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The Potential of Water Soluble Polymers in Targeted and Site - Specific Drug Delivery
Jindrich Kopecek 한국약제학회 1989 Journal of Pharmaceutical Investigation Vol.19 No.4
Anticancer drugs are usually low molecular weight compounds which penetrate into the majority of cells. The lack of specificity of action results in unwanted side effects. By attaching low molecular weight drugs to water soluble polymeric carriers, the mechanism of penetration into the cell changes to pinocytosis. This process gives the possibility to: a) Target the drug to the place where the action is needed. b) Influence the intracellular concentration for a prolonged period of time in order to achieve optimal action. We have been developing anticancer polymeric prodrugs based on N-(2-hydroxy-propyl) methacrylamide(HPMA) copolymers. The structure of these new drugs was tailormade to fulfil the following conditions: a) The drug carrier conjugate enters cells by pinocytosis. b) The drug is bound to the HPMA copolymer via an oligopeptide sidechain which remains stable in the blood stream but is susceptible to hydrolysis catalyzed by lysosomal enzymes. c) By binding specific recognition markers (targeting moieties) to the polymeric carrier, it is possible to increase substantially the concentration of HPMA copolymer anticancer drug conjugates in the target cell. HPMA copolymers containing daunomycin, adriamycin or sarcolysin have been modified with three different targeting moieties-galactosamine, fucosylamine and anti-Thy 1.2 antibodies. This enabled three targets to be reached-hepatocytes, mouse leukemia L1210 cells and T lymphocytes, respectively. The activity of the polymeric prodrugs was structure dependent. Drug conjugates where the drug was bound via oligopeptide side-chains degradable by lysosomal enzymes were active, whereas drugs bound via nondegradable ones were not. The results obtained verified the validity of our concept of intracellular drug delivery.
Citek, Jindrich,Brzakova, Michaela,Hanusova, Lenka,Hanus, Oto,Vecerek, Libor,Samkova, Eva,Krizova, Zuzana,Hostickova, Irena,Kavova, Tereza,Strakova, Karolina,Hasonova, Lucie Asian Australasian Association of Animal Productio 2021 Animal Bioscience Vol.34 No.1
Objective: The aim of the study was to evaluate the influence of polymorphic loci and other factors on milk performance and the technological properties of milk. Methods: The analysis was performed on Simmental and Holstein cows in field conditions (n = 748). Milk yield in kg, fat and protein percentage and yield were evaluated. Technological properties were evaluated by milk fermentation ability, renneting, and an alcohol test. Polymorphisms in the acyl-CoA diacylgycerol transferase 1 (DGAT1), leptin (LEP), fatty acid synthase (FASN), stearoyl CoA desaturase 1 (SCD1), casein beta (CSN2), casein kappa (CSN3), and lactoglobulin beta genes were genotyped, and association analysis was performed. Results: The DGAT1 AA genotype was associated with higher milk, protein and fat yields (p<0.05). The MM genotype in the LEP gene was associated with a lower protein percentage and the W allele with a higher protein percentage (p<0.05). In cows with the FASN GG genotype, the protein percentage was higher, but the A allele was associated with higher milk, protein and fat yields than the G allele. The TT genotype in SCD1 was associated with the lowest milk, protein and fat yields and with the highest milk protein percentage (p<0.01). The T allele had higher values than the C allele (p<0.05) except for fat percentage. The genotype CSN3 AA was associated with a significantly heightened milk yield; BB was associated with a high protein percentage. The effect of the alleles on the technological properties was not significant. The CSN2 BB genotype was associated with the best alcohol test (p<0.01), and the renneting order was inverse. Milk from cows with the CSN2 A1A1 genotype was best in the milk fermentation ability. CSN3 significantly affected the technological properties. Conclusion: The findings revealed the potential of some polymorphic loci for use in dairy cattle breeding and for the management of milk quality. In field research, the pivotal role of farms in milk yield, composition and technological properties was confirmed.
A New Concept of Hydraulic Design of Water Turbine Runners
Vesely, Jindrich,Pochyly, Frantisek,Obrovsky, Jiri,Mikulasek, Josef Korean Society for Fluid machinery 2009 International journal of fluid machinery and syste Vol.2 No.4
Vibrations at different frequencies with a different intensity as well as a pressure pulsation with different parameters are two phenomena which can be observed at different water turbines. Due to the vibration and the pressure pulsation some restrictions of water turbine operation range are applied. Similar problems with the efficiency level in a wide water turbine operation range are the basic problems which are solved for ages. A theoretical and practical solution of the above mentioned problems is very much time and money consuming. The paper describes a new theoretical solution of the excitation and pressure pulsation decrease as well as extension of the operational range with high efficiency level. The new concept to decrease the vibrations and pressure pulsations is based on a heterogeneous runner blade geometry generation. The new concept of the runner geometry design was numerically tested at a low specific speed pump turbine, see Fig. 1, and basic points of the concept are presented in this paper.
Martin Topiar,Marie Sajfrtova,Jindrich Karban,Helena Sovova 한국공업화학회 2019 Journal of Industrial and Engineering Chemistry Vol.77 No.-
Turmeric (Curcuma longa L.) was extracted with supercritical carbon dioxide (sc-CO2) and turmerones,compounds with strong biological activity, were concentrated using semi-preparative supercriticalchromatography (p-SFC) with sc-CO2. The extraction was performed at temperature of 40 C andpressures of 9–66 MPa. Influence of pressure, type of adsorbent and feed-to-sorbent ratio on the yield andconcentration of turmerones in p-SFC fractions was evaluated. Silica gel performed the best efficiency;the concentration of β-sesquiphellandrene in thefirst fraction increased more than 16 times, compared tothe feed, and the concentration of ar-turmerone and curlone in the following fraction was almostdoubled.
Petr Kubena,Mattia Arrigo,Jiri Parenica,Etienne Gayat,Malha Sadoune,Eva Ganovska,Marie Pavlusova,Simona Littnerova,Jindrich Spinar,Alexandre Mebazaa 대한진단검사의학회 2016 Annals of Laboratory Medicine Vol.36 No.4
Background: Acute heart failure negatively affects short-term outcomes of patients with acute coronary syndrome (ACS). Therefore, reliable and non-invasive assessment of pulmonary congestion is needed to select patients requiring more intensive monitoring and therapy. Since plasma levels of natriuretic peptides are influenced by myocardial ischemia, they might not reliably reflect congestion in the context of ACS. The novel endothelial biomarker, soluble CD146 (sCD146), presents discriminative power for detecting the cardiac origin of acute dyspnea similar to that of natriuretic peptides and is associated with systemic congestion. We evaluated the performance of sCD146 for the assessment of pulmonary congestion in the early phase of ACS. Methods: One thousand twenty-one consecutive patients with ACS were prospectively enrolled. Plasma levels of sCD146, brain natriuretic peptide (BNP), and high-sensitive troponin T were measured within 24 hr after the onset of chest pain. Pulmonary congestion on chest radiography was determined and classified in three groups according to the degree of congestion. Results: Nine hundred twenty-seven patients with ACS were analyzed. Ninety-two (10%) patients showed signs of pulmonary edema on chest radiography. Plasma levels of sCD146 reflected the radiological severity of pulmonary congestion. Higher plasma levels of sCD146 were associated with the worse degree of pulmonary congestion. In contrast to BNP, sCD146 levels were not affected by the level of troponin T. Conclusions: The novel endothelial biomarker, sCD146, correlates with radiological severity of pulmonary congestion in the early phase of ACS and, in contrast to BNP, is not affected by the amount of myocardial cell necrosis.