Biocompatibility of Bare Nanoparticles Based on Silicon and Gold for Nervous Cells

This work aimed to investigate the biocompatibility of bare (ligand-free) lasersynthesized nanoparticles (NPs) based on silicon (Si) and gold (Au) with primary hippocampal cultures. 1%, 5% and 7% of culture medium were replaced by 0.1 mg/mL NP solution on day 14 of culture development in vitro. Our studies revealed that the NPs caused a dose-dependent cytotoxic effect, which was manifested by an increase the number of dead cells and a decrease of the spontaneous functional calcium activity of neural networks. Au NPs revealed less pronounced cytotoxic effect than Si ones and it can be explained by larger size and better solubility of Si NPs. Keywords: bare nanoparticles, primary hippocampal cultures, neurotoxicit

The Influence of different types of upconversion nanoparticles surface coatings on neurotoxicity

The aim of the investigation was to study the effect of upconversion nanoparticles (UCNPs) with different surface coatings on viability and functional neural network activity of primary hippocampal cultures. Materials and Methods: The UCNPs with three surface coating modifications (tetramethylammonium hydroxide (TMAH), polymaleic acid octadecene and polyethyleneimine (PEI)) were synthesized by a solvothermal technique with further hydrophilization. Primary hippocampal cultures, obtained from C57BL/6 mice embryos (Е18), were incubated with tested UCNPs in the concentration of 0.8 and 8 mg/ml during 72 h. The cell viability detection, evaluation of morphological changes by immunocytochemical staining as well as the UCNPs influence on the main parameters of the functional neural network calcium activity and on the endocytosis processes were carried out. Results: Our studies revealed that UCNPs caused a dose-dependent cytotoxic effect on primary hippocampal cultures, wherein the severity of this effect directly related to the type of UCNPs surface coating. The greatest cytotoxicity was identified for UCNP–PEI, and the least — for UCNP–TMAH. UCNPs toxicity is manifested in significant morphological changes of neural networks and in the increase the number of dead cells (р<0.05) in primary hippocampal cultures. Moreover, a significant decrease (р<0.05) in the main parameters of spontaneous functional calcium activity was shown. Conclusion: A comprehensive investigation of the nanoparticles effects on primary hippocampal cultures showed that all tested UCNPs have the strong toxic effect to the nervous system cells.9 page(s

The First Results of the Evaluation of Long-Term Nicorandil Treatment Effect on the Probability of Cardiovascular Complications in Patients with Stable Coronary Artery Disease (Data of Observational NIKEA Study)

Aim. To assess the influence of addition of nicorandil on long-term cardiovascular complications in patients with chronic coronary artery disease (CAD) in the framework of a prospective observational study.Material and methods. Prospective observational multicenter NIKEA study included 590 patients with stable CAD. All patients were recommended to add nicorandil to their baseline therapy. After 21 months, 547 telephone contacts were made, the life status of 524 people was specified, 23 patients were lost to follow-up. The following complications were registered: death from any cause; non-fatal myocardial infarction (MI); non-fatal stroke; urgent myocardial revascularization; hospitalization due to deterioration of CAD, chronic heart failure (CHF) or atrial fibrillation (AF). In 479 patients, a telephone survey was performed to identify adherence (persistence) to nicorandil– i.e. to verify the continuing the treatment for the prescribed duration.Results. During the follow-up period, 15 deaths were recorded, the causes of which were as follows: 3 CAD (2 MI, 1 left ventricular aneurysm), 1 pulmonary embolism, 2 CHF; 1 stroke, 1 oncology, 1 bilateral pneumonia. In the remaining 6 cases, the causes of death were not known. Cardiovascular (CV) complications were MI (8 cases in 7 patients, 1 patient had 2 MI in the follow-up period, 3 patients from this group died), stroke in 6 patients (7 cases, 1 patient had 2 strokes, 1 patient died). Urgent percutaneous coronary intervention was performed in 3 patients (in 2 patients due to acute MI, in 1 patient due to unstable angina). During the observation period, 21 people were urgently hospitalized due to deterioration of clinical condition. According to the results of a medical survey, by the end of the follow-up period, 237 people were not adherent to prescribed nicorandil, and 242 patients took the recommended medication (adherent patients). The main cardiovascular complications and death from any cause (р&lt;0.001) as well as the number of urgent hospitalizations (р=0.017) were significantly more common in non-adherent to nicorandil patients in comparison with adherent patients.Conclusion. The overall rate of CAD complications in NIKEA study was typical for patients with stable CAD receiving contemporary medical therapy. Addition of nicorandil significantly reduced the rate of CV complications in adherent patients in comparison with non-adherent patients

TREATMENT ADHERENCE AND QUALITY OF LIFE OF PATIENTS WITH STABLE ISCHEMIC HEART DISEASE IN TREATMENT WITH NICORANDIL: INTERRELATION AND INTERACTION (ACCORDING TO THE RESULTS OF THE OBSERVATIONAL STUDY NIKEA)

Aim. To assess quality of life (QoL) and its dynamics during nicorandil treatment in patients with stable ischemic heart disease, to study the relationship of treatment adherence and QoL indicators when treated with nicorandil.Material and methods. Observational program NIKEA included 590 patients with angina pectoris. Seattle Angina Questionnaire (SAQ) was used to assess QoL. Patients completed SAQ at the visit of inclusion (V0) and at the visit after 3 months of observation (V3). Potential and actual adherence to therapy was assessed by medical interviews at visits V0, V1 (1 month of observation) and V3. During the visit V0 417 people (from 590 ones enrolled into the study) completed SAQ (71% response); after 3 months (V3) SAQ was filled in by 454 of 552 people who came to this visit (82% response). According to the results of medical interviews, potential adherence (visit V0) was determined in all 590 patients, actual adherence to nicorandil (visits V1 and V3) was assessed in 552 patients who came to these visits. In accordance with the degree of adherence, all patients were divided into 3 groups: (1) adherent to treatment (taking nicorandil for the first three months), (2) non-adherent (who refused to take nicorandil), and (3) partially non-adherent (who started nicorandil, but for various reasons stopped taking the drug).Results. In all patients, regardless of their adherence to the recommended drug, there was an increase in QoL according to all five scales of the SAQ after 3 months of follow-up. Statistically significant positive dynamics of all SAQ indicators was found only in adherent patients (p&lt;0.0001 for all aspects). Patients, who showed good adherence to nicorandil at V1, had more severe angina at the beginning of treatment (according to “Angina Stability” and “Angina Frequency” indicators). These patients also had lower QoL “Disease Perception” score and more confidence in the doctor (“Treatment Satisfaction” score) than non-adherent patients (p&lt;0.05). In non-adherent patients a mild degree of angina was determined 2 times more often according to “Angina Frequency” indicator (p=0.03).Conclusion. The results of the study confirm the interrelation and mutual influence of the QoL indicators and treatment adherence to nicorandil. Effective treatment with nicorandil in patients with lower health-related QoL indicators could increase treatment adherence. On the other hand, the mild degree of angina, the low level of confidence in the treating doctor, the side effects of the new drug reduce medication adherence of patients, which, as a result, negatively affects the QoL of these patient

ASSESSMENT OF ADHERENCE TO TREATMENT AND FACTORS AFFECTING IT IN PATIENTS WITH STABLE ISCHEMIC HEART DISEASE DURING THERAPY WITH NICORANDIL

Working Group of the NIKEA Program. Ekaterinburg: Akulina E.N.; Izhevsk: Shinkareva S. E., Grebnev S.A.; Krasnodar: Kudryashov E.A., Fendrikova A.V.; Krasnoyarsk: Nemik D.B., Pitaev R.R., Altaev V.D., Samokhvalov E.V., Stolbikov Y.Y.; Moscow: Dmitrieva N.A., Zagrebelnyy A.D., Zakharova A.V., Balashov I.S., Leonov A.S., Sladkova T.A., Zelenova T.I., Shestakova G.N., Kolganova E.V., Maksimova M.A.; Novosibirsk: Moskalenko I.V., Shurkevich A.A.; Omsk: Loginova E.N., Gudilin V.A.; Orel: Zhuravleva L.L., Lobanova G.N., Luneva M.M.; Orenburg: Kondratenko V.Y.; Rostov-on-Don: Kalacheva N.M., Kolomatskaia O.E., Dubishcheva N.F., Romadina G.V., Chugunova I.B., Skarzhinskaia N.S.; Ryazan: Bulanov A.V., Trofimova Y.M., Nikolaeva A.S.; St. Petersburg: Savinova E.B., Ievskaia E.V., Vasileva L.B.; Tula: Zubareva L.A., Berberfish L.D., Gorina G.I., Nadezhkina K.N., Iunusova K.N., Nikitina V.F., Dabizha V.G., Renko I.E., Soin I.A.Aim. To study the adherence to treatment and the factors that affect it in patients with stable coronary heart disease during the treatment with nicorandil. Material and methods. The use of nicorandil in addition to standard antianginal therapy was recommended to patients (n=590) in a prospective, observational, multicenter NIKEA study. Patients completed original questionnaires on adherence, including a Morisky-Green test at the enroll visit. The questionnaires were filled by 423 patients (73% response). The factors that influence adherence were studied.Results. All patients were divided into 3 groups, depending on the adherence to the use of nicorandil: immediately refused to take the drug (n=150; group 1); started, but stopped taking nicorandil in the first 3 months of observation (n=75; group 2); who took nicorandil for 3 months (n=327; group 3). Potentially adherents (intention to treat) were 582 out of 590 (98.6%) patients, and actually adherents – only 327 of 552 (59.2%) patients. The main reason for non-adherence to the beginning of therapy is polypharmacy; to the continuation of the treatment that had just started – adverse events; for termination of long-term therapy – polypharmacy, adverse events and insufficient effectiveness of treatment. Group 3 had initially more severe angina pectoris: more number of angina attacks (p=0.014) and the need of short-acting nitrates (p&lt;0.0001). Patients of the group 1 compared to the patients of group 3 did not visit the doctors more often or attended them only when necessary, violated the medical prescriptions for taking medications (p&lt;0.05). According to the results of the Morisky-Green test, 150 patients (36.2%) were not are committed to medical recommendations, 264 (63.8%) – are committed. Women were more adherent than men (p=0.47); patients with class I angina were more adherent than patients with class III angina (p=0.027), and patients who regularly attended the treating physician (more often than once a month) were more committed to medical recommendations than patients, not visiting the treating physician (p=0.004).Сonclusion. The levels of overall adherence according to Morisky-Green test, the potential adherence according to the survey and the actual adherence of patients to treatment vary considerably. The leading cause of non-adherence at the beginning of therapy is polypharmacy, for the continuation of the recently started treatment – the adverse events; for long-term sustained treatment – equally polypharmacy, drug adverse events and the lack of treatment efficacy