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Müller, Jens, Dominik Böhme, Patrick Lax, Marta Morell Cerdà, and Michael Roitzsch. "Metal Ion Coordination to Azole Nucleosides." Chemistry - A European Journal 11, no. 21 (October 21, 2005): 6246–53. http://dx.doi.org/10.1002/chem.200500511.
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Verweij, P. D., W. L. Driessen, J. Reedijk, and D. C. Sherrington. "Development of novel chelating ion-exchangers containing azole ligands." Reactive Polymers 17, no. 1 (April 1992): 137. http://dx.doi.org/10.1016/0923-1137(92)90640-n.
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Wang, Kangji, Zhenying Zhang, Xi Chen, Xianyun Sun, Cheng Jin, Hongwei Liu, and Shaojie Li. "Transcription Factor ADS-4 Regulates Adaptive Responses and Resistance to Antifungal Azole Stress." Antimicrobial Agents and Chemotherapy 59, no. 9 (June 22, 2015): 5396–404. http://dx.doi.org/10.1128/aac.00542-15.
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ABSTRACTAzoles are commonly used as antifungal drugs or pesticides to control fungal infections in medicine and agriculture. Fungi adapt to azole stress by rapidly activating the transcription of a number of genes, and transcriptional increases in some azole-responsive genes can elevate azole resistance. The regulatory mechanisms that control transcriptional responses to azole stress in filamentous fungi are not well understood. This study identified a bZIP transcription factor, ADS-4 (antifungaldrugsensitive-4), as a new regulator of adaptive responses and resistance to antifungal azoles. Transcription ofads-4inNeurospora crassacells increased when they were subjected to ketoconazole treatment, whereas the deletion ofads-4resulted in hypersensitivity to ketoconazole and fluconazole. In contrast, the overexpression ofads-4increased resistance to fluconazole and ketoconazole inN. crassa. Transcriptome sequencing (RNA-seq) analysis, followed by quantitative reverse transcription (qRT)-PCR confirmation, showed that ADS-4 positively regulated the transcriptional responses of at least six genes to ketoconazole stress inN. crassa. The gene products of four ADS-4-regulated genes are known contributors to azole resistance, including the major efflux pump CDR4 (Pdr5p ortholog), an ABC multidrug transporter (NcAbcB), sterol C-22 desaturase (ERG5), and a lipid transporter (NcRTA2) that is involved in calcineurin-mediated azole resistance. Deletion of theads-4-homologous gene Afads-4inAspergillus fumigatuscaused hypersensitivity to itraconazole and ketoconazole, which suggested that ADS-4 is a functionally conserved regulator of adaptive responses to azoles. This study provides important information on a new azole resistance factor that could be targeted by a new range of antifungal pesticides and drugs.
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van Berkel, P. M., W. L. Driessen, J. Reedijk, D. C. Sherrington, and A. Zitsmanis. "Metal-ion binding affinity of azole-modified oxirane and thiirane resins." Reactive and Functional Polymers 27, no. 1 (October 1995): 15–28. http://dx.doi.org/10.1016/1381-5148(95)00026-c.
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Valeikaitė, Ernesta, and Aušra Mažeikienė. "RESEARCH OF SMALL HOUSE HOLD SEWAGE TREATMENT PLANT WORKING / MAŽO BUITINIŲ NUOTEKŲ VALYMO ĮRENGINIO DARBO TYRIMAI." Mokslas – Lietuvos ateitis 7, no. 4 (September 29, 2015): 449–54. http://dx.doi.org/10.3846/mla.2015.833.
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In Lithuania centralized municipal wastewater treatment technologies are applied quite effectively, but there is little evidence of the functioning of individual small wastewater treatment plants. The paper presents the small device AT-6, in the city of Vilnius, and the treated sewage results (BDS7, nitrate, ammonium, total nitrogen, total phosphorus and phosphate concentrations). Studies have shown that treated sewage indicators based on ammonium and nitrate ion concentrations are good. These substances are 2–10 times less than it can be in drinking water according to HN 24: 2003. Concentration of phosphates in the treated sewage ranged from 3.57 to 9.33 mg/L and exceeded the indicators, which were compared. The phosphorus environmental aspect is not dangerous, because treated sewage is not discharged into surface water bodies. Dealing from the pattern of biological indicators and enzymatic activity, the quality of activated sludge is good. Treated sewage does not impair the natural state. Lietuvoje centralizuoto buitinių nuotekų valymo technologijos yra taikomos gana efektyviai, tačiau beveik nėra duomenų, kaip veikia maži individualaus buitinių nuotekų valymo įrenginiai. Straipsnyje analizuojami mažu buitinių nuotekų biologinio valymo įrenginiu AT-6 pasiekiami pagrindiniai išvalymo rodikliai (BDS7, nitratų azoto, amonio azoto, bendrojo azoto, bendrojo fosforo ir fosfatų fosforo koncentracijos). Nuotekų išvalymo laipsnis pagal amonio azoto ir nitratų azoto koncentracijas yra aukštas. Šių medžiagų yra 2–10 kartų mažiau, nei gali būti geriamajame vandenyje pagal HN 24:2003. Fosfatų fosforo (PO4-P) koncentracijos išvalytose nuotekose svyravo nuo 3,57 iki 9,33 mg/l ir viršijo rodiklius, su kuriais buvo lygintos. Šis fosforas aplinkosaugainiu aspektu yra nepavojingas, nes nuotekos nėra išleidžiamos į paviršinį vandens telkinį. Sprendžiant iš rastų biologinių indikatorių ir fermentinio aktyvumo, veikliojo dumblo kokybė yra gera. Išvalytos nuotekos nepablogina gamtos būklės.
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Sun, Xianyun, Kangji Wang, Xinxu Yu, Jie Liu, Hanxing Zhang, Fucai Zhou, Baogui Xie, and Shaojie Li. "Transcription Factor CCG-8 as a New Regulator in the Adaptation to Antifungal Azole Stress." Antimicrobial Agents and Chemotherapy 58, no. 3 (December 16, 2013): 1434–42. http://dx.doi.org/10.1128/aac.02244-13.
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ABSTRACTAntifungal azoles are widely used for controlling fungal infections. Fungi are able to change the expression of many genes when they adapt to azole stress, and increased expression of some of these genes can elevate resistance to azoles. However, the regulatory mechanisms behind transcriptional adaption to azoles in filamentous fungi are poorly understood. In this study, we found that deletion of the transcription factor geneccg-8, which is known to be a clock-controlled gene, madeNeurospora crassahypersensitive to azoles. A comparative genome-wide analysis of the responses to ketoconazole of the wild type and theccg-8mutant revealed that the transcriptional responses to ketoconazole of 78 of the 488 transcriptionally ketoconazole-upregulated genes and the 427 transcriptionally ketoconazole-downregulated genes in the wild type were regulated by CCG-8. Ketoconazole sensitivity testing of all available knockout mutants for CCG-8-regulated genes revealed that CCG-8 contributed to azole adaption by regulating the ketoconazole responses of many genes, including the target gene (erg11), an azole transporter gene (cdr4), a hexose transporter gene (hxt13), a stress response gene (locus number NCU06317, namedkts-1), two transcription factor genes (NCU01386 [namedkts-2] andfsd-1/ndt80), four enzyme-encoding genes, and six unknown-function genes. CCG-8 also regulated phospholipid synthesis inN. crassain a manner similar to that of its homolog inSaccharomyces cerevisiae, Opi1p. However, there was no cross talk between phospholipid synthesis and azole resistance inN. crassa. CCG-8 homologs are conserved and are common in filamentous fungi. Deletion of the CCG-8 homolog-encoding gene inFusarium verticillioides(Fvccg-8) also made this fungus hypersensitive to antifungal azoles.
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Baert, Bram, Jente Boonen, Céline Thierens, and Bart De Spiegeleer. "Ion mobility spectrometry of talarozole, a new azole drug, in cleaning quality control." International Journal for Ion Mobility Spectrometry 14, no. 2-3 (April 15, 2011): 109–16. http://dx.doi.org/10.1007/s12127-011-0063-z.
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Agnew, Christopher R. J., Andrew G. S. Warrilow, Nicholas M. Burton, David C. Lamb, Steven L. Kelly, and R. Leo Brady. "An Enlarged, Adaptable Active Site in CYP164 Family P450 Enzymes, the Sole P450 in Mycobacterium leprae." Antimicrobial Agents and Chemotherapy 56, no. 1 (October 28, 2011): 391–402. http://dx.doi.org/10.1128/aac.05227-11.
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ABSTRACTCYP164 family P450 enzymes are found in only a subset of mycobacteria and include CYP164A1, which is the sole P450 found inMycobacterium leprae, the causative agent of leprosy. This has previously led to interest in this enzyme as a potential drug target. Here we describe the first crystal structure of a CYP164 enzyme, CYP164A2 fromMycobacterium smegmatis. CYP164A2 has a distinctive, enlarged hydrophobic active site that extends above the porphyrin ring toward the access channels. Unusually, we find that CYP164A2 can simultaneously bind two econazole molecules in different regions of the enlarged active site and is accompanied by the rearrangement and ordering of the BC loop. The primary location is through a classic interaction of the azole group with the porphyrin iron. The second econazole molecule is bound to a unique site and is linked to a tetracoordinated metal ion complexed to one of the heme carboxylates and to the side chains of His 105 and His 364. All of these features are preserved in the closely homologousM. lepraeCYP164A1. The computational docking of azole compounds to a homology model of CYP164A1 suggests that these compounds will form effective inhibitors and is supported by the correlation of parallel docking with experimental binding studies of CYP164A2. The binding of econazole to CYP164A2 occurs primarily through the high-spin “open” conformation of the enzyme (Kd[dissociation constant] of 0.1 μM), with binding to the low-spin “closed” form being significantly hindered (Kdof 338 μM). These studies support previous suggestions that azole derivatives may provide an effective strategy to improve the treatment of leprosy.
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Xhanari, Klodian, and Matjaž Finšgar. "The Corrosion Inhibition of AA6082 Aluminium Alloy by Certain Azoles in Chloride Solution: Electrochemistry and Surface Analysis." Coatings 9, no. 6 (June 13, 2019): 380. http://dx.doi.org/10.3390/coatings9060380.
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The corrosion inhibition effect of five azole compounds on the corrosion of an AA6082 aluminium alloy in 5 wt.% NaCl solution at 25 and 50 °C was investigated using weight loss and electrochemical measurements. Only 2-mercaptobenzothiazole (MBT) showed a corrosion inhibition effect at both temperatures and was further studied in detail, including with the addition of potassium iodide as a possible intensifier. Surface analysis of the MBT surface layer was performed by means of attenuated total reflectance Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectrometry techniques. The hydrophobicity of the MBT surface layer was also investigated.
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Wadsworth, John M., Anna M. Milan, James Anson, and Andrew S. Davison. "Development of a liquid chromatography tandem mass spectrometry method for the simultaneous measurement of voriconazole, posaconazole and itraconazole." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 54, no. 6 (February 8, 2017): 686–95. http://dx.doi.org/10.1177/0004563216686378.
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Background Azole-based antifungals are the first-line therapy for some of the most common mycoses and are now also being used prophylactically to protect immunocompromised patients. However, due to variability in both their metabolism and bioavailability, therapeutic drug monitoring is essential to avoid toxicity but still gain maximum efficacy. Methods Following protein precipitation of serum with acetonitrile, 20 µL of extract was injected onto a 2.1 × 50 mm Waters Atlantis dC18 3 µm column. Detection was via a Waters Quattro Premier XE tandem mass spectrometer operating in ESI-positive mode. Multiple reaction monitoring (MRM) detected two product ions for each compound and one for each isotopically labelled internal standard. Ion suppression, linearity, stability, matrix effects, recovery, imprecision, lower limits of measuring interval and detection were all assessed. Results Optimal chromatographic separation was achieved using gradient elution over 8 minutes. Voriconazole, posaconazole and itraconazole eluted at 1.71, 2.73 and 3.41 min, respectively. The lower limits of measuring interval for all three compounds was 0.1 mg/L. The assay was linear to 10 mg/L for voriconazole (R2 = 0.995) and 5 mg/L for posaconazole (R2 = 0.990) and itraconazole (R2 = 0.991). The assay was both highly accurate and precise with % bias of voriconazole, posaconazole and itraconazole, respectively, when compared with previous NEQAS samples. The intra-assay precision (CV%) was 1.6%, 2.5% and 1.9% for voriconazole, posaconazole and itraconazole, respectively, across the linear range. Conclusion A simple and robust method has been validated for azole antifungal therapeutic drug monitoring. This new assay will result in a greatly improved sample turnaround time and will therefore vastly increase the clinical utility of azole antifungal drug monitoring.
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Lázaro-Martínez, Juan M., Gustavo A. Monti, and Ana K. Chattah. "Insights into the coordination sphere of copper ion in polymers containing carboxylic acid and azole groups." Polymer 54, no. 19 (August 2013): 5214–21. http://dx.doi.org/10.1016/j.polymer.2013.07.036.
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Tripathi, Krishna N., Devalina Ray, and Ravi P. Singh. "Pd-Catalyzed regioselective intramolecular dehydrogenative C-5 cross coupling in anN-substituted pyrrole-azole system." Organic & Biomolecular Chemistry 15, no. 47 (2017): 10082–86. http://dx.doi.org/10.1039/c7ob02676e.
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Sattarovich, Sattarov Abdumurod. "The Prtotein Content In Edible Insects And The Nutritional Value Of Macrophytes In Their Diet." American Journal of Agriculture and Biomedical Engineering 03, no. 06 (June 18, 2021): 71–90. http://dx.doi.org/10.37547/tajabe/volume03issue06-11.
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This article analyzes the synthesis of the Tenebrio molitor protein (Coleoptera: Tenebrionidae) belonging to a food insect, depending on its nutrient content. Differences in protein synthesis by Tenebrio molitor larvae were shown when wheat bran and flour from the macrophytesLemna minor and Azollacarolina were added. In particular, it was noted that TMO-2 and TMO-6 T.molitor F6 larvae are synthesized on average 31.02% protein in wheat bran, 38.13% in duckweed and 30.87% in azole. It was found that the larvae of variant F6 grown on wheat bran synthesized protein on average 4.79% less than the variant F1 of wheat. F6 larvae grown in duckweed synthesized 7.11% more protein than larvae grown in wheat bran and 0.15% less protein synthesis than larvae grown in azole. It was found that F6 larvae grown in duckweed produce 7.26% more protein than larvae grown in azole. Summarizing these indicators, it was noted that in the body of larvae eating macrophytes insufficient absorption of nutrients, low moisture content in the feed led to their death, egg laying and larvae of variant F6 produced significantly less protein than variant F1. When feeding macrophytes, it is advisable to takeintoaccountits moisture content or add flour based on them to other food sources. It was studied that egg-laying larvae grown on the basis of azole accounted for 38.14%, whereas in duckweed this indicator was 58.38%. It was found that in larvae grown on wheat bran, the percentage of egg-laying is 68.85%. The mortality rate of larvae feeding on wheat bran was 18.22%, in duckweed - 44.63%, in azole - 62.27%, this is due to insufficient moisture in the composition of duckweed and azole (average humidity 3.4-4.2%), relatively high humidity (average humidity 9.58-10.12%) in wheat bran. Survival coefficients of Tenebrio molitor F6 larvae were determined in three different compositions and sources of nutrients with different humidity (wheat bran, Lemna minor and flour Azollacarolina). Tenebrio molitor F6 larvae of the generation of variants TMO-2 and TMO-6 were grown on wheat bran with an average survival rate of 0.79, on duckweed flour - 0.50, on azolla flour - 0.64. It was noted that the survival rate of larvae grown on wheat bran was 15.5% higher than that of larvae grown on azolla, and it is advisable to explain the source not by the protein reserve, but by the amount of moisture in it. It was noted that the moisture content (9.58-10.12%) (protein 15%) in wheat bran was a factor in the high viability of the larvae compared to azolla (protein-27%, humidity 8.2%). Despite the easy protein synthesis in the body of larvae in duckweed flour (protein - 16.1%, humidity - 4.4%) compared to azolla flour, its content is 3.8% lower than that of azolla, due to the fact that survival the larvae in them were lower than in wheat and azolla. Therefore, along with the protein content, moisture is an important factor when choosing a food source. When summing the survival rates of larvae of the Tenebrio molitor F6 generation in the studied nutrient media, the average survival was calculated as 0.96. This means that based on the established ratios of wheat bran, duckweed and azolla flour, it will be possible to create a nutrient medium with a new content, high nutritional value and low cost
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Warrilow, Andrew G., Josie E. Parker, Diane E. Kelly, and Steven L. Kelly. "Azole Affinity of Sterol 14α-Demethylase (CYP51) Enzymes from Candida albicans and Homo sapiens." Antimicrobial Agents and Chemotherapy 57, no. 3 (December 28, 2012): 1352–60. http://dx.doi.org/10.1128/aac.02067-12.
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ABSTRACTCandida albicansCYP51 (CaCYP51) (Erg11), full-lengthHomo sapiensCYP51 (HsCYP51), and truncated Δ60HsCYP51 were expressed inEscherichia coliand purified to homogeneity. CaCYP51 and both HsCYP51 enzymes bound lanosterol (Ks, 14 to 18 μM) and catalyzed the 14α-demethylation of lanosterol usingHomo sapienscytochrome P450 reductase and NADPH as redox partners. Both HsCYP51 enzymes bound clotrimazole, itraconazole, and ketoconazole tightly (dissociation constants [Kds], 42 to 131 nM) but bound fluconazole (Kd, ∼30,500 nM) and voriconazole (Kd, ∼2,300 nM) weakly, whereas CaCYP51 bound all five medical azole drugs tightly (Kds, 10 to 56 nM). Selectivity for CaCYP51 over HsCYP51 ranged from 2-fold (clotrimazole) to 540-fold (fluconazole) among the medical azoles. In contrast, selectivity for CaCYP51 over Δ60HsCYP51 with agricultural azoles ranged from 3-fold (tebuconazole) to 9-fold (propiconazole). Prothioconazole bound extremely weakly to CaCYP51 and Δ60HsCYP51, producing atypical type I UV-visible difference spectra (Kds, 6,100 and 910 nM, respectively), indicating that binding was not accomplished through direct coordination with the heme ferric ion. Prothioconazole-desthio (the intracellular derivative of prothioconazole) bound tightly to both CaCYP51 and Δ60HsCYP51 (Kd, ∼40 nM). These differences in binding affinities were reflected in the observed 50% inhibitory concentration (IC50) values, which were 9- to 2,000-fold higher for Δ60HsCYP51 than for CaCYP51, with the exception of tebuconazole, which strongly inhibited both CYP51 enzymes. In contrast, prothioconazole weakly inhibited CaCYP51 (IC50, ∼150 μM) and did not significantly inhibit Δ60HsCYP51.
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Saganuwan, Saganuwan A. "Conversion of Benzimidazoles, Imidazothiazoles and Imidazoles into more Potent Central Nervous System Acting Drugs." Central Nervous System Agents in Medicinal Chemistry 20, no. 1 (March 3, 2020): 3–12. http://dx.doi.org/10.2174/1871524919666190621160323.
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Background: Benzimidazole (albendazole), imidazothiazole (levamisole) and imidazole (euconazole) are used in chemotherapy of helminthosis and mycosis respectively, with central nervous system (CNS) side effects. But only a limited number of azole groups are used clinically in the treatment of CNS diseases, which are on increase and could not be cured permanently. Due to increased incidence of more challenging new CNS diseases, there is a need for the synthesis of more potent CNS drugs. Methods: Hence, literature studies were carried out for the identification of common pathways for the synthesis of the three groups of compounds, their CNS properties and the possibility of modifying them to potent CNS drugs. Results: Findings have shown that gloxal with formaldehyde in the presence of ammonia can be converted into imidazole, imidazothiazole and benzimidazole via distillation, condensation, alkylation, acylation, oxidation, cyclization, sulphation and amidation. However, agents such as phosphorus pentoxide, ethanolic potassium hydroxide, sodium hypochlorite, sodium hexafluroaluminate, aniline, calcium acetate, calcium benzoate, sodium hydroxide, aromatic aldehydes, bromoketones, alpha dicarbonyl compounds among others are used as reagents. The furan ring(s) may have a strong capability of penetrating CNS for the treatment of neurological disorders. The products from the three groups have agonistic, antagonistic, mixed agonistic and mixed antagonistic depressant and stimulant activities due to the presence of heteroatoms such as nitrogen, oxygen and sulphur. Imidazole may be the most potent with best characteristics of CNS penetrability and activity followed by imidazothiazole and benzimidazole. Conclusion: Azole group is common to all the three classes and may be responsible for some of their CNS effects. The resultant compounds could act via all neurotransmitters, voltage and ligand-gated ion channels and may be chiral.
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Olajossy, Andrzej. "Method of Effective Use of Methane and Nitrogen Separated from Natural Gases / Metody Efektywnego Wykorzystania Metanu i Azotu z Naturalnych Gazów." Archives of Mining Sciences 57, no. 2 (November 12, 2012): 443–50. http://dx.doi.org/10.2478/v10267-012-0029-y.
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Abstract A mature concept of separation of natural gases, which usually contain methane and nitrogen, is the presented in the paper. As a result of ion-exchange with metal cations: Na, K, Mg followed by high-temperature roasting, clinoptilolite becomes a zeolite molecular sieve, that has kinetic diameter of 3.7 Å. As a result high-methane gas can be obtained 95 vol% methane, that can be directly sent to the gas network. The methane recovery exceeds 95%, whereas the outlet methane in nitrided gas losses are below 3 vol%. An idea was put forward to use the obtained nitrogen in enhanced oil recovery technology.
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Doğan, Özlem, Dolunay Gülmez, and Sevtap Arıkan Akdağlı. "Klinik ve Çevresel Örneklerden Elde Edilen Aspergillus fumigatus İzolatlarında Azol Direncinin Fenotipik ve Genotipik Olarak Değerlendirilmesi." Mikrobiyoloji Bulteni 54, no. 2 (April 15, 2020): 291–305. http://dx.doi.org/10.5578/mb.69024.
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Zrostlíková, Jitka, Jana Hajšlová, Tomáš Kovalczuk, Radim Štěpán, and Jan Poustka. "Determination of Seventeen Polar/Thermolabile Pesticides in Apples and Apricots by Liquid Chromatography/Mass Spectrometry." Journal of AOAC INTERNATIONAL 86, no. 3 (May 1, 2003): 612–22. http://dx.doi.org/10.1093/jaoac/86.3.612.
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Abstract A simple liquid chromatography/mass spectrome-try (LC/MS) approach for the determination of widely used representatives of polar/thermolabile pesticides in fruits was developed and validated. The group of pesticides comprised benzimidazoles and azoles (carbendazim, thiabendazole, imazalil, propiconazole, prochloraz, epoxiconazole, flusilazole, tebuconazole, bitertanol); N-methylcarbamates (carbaryl, carbofuran, methiocarb); and phenylureas and benzoylphenylureas (linuron, diflubenzuron, triflumuron, teflubenzuron, flufenoxuron). Matrixes (apple, apricot) were extracted with acetonitrile and crude extracts were cleaned up by solid-phase ex-traction (SPE) using either mixed cation exchange or hydrophilic lipophilic balance cartridges. LC separation of pesticides was performed on a reversed-phase column, Discovery C18. Electrospray ionization and ion trap MS/MS detection were applied. For most pesticides, overall recoveries ranged from 75 to 122%, and repeatability (as relative standard deviation) from 5 repetitive determinations of recovery ranged from 3 to 21%. Carbofuran was the only compound for which recovery was not satisfactory due to its loss in the SPE cleanup step. Limits of detection were 0.1–3 μg/kg for benzimidazole and azole fungicides and carbamate insecticides. For urea insecticides, detection limits were slightly higher (3–10 μg/kg).
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Eldesouky, Hassan E., Nadia A. Lanman, Tony R. Hazbun, and Mohamed N. Seleem. "Aprepitant, an antiemetic agent, interferes with metal ion homeostasis of Candida auris and displays potent synergistic interactions with azole drugs." Virulence 11, no. 1 (January 1, 2020): 1466–81. http://dx.doi.org/10.1080/21505594.2020.1838741.
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Janin, Amélie, Lucie Coudert, Guy Mercier, and Jean-François Blais. "Copper extraction and recovery from alkaline copper quaternary and copper azole treated wood using sulfuric acid leaching and ion exchange or electrodeposition." Journal of Cleaner Production 279 (January 2021): 123687. http://dx.doi.org/10.1016/j.jclepro.2020.123687.
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Cahill, Kirk, Juan Alban, Mylove Mortel, Emily Dworkin, Satyajit Kosuri, Adam Duvall, Hongtao Liu, Michael Russell Bishop, Richard A. Larson, and Wendy Stock. "Low incidence of hepatic veno-occlusive disease (VOD) in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with inotuzumab ozogamicin (INO) followed by allogeneic stem cell transplantation (allo-SCT)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e19024-e19024. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e19024.
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e19024 Background: Hepatic VOD is an uncommon, but often fatal complication of allo-SCT. The risk is increased after INO, an anti-CD22 antibody conjugated to calicheamicin with high remission rates in relapsed CD22-positive B-ALL. Previous reports have described VOD rates as high as 19% in INO-treated patients who then received allo-SCT. We report our safety experience using INO followed by allo-SCT. Methods: We identified patients >18 yrs with B-ALL treated with allo-SCT and INO in the University of Chicago IRB-approved SCT database. We reviewed the EMR for patient details, toxicities (CTCAE v5.0), and outcomes. Hepatic VOD was defined according to EBMT criteria. Overall survival (OS) was from time of allo-SCT to death or last follow-up. Results: Between 2010-2021, 72 adult patients with B-ALL received allo-SCT, and 17 also received INO as salvage therapy (Table). Median follow-up was 19 months (1-110). All received ursodiol prophylaxis and 15/17 received an azole for antifungal prophylaxis. They had median 2 cycles (1-3) of INO with median of 1.9 months (1-14) from the last dose of INO to allo-SCT. For cycle 1, 13/17 (77%) received 0.8 mg/m2 on D1 and 0.5 mg/m2 on D8 and D15. Of these, 11 had a subsequent cycle (5 with same dosing and 7 had 0.5 mg/m2 on D1, D8, and D15). 1 patient had 0.5 mg/m2 on D1, D8, and D15 for 2 cycles. 3 patients received 0.8 mg/m2 on D1 and 0.4 mg/m2 on D8 and D15 for 2 cycles. After INO, 10 patients achieved CR and 3 had CRi for ORR of 13/17 (76%). The 4 patients with persistent disease despite INO went into remission with a different salvage therapy prior to allo-SCT. Conditioning regimens are listed in Table 1. No patients developed VOD after allo-SCT. Within 2 yrs of allo-SCT, 3/17 (18%) relapsed and 7/17 (41%) died. The median OS was 21.2 months [18 - NR]. Conclusions: Limiting the number of INO cycles (median 2) prior to allo-SCT, delaying allo-SCT for 2 months after INO exposure, and avoiding dual alkylating agent conditioning may have contributed to the absence of VOD in our patients. Larger data sets will be useful to validate these important safety observations.[Table: see text]
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PATRIS, T., P. BALCH, C. JOANNIS, and A. CHAUBET. "Relations entre paramètres physiques et concentrations en polluants dans les effluents unitaires de Brest Métropole." Techniques Sciences Méthodes, no. 6 (June 22, 2020): 59–70. http://dx.doi.org/10.36904/tsm/202006059.
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Un volet du projet de R&D « Medisa » piloté par la société publique locale Eau du Ponant concerne les possibilités de conversion de mesures de conductivité et de turbidité en concentrations en matières en suspension (MES), demande chimique en oxygène (DCO), demande biochimique en oxygène à 5 jours (DBO5), azote Kjeldahl et phosphore total. Dans un premier temps, une analyse globalisée a été menée sur l’ensemble des 217 échantillons prélevés en temps sec et en temps de pluie au droit de six déversoirs d’orage situés sur le réseau unitaire de Brest Métropole. Elle permet d’identifier deux types de comportement des polluants associés aux fractions dissoutes et particulaires. Puis un indicateur de performance des relations de conversion a été élaboré, et a permis d’en comparer différents types de fonctions de conversion. L’ajustement de fonctions puissances permet une estimation raisonnable des paramètres réglementaires de pollution, sauf pour les valeurs les plus faibles, correspondant à des effluents très dilués. Enfin, une analyse plus détaillée a été menée pour évaluer les gains éventuels apportés par des relations spécifiques aux sites ou aux contextes hydrologiques (temps sec ou temps de pluie). Les résultats obtenus montrent que l’autosurveillance des rejets dans la rade de Brest peut s’appuyer sur une estimation des concentrations à partir de mesures en continu de conductivité et de turbidité, et être exploitée pour évaluer la conformité des rejets à un objectif exprimé en flux.
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Hanif, Muhammad, Muhammad Rafiq, Muhammad Mustaqeem, Muhammad A. Shaheen, Kaneez F. I. Qadri, Ishtiaq Qadri, and Muhammad Saleem. "Intracellular and Extracellular Zinc Detection by Organic Fluorescent Receptor." Current Organic Chemistry 23, no. 24 (January 10, 2020): 2664–78. http://dx.doi.org/10.2174/1385272823666191029114111.
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Keeping in view the ever growing demand and application of the organic small molecules based sensitive and selective fluorescence detection strategies for the trace metallic ions in the ecosystem, fluids and inside intracellular media, the present literature survey was focused on the recent development on the organic skeleton based fluorescence sensor for the zinc ion as Zn2+ is the second most abundant transition metal after iron in human body. The prominent organic based skeletons introduced during the past three years for zinc detection including azine, ((Z)-N´-(quinolin-2-ylmethylene)furan-2- carbohydrazide), nicotinohydrazide, hydrazone, phenolic cage, 4-methyl-2,6-bis[(E)-(2- (4-phenylthiazol-2-yl)hydrazono)methyl]phenol, bipyridine, N-(quinoline-8-yl)pyridine-2- carboxamide, anthracene, Schiff base, salen, helicene, Carbon Quantum Dots (CDs) functionalized with Calix[4]arene, coumarin, diaminomaleonitrile, peptide, hydroxypyrazole, salicylhydrazide were discussed in detail with particular focus on ligand-zinc complexation mechanism, UV-visible and fluorescence investigation, spectral variation, isosbestic emergence, limit of detection, ligand-zinc binding stoichiometry, association/binding constant and applications for intracellular tracing of metallic contamination via confocal fluorescence microscopic studies. Among the several discussed optical probes, rhodamine and fluorescein based material offer appreciable sensitivity, exhibiting drawback of pH sensitivity. Probes based on these ligands triggered “turn-on” signal even in the absence of metals upon fluctuation in pH e.g., acidic in former case and basic in the latter case. Hydroxypyrazole-based ligands also showed detection signal variation by switching the pH of the solution. Schiff base and bipyridyl scaffold were found to possess good ligation toward the several transition metals. Azole, oxazole, thiazole, thiadiazole, hydrazine carboxamide and hydrazine carbothiomide are the bioactive molecules exhibiting good cell viability and probes designed by using these central nucleus might be better to invest for intracellular imaging. Symmetrical heterocyclic cage like probe showed better chelation toward several transition metals and it is a good choice for the design and development of sensor for simultaneous detection of several transition metals.
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Váňová, M., J. Hajšlová, P. Havlová, P. Matušinsky, K. Lancová, and D. Spitzerová. "Effect of spring barley protection on the production of Fusarium spp. Mycotoxins in grain and malt using fungicides in field trials." Plant, Soil and Environment 50, No. 10 (December 10, 2011): 447–55. http://dx.doi.org/10.17221/4057-pse.
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The effects of different fungicides in four-year trials with a susceptible variety of spring barley, which was grown in field conditions with two previous crops (sugar beet and corn) and artificially inoculated with spores of Fusarium, were investigated. Field trials were laid down in plots of the Agricultural Research Institute Kroměříž, Ltd. (235 m above sea level, average annual temperature 8.7°C, annual precipitation sum 599 mm) in 2000–2003. The variety Kompakt, which was very sensitive to Fusarium head blight (FHB) in other trials, was used in all the trials examined. Incidence and severity of FHB and control with fungicides were measured by deoxynivalenol (DON) contamination of grain and malt. The content of Fusarium trichothecenes was evaluated in one fraction of kernels (diameter 2.5 mm) which is used in malting technology process. In 2000 and 2001, the treatments without adjuvants were applied. In the following two years, Silwet L-77 adjuvant (0.1 l/ha) was used with different rates of water (250 and 150 l/ha in 2002 and 2003, respectively). In all years, DON content increased in most cases after the grain samples were malted. The conditions of high grain moisture, moderate temperature and high relative humidity provide an ideal environment for Fusarium growth during germination. The greatest reduction of mycotoxins was achieved using a combination of azole fungicides with tebuconazole or metconazole or a mixture of metconazole + famoxadone + flusilazole with the addition of Silwet L-77 and a low rate of water.
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Mažeikienė, Aušra, Marina Valentukevičienė, Mindaugas Rimeika, Algirdas Bronislovas Matuzevičius, and Regimantas Dauknys. "REMOVAL OF NITRATES AND AMMONIUM IONS FROM WATER USING NATURAL SORBENT ZEOLITE (CLINOPTILOLITE)/NATŪRALIOJO SORBENTO CEOLITO (KLINOPTILOLITO) NAUDOJIMAS NITRATAMS IR AMONIO JONAMS ŠALINTI IŠ VANDENS/ ПРИМЕНЕНИЕ НАТУРАЛЬНОГО СОРБЕНТА ЦЕОЛИТА (КЛИНОПТИЛОЛИТА) ДЛЯ ОЧИСТКИ ВОДЫ ОТ НИТРАТОВ И АММОНИЯ." JOURNAL OF ENVIRONMENTAL ENGINEERING AND LANDSCAPE MANAGEMENT 16, no. 1 (March 31, 2008): 38–44. http://dx.doi.org/10.3846/1648-6897.2008.16.38-44.
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Experimental investigation of nitrogen compound (nitrates and ammonium ions) removal from water using natural zeolite was carried out in the laboratory of Water Management Department in VGTU. Shallow‐well water samples were taken from a few place situated in Vilnius city and Vilnius district, nitrate concentration was enhanced adding Na NO3 into the samples. Nitrate removal from water solutions was carried out under static conditions: solutions with nitrate concentration of 74–288 mg/l were mixed during one hour with 5 g of 0.315 mm particle‐sized zeolite in an automatic mixer when mixing intensity was 100 min.−1; after 30 min. sedimentation nitrate concentration was measured in all the samples. Ammonium ion removal from water solutions (made of shallow‐well and tap water with NH4Cl) was carried out under static and dynamic conditions (water solutions with 10–15 mg/l of ammonium ion concentration were filtered through 0.315–0.63 mm particle‐sized filter medium). Experimental results show that shallow‐well water (with nitrate concentration of 74–288 mg/l), after one‐hour mixing with 5 g of 0.315 mm particle‐sized zeolite and after 30 min. sedimentation, nitrate concentration stayed the same without any reduction. The same shallow‐well water (with 1–10 mg/l ammonium ion concentration) mixed with 5 g of 0.315–0.63 mm particle‐sized zeolite showed ammonium ion removal efficiency of 72–86 %. For ammonium ion removal from tap water and NH4Cl solution (primary concentration was 15 mg/l) under dynamic conditions, filtering through 400 mm high, 0.315–0.63 mm particle‐sized zeolite filter medium, when filtration rate was 5 mg/l, NH4 + removal efficiency was 95–99.9 %. Ammonium ion removal from shallow‐well water and NH4Cl solution (primary concentration was 10 mg/l) under dynamic conditions, filtered through 95 mm high, 0.315–0.63 mm particle‐sized zeolite filter medium, when filtration rate was 3 mg/l, NH4 + removal in filtered water samples decreased with exponential dependency. The obtained results show that zeolite particles are not suitable for nitrate sorption from water solutions, but 0.315–0.63 mm particle‐sized zeolite can be a very useful sorbent for NH4 + removal from water because of the above mentioned reasons, therefore, further investigations are needed in this area. Santrauka VGTU Vandentvarkos katedros laboratorijoje vykdyti eksperimentiniai azoto junginių (nitratų bei amonio jonų) šalinimo iš vandens, naudojant gamtinius ceolitus, tyrimai. Iš kelių Vilniaus mieste ir rajone esančių šachtinių šulinių paimti vandens mėginiai. Nitratų koncentracijos juose padidėjo pridėjus NaNO3. Nitratai šalinti iš vandeninių tirpalų statiniu būdu, tirpalus (kuriuose nitratų koncentracijos siekė 74–288 mg/l) 1 h maišant su 5 g 0,315 mm stambumo ceolito grūdelių frakcija automatinėje maišyklėje 100 aps./min intensyvumu ir po 30 min nusodinimo išmatuojant juose nitratų koncentraciją. Amonio jonų šalinimas iš vandeninių tirpalų (kurie buvo pasigaminti iš šachtinio šulinio ir vandentiekio vandens pridedant NH4Cl) atliktas statiniu ir dinaminiu būdu (filtruojant vandens tirpalus, kuriuose amonio jonų koncentracijos siekė 10–15 mg/l, per 0,315–0,63 mm ceolito grūdelių užpildo sluoksnį). Eksperimentų rezultatai parodė, kad, maišant šachtinio šulinio vandenį (kuriame nitratų koncentracijos buvo 74–288 mg/l) vieną valandą su 5 g 0,315 mm grūdelių stambumo ceolito frakcija, po 30 min tirpalams nusistovėjus, nustatyta, kad nitratų koncentracija juose nesumažėjo. Tokiu pat būdu maišant šachtinio šulinio vandenį (kuriame amonio jonų koncentracijos buvo 1–10 mg/l) su 5 g 0,315–0,63 mm grūdelių stambumo ceolito frakcija, nustatyta, kad amonio jonų šalinimo efektyvumas mėginiuose siekė 72–86 %. Šalinant amonio jonus iš vandentiekio vandens ir NH4Cl tirpalo (pradinė koncentracija 15 mg/l) dinaminiu būdu, filtruojant per 400 mm aukščio 0,315–0,63 mm stambumo ceolito grūdelių užpildą 5 m/h greičiu, NH4 + šalinimo efektyvumas siekė 95–99,9 %. Šalinant amonio jonus iš šachtinio šulinio vandens ir NH4Cl tirpalo (pradinė koncentracija 10 mg/l) dinaminiu būdu, filtruojant per 95 mm aukščio 0,315–0,63 mm stambumo ceolito grūdelių užpildą 3 m/h greičiu, NH+ 4 koncentracija filtrato mėginiuose mažėjo pagal eksponentinę priklausomybę. Gauti rezultatai parodė, kad ceolito grūdeliai netinka nitratų sorbcijai iš vandeninių tirpalų, bet 0,315–0,63 mm stambumo ceolito grūdelių frakcija galėtų būti ypač tinkamas sorbentas NH+ 4 šalinti iš vandens, todėl būtų tikslinga atlikti daugiau tyrimų šioje srityje. Резюме Экспериментальные исследования очистки воды от азотосодержащих соединений (нитратов и аммония) с применением природного цеолита были проведены в лаборатории кафедры водоснабжения Вильнюсского технического университета им. Гедиминаса. Для этой цели использовалась вода из нескольких шахтных колодцев, находящихся в г. Вильнюсе и его районе, концентрация нитратов была увеличена, дозируя NaNO3. Очистка водных растворов от нитратов производилась статическим методом, растворы (концентрация нитратов составляла 74–288 мг/л) в течение часа смешивали с 5 г цеолита (фракция – до 0,315 мм) автоматической мешалкой при интенсивности 100 об/мин. После 30 мин отстаивания определялась концентрация нитратов. Очистка от аммония водных растворов, полученных из воды шахтных колодцев и водопроводной воды с добавлением NH4Cl, производилась статическим и динамическим методами (водные растворы, в которых концентрация аммония достигала 10–15 мг/л, фильтрировались через загрузочный материал из цеолита с фракцией 0,315–0,63 мм). Результаты эксперимента показали, что концентрация нитратов в растворах не уменьшилась, когда воду из шахтных колодцев, в которых концентрация нитратов достигала 74–288 мг/л, смешивали в течение часа с 5 г цеолита, фракция которого составляла 0,315 мм, и отстаивали в течение 30 мин. При смешивании воды из шахтного колодца, в котором концентрация аммония достигала 10–15 мг/л, с 5 г цеолита, фракция которого составляла 0,315–0,63 мм, эффективность очистки от аммония достигала 72–86 %. При очистке водопроводной воды с раствором NH4Cl от аммония, концентрация которого составляла 15 мг/л, в динамических условиях, фильтруя через загрузочный материал высотой в 400 мм и фракцией 0,315–0,63 мм со скоростью 5 м/ч, эффективность очистки достигала 95–99,9 %. При очистке воды из шахтных колодцев с раствором NH4Cl от аммония (концентрация составляла 10 мг/л) в динамических условиях, фильтруя через загрузочный материал высотой в 95 мм со скоростью 3 м/ч, концентрация NH4 + в фильтрате уменьшалась с закономерностью экспонентной функции. Полученные результаты показали, что загрузка цеолита не способствует сорбции нитратов из водных растворов, в то время как цеолит с фракцией в 0,315–0,63 мм может быть приемлемым сорбентом для очистки воды от NH4 + , поэтому целесообразно проведение дополнительных исследований.
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Agbodan, Kokou Agbékonyi, Oudjaniyobi Simalou, Gneiny Whad Tchani, and Koffi Jondo. "Etude de l’influence de la basicité sur l’enthalpie de réaction des sels N-méthoxycarbonyl-(oxy)-pyridiniums." International Journal of Biological and Chemical Sciences 14, no. 4 (August 17, 2020): 1489–98. http://dx.doi.org/10.4314/ijbcs.v14i4.26.
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Les hétérocycles sont importants, aussi bien dans les domaines biologique, médicinal et thérapeutique (vitamines, hormones, antibiotiques, etc), que dans le secteur industriel et technologique (inhibiteurs de corrosion, colorants, agents stabilisants, pesticides, herbicides. Les chloroformiates ou chlorocarbonates sont les esters dérivés de l’acide chloroformique. La chimie des N-oxydes hétérocycliques (pyridine et N-oxydes) a connu un important développement au cours des dernières années. L’objectif principal du présent travail est l’étude de l’action du métoxycarbonylchloride sur la pyridine et certains de ses dérivés. Après avoir trouvé les conditions optimales, de nouveaux composés à base de pyridine ont été synthétisés. En remplaçant l’ion chlorure par d’autres ions, les produits synthétisés ont été cristallisés avec un bon rendement. La structure des produits a été caractérisée à l’aide de la spectroscopie infra rouge et la résonnance magnétique nucléaire. Spécifiquement, l’influence de la basicité du noyau hétérocyclique sur les enthalpies de formation des sels produits a été étudiée. En conclusion, la réaction chimique de formation est exothermique avec ΔH° < 0 pour tous les sels étudiés. En utilisant les constantes de Hammett sur le noyau de la pyridine, l’étude a monté que ces chaleurs de réaction dépendent de la basicité du noyau hétérocyclique. En perspective on peut envisager une étude de l’influence de la basicité des différents noyaux pyridiniques sur les effets de conjugaison polaire directe sur le groupe azoté dans les sels N-méthoxycarbonyl-(oxy)-pyridiniums.Mots clés: Pyridine N-Oxyde, chloroformiates, synthèse, constante de Hammett.
English Title: Study of the influence of basicity on the enthalpy of reaction of N-methoxycarbonyl- (oxy) -pyridinium salts
Heterocycles are important, as well in the biological, medicinal and therapeutic fields (vitamins, hormones, antibiotics, etc.), as in the industrial and technological sector (corrosion inhibitors, dyes, stabilizing agents, pesticides, herbicides). Chloroformates or chlorocarbonates are esters derived from chloroformic acid. The chemistry of heterocyclic N-oxides (pyridine and N-oxides) has experienced significant development in recent years. The main objective of this work is to study the action of metoxycarbonylchloride on pyridine and some of its derivatives. After finding the optimal conditions, new pyridine-based compounds were synthesized. By replacing the chloride ion with other ions, the synthesized products have been crystallized with good yield. Specifically, the influence of the basicity of the heterocyclic nucleus on the enthalpies of salt formation produced has been studied. The enthalpies formation of salt produced have been determined. In conclusion, the chemical reaction of formation is exothermic with ΔH ° < 0 for all the salts studied. Using Hammett's constants on the pyridine nucleus, the study has shown that these reaction heats depend on the basicity of the heterocyclic nucleus. In perspective, we can study the influence of the basicity of the different pyridine rings on the effects of direct polar conjugation on the nitrogen group in the N-methoxycarbonyl- (oxy) -pyridinium salts.Keywords: Pyridine N-Oxide, chloroformates, synthesis, Hammett constant.
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"Industry Watch." Asia-Pacific Biotech News 14, no. 03 (March 2010): 35–49. http://dx.doi.org/10.1142/s0219030310000157.
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Mesoblast Limited Key Bone Repair Patent Granted In The United States. Lilly to Acquire Global License to AXIRON Testosterone Solution from Acrux Tools. China Cord Blood Corporation Acquires Stake in Shandong Cord Blood Bank. AutekBio to Build Largest Biologic CMO in Asia. 3SBio, Ascentage Pharma to Jointly Develop Cancer Therapeutics. SIRO Clinpharm Forms Alliance with Korean CRO DreamCIS. Ceragenix Enters into Agreement with Korea's BexPharm. SRL Launches Sports Gene Test for the First Time in India. Fortis Acquires Stake in Singapore's Parkway Holdings. Sony Enters the Flow Cytometry Business in Life Science Field by Acquiring iCyt. AMPAC Fine Chemicals Partners With Inabata & Co., Ltd. of Japan. Astellas Entered into Global Partnership with Basilea for an Azole Antifungal Agent Isavuconazole. Medicago, NITT to Develop Vaccine in Japan. Millipore Launches New Water Purification System for Ion Chromatography.
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Lütjohann, Dieter, Frans Stellaard, Anja Kerksiek, Jörn Lötsch, and Bruno G. Oertel. "Serum 4β-hydroxycholesterol increases during fluconazole treatment." European Journal of Clinical Pharmacology, November 17, 2020. http://dx.doi.org/10.1007/s00228-020-03041-5.
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Abstract Purpose The antifungal drugs ketoconazole and itraconazole reduce serum concentrations of 4β-hydroxycholesterol, which is a validated marker for hepatic cytochrome P450 (CYP) 3A4 activity. We tested the effect of another antifungal triazole agent, fluconazole, on serum concentrations of different sterols and oxysterols within the cholesterol metabolism to see if this inhibitory reaction is a general side effect of azole antifungal agents. Methods In a prospective, double-blind, placebo-controlled, two-way crossover design, we studied 17 healthy subjects (nine men, eight women) who received 400 mg fluconazole or placebo daily for 8 days. On day 1 before treatment and on day 8 after the last dose, fasting blood samples were collected. Serum cholesterol precursors and oxysterols were measured by gas chromatography-mass spectrometry-selected ion monitoring and expressed as the ratio to cholesterol (R_sterol). Results Under fluconazole treatment, serum R_lanosterol and R_24,25-dihydrolanosterol increased significantly without affecting serum cholesterol or metabolic downstream markers of hepatic cholesterol synthesis. Serum R_4β-, R_24S-, and R_27-hydroxycholesterol increased significantly. Conclusion Fluconazole inhibits the 14α-demethylation of lanosterol and 24,25-dihydrolanosterol, regulated by CYP51A1, without reduction of total cholesterol synthesis. The increased serum level of R_4β-hydroxycholesterol under fluconazole treatment is in contrast to the reductions observed under ketoconazole and itraconazole treatments. The question, whether this increase is caused by induction of CYP3A4 or by inhibition of the catabolism of 4β-hydroxycholesterol, must be answered by mechanistic in vitro and in vivo studies comparing effects of various azole antifungal agents on hepatic CYP3A4 activity.
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GENÇOĞLU, Hıdır, Çağdaş KARA, Mukaddes Merve EFİL, Hakan BİRİCİK, İbrahim İsmet TÜRKMEN, Gülay DENİZ, Arda KOVANLIKAYA, Randy Duncan SHAVER, Recep Tolga KIVANÇ, and Ramazan YILDIRIM. "Düşük Nişastalı Rasyonlarla Beslenen Geçiş Dönemindeki İneklerde Amilaz Enziminin Etkisi: 2. Toplam Sindirilebilirlik ve Kan Üre Azotu." Kafkas Universitesi Veteriner Fakultesi Dergisi, 2019. http://dx.doi.org/10.9775/kvfd.2018.21401.
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AYHAN, Veysel, Ibrahim DILER, Muhammet ARABACI, and Hüseyin SEVGILI. "Soya Küspesi Temeline Dayalı Çipura (Sparus aurata) Yemlerine Enzim İlavesi: Azot-Fosfor Atılımı ve Büyüme Özellikleri Üzerine Etkileri." Kafkas Universitesi Veteriner Fakultesi Dergisi, 2008. http://dx.doi.org/10.9775/kvfd.2008.33-a.
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Nizhenkovska, І. V., O. V. Romanenko, K. V. Sedko, M. M. Hrusha, V. S. Brovarets, and O. V. Holovchenko. "ВПЛИВ БЛОКАДИ Ш-СИНТАЗИ НА ВАЗОДИЛАТАЦІЙНИЙ ЕФЕКТ ДІЕТИЛОВОГО ЕСТЕРУ 5-АЛКІЛАМІНО-2-{М-[М-БЕНЗОЇЛ-(4-МЕТИЛБЕНЗИЛІДЕН) ГЛІЦИЛ] АМІНОМЕТИЛ}-1,3-ОКСАЗОЛ-4-ІЛФОСФОНОВОЇ КИСЛОТИ НА СЕГМЕНТАХ ІЗОЛЬОВАНОЇ АОРТИ ЩУРІВ." Фармацевтичний часопис, no. 4 (January 19, 2016). http://dx.doi.org/10.11603/2312-0967.2015.4.5557.
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<p align="center"><strong>INFLUENCE</strong><strong> </strong><strong>OF</strong><strong> </strong><strong>NO</strong><strong> - </strong><strong>SYNTHASE</strong><strong> </strong><strong>BLOCKADE</strong><strong> </strong><strong>ON</strong><strong> </strong><strong>VASODILATORY</strong><strong> </strong><strong>EFFECT</strong><strong> </strong><strong>OF</strong><strong> </strong><strong>DIETHYL</strong><strong> </strong><strong>ESTER</strong><strong> </strong><strong>OF</strong><strong> 5-</strong><strong>ALKILAMINE</strong><strong>-2-{</strong><strong>N</strong><strong>-[</strong><strong>N</strong><strong>-</strong><strong>BENZOYL</strong><strong>-(4-</strong><strong>METHYLBENZILIDEN</strong><strong>) </strong><strong>GLYCYL</strong><strong>] </strong><strong>AMINOMETHYL</strong><strong>}- 1,3 -</strong> <strong>OXASOL</strong><strong>-4-</strong><strong>YLPHOSPHONIC</strong><strong> </strong><strong>ACID</strong> <strong>ON</strong><strong> </strong><strong>RAT</strong><strong>’</strong><strong>S</strong><strong> </strong><strong>ISOLATED</strong><strong> </strong><strong>AORTA</strong><strong> </strong><strong></strong></p><p align="center"><strong>I</strong><strong>.</strong><strong>V</strong><strong>. </strong><strong>Nizhenkovska</strong><strong><sup>1</sup></strong><strong>, </strong><strong>A</strong><strong>.</strong><strong>V</strong><strong>. </strong><strong>Romanenko</strong><strong><sup>1</sup></strong><strong>, </strong><strong>K</strong><strong>.</strong><strong>V</strong><strong>. </strong><strong>Sedko</strong><strong><sup>1</sup></strong><strong>, </strong><strong>M</strong><strong>.М. Grusha<sup>1</sup>, V.S. Brovarets<sup>2</sup>, A.V.<em></em> Golovchenko<sup>2<em></em></sup></strong></p><p align="center"><sup>1</sup> Bogomolets National Medical University</p><p align="center"><em><sup>2 </sup></em>Institute of Bioorganic Chemistry and Petrochemistry at NAS of Ukraine</p><p> </p><p>Essential hypertension, hypertensive heart disease, secondary hypertension and related diseases caused by them are the result of a lot of pathological changes in the cardiovascular system. One of the main mechanisms which affects the blood pressure is increasing of the tone of smooth muscle vascular wall component.</p><p>A significant number of endogenous vasodilators exert their activity by mechanisms which are directly or indirectly related to the production of nitric oxide by endothelial cells, so the effects associated with its release, is a target for pharmacological correction of muscle tone in clinical practice.</p><p>Previously, it was found that phosphorylated peptidomimetics, which are derivatives of 1,3-oxazole, have vasodilatative effects. However, the contribution of mechanisms of NO production and its release on vasotropic action of these compounds was not researched. That`s why the aim of our experiment was to study the vasodilatative effects of new synthesized derivative of 1,3-oxazole - diethyl ester of 5-alkilamine-2-{N-[N-benzoyl-(4-methylbenziliden) glycyl] aminomethyl}- 1,3 - oxasol-4-ylphosphonic acid (oxazole containing peptidomimetic) on rat’s isolated aorta on the background of the NO-synthase blockade.</p><p>For experiment it was used isolated segments (n=5) of the thoracic descending aorta of Wistar rats with average weight 200-250 g. Received aortic segments before the experiment were kept at least 30 minutes at a temperature 35-37 °C in Krebs solution. To register the tone of aortic segments it was used installation consisting of a flow chamber (volume - 2 ml) at 36,5 °C.</p><p>Vasodilatative activity of the compound was estimated by the effect on basal tone and amplitude of smooth muscle contraction of blood vessels in response to the including of α<sub>1</sub>-adrenoreceptor agonist -adrenalin (5•10<sup>-6</sup> M) in the incubation medium. In assessing the effectiveness of vasoactive impact of the researched substance as 100% was taken the amplitude of tonic contraction of muscle in control in response to adrenaline (5•10<sup>-6</sup> M) application for 10 sec.</p><p>Average amplitude of adrenoreaction in control was 3,34 ± 1,07 mN. Adding of NO-synthase blocker - L-NAME (1•10<sup>-4</sup> M) to Krebs solution had not an effect on basal tone of smooth muscles isolated segment of the thoracic descending aorta. However, the adding of L-NAME (1•10<sup>-4</sup> M) to perfusate caused increasing the amplitude of adrenoreaction on 71% from baseline on 90th minute. The received changes in the amplitude are probably related to the blockade by L-NAME of NO production and release, and reducing the effect of vasodilatative component in providing the vascular reactivity to the action of α<sub>1</sub>-adrenergic receptors agonist - adrenaline (5•10<sup>-6</sup> M).</p><p>Additional including of oxazole containing peptidomimetic (1•10<sup>-5</sup> M) to perfusate, after 30 minutes from beginning of application caused the amplitude reduction of adrenoreaction by 33% comparatively with its amplitude in conditions of only L-NAME (1•10<sup>-4</sup> M) presence in the perfusate.</p><p>The effect, which was caused by the including of oxazole containing peptidomimetic (1•10<sup>-5</sup> M) to Krebs solution, was reversible. Within 30 min after removing of the last substance of perfusate, amplitude of adrenoreaction increased by 26% comparatively with its amplitude in conditions of simultaneous presence both of these compounds in solution. L-NAME removing of Krebs solution lead to regular amplitude decreasing of adrenoreaction.</p><p>Experiments, conducted by using isolated segments of the rat`s thoracic descending aorta give reason to consider that diethyl ester of 5-alkilamine-2-{N-[N-benzoyl-(4-methylbenziliden) glycyl] aminomethyl}- 1,3 - oxasol-4-ylphosphonic acid (1•10<sup>-5</sup> M) is able to keep its vasodilatative properties in conditions of NO-synthase blockade. The fact of saving of oxazole containing peptidomimetic effective action on the background of NO-synthase blockade by L-NAME (1•10<sup>-4</sup> M) shows that vasodilatative effect of these two compounds is realized through various targets. 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