Ukraine data on prognostic factors and treatment outcomes in patients with peripheral t-cell lymphomas

Background: Peripheral T-cell lymphomas (PTCLs) is a diverse group of lymphomas (10-15% of all non-Hodgkin’s lymphomas) with aggressive behavior. Despite the standard of 1st line anthracycline-contain ingregimens, clinical outcomes are poor compared to B-cell lymphomas. In addition, there are still debates about specific prognostic factors (PF) in PTCLs. Aims: Primary endpoints -event-free survival (EFS) and over all survival (OS). To evaluate the prognostic significance of five PTCLs scores (International Prognostic Index -IPI, International Peripheral T-cell lymphoma Project Score -IPTCL, Prognostic Index for T-cell lymphoma -PIT, modified Prognostic Index for T-cell lymphoma -mPIT and T-cell score). Patients and methods: From 67 enrolled patients, only 50 were included: PTCL not otherwise specified (22, 44%), anaplastic large cell lymphoma ALK+ (anaplastic lymphoma kinase-positive) (10, 20%) and ALK− (anaplastic lymphoma kinase-negative) (18, 36%). Patients received CHOP-like regimens (CHOP, CHOEP, EPOCH). Results: The over all rate response was observed in 66% of cases (complete response 78%). There were 48% of relapses after the 1st line therapy during follow-up (median 11 months; range 1-85 months). Median age 57 (range 22-80) with male predominance 62%. In total, 40% of patients were > 60 years old, 48% had stage III-IV. Majority of patients were assessed by five prognostic scores. IPI (45 patients): The 3-year EFS and OS were higher for IPI ≤ 1 vs. IPI > 2 (80 vs. 18% and 87 vs. 27%, respectively; p = 0.0002). Receiver operating characteristic analysis confirmed poor clinical outcome to patients with PF > 1 (Se = 88 %; Sp = 68 %; AUC = 0.7; p = 0.0081). IPTCLP (41 patients): The presence of PF = 1-2 showed EFS and OS reduction. A 3-year EFS rate for 1-2 PF was 25 vs. 70% for PF = 0 (p = 0.003). Thus, 3-year OS in patients with PF = 0 vs. PF = 1-2 was 100 vs. 20% (p = 0.0001). PIT (42 patients): Better 3-year EFS and OS in patients with PF = 0 vs. PF = 1-3 (88 vs. 28% and 100 vs. 34%, respectively, p = 0.001). Patients with PF = 1-3 have a higher rate of relapses vs. PF = 0 (p = 0.0005 by Cox-test). mPIT (21 patients): No significant difference between PF and clinical outcomes. T-cell score (18 patients): Higher survival rates with PF ≤ 2. More than 2 PF have an impact on EFS (p = 0.005). The 3-years OS in patients with PF ≤ 2 was 77 vs. 25% in cases with PF ≥ 3 (p = 0.001). Conclusion: IPI, PIT, IPTCLP are still very useful in defining risk stratification. As to mPIT and T-cell score, more patients to evaluate their prognostication possibility are needed

Catalytic molecularly imprinted polymer membranes: Development of the biomimetic sensor for phenols detection

Portable biomimetic sensor devices for the express control of phenols content in water were developed. The synthetic binding sites mimicking active site of the enzyme tyrosinase were formed in the structure of free-standing molecularly imprinted polymer membranes. Molecularly imprinted polymer membranes with the catalytic activity were obtained by co-polymerization of the complex Cu (II)–catechol–urocanic acid ethyl ester with (tri)ethyleneglycoldimethacrylate, and oligourethaneacrylate. Addition of the elastic component oligourethaneacrylate provided formation of the highly cross-linked polymer with the catalytic activity in a form of thin, flexible, and mechanically stable membrane. High accessibility of the artificial catalytic sites for the interaction with the analyzed phenol molecules was achieved due to addition of linear polymer (polyethyleneglycol Mw 20,000) to the initial monomer mixture before the polymerization. As a result, typical semi-interpenetrating polymer networks (semi-IPNs) were formed. The cross-linked component of the semi-IPN was represented by the highly cross-linked catalytic molecularly imprinted polymer, while the linear one was represented by polyethyleneglycol Mw 20,000. Extraction of the linear polymer from the fully formed semi-IPN resulted in formation of large pores in the membranes’ structure. Concentration of phenols in the analyzed samples was detected using universal portable device oxymeter with the oxygen electrode in a close contact with the catalytic molecularly imprinted polymer membrane as a transducer. The detection limit of phenols detection using the developed sensor system based on polymers–biomimics with the optimized composition comprised 0.063 mM, while the linear range of the sensor comprised 0.063–1 mM. The working characteristics of the portable sensor devices were investigated. Storage stability of sensor systems at room temperature comprised 12 months (87%). As compared to traditional methods of phenols detection the developed sensor system is characterized by simplicity of operation, compactness, an

Providence Independent, V. 8, Thursday, December 14, 1882, [Whole Number: 392]

[4] p. “Persistent in the Right – Fearless in Opposing Wrong.” Newspaper published in Trappe, Pa. Weekly. Contains local, national and international news, fiction and advertisements.https://digitalcommons.ursinus.edu/providence/1172/thumbnail.jp

АТP as the marker of power exchange condition at the experimental ischemia of the myocardium due to metabolic drugs introduction

For the purpose of definition of an adequate marker of a power exchange condition at the experimental ischemia of the myocardium due introduction of metabolic drugs, the experimental research on 60 rats-males of Wistar line has been spent. At experimental myocardial ischemia it has been found out energy-saving effects of trimetazidine, cytoflavin, meldonium, phosphocreatine, which were reached by different ways and in different degre

Comparison of the Methods for Determining Pyrogenically Modified Carbon Compounds

The soil organic matter (SOM) is searched for the biomarkers and specific features associated with the effect of wildfires by the case study of peat soil, Rheic Hemic Histosol (Lignic), in the south of the middle taiga of the Komi Republic. It is shown that fires considerably influence the peat organic matter. Pyrogenic activity is assessed according to the content of charcoal particles. SOM is examined using solid-state 13C-NMR spectroscopy to determine the concentrations of polycyclic aromatic hydrocarbons (PAHs) and benzene polycarboxylic acids (BPCAs). The used methods allow for diagnosing the effects of wildfires on the SOM composition. In the horizons with the signs of pyrogenesis, the share of carbon represented by aromatic fragments increases as well as the PAH concentration, mainly at the expense of naphthalene, phenanthrene, and chrysene. The carbon stock of pyrogenically modified compounds, amounting to 4.4 kg/m2, is for the first time assessed in the European north based on the BPCA content. The characteristics of pyrogenically changed organic compounds and their fragments obtained by different methods correlate well: the Pearson coefficient for the correlation of the carbon content in aromatic compounds (Caryl) with total BPCA content is R = 0.84 (p < 0.05) and with individual BPCAs, R = 0.81–0.90 (p < 0.05)

Transformation of Optical Vortices by Polarization Dynamic Holograms

Results of theoretical and experimental studies of regularities in the transformation of the topological and polarization structures of optical vortices by polarization dynamic holograms formed by pulse Gaussian and singular light beams in dye solutions are presented

Преобразование сингулярных световых пучков при невырожденном четырехволновом взаимодействии в растворах красителей

An analysis of a frequency transformation of singular light beams by the dynamic hologram at a frequency nondegenerated four-wave mixing in dye solutions has been carried out. The transformation of optical vortices of the first and second order from the infrared spectrum to the visible one has been demonstrated experimentally with simultaneous inversion of the topological charge

Ноотропні властивості тетрапептиду acetyl-(D-lys)-lys-arg-arg-amide (KK-1) на моделі хвороби альцгеймера у щурів, зумовленої хронічним введенням скополаміну

Improvement of Alzheimer’s disease (AD) therapy is one of the most important tasks of the modern medicine and pharmacy. Creation and the pharmacological study of the original medicines for treating AD are promising. The most promising class of these drugs is neuroprotectors. In the Research Institute of Highly Pure Biopreparations the tetrapeptide acetyl-(D-Lys)-Lys-Arg-Arg-amide (the laboratory code – KK-1) has been synthesized. Under the conditions of the pre-clinical study it has demonstrated the pronounced neuroprotective and nootropic properties on the model of cerebral ischemia. The aim of the current work is to study the nootropic properties of KK-1 on the model of AD in rats. The scopolamine-induced AD in rats was reproduced. For 10 days the rats with AD model were treated with KK-1 (0.1 mg/kg intranasally once a day) or with the reference medicine donepezil (1 mg/kg orally once a day). After the therapy the functional state of the rats’ CNS was evaluated using the open-field test (OFT), extrapolation escape task (EET) and the test of the conditioned reflex of passive avoidance (CRPA). The level of acetylcholine (Ach) and the activity of acetylcholinesterase (ACE) were measured using spectrophotometry in the whole brain homogenate and brain synaptosoms. The peptide KK-1 studied reduced the stress-related anxiety in OFT in rats, increased their exploratory activity (by 1.4 times, р&lt;0.05 compared to the pathology group) and decreased the emotional response on the stress (by 44%, р&lt;0.05). In EET the tetrapeptide KK-1 stimulated the rats’ cognitive functions, decreased the time of escape by 4.7 times (р&lt;0.05 compared to the pathology group). Under the conditions of the CRPA test the high anti-amnestic activity of KK-1 was found (56.5% on the 1st day after the therapy and 81.5% on the 10th day). According to all indices the activity of KK-1 exceeded the reference medicine donepezil. The mechanism of the KK-1 nootropic action is in the increase of the Ach level in the rats’ brain synaptosoms probably due to stimulation of its synthesis. The peptide KK-1 moderately inhibits the ACE leading also to the Ach level increase in the cholinergic synapse synaptic cleft. It is likely that the peptide KK-1 has an effect on the Gq/G11-peptide-coupled M1-, M3-, and M5-cholinergic receptors as a positive allosteric modulator.Усовершенствование терапии болезни Альцгеймера (БА) – одно из наиболее актуальных заданий современной медицины и фармации. Перспективно создание и фармакологическое исследование оригинальных лекарственных средств для ее терапии. Перспективным классом таких средств являются нейропротекторы. В НИИ Особо чистых биопрепаратов создан пептид acetyl-(D-Lys)-Lys-Arg-Arg-amide (лабораторный шифр КК-1). В эксперименте на модели церебральной ишемии КК-1 демонстрирует выраженные нейропротекторные и ноотропные свойства. Цель исследования – изучить ноотропные свойства КК-1 на модели БА. У крыс моделировали скополамин-обусловленную БА. На протяжении 10 дней осуществляли терапию фармакологическим препаратом КК-1 (0,1 мг/кг интраназально 1 раз в день) или препаратом сравнения (донепезил, 1 мг/кг внутрижелудочно 1 раз в день). После терапии оценивали функциональное состояние животных по тестам открытого поля (ОП), экстраполяционного избавления (ЭИ) и условного рефлекса пассивного избегания (УРПИ). В гомогенате целого головного мозга (ГМ) и синаптосомах ГМ спектрофотометрически определяли уровень ацетилхолина (АХ) и активность ацетилхолинэстеразы (АХЭ). Исследуемый препарат КК-1 уменьшает стресс-обусловленную тревожность крыс с моделью БА в тесте ОП, повышая их ориентировочно-исследовательскую активность (в 1,4 раза, р&lt;0,05) и уменьшая уровень эмоциональных реакций (на 44%, р&lt;0,05). В тесте ЭИ тетрапептид КК-1 повышает когнитивные функции крыс, уменьшая время подныривания под край цилиндра в 4,7 раза (р&lt;0,05 с группой патологии). По тесту УРПИ установлена высокая антиамнестическая активность КК-1 (56,5% и 81,5% на первые и десятые сутки соответственно). По всем показателям КК-1 превышает активность препарата сравнения донепезила.  Механизм ноотропного действия КК-1 на модели БА заключается в повышении уровня АХ в синаптосомах ГМ, вероятно, за счет стимуляции его синтеза. КК-1 умеренно угнетает АХЭ, чем дополнительно способствует накоплению АХ в синаптической щели холинергического синапса. Вероятно также взаимодействие пептида КК-1 с Gq/G11-связанным М1-, М3-, и М5-холинергическими рецепторами по принципу позитивной аллостерической модуляции.Удосконалення терапії хвороби Альцгеймера (ХА) – одне з найактуальніших завдань сучасної медицини та фармації. Перспективним є створення та фармакологічне вивчення оригінальних лікарських засобів для її терапії. Перспективним класом таких засобів є нейропротектори. У НДІ Особливо чистих біопрепаратів створено тетрапептид acetyl-(D-Lys)-Lys-Arg-Arg-amide (лабораторний шифр КК-1). В експерименті на моделі церебральної ішемії КК-1 виявляє потужні нейропротекторні та ноотропні властивості. Мета дослідження – дослідити ноотропні властивості КК-1 на моделі ХА. У щурів моделювали скополамін-зумовлену ХА. Протягом 10 днів їх лікували пептидом КК-1 (0,1 мг/кг інтраназально, 1 раз на день) або препаратом порівняння (донепезил, 1 мг/кг внутрішньошлунково, 1 раз на день). Після терапії оцінювали функціональний стан ЦНС щурів за тестами відкритого поля (ВП), екстраполяційного вивільнення (ЕВ) та умовного рефлексу пасивного уникнення (УРПУ). У гомогенаті цілого головного мозку (ГМ) та синаптосомах ГМ спектрофотометрично визначали рівень ацетилхоліну (АХ) та активність ацетилхолінестерази (АХЕ). Досліджуваний фармакологічний препарат КК-1 зменшує стрес-зумовлену тривожну поведінку щурів із модельною ХА за тестом ВП, підвищуючи їх орієнтовно-дослідницьку активність (у 1,4 рази, р&lt;0,05) та зменшуючи емоційні реакції (на 44%, р&lt;0,05). В тесті ЕВ пептид КК-1 покращує когнітивні функції щурів, зменшуючи час пірнання під край циліндра у 4,7 рази (р&lt;0,05). За тестом УРПУ встановлено високу антиамнестичну активність досліджуваного препарату (56,5% та 81,5% на 1 та 10 день після терапії відповідно). За усіма показниками КК-1 перевершує активність донепезилу. Механізм ноотропної дії КК-1 на моделі ХА полягає у підвищенні рівня АХ в синаптосомах М-холінергічних рецепторів, імовірно, шляхом стимуляції його синтезу. КК-1 помірно пригнічує АХЕ, чим додатково сприяє накопиченню АХ в синаптичній щілині холінергічного синапсу. Можливою є також взаємодія тетрапептиду КК-1 із Gq/G11-зв’язаними М1-, М3-, та М5- холінергічними рецепторами за принципом позитивної алостеричної модуляції

Optical Cherenkov radiation by cascaded nonlinear interaction: an efficient source of few-cycle energetic near- to mid-IR pulses

When ultrafast noncritical cascaded second-harmonic generation of energetic femtosecond pulses occur in a bulk lithium niobate crystal optical Cherenkov waves are formed in the near- to mid-IR. Numerical simulations show that the few-cycle solitons radiate Cherenkov (dispersive) waves in the \lambda=2.2-4.5\mic range when pumping at \lambda_1=1.2-1.8\mic. The exact phase-matching point depends on the soliton wavelength, and we show that a simple longpass filter can separate the Cherenkov waves from the solitons. The Cherenkov waves are born few-cycle with an excellent Gaussian pulse shape, and the conversion efficiency is up to 25%. Thus, optical Cherenkov waves formed with cascaded nonlinearities could become an efficient source of energetic near- to mid-IR few-cycle pulses.Comment: Extended version of Nonlinear Optics 2011 contribution http://www.opticsinfobase.org/abstract.cfm?URI=NLO-2011-NTuA7. Submitted for Optics Express special issue for NLO conferenc