Π½ΠΊΠΈ влияния доксорубицина Π½Π° ΠΆΠΈΠ·Π½Π΅ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡ‚ΡŒ Π»Π°ΠΊΡ‚ΠΎΠ±Π°ΠΊΡ‚Π΅Ρ€ΠΈΠΉ. Π’ Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Π΅ исслСдования Ρ€Π°Π·Ρ€Π°Π±ΠΎΡ‚Π°Π½Π° флуоримСтричСская ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΈΠΊΠ° ΠΎΡ†Π΅Π½ΠΊΠΈ влияния доксорубицина Π½Π° Π»Π°ΠΊΡ‚ΠΎΠ±Π°ΠΊΡ‚Π΅Ρ€ΠΈΠΈ.The object of study are drugs "Lactobacterin" and "Doxorubicin". The purpose of the work is to develop a fluorimetric methodology for assessing the effect of doxorubicin on the viability of lactobacillus. As a result of the study, a fluorimetric method for assessing the effect of doxorubicin on the viability of lactobacillus

    Physiologically-based pharmacokinetic modeling of quinidine to establish a CYP3A4, P-gp, and CYP2D6 drug-drug-gene interaction network

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    The antiarrhythmic agent quinidine is a potent inhibitor of cytochrome P450 (CYP) 2D6 and P-glycoprotein (P-gp) and is therefore recommended for use in clinical drug-drug interaction (DDI) studies. However, as quinidine is also a substrate of CYP3A4 and P-gp, it is susceptible to DDIs involving these proteins. Physiologically-based pharmacokinetic (PBPK) modeling can help to mechanistically assess the absorption, distribution, metabolism, and excretion processes of a drug and has proven its usefulness in predicting even complex interaction scenarios. The objectives of the presented work were to develop a PBPK model of quinidine and to integrate the model into a comprehensive drug-drug(-gene) interaction (DD(G)I) network with a diverse set of CYP3A4 and P-gp perpetrators as well as CYP2D6 and P-gp victims. The quinidine parent-metabolite model including 3-hydroxyquinidine was developed using pharmacokinetic profiles from clinical studies after intravenous and oral administration covering a broad dosing range (0.1-600 mg). The model covers efflux transport via P-gp and metabolic transformation to either 3-hydroxyquinidine or unspecified metabolites via CYP3A4. The 3-hydroxyquinidine model includes further metabolism by CYP3A4 as well as an unspecific hepatic clearance. Model performance was assessed graphically and quantitatively with greater than 90% of predicted pharmacokinetic parameters within two-fold of corresponding observed values. The model was successfully used to simulate various DD(G)I scenarios with greater than 90% of predicted DD(G)I pharmacokinetic parameter ratios within two-fold prediction success limits. The presented network will be provided to the research community and can be extended to include further perpetrators, victims, and targets, to support investigations of DD(G)Is.Horizon 2020 (H2020)Personalised Therapeutic

    Prognosis of ventilator-associated pneumonia: what lies beneath

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    Assessment of the Inhibitory Potential of Spasmolytics on Major Human Cytochrome P450 Enzymes

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