Technology for the Industrial Production of K3 Series Vitamins Based on Menadione

Received: 15.04.2020. Accepted: 27.06.2020. Published: 30.06.2020.An improved technology for the industrial production of K3 series vitamins based on menadion is reported. The procedure involves the Cr(VI) — promoted oxidation of the corresponding methyl-naphtahelenes with the following purification by precipitation/recrystallization. The best results were obtained under the process temperature between 20–40 °C, solution pH after dilution of MNB in a range of 5.5–5.7, and MNB content in initial solution of 25–30%

Case of parvovirus B19 infection and immunodeficiency in the patient with Gilbert syndrome

A case of long-term persistence of parvovirus B19 is described for the first time in a patient with Gilbert's syndrome against the background of immunodeficiency with predominance of infectious symptoms (chronic herpesvirus infection). Previously, the patient (male, 48 years old) was diagnosed with Gilbert's syndrome, chronic rhinosinusopharyngitis, and chronic herpesvirus infection. In July 2017, parvovirus B19 DNA was detected in blood. No clinical manifestations of infectious erythema were noted. The patient was admitted to the medical center of St. Petersburg Pasteur Institute. His blood samples obtained under informed consent were examined at the medical center in Central Clinical and Diagnostic Laboratory of St. Petersburg Pasteur Institute in January and June 2018 and in November 2019. ELISA test systems “Anti-Parvovirus B19 ELISA (IgM)” and “Anti-Parvovirus B19 ELISA (IgG)” (Euroimmune, Germany), as well PCR reagent kit “AmpliSens Parvovirus B19-FL” (FSB Central Research Institute of Epidemiology of Rospotrebnadzor, Russia) were used for specific diagnostics. Interferon status was determined by the induced production of IFN types I, II and circulating (serum) interferons. Moreover, we considered the laboratory data obtained earlier at different medical facilities of St. Petersburg. IgM class antibodies to the parvovirus B19 were not detected in the blood samples obtained in 2018. IgG antibody titer was 96 IU/ml and 264 IU /ml, respectively. Parvovirus B19 DNA was isolated from blood plasma, but the viral load was less than 720 IU of PVB19 DNA/ml (1.5 x 102 and 1.9 x 102 copies of DNA/ml, respectively). Clinical blood analysis, showed only minor (no more than 7%) deviations from the reference values, increased hemoglobin saturation of red blood cells (RBC), a decreased width of RBC distribution curve, and relative lymphocytosis. A deficiency of various interferon types was revealed: IFNγ level was 80 IU/ml in both samples, IFNα, IFNβ amounts varied from 80 to 160 IU/ml, respectively. The period of parvovirus B19 DNA persistence in blood was 11 months in presence of immunodeficiency. The patient was administered drugs of the interferon group. Parvovirus B19 DNA was not detected in clinical samples of November 2019; IFNα, IFNβ and IFNγ values were 160 IU/ml. We have detected recovery of lymphoid cell ratio, increase in their number, and improved indexes of interferon status

FUNCTIONAL FOOD COMPOSITIONS BASED ON WHEY PROTEIN ISOLATE, FISH OIL AND SOY PHOSPHOLIPIDS

The aim of the research was to study the impact of whey protein isolate on the solubility and oxidative stability of the lipid composition based on soy phosphatidylcholine and fish oil. The relationship between the molecular parameters (density; ζ-potential) of the formed complex particles and their functional properties was found using laser light scattering (static, dynamic, electrophoretic) and spectrophotometry. The studied compositions could be used as the basis for the development of multifunctional food additives with an objective of the enrichment of foods and beverages with omega-3 polyunsaturated fatty acids (PUFAs). The main advantages of such composition are a high level of protection of the lipids against oxidation and degradation, a high solubility in an aqueous medium and the clean label.The aim of the research was to study the impact of whey protein isolate on the solubility and oxidative stability of the lipid composition based on soy phosphatidylcholine and fish oil. The relationship between the molecular parameters (density; ζ-potential) of the formed complex particles and their functional properties was found using laser light scattering (static, dynamic, electrophoretic) and spectrophotometry. The studied compositions could be used as the basis for the development of multifunctional food additives with an objective of the enrichment of foods and beverages with omega-3 polyunsaturated fatty acids (PUFAs). The main advantages of such composition are a high level of protection of the lipids against oxidation and degradation, a high solubility in an aqueous medium and the clean label

A herd immunity to measles and rubella viruses in the population of the Republic of Serbia

According to the WHO Strategic Plan, measles should be eradicated in 2020 in the five WHO Regions including European Region. However, large measles outbreaks are being periodically registered in diverse European countries. In the Republic of Serbia (SRB), 5,076 measles cases were detected in 2018, among which 15 cases were fatal.Aim of the study was to examine herd immunity to measles and rubella viruses in the population of the Republic of Serbia.Materials and methods. Blood serum samples obtained in 2018 and 2019 from conditionally healthy residents of the Republic of Serbia were tested for the presence of IgG antibodies to measles and rubella viruses in five age groups: I — children from 2 to 6 years old, II — children from 8 to 14 years old, III — 15 to 24 years old, IV — 25 to 49 years old and V — over 50 years old. A total of 1000 samples were obtained, 200 sera in each group. Enzygnost® Anti-Measles virus/IgG and Enzygnost® Anti-Rubella virus/IgG ELISA test systems (Siemens Healthcare Diagnostics Products GmbH, Germany) were used according to the manufacturer's instructions.Results. Overall, around 23.0% and 33.7% of the surveyed persons had no or low level of anti-measles IgG antibody (≥ 275.0 — ≤ 1000.0 IU/1). In age group I, 60% children contained no or “low” anti-measles antibodies titer (29.5% and 30.5%, respectively). In addition, low antibody titer level was mainly detected in individuals from age group II and III (p < 0.05). A third of children under 8—14 contained high IgG-antibodies titer against measles (> 3000.0 IU/l) that might serve as an evidence that such subjects recently recovered after measles. Similar results were obtained for IgG antibodies to rubella in the same age groups.Discussion. The study results evidence about altered routine immunization against measles and rubella in children aged 12—15 months (first vaccination) and those at age of 6—7 years (revaccination) with MMR vaccine. The data obtained correlate with official data on coverage with measles and rubella vaccines in the Republic of Serbia

Implementation of the program of measles elimination in the WHO African region

The review is devoted to the analysis of the available literature on the elimination of measles. The review focuses on the current measles epidemic situation in the African Region (AFR) and the implementation of the WHO strategic plan for the elimination of measles in AFR by 2020. Measles in the AFR is characterized by a severe course with a high risk of death due to malnutrition, vitamin A deficiency, concomitant bacterial and viral infections, and malaria. In 2015, 105,256 cases of measles were reported in the WHO African Region, most of them among children under 5 years old, 79% of whom were not vaccinated or had unknown vaccine status. Initially, the strategy for implementing the measles elimination program in AFRs was based on a combination of immunization campaigns for children under 14 years of age (coverage of more than 90%) and routine vaccination of at least 90% of children aged 9–15 months. It was recommended to repeat the campaign of mass immunization of children aged 9 months up to 4 years every 3–5 years. The use of this strategy has reduced the number of measles cases by 83–97% during the first year of additional immunization programs. The recommended age of routine measles vaccination in AFRs is 9 months — a strategy to reduce infant mortality, including that due to complications of measles. In 2016, measles vaccination was introduced into the national immunization schedule in all AFR countries, and 24 countries introduced revaccination. Currently, the measles elimination program in a number of AFR countries is based on two-dose immunization (MCV1 and MCV2). The measles prevention program in a number of AFR countries was disrupted due to the Ebola epidemic. There are some common problems in the realization of the program in AFR countries. All AFR countries are committed to the measles elimination program. The review provides information on strategies and successes in overcoming challenges to achieve the goals set for the WHO African Region in the implementation of the programme of measles elimination

Glyproline Pro-Ampakine with Neuroprotective Activity

Previously it was shown that neuropeptide cyclo-L-prolylglycine (CPG) is a positive modulator of AMPA receptors, which increases BDNF level in neuronal cell cultures. The spectrum of CPG’s pharmacological effects corresponds to that of BDNF. Dipeptide N-phenylacetyl-glycyl-L-proline ethyl ester (GZK-111) was designed and synthesized as a linear analog of CPG. The aim of the present work was to reveal the pharmacological profile of GZK-111. Dipeptide GZK-111 was shown to metabolize into CPG in vitro and increased cell survival by 28% at concentrations of 10-7–10-6 M in a Parkinson’s disease cell model. In a model of cerebral ischemia, GZK-111, at a dose of 0.5 mg/kg, i.p., was found to have neuroprotective effects, reducing the cerebral infarct volume by 1.6 times. Similar to CPG, GZK-111, at the range 0.1–1.0 mg/kg, i.p., possessed a stereospecific antiamnesic activity. A significant anxiolytic effect was observed at a dose of 1.5 mg/kg. GZK-111, at the range 0.5–4.0 mg/kg, i.p., demonstrated analgesic activity. GZK-111, at a dose of 10 mg/kg/7 days, i.p., possessed antidepressant-like activity. So, the neuroprotective, nootropic, antihypoxic, anxiolytic, antidepressant-like, and analgesic effects of GZK-111 were revealed. Thus, GZK-111 can be considered as a pharmacologically active pro-ampakine with a BDNF-ergic mechanism of action

A herd immunity to rubella virus in selected geographical regions

Since 2017, the incidence rate of rubella in the Russian Federation has been below 1 case per million total population. In addition, no circulation of endemic strains of the rubella virus is recorded evidencing about achieving infection elimination phase. In modern conditions, it is important to constantly monitor the level of herd immunity to the rubella virus to identify epidemically significant population groups, especially in countries lacking rubella vaccination or featured with insufficient disease control. Purpose: to study herd immunity to the rubella virus in selected countries in Eurasia and Africa. Materials and methods. Between 2018 and 2021, 15,594 samples of blood sera were tested for IgG and IgM antibodies to the rubella virus from subjects of different ages obtained from regional measles and rubella surveillance centers in the Northwestern Federal District (NWFD) of the Russian Federation, the Republic of Serbia, South Vietnam, and the Republic of Guinea. The “Anti-Rubella Virus ELISA (IgМ)” and “Anti-Rubella Virus ELISA (IgG)” (Euroimmun, Germany) test kits were used. Statistical data processing was carried out using the MS Excel, Prizm 5.0 (GraphPad Software Inc.), and Statistica 8.0 (StatSoft Inc.) software package. Results. During the observation period (2018–2020) the population seroprevalence of the to the rubella virus in the NWFD of the Russian Federation was 96.6–97.7% and fluctuated slightly both in separate years and among individual age groups evidencing about high coverage of rubella vaccination. In the Republic of Serbia conducting two-fold immunization against rubella the overall seroprevalence rate was lower than in the Russian Federation and comprising 86.8%. The minimum number of IgGpositive sera was recorded in the 2–4-year-old age group pointing to the shortcomings of routine vaccination. In South Vietnam, children aged 1–3 years (41.9%) predominated among those recovering from rubella, i.e. the age cohort that should be protected by vaccination at the age of 18 months. No rubella vaccination is carried out in Guinea. The total proportion of seropositive individuals was 75%; herd immunity to the rubella virus was established mainly among children and adolescents, reaching 90% only in the older age group. 30% of unprotected subjects of the most active reproductive age were identified among the females surveyed in Guinea. Conclusion. Insufficient herd immunity to the rubella virus, identified in a number of countries, may contribute to the maintenance of the infectious process and the spread of infection. Globalization contributes to the virus importation into regions being at the stage of measles and rubella elimination. The results obtained suggest about a need to continue efforts aimed at maintaining epidemiological wellbeing regarding rubella in diverse countries of the world.Начиная с 2017 г. в Российской Федерации показатель заболеваемости краснухой находится на уровне ниже 1 случая на 1 млн населения. Также отсутствует циркуляция эндемичных штаммов вируса краснухи. Это свидетельствует о достижении фазы элиминации инфекции. В современных условиях важным является постоянный мониторинг уровня коллективного иммунитета к вирусу краснухи для выявления эпидемически значимых групп населения, особенно в странах, где вакцинация против краснухи не проводится или контроль недостаточен. Цель исследования: изучение коллективного иммунитета к вирусу краснухи в ряде стран Евразии и Африки. Материалы и методы. В период с 2017 по 2021 г. на IgG- и IgM-антитела к вирусу краснухи исследовано 15 594 образца сывороток крови лиц разного возраста, полученные из региональных центров по надзору за корью и краснухой в СЗФО РФ, Республике Сербия, в Южном Вьетнаме, в Гвинейской Республике. Использовали ИФА тест-наборы «Anti-Rubella Virus ELISA IgМ» и «Anti-Rubella Virus ELISA (IgG)» (Euroimmun, Германия). Статистическая обработка результатов проводилась с помощью пакета программ MS Excel, Prizm 5.0 (GraphPadSoftware Inc.), Statistica 8.0 (StatSoft Inc.). Результаты. В СЗФО РФ за период наблюдения серопревалентность населения к вирусу краснухи составляла 96,6–97,7% и колебалась незначительно как по отельным годам, так и среди отдельных возрастных групп, что свидетельствуют о высоком охвате вакцинацией против краснухи. В Республике Сербия общий показатель серопревалентности оказался ниже, чем в РФ, и составил 86,8%. Наименьшее количество IgG-положительных сывороток регистрировали в возрастной группе 2–4 года, что говорит о недостатках плановой вакцинации. В Южном Вьетнаме среди переболевших краснухой преобладали дети в возрасте 1–3 года (41,9%), то есть та группа, которая должна быть максимально защищена плановой прививкой против краснухи в 18 месяцев. В Гвинее специфическая профилактика краснухи не проводится. Общая доля серопозитивных лиц составила 75%, коллективный иммунитет к вирусу краснухи формировался, в основном, среди детей и подростков, достигая 90% лишь в старшей возрастной группе. Среди обследованных женщин Гвинеи выявлено 30% незащищенных лиц наиболее активного репродуктивного возраста. Заключение. Недостаточный уровень коллективного иммунитета к вирусу краснухи, выявленный в ряде стран, может способствовать распространению инфекции, а условия глобализации — импортированию вируса в регионы, находящиеся на этапе элиминации кори и краснухи. Полученные результаты свидетельствуют о необходимости продолжения усилий, направленных на поддержание эпидемиологического благополучия в отношении краснухи в разных странах мира

Миметик мозгового нейротрофического фактора ГСБ-106 оказывает нейропротекторные и нейрорегенеративные эффекты в условиях экспериментального ишемического инсульта

   Background. A dimeric dipeptide mimetic of the brain-derived neurotrophic factor loop 4, bis(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide (GSB-106), which activates TrkB, PI3K/AKT, MAPK/ERK and PLC-γ1 was created at the V. V. Zakusov Research Institute of Pharmacology. GSB-106 showed neuroprotective activity in vitro and in vivo at systemic administration.   Objective. In the present study, we studied the effect of GSB-106 on the brain infarct volume, as well as on neurogenesis and synaptogenesis under conditions of experimental ischemic stroke induced by transient occlusion of the middle cerebral artery in rats, when it was first administered 24 h after ischemia onset.   Methods. Dipeptide GSB-106 was administered i.p. in a dose of 0.1 mg/kg 24 h after surgery and then once a day, with the end of administration on theday 6 after surgery. On the day 7 brain samples were collected for morphometric and biochemical (Western-blot) analysis.   Results. It was established that GSB-106 reduced the brain damage volume by 24%, restores impaired neurogenesis and/or gliogenesis (by Ki-67) in the hippocampus and in the striatum and completely restored the reduced immunoreactivity to synaptic markers synaptophysin and PSD-95 in the striatum.   Conclusions. Thus, the dimeric dipeptide BDNF mimetic GSB-106 exhibits neuroregenerative properties at clinically relevant time window (24 h) in a model of ischemic stroke presumably due to stimulation of neurogenesis (and / or gliogenesis) and synaptogenesis.   Актуальность. Димерный дипептидный миметик 4-й петли мозгового нейротрофического фактора (brain-derived neurotrophic factor, BDNF) гексаметилендиамид бис(N-моносукцинил-L-серил-L-лизина) (GSB-106), активирующий TrkB, PI3K/AKT, MAPK/ERK и PLC-γ1, был создан в НИИ фармакологии имени В. В. Закусова. Для ГСБ-106 была выявлена нейропротекторная активность в экспериментах in vitro и in vivo при системном введении.   Цель. В настоящем исследовании мы изучили влияние ГСБ-106 на объём инфаркта мозга, а также на нейрогенез и синаптогенез в условиях экспериментального ишемического инсульта, индуцированного транзиторной окклюзией средней мозговой артерии у крыс, при его первом введении через 24 ч после моделирования ишемии.   Методы. Дипептид ГСБ-106 вводили внутрибрюшинно в дозе 0,1 мг/кг 1 раз в день в течение 6 дней. На 7-й день мозговой материал собирали для морфометрических и биохимических (Вестерн-блот анализ) исследований.   Результаты. Было установлено, что ГСБ-106 снижал объём инфаркта мозга в среднем на 24 %, стимулировал угнетённый нейро- и/или глиогенез (по маркеру пролиферации Ki-67) в гиппокампе и стриатуме и полностью восстанавливал иммунореактивность к синаптическим маркерам синаптофизину и PSD-95 в стриатуме ишемизированного полушария.   Заключение. Таким образом, димерный дипептидный миметик BDNF ГСБ-106 проявляет нейрорегенеративные свойства в условиях клинически значимого (24 ч) терапевтического окна на модели ишемического инсульта, и эти свойства предположительно обусловлены стимуляцией нейрогенеза (и / или глиогенеза) и синаптогенеза

МАРКЕРЫ ПАРВОВИРУСНОЙ ИНФЕКЦИИ У ЛИЦ С ЭКЗАНТЕМНЫМИ ЗАБОЛЕВАНИЯМИ И В ГРУППАХ РИСКА

Background. In the Russian Federation the number of a parvovirus В19 infection cases has increased significantly with the introduction of rubella into the measles elimination program and laboratory examination of patients with maculopapular rash and fever. The aim of study was the examination of the distribution of the parvovirus В19 infection in the North-Western Federal District. Materials and methods. In 2014–2017, 1044 blood sera of patients with exanthema diseases from different territories of the North-Western Federal District have been investigated with «Anti-Parvovirus B19 ELISA IgM» kit (EUROIMMUN, Germany) to detect IgM antibody, and 733 blood sera of clinically healthy men and women 18 to 60 years old have been tested for IgG antibodies using the «Anti-Parvovirus B19 ELISA IgG» kit (EUROIMMUN, Germany). Results. Parvovirus В19 infection is contentiously detected in 10 of the 11 territories of the district. Typical is the winterspring seasonality; in terms of the age structure – prevalence of children 3–6 (25,3% of cases) and 7–14 (33,3% of cases) years old was detected. A high proportion of seropositivity was established among the examined donors from the higher educational institutions of Saint Petersburg (75,4–88,9%%). Low rate of seropositivity (56,7%) was detected among pregnant women. A high proportion of false negative results in the primary diagnosis of parvovirus infection has been revealed. Conclusion. Parvovirus В19 infection is widespread in the territories of the North-Western of the Russia, mainly among children. The results indicate the feasibility of conducting a laboratory examination of pregnant women who are contact for exanthemous diseases, for markers of parvovirus infection; on the importance of screening donor blood for PV B19 DNA with “culling” pools characterized by high viral load; on the need for differential laboratory diagnosis between rubella and parvovirus infection.Введение. Выявление случаев парвовирусной инфекции в России существенно возросло при интеграции краснухи в программу элиминации кори и лабораторном обследовании больных с пятнисто-папулёзной сыпью и лихорадкой. Цель: выявление маркеров парвовирусной инфекции на территориях Северо-Западного федерального округа России, в том числе в группах риска, для оценки распространения инфекции. Материалы и методы. В 2014–2017 гг. исследованы 1044 сыворотки крови больных с экзантемными заболеваниями, проживающих на разных территориях Северо-Запада. IgМ-антитела выявляли в ИФА с тестсистемой «Anti-Parvovirus B19 ELISA IgМ» (EUROIMMUN, Германия). На IgG-антитела были исследованы 733 сыворотки крови клинически здоровых мужчин и женщин 18–60 лет в ИФА с тест-системой «Anti-Parvovirus B19 ELISA IgG» (EUROIMMUN, Германия). Результаты. Парвовирусная инфекция выявлена на 10 из 11 территорий округа. Характерно преобладание в возрастной структуре заболевших детей 3–6 (25,3% случаев) и 7–14 лет (33,3% случаев). Установлена высокая доля серопозитивных лиц среди обследованных доноров г. Санкт-Петербурга (85,2%). Выявлена низкая доля серопозитивных (56,7%) среди обследованных беременных женщин. Показана высокая доля ошибок первичной диагностики. Заключение. Парвовирусная инфекция широко распространена на Северо-Западе России. Полученные результаты указывают на целесообразность проведения лабораторного обследования беременных женщин, контактных по экзантемным заболеваниям, на маркеры парвовирусной инфекции; на важность скринингового исследования донорской крови на ДНК PV B19 с «выбраковкой» пулов, характеризующихся высокой вирусной нагрузкой; на необходимость проведения дифференциальной лабораторной диагностики между краснухой и парвовирусной инфекцией