Structure of Carbon Nanotubes in Colloidal Solutions under the Influence of a Constant Electric Field

Processes of self-organization in diffusive and limited conditions of colloidal solutions of carbon nanotubes under the influence of constant electric fields are studied. It is established that functionalized MCNT – COOH in a drop of colloidal solution is oriented in an electric field in a controllable way, which is of great practical value

Экспрессия белков с-fos, ERK1/2, MAP2, NOTCH1 в нейронах коры головного мозга человека после ишемического инсульта

Background. The search for protein (these include c-fos, ERK1/2, MAP2, NOTCH1) expression that provide neuroplasticity mechanisms of the cerebral cortex after ischemic stroke (IS) patterns is an urgent task. Aims to reveal c-fos, ERK1/2, MAP2, NOTCH1 proteins expression patterns in human cerebral cortex neurons after IS. Materials and methods. We studied 9 left middle cerebral artery (LMCA) IS patients cerebral cortex samples from 3 zones: 1 the zone adjacent to the necrotic tissue focus; 2 zone remote from the previous one by 47 cm; 3 zone of the contralateral hemisphere, symmetric to the IS focus. Control samples were obtained from 3 accident died people. Identification of targeted proteins NSE, c-fos, ERK1/2, MAP2, NOTCH1 was performed by indirect immunoperoxidase immunohistochemical method. Results. Moving away from the ischemic focus, there is an increase in the density of neurons and a decrease in the damaged neurons proportion, the largest share of c-fos protein positive neurons in zone 2, NOTCH1 positive neurons in zone 1, smaller fractions of ERK1/2 and MAP2 positive neurons compared to the control only in samples of zone 1. Conclusions. With the IS development, the contralateral hemisphere is intact tissue increased activation zone, while the zones 1 and 2 have pathological activation signs. In zone 1 of the range, the adaptive response of the tissue decreases, and in zone 2 it expands. Therefore, a key target for therapeutic intervention is zone 2.Обоснование. Поиск новых направлений патогенетически обоснованной терапии и реабилитации пациентов после ишемического инсульта является актуальной задачей. Для ее решения необходимы новые знания о закономерностях экспрессии после ишемического инсульта в нейронах коры головного мозга белков, обеспечивающих механизмы нейропластичности. К ним относят с-fos, ERK1/2, MAP2, NOTCH1. Цель исследования выявить закономерности экспрессии белков с-fos, ERK1/2, MAP2, NOTCH1 в нейронах коры головного мозга человека после ишемического инсульта. Методы. Анализировали парафиновые срезы образцов коры головного мозга 9 пациентов, умерших в срок от 2 до 6 сут после развития ишемического инсульта в бассейне левой средней мозговой артерии (ЛСМА) из трех зон: 1 зоны, прилежащей непосредственно к очагу некротической ткани; 2 зоны, отдаленной от предыдущей на 47 см; 3 зоны контралатерального полушария, симметричной очагу ишемического инсульта. Контрольные образцы получены от погибших в результате несчастного случая (3 человека). Оценку экспрессии белков NSE, с-fos, ERK1/2, MAP2, NOTCH1 нейронами проводили непрямым иммунопероксидазным иммуногистохимическим методом. Результаты. Выявлены увеличение плотности и уменьшение доли поврежденных нейронов при удалении от ишемического очага, наибольшая доля с-fos протеин-позитивных нейронов в зоне 2, NOTCH1- позитивных нейронов в зоне 1, меньшие доли ERK1/2- и MAP2-позитивных нейронов по сравнению с контрольными только в образцах зоны 1. Заключение. При развитии ишемического инсульта контралатеральное очагу полушарие является зоной повышенной активации интактной ткани, тогда как участки коры, прилежащие непосредственно к очагу и отдаленные от него, имеют признаки патологической активации. При этом для зоны 1 характерно снижение диапазона адаптационного ответа ткани, а для зоны 2 его расширение. Поэтому ключевой мишенью для терапевтического воздействия является зона 2

Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4·5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial

Background: Non-immunogenic staphylokinase is modified recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and selectivity to fibrin. We aimed to assess the safety and efficacy of a single intravenous bolus of non-immunogenic staphylokinase compared with alteplase in patients with acute ischaemic stroke within 4·5 h after symptom onset. Methods: We did a randomised, open-label, multicentre, parallel-group, non-inferiority trial in 18 clinical sites in Russia. We included patients aged 18 years and older with a diagnosis of acute ischaemic stroke (up to 25 points on the National Institutes of Health Stroke Scale). The study drug had to be administered within 4·5 h after the onset of symptoms. Patients were randomly assigned to receive either non-immunogenic staphylokinase (10 mg) or alteplase (0·9 mg/kg, maximum 90 mg), both administered intravenously. The randomisation sequence was created by an independent biostatistician using computer-generated random numbers. 84 blocks (block size of four) of opaque sealed envelopes were numbered sequentially from 1 to 336 and were opened in numerical order. Patients were unaware of their assigned treatment and were assessed by the study investigators who were also unaware of the treatment assignment on all trial days. Emergency department staff, who administered the assigned drug and opened the envelopes, were not masked to treatment. The primary efficacy endpoint was a favourable outcome, defined as a modified Rankin scale (mRS) score of 0–1 on day 90. The margin of non-inferiority was established as 16% for the difference in mRS score of 0–1 on day 90. Non-inferiority was tested using Welch's t-test for the primary outcome only. Endpoints were analysed in the per-protocol population, which comprised all randomly assigned patients who completed treatment without any protocol violations; this population was identical to the intention-to-treat population. This trial is completed and registered at ClinicalTrials.gov, NCT03151993. Findings: Of 385 patients recruited from March 18, 2017, to March 23, 2019, 336 (87%) were included in the trial. 168 (50%) patients were randomly assigned to receive non-immunogenic staphylokinase and 168 (50%) to receive alteplase. The median duration of follow-up was 89 days (IQR 89–89). 84 (50%) of 168 patients in the non-immunogenic staphylokinase group had a favourable outcome at day 90 compared with 68 (40%) of 168 patients in the alteplase group (odds ratio [OR] 1·47, 95% CI 0·93 to 2·32; p=0·10). The difference in the rate of favourable outcome at day 90 was 9·5% (95% CI –1·7 to 20·7) and the lower limit did not cross the margin of non-inferiority (pnon-inferiority <0·0001). Symptomatic intracranial haemorrhage occurred in five (3%) patients in the non-immunogenic staphylokinase group and in 13 (8%) patients in the alteplase group (p=0·087). On day 90, 17 (10%) patients in the non-immunogenic staphylokinase group and 24 (14%) patients in the alteplase group had died (p=0·32). 22 (13%) patients in the non-immunogenic staphylokinase group had serious adverse events, compared with 37 (22%) patients in the alteplase group (p=0·044). Interpretation: Non-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Future studies are needed to continue to assess the safety and efficacy of non-immunogenic staphylokinase in patients with acute ischaemic stroke within the 4·5 h time window, and to assess the drug in patients with acute ischaemic stroke outside this time window with reperfusion CT or magnetic resonance angiography followed by thrombectomy if necessary. Funding: The Russian Academy of Sciences. © 2021 Elsevier Lt