[Clinical and Laboratory Parameters and Complication Rates In Patients With Myocardial Infarction Without Obstructive Coronary Artery Disease].

AIM: To evaluate clinical, anamnestic and laboratory data and the incidence rate of complications in patients with myocardial infarction (MI) without obstructive coronary artery (CA) disease. MATERIAL AND METHODS: This study included 158 patients with MI without obstructive CA disease (main group), 150 patients with MI and obstructive CA disease (comparison group), and 55 patients without documented ischemic heart disease (IHD) (control group). Clinical and anamnestic data, carbohydrate and lipid metabolism, concentrations of high-sensitivity troponin and C-reactive protein (CRP) were evaluated, and electrocardiography, Holter electrocardiogram monitoring, echocardiography, and coronary angiography were performed for all patients. RESULTS: The incidence rate of MI without obstructive CA disease was 1.9%, which was in general consistent with international data. Patients with MI without obstructive CA disease were somewhat younger than patients of the comparison group. Traditional risk factors, such as arterial hypertension (AH), acute cerebrovascular disease, diabetes mellitus (DM), and obesity were more frequently observed in patients with MI and obstructive CA disease, but the body weight index was significantly higher in MI patients without obstructive CA disease. The multivariate regression analysis identified the most significant factors associated with the development of MI in the group without obstructive CA disease: lipid metabolism disorders, AH, DM, male gender, smoking, and family history of IHD. Patients with MI without obstructive CA disease had a lower troponin level but a higher CRP level. Patients with MI without obstructive CA disease had a higher left ventricular (LV) ejection fraction (EF); acute heart failure (AHF), acute LV aneurism, and arrhythmias were the most frequent complication in this group. CONCLUSION: Patients with MI without obstructive CA disease had a higher LV EF, and their most frequent complications were AHF, acute LV aneurism, and arrhythmias.

Predictive modeling of antibacterial activity of ionic liquids by machine learning methods.

Structural variation and different bioactivity of ionic liquids (ILs) make them highly promising for the development of novel biocides. Application of computational methods to the evaluation of potential antibacterial activity of chemical compounds is a useful, time- and cost-saving tool replacing numerous experimental syntheses. In the present study, quantitative structure-activity relationship (QSAR) modeling is applied to develop models (based on more than 800 data points) aiming to predict the minimal inhibitory concentration (MIC) of ILs against three types of human pathogens - Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The random forest model with the AlvaDesc descriptors in general demonstrates the best performance for all the three types of bacteria and is suggested as a final model. To interpret the final model and determine the most significant descriptors, a SHapley Additive exPlanation (SHAP) method was applied. Six amino acid ILs, which were synthesized for the first time, and five halogenide ionic liquids purchased, all based on 1-alkyl-3methylimidozolium cations with different alkyl chain lengths, C10, C12 and C14, are tested in vitro and used to validate the developed QSAR models. The data sets and developed model are available free of charge at http://ochem.eu/article/147386.

Some Aspects of Investigation of the Central Mechanism of Antinociceptive Effect of a New Analgetic from the Hexaazaisowurtzitane Group.

Possible involvement of µ1- and κ-opioid receptors and cannabinoid type 1 receptors (CB1) into the mechanism of analgesic activity of the experimental drug product "Thiowurtzine, (capsule 120 mg)" synthesized on the basis of active pharmaceutical substance 4-(3,4-dibromthiophencarbonyl)-2,6,8,12-tetraacethyl-2,4,6,8,10,12hexaazatetracyclo [5,5,0,03,11,05,9]dodecane was studied in vivo using the hot plate test and acetic acid writhing test. The involvement of κ-opioid receptors and noninvolvement of µ1-receptors and CB1 receptors in the mechanism of thiowurtzine analgesia were demonstrated. The mechanism of interaction of the test analgesic with opioid receptors differs from that of the reference drug tramadol. The interaction of thiowurtzine with serotonergic, GABAergic, and muscarinic cholinergic neurotransmitter systems was studied in vivo using pharmacological analyzers. The absence of muscarinic cholinolytic effect of thiowurtzine was demonstrated in the model of arecoline-induced tremor. The central serotonin-blocking activity of the analgesic was revealed in the model of 5-hydroxytryptophan hyperkinesis in mice. Anticonvulsant activity was demonstrated in the corazol convulsions test, which attested to the presence of a GABAergic component. The mechanism of central analgesia caused by the drug product "Thiowurtzine, capsule 120 mg" appeared to be polymodal. The antinociceptive activity of the analgesic was comparable to that of tramadol.

Effect of Tussilago farfara L. Polysaccharides on the Content of Hematopoietic Stem Cells (CD117+34+) in the Bone Marrow of Mice Treated with Cyclophosphamide.

Myelotoxicity is a serious side effect of anticancer drugs. The search for drugs that can reduce the hematological complications of chemotherapy through modulation of hematopoietic stem cells is an urgent task of oncopharmacology. In the present study we showed that administration of Tussilago farfara L. polysaccharides to C57BL/6 mice treated with cyclophosphamide can increase the number of hematopoietic stem cells (CD117+34+) in the bone marrow.

Effects of Tussilago farfara L. Polysaccharides on the Expression of PD-1 (CD279) and PD-L1 (CD274) in Peripheral Blood and Tumor Tissue Lymphocytes in Mice with Lewis Lung Carcinoma.

One of prospective methods for immunotherapy of tumors is modulation via immunological checkpoints, specifically, via the PD-1(CD279)/PD-L1(CD274) system. Interactions between tumor cell receptor (CD279) and the ligand on lymphocytes (CD274) leads to lymphocyte inactivation, which allows tumor escape from the immune control. Experiments on C57BL/6 mice with Lewis lung carcinoma demonstrate the possibility of reducing the expression of CD279 and CD274 on the peripheral blood and tumor tissue lymphocytes under the effects of Tussilago farfara L. polysaccharides. This phenomenon can underlie the antitumor and antimetastatic effects of these substances.

Correction of Damaging Effects of Cisplatin-Containing Polychemotherapy on the Intestinal Epithelium with Tussilago farfara L. Polysaccharides.

A possibility for correction of damaging effects of polychemotherapy on the intestinal epithelium with Tussilago farfara L. polysaccharides was studied on C57Bl/6 mice with Lewis lung carcinoma. The polysaccharides had protective and/or stimulating effects on the intestinal epithelium during polychemotherapy and promoted reparative regeneration in the intestine.

Protective Effect of Polysaccharides from Tussilago farfara L. on Bone Marrow Cells and Small Intestinal Epithelium Under Conditions of Polychemotherapy Evaluated by DNA Comet Assay.

Using DNA comet assay we found that polysaccharides from Tussilago farfara L. reduced the intensity of polychemotherapy-induced apoptosis and DNA damage in bone marrow cells and small intestinal epithelium of C57Bl/6 mice, which attested to genoprotective properties of these polysaccharides.

Modification of the Myelotoxic and Antitumor Effects of Polychemotherapy by Polysaccharides from Tussilago farfara L.

The experiments on C57Bl/6 mice with Lewis lung carcinoma showed that addition of Tussilago farfara L. polysaccharides to conventional cisplatin/paclitaxel polychemotherapy moderated neutropenia caused by antitumor therapy and increased its efficiency. The stimulating effect of polysaccharides on the granulopoietic lineage cells is comparable with that of recombinant CSF Neupogen.

Effect of Acorus calamus L. Polysaccharide on CD274 and CD326 Expression by Lewis Lung Carcinoma Cells in Mice.

Tumor cells can maintain their growth via immunosuppression and escape from host antitumor immunity by controlling the PD-1/PD-L1 system. Expression of PD-L1 (CD274) is an inhibitory signal for T cells, while the increase in CD326 expression in the tumor tissue correlates with metastasis development. The experimental preparation on the basis of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronan from Acorus calamus L. produces an antitumor effect: it reduces tumor node size and the number and area of metastases after transplantation of Lewis lung carcinoma. Using flow cytometry, we demonstrated a decrease in the population of tumor cells expressing surface CD274 (PD-L1) and CD326 antigens after 20-day course of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronan.

Plant Polysaccharides Attenuate Fluorouracil Toxicity for the Small Intestinal Epithelium.

Polysaccharides from Tussilago farfara L., Acorus calamus L., and Echinacea purpurea (L.) Moench attenuated the toxic effect of fl uorouracil on the small intestinal epithelium of mice with Lewis lung carcinoma. Addition of polysaccharides to chemotherapy protocols stimulated reparative regeneration processes in the small intestine damaged by the cytostatic treatment. No stimulating effects of the polysaccharides on tumor growth and metastasizing were revealed.

Effects of nonstarch polysaccharides with different molecular weights on the development of Lewis lung carcinoma in mice and efficiency of cytostatic therapy.

The effects of nonstarch polysaccharides with different molecular weights on the development of Lewis' lung carcinoma and efficiency of cyclophosphamide therapy in mice were studied. Treatment with these substances with low molecular weights (<30 kDa) caused no changes in the primary tumor growth, but inhibited its metastasizing, while nonstarch polysaccharides with high molecular weights (>400 kDa) inhibited the growth of Lewis' lung carcinoma node. Antimetastatic effects of cyclophosphamide were stimulated by low and high molecular weight polysaccharides.

[Prospects for the use of plant polysaccharides in complex treatment of malignant tumors].

The pharmacological properties of plant polysaccharides are reviewed and original experimental data on the properties of water-soluble polysaccharides isolated from Acorus calamus L. are presented. The possibility of using plant (in particular, Acorus calamus) polysaccharides to increase the effectiveness of anticancer treatment of transferred tumors and to reduce the toxic effects of cytostatic treatment on the normal cells of blood, liver, and epithelium of thin intestine in experimental animals has been demonstrated.

[Prolonged peripheral arteriovenous perfusion with a membrane oxygenator]. / Dlitel'naia perifericheskaia veno-arterial'naia perfuziia s membrannym oksigenatorom.

The authors have developed the optimal method of performing prolonged veno-arterial perfusion and studied its influence on the animal organism. In 22 experiments a membrane oxygenator on the national film "Sigma" was used. It has been established that for successful performing of prolonged veno-arterial perfusion it is necessary to strictly maintain the circulating blood volume and take measures to prevent disorders in the microcirculation. The blood trauma in the membrane oxygenator with the "Sigma" film is inimal.