On the governing equations for Poisson and Skellam processes time-changed by inverse subordinators

In the paper we present the governing equations for marginal distributions of Poisson and Skellam processes time-changed by inverse subordinators. The equations are given in terms of convolution-type derivatives

Мiжнародна наукова конференцiя “Сучасна стохастика: теорiя та застосування. V” (MSTA-V). 1-4 червня 2021

Pages of the article in the issue: 9 Language of the article: UkrainianPages of the article in the issue: 9 Language of the article: Ukrainia

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

Substituted 1H-pyrazolo[3,4-b]pyridine-4- and 1H-pyrazolo[3,4-b]pyridine-6-carboxamides have been synthetized through a Doebner–Ugi multicomponent reaction sequence in a convergent and versatile manner using diversity generation strategies: combination of two multicomponent reactions and conditions-based divergence strategy. The target products contain as pharmacophores pyrazolopyridine and peptidomimetic moieties with four points of diversity introduced from readily available starting materials including scaffold diversity. A small focused compound library of 23 Ugi products was created and screened for antibacterial activity

ELIMINATION OF FALSE RESULTS OF MEDICINES MICROBIOLOGICAL TESTING

The validity of medicines microbial quality testing relies on the adequacy of the test procedure employed. The aim of the study was to analyse factors triggering false results during microbial quality testing of non-sterile  medicinal products, as well as to find ways of their elimination.  Materials and methods: the study was focused on non-sterile  medicinal products tested for microbial quality: N-methylglucamine, L-Malic  acid, Xeroform, Fingolimod hydrochloride, Succinic  acid, Streptocide,  Aripiprazole, Doxazosin, Clopidogrel,  Moxonidine, Tilorone,  Mycophenolic acid, Folic acid, Gabapentin, Dutasteride, Imatinib,  Temozolomide. The study involved the use of the following test strains: Bacillus subtilis, Bacillus cereus, Candida albicans, Escherichia coli, Aspergillus brasiliensis, as well as of reagents and growth media. The methods  used were determination of antimicrobial  activity under conditions of microbial quality testing, and modified in-depth  testing of microbial quality of medicinal products according to the requirements of the State Pharmacopoeia of the Russian Federation, 13th edition. Results: the analysis of literature sources helped reveal the main factors causing false results of microbiological  testing and determine  ways of their elimination.  The article sets forth the results of experimental comparison of two ways of sample preparation  for solid formulations: the standard one described in the State Pharmacopoeia of the Russian Federation, 13th edition, and the one involving the use of a laboratory shaker. The article provides experimental data on specific aspects of elimination of antimicrobial activity against B. subtilis and B. cereus and the use of specific inactivators for particular medicinal products. Conclusions: a set of measures aimed at prevention of false-positive and false-negative testing results should include: sterility control of the growth media and reagents used, monitoring  of facilities; control of growth promotion  properties and selectivity of the growth media; selection of adequate incubation  conditions  and inoculation procedure with due regard to the dosage form; justification of the amount of sample, diluents and dilution factor used; consideration  of the antimicrobial activity of a medicinal product

Long-term programme of biophysical monitoring of the personnel involved in the construction of the new safe confinement

The international Shelter Implementation Plan (SIP) foresees a step-by-step transformation of the Chornobyl site into the safe condition. The New Safe Confinement (NSC), is an unprecedented 108-meter tall structure over the destroyed Unit 4 of the Chernobyl Nuclear Power Plant, and is a central element of SIP. Many workers involved in SIP may have a direct contact with fragments of the irradiated fuel, fuel-containing aerosols, and other contaminated material at the Chornobyl industrial site. Isotopes of plutonium, americium, strontium, and cesium are dominating in internal exposure of SIP workers. The safety of workers is a high priority of SIP. Starting from 2004 the Ukrainian Radiation Protection Institute (RPI) is performing a large-scale Internal Dosimetry Program as an integral part of SIP. Pu contents in fecal and urine samples and the whole-body counters‟ (WBC) data and are the main source of the quantitative data used for the dose assessment. The RPI radiochemical laboratories in Kyiv and at the Chornobyl site employed the standard radiochemical technique and equipped with ninety six alpha-spectrometers. The range of WBCs includes the scanning low-background WBC, four Canberra FastScan WBCs, and four chair-type WBCs. The car-borne WBC is located in Kiev and reserved for the emergency purposes. As on September 2017 the Internal Dosimetry Program has covered more than 17 000 workers, which undergone 1 230 000 measurements of ¹³⁷Cs on WBCs, 87 000 measurements of ²³⁹⁺²⁴⁰Pu contents in fecal samples and 4 400 measurements of ²³⁹⁺²⁴⁰Pu contents in urine samples. Such a large-scale programme ensured a reliable monitoring of intakes of the insoluble radioactive material.У міжнародному Плані здійснення заходів (ПЗЗ) передбачається поетапне перетворення чорнобильського майданчика у безпечний стан. Новий безпечний конфайнмент є безпрецедентною структурою заввишки 108 м над зруйнованим 4-м блоком ЧАЕС, він є центральним елементом ПЗЗ. Багато працівників, залучених у ПЗЗ, можуть мати прямий контакт із фрагментами опроміненого палива, паливовмісними аерозолями та іншими забрудненими матеріалами на промисловому майданчику в Чорнобилі. Ізотопи плутонію, америцію, стронцію і цезію домінують у внутрішньому опроміненні працівників ПЗЗ. Безпека працівників має високий пріоритет у ПЗЗ. Починаючи з 2004 р., Науково-дослідний інститут радіаційного захисту АТН України (ІРЗ) здійснює великомасштабну програму дозиметрії внутрішнього опромінення як невід‟ємну частину ПЗЗ. Дані вмісту плутонію у пробах калу і сечі та лічильників випромінювань людини (ЛВЛ) і основним джерелом кількісних даних, що використовуються для оцінки дози. Радіохімічні лабораторії ІРЗ у Києві і на майданчику в Чорнобилі використовували стандартну радіохімічну методику, вони оснащені 96 альфа-спектрометрами. Номенклатура ЛВЛ включає в себе скануючий низькофоновий ЛВЛ, чотири ЛВЛ Canberra FastScan і чотири ЛВЛ типу “крісло”. Мобільний ЛВЛ розташований у Києві і зарезервований для надзвичайних цілей. Станом на вересень 2017 р. рамками програми дозиметрії внутрішнього опромінення було охоплено понад 17 000 працівників, які пройшли 1 230 000 вимірювань ¹³⁷Cs на ЛВЛ, 87 000 вимірювань вмісту ²³⁹⁺²⁴⁰Pu у пробах калу і 4 400 вимірювань вмісту ²³⁹⁺²⁴⁰Pu у пробах сечі. Така великомасштабна програма забезпечила надійний контроль надходжень нерозчинного радіоактивного матеріалу.В международном Плане осуществления мероприятий (ПОМ) предусматривается поэтапное преобразование чернобыльской площадки в безопасное состояние. Новый безопасный конфайнмент – это беспрецедентная структура высотой 108 м над разрушенным 4-м блоком ЧАЭС, он является центральным элементом ПОМ. Многие работники, вовлеченные в ПОМ, могут иметь прямой контакт с фрагментами облученного топлива, топливосодержащими аэрозолями и другими загрязненными материалами на промышленной площадке в Чернобыле. Изотопы плутония, америция, стронция и цезия доминируют во внутреннем облучении работников ПОМ. Безопасность работников имеет высокий приоритет в ПОМ. Начиная с 2004 г., Научно-исследовательский институт радиационной защиты АТН Украины (ИРЗ) осуществляет крупномасштабную программу дозиметрии внутреннего облучения как неотъемлемую часть ПОМ. Данные содержания плутония в пробах кала и мочи, а также счетчиков излучений человека (СИЧ) являются основным источником количественных данных, используемых для оценки дозы. Радиохимические лаборатории ИРЗ в Киеве и на площадке в Чернобыле использовали стандартную радиохимическую методику, они оснащены 96 альфа-спектрометрами. Номенклатура СИЧ включает в себя сканирующий низкофоновый СИЧ, четыре СИЧ Canberra FastScan и четыре СИЧ типа “кресло”. Мобильный СИЧ расположен в Киеве и зарезервирован для чрезвычайных целей. По состоянию на сентябрь 2017 г. в рамках программы дозиметрии внутреннего облучения было охвачено более 17 000 работников, которые прошли 1 230 000 измерений ¹³⁷Cs на СИЧ, 87 000 измерений содержания ²³⁹⁺²⁴⁰Pu в пробах кала и 4 400 измерений содержания ²³⁹⁺²⁴⁰Pu в пробах мочи. Такая крупномасштабная программа обеспечила надежный контроль поступлений нерастворимого радиоактивного материала

Differentiated approach to pancreatic-enteroanastomosis in pancreaticoduodenal resection: a clinical experimental controlled trial

Background. Despite decreasing mortality in pancreaticoduodenal resection, the incidence of postoperative complications in such patients remains high. The choice and formation of “reliable” pancreatic-enteroanastomosis remain relevant.Objectives. The improvement of immediate surgery outcomes in pancreaticoduodenal resection via development of a differentiated algorithm for pancreatic-enteroanastomosis formation.Methods. A prospective non-randomised controlled trial enrolled 90 patients with a pancreaticoduodenal resection surgery. The patients were divided in three cohorts, A (n = 30), B (n = 30) and control C (n = 30). Pancreatic shear wave ultrasound elastography was conducted pre-surgery in main cohorts A and B. Average parenchymal stiffness and intraoperative data decided between the two pancreatico-enteric anastomosis techniques, end-to-side or the original pancreatic-enteroanastomosis. Control cohort C had pancreatico-enteric anastomosis without taking into account the pancreas stiffness and macrocondition.Results. Class A postoperative pancreatic fistula was registered in 2 (6.7%) of 30 patients in cohort B; it was transient, asymptomatic, not requiring additional treatment or a longer postoperative period. No class B and C pancreatic-enteroanastomosis failures or stump pancreonecroses were observed in main cohorts A and B. Clinically significant class B and C postoperative pancreatic fistulae were registered in 5 (16.7%) of 30 patients in control cohort C (inter-cohort comparison statistically significant).Conclusion. The proposed differentiated approach to pancreatic-enteroanastomosis formation associates with a reliably low postoperative complication frequency and lack of clinically significant class B and C postoperative pancreatic fistulae

INTERLEUKIN-10 REGULATES PD-1-B7-H1-MEDIATED CYTOTOXIC ACTIVITY OF DENDRITIC CELLS

In this investigation the phenotypic and functional properties of healthy donor and patient with pulmonary tuberculosis (PT) dendritic cells (DCs) were characterized. We also studied the influence of IL-10 on the phenotype and apoptosis-inducing activity of healthy donor DCs. 60 patients with pulmonary tuberculosis with different proliferative response to antigens of M. tuberculosis (purified protein derivative, PPD) and 40 healthy donors were enrolled in this study. It was revealed that DCs, generated in vitro from PT patient's blood monocytes with GM-CSF+IFN-α, were characterized by increased B7-H1 expression, up-production of IL-10 and reducing of allostimulatory activity in mixed lymphocyte culture (MLC). The endogenous IL-10 production by DCs was correlated with expression of B7-H1 in the general group of persons. It was revealed that addition of IL-10 to semi-mature DCs of healthy donor results in increasing of B7-H1 expression, diminishing of allostimulatory activity and enlargement of pro-apoptogenic activity of DCs

INTRANASAL INHALATIONS OF BIOACTIVE FACTORS PRODUCED BY M2 MACROPHAGES IN THE TREATMENT OF PATIENTS WITH ORGANIC BRAIN SYNDROME

The aim of present study was to evaluate safety and clinical efficacy of inhalatory immunotherapy based on intranasal delivery of bioactive factors produced by M2 macrophages applied for treatment of patients with organic brain syndrome (OBS).Materials and methods. The study under the NCT02957123 protocol (www.ClinicalTrails.gov) included thirty patients with OBS of various genesis (10 men and 20 women aged 18 to 81; Me, 62.5 years). Neurological assessment and the levels of 32 cytokines in the blood serum of patients were evaluated before and 2-3 days after completion of inhalation immunotherapy.Intranasal inhalations of cell-free culture medium of M2 macrophages (2 mL, once a day for 28-30 days) were safe and well tolerated. None of 30 treated patients had severe adverse events and serious treatmentrelated side reactions. One month after starting the inhalations, a positive dynamics in neurological status was noted in all the patients. A marked clinical response was documented in twenty out of thirty patients (67%), which manifested as improvement, according to all scales and questionnaires. The neurological improvement was not reversed over 6 months of follow-up period. In other ten patients (33%), a moderate clinical response was shown as improvement of individual scores. The positive changes were as follows: 1) a 43% decrease in anxiety and depression scores (according to HADS scale, pU = 0.0008); 2) an increase of total motor activity (stability and gait) by 25%, pU = 0.0001); 3) correction of cognitive functions (MoCa test, pU = 0.007); 4) reduced number and intensity of the disease symptoms by 52% (pU = 0.0001). This marked clinical response to immunotherapy is shown to be associated with correction/normalization of serum hepatocyte growth factor (HGF) level.Conclusion. Inhalation immunotherapy based on intranasal delivery of bioactive factors produced by M2 macrophages can improve neurological and functional recovery in patients with organic brain syndrome

Expression of arginase 1 and tyrosine kinase Mer by blood monocytes in the dynamics of physiological pregnancy

During pregnancy, the maternal immune system must maintain tolerance to paternal antigens, at the same time being able to eliminate pathogens, which is achieved by the weakening of adoptive immunity and the activation of innate immunity, in particular, monocytes. However, the question about the functional phenotype of monocytes, having not only pro-inflammatory, but also anti-inflammatory activity, remains open. In the given work, we have investigated the expression of M2-associated suppressive markers Arg1 and MerTK in monocyte subpopulations during uncomplicated pregnancy. Fifty-three pregnant women with uncomplicated gestation were recruited, including 14 pregnant in the 1st trimester, 20 – in the 2nd and 19 – in the third pregnancy trimester. The comparison group consisted of 15 fertile unpregnant women without aggravated somatic anamnesis, with a history of at least one childbirth. The findings showed that in the unpregnant group circulating Mo express Arg1 and MerTK, and the most relative number of Arg1+ and MerTK+ cells is concentrated in intermediate and nonclassic monocytes. During pregnancy the expression of researched molecules in monocytes reliably increases. An increase in MerTK expression is manifested by a simultaneous increase in the number of MerTK+ cells and the mean fluorescence intensity of this marker; it is observed in the 1st and 2nd trimesters and registered in all three monocyte subpopulations. At the same time, an increase in Arg1 expression is manifested either by an enhancement of Arg1+ cells, or an increase in receptor density; it is registered throughout pregnancy, including the 3rd trimester, and is maximally expressed in classic monocytes. There is a direct correlation between the number of Arg1+ and MerTK+ cells in intermediate Mo, which increases with the progression of pregnancy, and in the 3rd trimester is also detected in classical and non-classical Mo. In general, the revealed increase in the expression of Arg1 and MerTK by monocytes indicates an increase in the anti-inflammatory potential of monocytes during pregnancy, and the involvement of monocytes in the regulation of the inflammatory process at the system level. Moreover, the features of Arg1 and MerTK expression in various monocyte subpopulations during pregnancy suggest that monocytes expressing Arg1 and MerTK can mediate different mechanisms of immune adaptation during pregnancy