Сравнительный анализ экспериментальной фармакокинетики новых нейротропных пептидных лекарственных средств

Experimental pharmacokinetics of new pharmacologically active peptides, modified analogues of endogenous neuropeptides, has been investigated in rats and rabbits. The study icluded 3 new drugs: (i) the nootropic drug noopept (phenylacetyl-prolyl-glycine ethyl ester); (ii) dilept (N-caproyl-L-prolyl-L-tyrosine methyl ester) – the antipsychotic with positive mnemotropic action; (iii) compound GB-115 – selective anxiolytic (phenylhexanoyl-prolyl-tryptophan amide). Differences in pharmacokinetics and biotransformation of the studied drugs depended on their structural features. The ether derivatives noopept and dilept underwent intensive metabolism by rat gastrointestinal esterases and peptidases with the formation of active metabolites. Being an amide, the compound GB-115 was more resistant to the enzymatic effects of peptidases and was detected for a longer period in the blood of experimental animals. In rabbits the studied compounds were less exposed to the enzymatic action by gastrointestinal peptidases, and were detected plasma of rabbits for a longer period. The higher stability of the compounds studied in rabbits may be attributed not only to the structural features of the studied dipeptides, but also to differences in the activity of the enzymatic systems of the gastrointestinal tract participating in their metabolism, as well as differences in the rate of hepatic and renal blood flow in rats and rabbits.Приведены результаты изучения сравнительной экспериментальной фармакокинетики и метаболизма новых фармакологически активных лекарственных средств (ЛС) пептидной природы у животных 2 видов (крысы, кролики). Объектами исследований были 3 новых ЛС: (i) ноотропный препарат ноопепт – этиловый эфир фенилацетил-пролил-глицина; (ii) антипсихотик с положительным мнемотропным действием дилепт – метиловый эфир N-капроил-L-пролил-L-тирозина; (iii) селективный анксиолитик – соединение ГБ-115 – амид фенилгексаноил-пролил-триптофана. Установлены различия фармакокинетики и биотрансформации изучаемых ЛС в зависимости от структурных особенностей субстанций этих соединений. Установлено, что эфирные производные ноопепт и дилепт подвергаются интенсивному метаболизму в организме крыс под влиянием эстераз и пептидаз ЖКТ с образованием активных метаболитов. Соединение ГБ-115, являющееся амидом, более устойчиво к энзиматическому воздействию пептидаз и более продолжительное время определяется в крови экспериментальных животных в неизмененном виде. В организме кроликов изучаемые соединения в меньшей степени подвергаются энзиматическому воздействию со стороны пептидаз ЖКТ и более продолжительное время определяются в плазме крови этих животных в неизмененном виде, что связано не только со структурными особенностями изучаемых дипептидов, но и различиями активности энзиматических систем ЖКТ, принимающих участие в их метаболизме, а также с различиями в скорости печеночного и почечного кровотока у крыс и кроликов

Spectrum of confining strings in SU(N) gauge theories

We study the spectrum of the confining strings in four-dimensional SU(N) gauge theories. We compute, for the SU(4) and SU(6) gauge theories formulated on a lattice, the string tensions sigma_k related to sources with Z_N charge k, using Monte Carlo simulations. Our results are consistent with the sine formula sigma_k/sigma = sin k pi/N / sin pi/N for the ratio between sigma_k and the standard string tension sigma. For the SU(4) and SU(6) cases the accuracy is approximately 1% and 2%, respectively. The sine formula is known to emerge in various realizations of supersymmetric SU(N) gauge theories. On the other hand, our results show deviations from Casimir scaling. We also discuss an analogous behavior exhibited by two-dimensional SU(N) x SU(N) chiral models.Comment: Latex, 34 pages, 10 figures. Results of new SU(4) simulations added. The new data are included in the analysis, leading to improved final estimates for SU(4). Conclusions unchange

Definition of recessive mutations of Blad, Cvm and Bs in population of cattle of the lactic direction of Republic of Belarus

Intensive selection on increase in lactic efficiency, and use of import genetic material in breeding livestock production of Republic of Belarus led to distribution of genetic mutations, which cause death, and frailty of young growth. Detection of genetic anomalies at animals is obligatory, without exception at them lethal mutations sale of breeding bull-calves is impossible. Molecular and genetic methods allow revealing genetic anomalies at the level of DNA such as CVM, BLAD, BS at early age. Identification of undesirable alleles will allow excluding from process of reproduction of carriers of diseases and a message selection on an elimination of mutations. In work, the technique of definition of recessive mutations is pr esented to populations of cattle of the lactic direction of Republic of Belarus. The characteristic of genetic structure of the studied population is given.Интенсивная селекция на увеличение молочной продуктивности, а также использование импортного генетического материала в племенном животноводстве Республики Беларусь привела к распространению генетических мутаций, которые вызывают гибель и нежизнеспособность молодняка. Выявление генетических аномалий у животных обязательно, т.к. без исключения у них летальных мутаций продажа племенных бычков невозможна. Молекулярно-генетические методы позволяют выявлять генетические аномалии на уровне ДНК, такие как CVM, BLAD, BS в раннем возрасте. Выявление нежелательных аллелей позволит исключить из процесса воспроизводства носителей заболеваний и вести селекцию на элиминацию мутаций. В статье представлена методика определения рецессивных мутаций у животных белорусской черно-пестрой породы и популяции голштинизированного черно-пестрого скота Республики Беларусь. Дана характеристика генетической структуры изучаемой популяции

Identification of the allosteric P2X7 receptor antagonist [11C]SMW139 as a PET tracer of microglial activation

The P2X7 receptor plays a significant role in microglial activation, and as a potential drug target, the P2X7 receptor is also an interesting target in positron emission tomography. The current study aimed at the development and evaluation of a potent tracer targeting the P2X7 receptor, to which end four adamantanyl benzamide analogues with high affinity for the human P2X7 receptor were labelled with carbon-11. All four analogues could be obtained in excellent radiochemical yield and high radiochemical purity and molar activity, and all analogues entered the rat brain. [11C]SMW139 showed the highest metabolic stability in rat plasma, and showed high binding to the hP2X7 receptor in vivo in a hP2X7 receptor overexpressing rat model. Although no significant difference in binding of [11C]SMW139 was observed between post mortem brain tissue of Alzheimer's disease patients and that of healthy controls in in vitro autoradiography experiments, [11C]SMW139 could be a promising tracer for P2X7 receptor imaging using positron emission tomography, due to high receptor binding in vivo in the hP2X7 receptor overexpressing rat model. However, further investigation of both P2X7 receptor expression and binding of [11C]SMW139 in other neurological diseases involving microglial activation is warranted

Морфобіологічні особливості Davidia involucrata Baill. var. vilmoriniana (Dode) Wagner i Camptotheca acuminata Decne

The results of the comparative study two species woody ornamental plants. (Davidia involucrata Baill. var. vilmoriniana (Dode) Wagner and Camptotheca acuminata Decne) in the conditions of the introduction of the South coast of the Crimea in connection with the systematic position are shown. The specific morpho-biological peculiarities of every species, which confirmative their taxonomic belonging, are revealed.Представлено результати порівняльного вивчення двох видів деревних декоративних рослин (Davidia involucrata Baill. var. vilmoriniana (Dode) Wagner і Camptotheca acuminata Decne) в умовах інтродукції на Південному березі Криму й у зв'язку з їх систематичним положенням. Виявлено специфічні морфобіологічні особливості, властиві кожному з цих видів, що підтверджують їх таксономічну належність

Monitoring of the sensitivity of epidemic influenza virus strains isolated in Russia to etiotropic chemical agents

The paper presents the results of studying the spectrum of influenza A and ? virusee to rimantadine, arbidol, and oseitamivir and describes the methods used for these purposes for epidemiological surveillance. Different sensitivities to rimantadine were found among influenza A viruses During the 2007-2008 season, the vast majority of influenza A(H3N2) virus strains were resistant to rimantadine (77%) while all influenza A(H1N1) virus strains preserved their resistance to this drug. The fact that the epidemic Influenza A(H1N1) virus strains that cany the mutation responsible for resistance to the neuraminidase inhibitor oseitamivir (Tamiflu) circulated in the Russian Federation was first established. At the same time ail the study influenza A(H1N1) virus strains preserved their susceptibility to rimantadine. The sensitivity of the epidemic strains to arbidol has been confirmed

Monitoring of the sensitivity of epidemic influenza virus strains isolated in Russia to etiotropic chemical agents

The paper presents the results of studying the spectrum of influenza A and ? virusee to rimantadine, arbidol, and oseitamivir and describes the methods used for these purposes for epidemiological surveillance. Different sensitivities to rimantadine were found among influenza A viruses During the 2007-2008 season, the vast majority of influenza A(H3N2) virus strains were resistant to rimantadine (77%) while all influenza A(H1N1) virus strains preserved their resistance to this drug. The fact that the epidemic Influenza A(H1N1) virus strains that cany the mutation responsible for resistance to the neuraminidase inhibitor oseitamivir (Tamiflu) circulated in the Russian Federation was first established. At the same time ail the study influenza A(H1N1) virus strains preserved their susceptibility to rimantadine. The sensitivity of the epidemic strains to arbidol has been confirmed

Unbiased and efficient Greeks of financial options

Option pricing, Rainbow options, Path-dependent options, Monte Carlo simulation, Greeks, Importance sampling, 65C05, 65D25, 65L12, C02, C15, G13,