CAR-cell therapy is a promising new method of cancer treatment. The biomedical cell product Anti-HER2-CAR-T-NK cells has been found safe in a course of intraperitoneal injection at a human-equivalent therapeutic dose in male and female ICR mice. The obtained information can help in the future to form the basis of recommendations for preclinical studies of CAR-cell immunopreparations.
В статье описаны физико-химические свойства и механизмы действия диоксида кремния. Вследствие широкого спектра терапевтического действия диоксида кремния (снижение эндогенной интоксикации, нормализация кишечного микробиоценоза, уменьшение системной воспалительной реакции, активация детоксикационной функции) использование аэросила как матрицы при производстве лекарственных средств для лечения и профилактики хирургической инфекции является интересным направлением для научных исследований. Использование сорбционных матриц при моделировании новых препаратов средств для комплексного лечения гнойно-воспалительных процессов мягких тканей, по нашему мнению, является эволюционно обоснованным подходом, что требует дальнейшего изучения с целью определения показаний к широкому применению в хирургической практике.
The influence of new promising peptide (APCH3 and PT1) and nonpeptide analgesics (sevanol) on the behavior of male ICR mice was studied. All studied compounds at doses producing significant analgesic effects did not influence the behavior of mice in open-field tests. However, APCH at doses 10,000 times greater than the pharmacologically active dose produced sedative effects. Also, sevanol at a dose of 35 mg/kg caused statistically significant behavioral changes relative to the pharmacologically active dose (1 mg/kg) but not to the controls.
Проведено исследование влияния на поведение самцов мышей ICR новых потенциальных обезболивающих соединении пептидной (APCH3 и РТ1) и непептидной (севанол) природы. Все исследуемые вещества в тесте «открытое поле» не оказывали влияния на поведение мышей в дозах, вызывающих эффективную анальгезию. Однако APCH3 оказывает седативное действие на мышей в дозах, в 10000 раз превышающих фармакологически активную. Тогда как севанол в дозе в 35 мг/кг вызывал достоверное изменение поведения относительно фармакологически активной дозы 1 мг/кг, но не от контроля.
Показано, что полипептидные анальгетические соединения APCH3 (ингибитор TRPV1 рецептора) и РТ1 (ингибитор P2X3 рецептора) не оказывают действия на сердечно-сосудистую и дыхательную системы как при однократном, так и при многократном введении мышам. Низкомолекулярное вещество севанол (ингибитор ASIC3 рецепторов) не влияет на сердечно-сосудистой систему, однако при длительном применении в течение 14 дней влияет на параметры дыхательной системы, достоверно увеличивая частоту дыхания и максимальный поток выдоха.
The polypeptide analgesic compounds APCH3 (a TRPV1 receptor inhibitor) and PT1 (a P2X3 receptor inhibitor) were shown not to act on the cardiovascular system or respiratory system when given either as single or multiple doses in mice. The low molecular weight compound sevanol (an ASIC3 receptor inhibitor) had no effect on the cardiovascular system, but prolonged use for 14 days affected measures of the respiratory system, significantly increasing respiratory rate and peak expiratory flow rate.
The authors have analyzed international experience in creating legal documents regulating the use of animals for scientific purposes. Topical issues related to the use of laboratory animals for scientific purposes in the Russian Federation, including for the purpose of preclinical studies on the efficacy and safety of new medicines, are discussed. The negative effects of the lack a clear and consistent legal framework for the organization and limits of the use of laboratory animals for research purposes in the Russian Federation are identified. Particular attention is paid to the issue of bioethics, the principles of ethical expertise of research activities involving laboratory animals and the issues of bioethical committees activities. The basic directions of perfection of normative-legal acts and methodological documents in the field of organization and limits of the use of laboratory animals for research purposes are proposed.
Morphometric characters of laboratory animals measured in different laboratories by different investigators are varied essentially. Apparently, this difference is caused by various influences of environment, depends on the way, moment and a place of blood sampling, dietary, animal age and some other factors. Standard conditions of animal’s maintenance are necessary for valid and reproducible research data therefore much attention now is given to the experimental animals care and use. This paper summarizes morphometric characters of SD (Sprague Dawley) rats mice which had SPF status (specific pathogen free) and were housed in standard conditions recommended for laboratory rodents maintenance.
The historical blood test data of control CD (Sprague-Dawley) rats having SPF category (pathogenic flora free) are presented. The data have been received by using hematological analyzers. The comparison of the results of rat' 3-part white blood cells differential leukogram with the data of microscopic studying revealed the difference in the quantitative formula of leukocyte subpopulations.
This article shows 4 models of arrhythmias: adrenaline, barium chloride, calcium chloride and aconitine. This combination of models allows to fully explore the wide range of antiarrhythmic drugs and to study the mechanism of their effects. In addition, in the main parameters for study of new antiarrhythmic drugs were selected: it has been shown that the study of blood pressure and ECG-charts, as well as variability in heart rate period - sufficient basis for primary screening of antiarrhythmic drugs.
Hemodynamic activity of peptides from differentiation factor HLDF (promyelocytic HL-60 line) was studied on WKY and SHR-SP rats. Intravenous infusion of the test peptides was accompanied by changes in blood pressure and heart rate, which depended on the structure of peptides and functional activity of the organism and differed in normotensive and hypertensive animals.
We studied the effects of blockade of nicotinic receptors in sympathetic and parasympathetic ganglia (hexamethonium), muscarinic receptors (atropine), and β1-adrenoceptors (atenolol) on arrhythmogenic activity of endothelin-1 during inhibition of nitric oxide synthesis with Nω-nitro-L-arginine in NMRI mice. Atropine reduced, while hexamethonium completely abolished the arrhythmogenic effect of endothelin-1 during nitric oxide synthase inhibition. Atenolol potentiated arrhythmogenic activity of Nω-nitro-L-arginine, but endothelin-1 had no effect on the incidence of arrhythmias under these conditions.
Arrythmogenic effects of endothelin-1 were studied in NMRI mice under conditions of NO-synthase blockade with Nω-nitro-L-arginine methyl ester. Intravenous injection of endothelin-1 increased heart rate variability in awake mice. NO-synthase blockade potentiated the arrythmogenic effects of endothelin-1. In narcotized animals the arrythmogenic effect of endothelin-1 was not observed and was considerably weakened under conditions of NO-synthase blockade. Arrhythmia was paralleled by atrioventricular block and lengthening of the ST segment.
The weak neurotoxin from the Naja kaouthia cobra venom was found, under the intravenous administration to rats, to reduce the arterial blood pressure and increase the heart rate.
Anaphylactic response intensity was quantitatively estimated by means of measuring mean arterial pressure (MAP) and heart rate (HR). Damage to intestinal mucosa was studied by means of morphometry. These indices grew in a dose-dependent way along with the amount of administered egg ovalbumin (OVA). The MAP and HR measurements seem to be useful in a quantitative elucidation of allergic sensitivity in laboratory animals.