Metabolic model for laboratory control of anti-ischaemic therapy effectiveness: a case study of nicorandil

Scientific relevance. A key anti-ischaemic mechanism of some medicinal products involves their effects on the metabolism of endothelial vasodilators, particularly the synthesis of nitric oxide from arginine and its precursor citrulline.Aim. The study was aimed to determine whether the plasma time course of guanidine derivatives (arginine precursors) is applicable to laboratory control of anti-ischaemic therapy effectiveness using a single oral dose of nicorandil in patients with coronary heart disease as a case study.Materials and methods. The authors used high-performance liquid chromatography to determine metabolites. Blood samples for analysis were obtained from 30 patients with angina pectoris (Grade II–III, Canadian Cardiovascular Society) and 30 healthy donors. All the study participants received a single oral dose of 20 mg nicorandil after 10 h of fasting.Results. At baseline, patients showed significantly higher plasma citrulline levels than donors. However, the elevated levels decreased to the healthy range after nicorandil administration. Plasma arginine levels in patients showed a statistically significant increase following nicorandil administration. Plasma homoarginine levels in patients remained reduced both before and after dosing. Nicorandil did not influence elevated levels of the endogenous nitric oxide synthase inhibitor (asymmetrical dimethylarginine).Conclusions. In addition to the established mechanisms responsible for altering cell metabolism, nicorandil enhances the contribution of citrulline to arginine resynthesis. It is reasonable to include citrulline and arginine, which are involved in the vasodilator response, in model schemes for laboratory control of the effectiveness of anti-ischaemic therapy

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy

Метаболическая модель для лабораторного контроля эффективности антиишемической терапии на примере использования никорандила

A key anti-ischaemic mechanism of some medicinal products involves their effects on the metabolism of endothelial vasodilators, particularly the synthesis of nitric oxide from arginine and its precursor citrulline.The aim of the study was to determine whether the plasma time course of guanidine derivatives (arginine precursors) is applicable to laboratory control of anti-ischaemic therapy effectiveness using a single oral dose of nicorandil in patients with coronary heart disease as a case study.Materials and methods. The authors used high-performance liquid chromatography to determine metabolites. Blood samples for analysis were obtained from 30 patients with angina pectoris (Grade II–III, Canadian Cardiovascular Society) and 30 healthy donors. All the study participants received a single oral dose of 20 mg nicorandil after 10 h of fasting.Results. At baseline, patients showed significantly higher plasma citrulline levels than donors. However, the elevated levels decreased to the healthy range after nicorandil administration. Plasma arginine levels in patients showed a statistically significant increase following nicorandil administration. Plasma homoarginine levels in patients remained reduced both before and after dosing. Nicorandil did not influence elevated levels of the endogenous nitric oxide synthase inhibitor (asymmetrical dimethylarginine).Conclusions. In addition to the established mechanisms responsible for altering cell metabolism, nicorandil enhances the contribution of citrulline to arginine resynthesis. It is reasonable to include citrulline and arginine, which are involved in the vasodilator response, in model schemes for laboratory control of the effectiveness of anti-ischaemic therapy.Важным механизмом антиишемического действия некоторых препаратов является их влияние на метаболизм эндотелиальных факторов вазодилатации, в частности на образование оксида азота из аминокислоты аргинина и его предшественника цитруллина.Цель работы: изучение возможности использования показателей динамики гуанидиновых производных — предшественников аргинина — в плазме крови для лабораторного контроля эффективности антиишемической терапии на примере однократного перорального приема никорандила у пациентов с ишемической болезнью сердца.Материалы и методы: метаболиты определяли методом высокоэффективной жидкостной хроматографии в образцах крови, взятых у 30 пациентов со стенокардией напряжения II–III функционального класса. Референтной группой являлись 30 здоровых доноров. Никорандил использовали перорально в разовой дозе 20 мг после 10-часового голодания.Результаты: у пациентов исходный уровень цитруллина был достоверно выше, чем у здоровых доноров. После приема никорандила содержание цитруллина снижалось до уровня, не отличающегося от уровня в плазме крови здоровых доноров группы сравнения. Содержание аргинина в плазме крови пациентов после приема препарата достоверно возрастало. При этом у них сохранялся пониженный уровень гомоаргинина как до, так и после приема никорандила. Обнаружено также отсутствие влияния приема никорандила на уровень эндогенного ингибитора синтазы оксида азота — асимметричного диметиларгинина.Вывод: в дополнение к известным механизмам воздействия никорандила на клеточный метаболизм показано усиление участия цитруллина в ресинтезе аргинина. При оценке эффективности антиишемической терапии в модельную схему для лабораторного контроля целесообразно включать цитруллин и аргинин, которые являются участниками вазодилатационного ответа

Physics Performance Report for PANDA: Strong Interaction Studies with Antiprotons

To study fundamental questions of hadron and nuclear physics in interactions of antiprotons with nucleons and nuclei, the universal PANDA detector will be built. Gluonic excitations, the physics of strange and charm quarks and nucleon structure studies will be performed with unprecedented accuracy thereby allowing high-precision tests of the strong interaction. The proposed PANDA detector is a state-of-the art internal target detector at the HESR at FAIR allowing the detection and identification of neutral and charged particles generated within the relevant angular and energy range. This report presents a summary of the physics accessible at PANDA and what performance can be expected.Comment: 216 page

POSSIBILITIES OF APPLYING MATHEMATICAL ANALYSIS OF BLOOD FLOW CHARACTERISTICS IN ENDOVASCULAR TREATMENT OF AORTIC DISEASES USING HOLOMETALLIC STENTS

Purpose. The purpose of the article is to access possibilities of blood flow mathematical analysis in aortic aneurysm before and after bare metal stent implantation.Materials and methods. Mathematical models of aortic blood flow were based on data received at studying 15 CT-scans of patients with abdominal aorta aneurysms (12) and dissections (3) and their duplex ultra-sound hemodynamic data. At constructing mathematical model the program SolidWorks was used. Working with the program consisted of two stages: establishment of conditions for geometric objects; forming of abdominal aorta model from these objects. In the study hemodinamic aneurysm indexes was evaluated on rectilinear and curvilinear segments. Some of characteristics were variable: diameter, aneurysm wall thickness, its length, elasticity.Results. Correlation of extreme tension into aneurysm wall on rectilinear and curvilinear segments according to aneu­rysm wall thickness was assessed. Possibilities of pathological blood flow changes correction at bare metal stent im­plantation into aortic aneurysm were estimated: if presence of bare metal stent were introduced into mathematical parameters blood flow characteristics became almost as standard characteristics. Received data can enhance successful endovascular treatment of aortic diseases with using of bare metal stents.Conclusion. Mathematical models of aortic and vascular aneurysms before and after surgery can be an effective tool in bettering quality of medical help for vascular patients

Perioperative myocardial injury in patients with coronary artery disease during elective lower limb surgery

Aim. To assess the prevalence of ischemic myocardial injury and the cardioprotective effect of nicorandil by assessing high-sensitivity cardiac troponin (hs-cTn) in patients with stable coronary artery disease (CAD) during elective lower limb surgery, as well as to identify predictors of adverse cardiac events.Material and methods. The study included 70 patients with stable coronary artery disease hospitalized for elective autogenous femoropopliteal bypass (FPB) surgery. After randomization, all patients were divided into two following groups: control group — 35 patients; main group — 35 patients, who, in addition to standard therapy, were prescribed nicorandil (Cordinic, PIQ-PHARMA) in a single dose of 20 mg 2 hours before surgery. In the postoperative period, the incidence of myocardial injury was assessed by hs-cTn increase. The obtained primary data were subjected to mathematical processing using the R-Studio software package (R language).Results. At baseline, patients in both groups were comparable in clinical characteristics, therapy, and duration of vascular surgery. In the main group of patients receiving nicorandil, a significant decrease in the incidence of perioperative myocardial injury was noted. In 5 patients of the control group, hs-cTn level 24 hours after surgery exceeded the threshold value, which indicated myocardial injury in the early postoperative period. In the nicorandil group, there was no hs-cTn increase (14% vs 0%, p=0,027). Regression analysis identified a predictor of perioperative myocardial injury — left ventricular ejection fraction (LVEF) <50%. LVEF <50% increases the risk of myocardial injury in the early postoperative period by 7,36 times (p=0,04) and 9,15 times (p=0,048) according to univariate and multivariate regression analysis, respectively.Conclusion. Perioperative myocardial injury is a common complication in patients with CAD undergoing lower extremity revascularization. The use of nicorandil (Cordinic, PIQ-PHARMA) before elective revascularization surgery helps reduce the incidence of ischemic myocardial injury in the early postoperative period and is not accompanied by adverse reactions, which rationales this approach to improve the clinical outcomes of lower extremity revascularization in patients with stable CAD. A predictor of myocardial injury, determined by hs-cTn, is a LVEF <50%