ДИНАМИКА ЛИПОПОЛИСАХАРИДСВЯЗЫВАЮЩЕГО ПРОТЕИНА И ЛАКТАТА В КРОВИ ПАЦИЕНТОВ С ПОЛИТРАВМОЙ

Objective: to estimate the clinical and prognostic value of the blood levels of lipopolysaharidebinding protein (LPSBP) and lactate in critically ill polytrauma patients.Subjects and methods. An analysis was made of the results of an examination in critical ly ill polytrauma victims who were retrospectively classified in accordance with the 1992 ACCP/SCCM criteria: systemic inflammatory response syndrome (n=18), local infection (n=36), sepsis (n=27), severe sepsis (n=12), and septic shock (n=6). A case was regarded as infection when the source of the latter was established and it was microbiologically verified. The investigators determined serum LPSBP levels by an immunochemiluminescence analyzer (IMMULITE ONE, USA) and venous whole blood lactate concentrations by a Roche Omni S analyzer (Germany).Results. The development of infectious complications was notedin 81% of the polytrauma patients by days 5—7; by days 8—10, 45% were diagnosed as having sepsis whose severe course was characterized by the addition of polyresistant gramnegative microorganisms. An early increase in the concentration and frequency of diagnostic levels of serum LPSBP was ascertained in the polytrauma patients before infection was microbiologically verified. There was a strong direct correlation between lactate and LPSBP levels.Conclusion. The findings suggest that LPS BP and lactate are of diagnostic and prognostic value and may be used as early markers of pyoseptic complications.Цель исследования — оценить клиническую и прогностическую значимость уровней липополисахаридсвязывающего протеина (ЛПССП) и лактата в крови пациентов с политравмой в критическом состоянии.Материал и методы. Проведен анализ результатов обследования пострадавших с политравмой в критическом состоянии, которые ретроспективно были классифицированы в соответствии с критериями ACCP/SCCM (1992 г.): SIRS (n=18), локальная инфекция (n=36), сепсис (n=27), тяжелый сепсис (n=12) и септический шок (n=6). Случай считали инфекцией при установлении источника инфекции и его микробиологическом подтверждении. Содержание ЛПССП в сыворотке крови определяли на иммунохемилюминесцентном анализаторе «IMMULITE ONE» (США), лактата в цельной венозной крови — на анализаторе «Roche Omni S» (Германия).Результаты. У 81% пациентов с политравмой к 5—7 суткам отмечается развитие инфекционных осложнений; у 45% к 8—10 суткам диагностируется сепсис, тяжелое течение которого характеризуется присоединением полирезистентной грамотрицательной микрофлоры. Установлено раннее увеличение концентрации и частоты встречаемости диагностических уровней липополисахаридсвязывающего протеина (ЛПССП) в сыворотке крови у пациентов с политравмой до микробиологического подтверждения инфицирования. Показана сильная прямая корреляционная связь между уровнями лактата и ЛПССП.Заключение. Полученные данные свидетельствуют о диагностической и прогностической значимости ЛПССП и лактата и о возможности использования этих показателей в качестве ранних маркеров гнойносептических осложнений

Test Items Validation in the Context of Education Export

It is necessary to develop special assessment tools for international students, which will comply with the principles of evidence-based education. This is especially important in the context of Russian higher education export. Multiple choice questions (MCQs) are an essential part of the assessment and are suited for assessing the knowledge level of international students. The “Organic chemistry” is a basic course for pharmaceutical students, which is necessary for the understanding of principal subjects. The study objective was to develop a normative-oriented model of the “Organic chemistry” MCQs based examination for international students (the specialty 33.05.01 “Pharmacy”) in accordance with the recommendations of the Association for Medical Education in Europe (AMEE). The previously developed interactive “Organic Chemistry Test Simulator”, created at the Sechenov University, was used as the basis for the examination MSQs bank. It was analyzed by five independent experts, who work as teachers of organic chemistry. The average timing and the cut score were determined by the Angoff method, 90 sec and 64%, respectively. Among analyzed MCQs the 3% were found irrelevant, 22% were recommended for revision and modernization. Valid MSCs (600 items) served as the basis for the creation of extended examination MSQs bank. An algorithm for modeling the “Organic chemistry” MCQs based examination was proposed. The standardized examination test has 30 MSQs of different types. The standardized normative-oriented model of the “Organic chemistry” MCQs based examination for international students (the specialty 33.05.01 “Pharmacy”) was validated in terms of relevance and representativeness, optimized in time and cut score

Some Aspects of Formation of a Systemic Inflammatory Response in Critically Ill Patients

Objective: to study the general regularities and pathogenetic significance of changes in primary and secondary inflammatory mediator ratios in the formation of a systemic inflammatory response in critically ill patients. Subjects and methods. Three hundred and eighty-seven critically ill inpatients from intensive care units were examined. Results. The systemic inflammatory response syndrome develops in critical conditions, which is characterized by the increased serum levels of primary (proinflammatory cytokines) and secondary (C-reactive protein, fibrinogen) inflammatory mediators, which was more substantial in infected patients. When the hyperproduction of proinflammatory cytokines was evident, there was no adequate proinflammatory response, as suggested by the negative IL-10 level changes. Correlations were established between the serum content of inflammatory mediators and the indices of external respiration function, respiration rate, and heart rate. Conclusion. The nature of changes in the quantitative (mediator concentrations) and qualitative (mediator ratio) indices enables one to estimate the intensity of a systemic inflammatory response and to predict its further progression. Key words: critical condition, systemic inflammatory response, inflammatory mediators

Solubility Enhancement of Dihydroquercetin via “Green” Phase Modification

Dihydroquercetin (DHQ) is a promising antioxidant for medical applications. The poor water solubility of this flavanonol at ambient conditions inhibits its implementation in clinical practice as an injectable dosage form. Thus, increasing water solubility is a critical step toward solving this problem. Herein we attempted to deal with this problem via DHQ phase modification while at the same time adhering to the principles of green chemistry as much as possible. Lyophilization is an appropriate method to achieve phase modification in an environment-friendly way. This method was employed to generate new phase modifications of DHQ that were then characterized. Mixtures of water with ethanol or acetonitrile were used as solvents for the preparation of the lyophilizates, DHQE, and DHQA, respectively. The results of dissolution testing of the obtained DHQE and DHQA demonstrated that the lyophilization increased water solubility at least 30-fold times. These new DHQ modifications were studied by scanning electron microscopy, mass-spectrometry, nuclear magnetic resonance spectroscopy, infrared spectroscopy, X-ray powder diffraction, and thermal analysis. Their solid-state phases were confirmed to differ from the initial DHQ substance without any changes in the molecular structure. Both DHQE and DHQA showed as high antioxidant activity as the initial DHQ. These data demonstrate the potential of DHQE and DHQA as active pharmaceutical ingredients for injectable dosage forms

РЕЗУЛЬТАТЫ МНОГОЦЕНТРОВОГО ДВОЙНОГО СЛЕПОГО РАНДОМИЗИРОВАННОГО КЛИНИЧЕСКОГО ИССЛЕДОВАНИЯ ПЕРВОЙ ФАЗЫ ПРЕПАРАТА BCD-022 ПО СРАВНЕНИЮ С ПРЕПАРАТОМ ГЕРЦЕПТИН®, ПРИМЕНЯЕМЫХ В СОЧЕТАНИИ С ПАКЛИТАКСЕЛОМ У БОЛЬНЫХ МЕТАСТАТИЧЕСКИМ РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ

Within the framework of multicenter double-blind randomized clinical trial studied pharmacokinetics and safety of BCD-022 (trastuzumab, "Biocad" company, Russia), compared with the drug Herceptin (trastuzumab, F. Hoffmann-La Roche Ltd., Switzerland). Evaluation of the effectiveness was not the aim of the interim analysis, the results of which are shown. BCD-022 and Herceptin were used in combination with paclitaxel in patients with metastatic breast cancer with HER2 overexpressing (HER2 (+), mBC).Methods. The analysis included 46 patients with HER2 (+) metastatic breast cancer (mBC) at the age of 29 to 71 years (22 - in the group of studied drug BCD-022 and 24 - in the Herceptin group). All patients received one course of therapy of BCD-022 or Herceptin 8 mg/kg intravenously and paclitaxel 175 mg/m2 intravenously on day 1 of a three-week course of treatment and continue to receive treatment with the same scheme with the use of trastuzumab 6 mg/kg (mandatory in the study is to conduct 6 courses of therapy). Randomization was carried out in groups in a ratio of 1: 1. The primary endpoint of pharmacokinetics evaluation was the area under the curve "concentration-time» (AUC0-504) of trastuzumab after a single application, the secondary - Cmax, T1 / 2 and Tmax. Safety was assessed based on the incidence of adverse events after the first course of therapy.Results. Haematological toxicity, myalgia and arthralgia were the most frequent adverse events. Most reported adverse events had mild to moderate grade according to CTCA 4.03 and were caused  by effect of myelosuppressive chemotherapy. There were no statistically significant differences in adverse events frequency between the groups. There were 6 serious adverse events: 2 - in the BCD-022 group and 4 - in the Herceptin group. All pharmacokinetic parameters, including the primary endpoint (AUC 0-504) and secondary endpoints (Cmax, T1 / 2 and Tmax), of studied drug BCD-022 and Herceptin had no statistically significant difference.Conclusion. BCD-022 (trastuzumab, "Biocad" company, Russia) regarding to its safety profile and pharmacokinetic properties is fully consistent with the original drug trastuzumab Herceptin (F. Hoffmann-La Roche Ltd., Switzerland) and can be recommended for further clinical study.В рамках многоцентрового двойного слепого рандомизированного клинического исследования была изучена фармакокинетика и безопасность препарата BCD-022 (трастузумаб, ЗАО «БИОКАД», Россия) по сравнению с препаратом Герцептин® (трастузумаб, Ф. Хоффманн-Ля Рош Лтд, Швейцария). Оценка эффективности не входила в задачи промежуточного анализа, результаты которого представлены. BCD-022 и Герцептин® применялись в комбинации с паклитакселом у пациенток метастатическим раком молочной железы с гиперэкспрессией HER2 (HER2 (+) мРМЖ).Методы. В анализ включено 46 больных HER2 (+) мРМЖ в возрасте от 29 до 71 года (22 — в группу исследуемого препарата BCD-022, 24 — в группу Герцептин®). Все пациентки получили 1 курс терапии по схеме BCD-022 или Герцептин® 8 мг/кг внутривенно капельно и паклитаксел 175 мг/м2 внутривенно в 1 день трехнедельного курса и продолжают лечение по той же схеме с использованием трастузумаба в дозе 6 мг/кг (обязательным в исследовании является проведение 6 курсов терапии). Рандомизация в группы производилась в соотношении 1:1. Первичной конечной точкой для оценки фармакокинетики была площадь под кривой «концентрация-время» (AUC0–504) трастузумаба после однократного применения, вторичными — Cmax, T1/2 и Tmax. Безопасность оценивалась на основании частоты нежелательных явлений после первого курса терапии.Результаты. Среди нежелательных явлений наиболее часто встречалась гематологическая токсичность, миалгия, артралгия. Большинство зарегистрированных нежелательных явлений имели легкую и умеренную степень по СТСАЕ 4.03 и были обусловлены проведением миелосупрессивной химиотерапии. Статистически значимых различий между группами не было выявлено ни по одному из нежелательных явлений. Зарегистрировано 6 серьезных нежелательных явлений: 2 — в группе исследуемого препарата BCD-022 и 4 — в группе Герцептин®. Все фармакокинетические показатели, включая первичную конечную точку (AUC0–504) и вторичные конечные точки (Cmax, T1/2 и Tmax), исследуемого препарата BCD-022 и Герцептин® не имели статистически значимых отличий.Заключение. BCD-022 (трастузумаб, ЗАО «БИОКАД», Россия) по своему профилю безопасности и фармакокинетическим свойствам полностью соответствует оригинальному препарату трастузумаба Герцептин® (Ф. Хоффманн-Ля Рош Лтд, Швейцария) и может быть рекомендован для дальнейшего клинического изучения