In Vitro and In Vivo Antitumor Activities of Isothiourea and Cinnamic Acid Derivative with NOS/MCT Inhibitory Effect.

This work presents the method of synthesis and physicochemical characterization of isothiourea and cinnamic acid original derivative α-cyano-4-hydroxycinnamate 1-cyclohexanoy-l-2-ethylisothiourea (T1114). In studies of the cytotoxic and antitumor activity of T1114, it has been found that the combination in one molecular structure of NOS-inhibitory fragment (1-cyclohexanoyl-2-ethylisothiourea) and a fragment inhibiting monocarboxylate lactate transporters (MCT) (α-cyano-4-hydroxycinnamic acid) does not modify the cytotoxic activity of bifunctional NOS/MCT-inhibitor T1114 in vitro. But in vivo inhibition of NOS and MCT is able to realize effects on the tumor microenvironment and hypoxic tumor cells.

In Vitro Cytotoxic Potential and In Vivo Antitumor Effects of NOS/PDK-Inhibitor T1084.

Previously, we showed the antitumor activity of the new NOS/PDK inhibitor T1084 (1-isobutanoyl-2-isopropylisothiourea dichloroacetate). The present study included an assessment of in vitro cytotoxicity against human malignant and normal cells according to the MTT-test and in vivo antitumor effects in solid tumor models in comparison with precursor compounds T1023 (NOS inhibitor; 1-isobutanoyl-2-isopropylisothiourea hydrobromide) and Na-DCA (PDK inhibitor; sodium dichloroacetate), using morphological, histological, and immunohistochemical methods. The effects of T1084 and T1023 on the in vitro survival of normal (MRC-5) and most malignant cells (A375, MFC-7, K562, OAW42, and PC-3) were similar and quantitatively equal.

Burnout dynamic among Ukrainian academic staff during the war.

This study examined burnout dynamics among Ukrainian academic staff during the full-scale war. A cross-sectional study was conducted twice: the first wave in July 2022 and the second in January 2023. To assess the burnout syndrome as the final outcome, the self-reported Maslach Burnout Inventory-Human Services adapted for socioeconomic professions by Vodopyanova was used and correlated with different characteristics.

Effect of Non-Specific Porins from the Outer Membrane of Yersinia pseudotuberculosis on Mice Brain Cortex Tissues.

It was found that a single-dose immunization of mice with Yersinia pseudotuberculosis porins OmpF and OmpC causes development of pathological changes in the deep layers of cerebral cortex characterized by dystrophic changes in the cells against the background of the increasing titer of specific antibodies. At the same time, the increased level of caspase-3 expression is observed in the neurons, which indicates induction of proapoptotic signaling pathways. The obtained results indicate potential ability of nonspecific pore-forming proteins of the outer membrane of Gram-negative bacteria to initiate development of degenerative changes in brain cells.

Features of Kidney Function in Patients With Comorbidity of Arterial Hypertension and Chronic Obstructive Pulmonary Disease.

Background and objective Chronic kidney disease (CKD) and hypertension are closely linked in terms of cause and effect. Decreased renal function is usually associated with increased blood pressure, and a steady increase in blood pressure accelerates the decline in renal function. In this study, we aimed to investigate laboratory parameters of renal function - blood creatinine level, urine creatinine level, urea blood level, urine albumin level, and in particular, serum cystatin C level - as early predictors of kidney damage and assess the filtration function of the kidneys based on the glomerular filtration rate (GFR) in patients with isolated arterial hypertension, those with a comorbid pathology of hypertension and chronic obstructive pulmonary disease (COPD).

Preclinical studies of NOS inhibitor T1059 vasopressor activity on the models of acute hemorrhagic shock in rats and dogs.

The development of new effective and safe vasopressors is one of the ways to increase the effectiveness of the treatment of hypotensive disorders, the severe forms of which remain a common cause of death in all countries of the world. Previously, we synthesized the original compound T1059, a selective inhibitor of eNOS/iNOS which has a pronounced vasoconstrictive effect. Here we show its vasopressor activity in models of the early stage of acute hemorrhagic shock in rats and dogs, as part of preclinical studies.

1-Isobutanoil-2-isopropylisothiourea Phosphate, T1082: A Safe and Effective Prevention of Radiotherapy Complications in Oncology.

The radioprotective effects of a new 1-isobutanoil-2-isopropylisothiourea derivative named T1082 are presented. Research methods included toxic characteristics, radioprotective activity (Till-McCulloch's test and 30-day survival test) in γ-ray total-body-irradiated mice, and a clinical and histological study of the effect of T1082 on acute radiation skin reactions (RSR) in rats after a single or fractionated β-ray local irradiation. T1082 is more effective than its analogue, the NOS inhibitor T1023, at low concentrations and doses (1/12-1/8 LD), both parenterally and intragastrically.

Influence of lycopene and astaxanthin in feed on metabolic parameters of laying hens, yolk color of eggs and their content of carotenoids and vitamin A when stored under refrigerated conditions.

Orientating investigations were carried out in order to test the influence of oil extracts of lycopene (20, 40 and 60 mg/kg feed) and astaxanthin (10, 20 and 30 mg/kg feed) as feed additives on the metabolic parameters (glucose, creatinine, cholesterol) and enzyme activities (alanine aminotransferase, ALT; aspartate transaminase, AST) of laying hens. Eggs from these hens were stored at refrigerator temperatures of 4°C and 12°C for up to 30 days and analyzed for vitamin A, carotenoid and yolk color. 45 laying hens (Hy-Line W36 cross, 23 weeks of age) were divided in three groups of 15 birds each (control, lycopene fed group, astaxanthin fed group).

Combination of NOS- and PDK-Inhibitory Activity: Possible Way to Enhance Antitumor Effects.

We have previously demonstrated a high antitumor potential of NOS inhibitor T1023 (1-isobutanoyl-2-isopropylisothiourea hydrobromide): antitumor antiangiogenic activity in several animal tumor models and its ability to synergistically enhance the antitumor effects of bevacizumab, cyclophosphamide and γ-radiation. At the same time, rather rapid adaptation of experimental neoplasias to T1023 treatment was often observed. We attempted to enhance the antitumor activity of this NOS inhibitor by supplementing its molecular structure with a PDK-inhibiting fragment, dichloroacetate (DCA), which is capable of hypoxia-oriented toxic effects.

Radioprotective Activity of the Nitric Oxide Synthase Inhibitor T1023. Toxicological and Biochemical Properties, Cardiovascular and Radioprotective Effects.

In this work, studies were performed to investigate the toxicological, biochemical, vasotropic and radiomodifying properties of the new nitric oxide synthase (NOS) inhibitor, compound T1023. Toxicological studies included the estimation of acute toxicity in mice after i.p.

The Ability of the Nitric Oxide Synthases Inhibitor T1023 to Selectively Protect the Non-Malignant Tissues.

Previously, we showed that a nitric oxide synthase (NOS) inhibitor, compound T1023, induces transient hypoxia and prevents acute radiation syndrome (ARS) in mice. Significant efficacy (according to various tests, dose modifying factor (DMF)-1.6-1.

Are the Closely Related Strains of Different Species?

Marine bacteria of the genus which are promising sources of unique enzymes and secondary metabolites, were found to be complicatedly identified both by phenotypic indicators due to their ecophysiology diversity and 16S rRNA sequences because of their high homology. Therefore, searching for the additional methods for the species identification of isolates is significant. The species-specific coding sequences for the enzymes of each functional category and different structural families were applied as additional molecular markers.

OmpF porin from Yersinia ruckeri as pathogenic factor: Surface antigenic sites and biological properties.

Bacterium Yersinia ruckeri as a pathogen induces causative agent of intestinal fish disease called enteric redmouth disease (ERM) is known. In this study, outer membrane OmpF porin from the Y. ruckeri (YrOmpF) has been identified as a pathogenic factor which affects host macrophage activation and life cycle of eukaryotic cells.

Synthesis and Evaluation of Antimicrobial and Cytotoxic Activity of Oxathiine-Fused Quinone-Thioglucoside Conjugates of Substituted 1,4-Naphthoquinones.

A series of new tetracyclic oxathiine-fused quinone-thioglycoside conjugates based on biologically active 1,4-naphthoquinones and 1-mercapto derivatives of per--acetyl d-glucose, d-galactose, d-xylose, and l-arabinose have been synthesized, characterized, and evaluated for their cytotoxic and antimicrobial activities. Six tetracyclic conjugates bearing a hydroxyl group in naphthoquinone core showed high cytotoxic activity with EC values in the range of 0.3 to 0.

[MULTI-FACTOR MODEL OF FINANCING PREVENTION AND TREATMENT OF DIROPHILARIOSIS (BASIC PRINCIPLES AND INDICATORS OF EFFICIENCY)].

The aim of the study was to substantiate the effectiveness and feasibility of the practical application of the multifactorial model of financing the prevention and treatment of dirofilariasis, its principles and methodological approaches. The basic principles of the multifactor model - an integrated approach, a combination of public and private financing, ensuring continuity of financing, discreteness of expenses; methodology for determining the effectiveness of the use of financial resources on the calculation of the return on costs for the prevention and treatment of dirofilariasis were justified. The effectiveness of local budget spending on the treatment of territories of the Kharkov region from mosquitoes on the base on the proposed principles and methodology was analyzed.

Comparison of Antitumor Effects of Combined and Separate Treatment with NO Synthase Inhibitor T1023 and PDK1 Inhibitor Dichloroacetate.

Combined chronic treatment of Ehrlich solid carcinoma (EC) with an NOS inhibitor 1-isobutanoyl-2-isopropylisothiourea hydrobromide (T1023) and a PDK1 inhibitor dichloroacetate was accompanied by statistically significant synergetic antitumor effects manifested in a significant and stable suppression of neoplasm growth (by 55-65%). Separate treatment with T1023 and dichloroacetate induced moderate short-term inhibition of tumor growth (by 30-35%) followed by weakening of tumor sensitivity to these substances. These results attest to synergetic antitumor effects NOS inhibitor T1023 and PDK1 inhibitor dichloroacetate producing antiangiogenic and hypoxia-targeted cytotoxic effects, during their combined administration, which allows overcoming the adaptive potential of the tumors.

Magnificamide, a β-Defensin-Like Peptide from the Mucus of the Sea Anemone , Is a Strong Inhibitor of Mammalian α-Amylases.

Sea anemones' venom is rich in peptides acting on different biological targets, mainly on cytoplasmic membranes and ion channels. These animals are also a source of pancreatic α-amylase inhibitors, which have the ability to control the glucose level in the blood and can be used for the treatment of prediabetes and type 2 diabetes mellitus. Recently we have isolated and characterized magnificamide (44 aa, 4770 Da), the major α-amylase inhibitor of the sea anemone mucus, which shares 84% sequence identity with helianthamide from .

[COMPARATIVE ANALYSIS OF THE COST OF TREATMENT OF ECHINOCOCCOSIS BY THERAPEUTIC AND SURGICAL METHODS (BASED ON THE STEP-DOWN METHODOLOGY)].

The aim of the study was to carry out a comparative economic analysis of the costs of therapeutic and surgical treatment of liver echinococcosis based on the developed methodological approaches and principles for calculating the cost of complex medical services in accordance with the «step-down» methodology. The model for calculating the cost of complex medical services for the treatment of echinococcosis was justified. The sum of costs of outpatient and inpatient units that directly provide medical care (direct costs) to the costs of support centers (indirect costs) was adjusted, which among simple medical services based on the chosen criterion were distributed.

Non-Specific Porins of Yersinia pseudotuberculosis as Inductors of Experimental Hyperthyroidism in Mice.

In vivo experiments showed that antibodies to OmpC and OmpF porins of Yersinia pseudotuberculosis increased thyroxine (T4) level in the blood of experimental animals. The mice were immunized with different antigens: recombinant OmpF porin in a soluble monomeric form, trimers of OmpC and OmpF porins isolated from the outer membrane, or antibodies to them. The level of thyroxine in the blood of mice immunized with OmpF and OmpC porins increased by 5.

[THE ITERATIVE APPROACH TO PRICING LABORATORY SERVICES FOR THE PROVISION OF MEDICAL AID (COPROPROCYCOSOPHICAL EXAMINATION ON LYAMBLIOSIS)].

The purpose of the study was to substantiate the theoretical and methodical principles of pricing for laboratory services in the diagnosis of giardiasis, taking into account their iterability and peculiarities of parasitic research methods. The methods of laboratory study of gum disease of native smear, treated with Lyulol solution, and ether-formalin enrichment on the criteria of their quality and effectiveness are analyzed. On the basis of the study of the effectiveness of the first and repeated analyzes, the conclusion on the iterative nature of laboratory studies of giardiasis and the effectiveness of the use of an iterative approach to the determination of prices for laboratory services is substantiated.

Data supporting functional diversity of the marine bacterium Cobetia amphilecti KMM 296.

Data is presented in support of functionality of hyper-diverse protein families encoded by the Cobetia amphilecti KMM 296 (formerly Cobetia marina KMM 296) genome ("The genome of the marine bacterium Cobetia marina KMM 296 isolated from the mussel Crenomytilus grayanus (Dunker, 1853)" [1]) providing its nutritional versatility, adaptability and biocontrol that could be the basis of the marine bacterium evolutionary and application potential. Presented data include the information of growth and biofilm-forming properties of the food-associated isolates of Pseudomonas, Bacillus, Listeria, Salmonella and Staphylococcus under the conditions of their co-culturing with C. amphilecti KMM 296 to confirm its high inter-species communication and anti-microbial activity.

Performance Assessment in the PILOT Experiment On Board Space Stations Mir and ISS.

Background: The aim of this investigation into the performance and reliability of Russian cosmonauts in hand-controlled docking of a spacecraft on a space station (experiment PILOT) was to enhance overall mission safety and crew training efficiency. The preliminary findings on the Mir space station suggested that a break in docking training of about 90 d significantly degraded performance.

Methods: Intensified experiment schedules on the International Space Station (ISS) have allowed for a monthly experiment using an on-board simulator.

[Chemoradioresistance of the female reproductive system cancer--can local laser hyperthermia contribute to its overcoming?].

There is presented the method of local laser hyperthermia on the domestic nanotechnological optic-fiber device LAZON-FT integrated into the program of brachytherapy for tumors of the female reproductive system. This is a universal radiosensibilizator that demonstrates the acceleration of tumor regression also during local and systemic chemotherapy--tumor regression at 50-705 in such conditions permits recommend it in locally advanced cervical and endometrial cancer as well as cancer of the vulva and vagina in the frames of combined use with brachytherapy and chemotherapy.

[Planning and implementation of conformal radiotherapy for patients with gynecologic neoplasms with urinary tract obstruction].

Urinary tract pathology is one of the reasons limiting possibility of all kind of radical treatment followed by proper rehabilitation in patients with cancer of the female genital organs. 469 patients suffering from cancer of the female genital organs with urological obstructive complications were successfully treated by means of conformal external beam radiotherapy and brachytherapy for the period 2003-2012 after correction of urological pathology. A use of interventional technologies for urinary tract drainage that minimize the frequency of repeated invasive procedures to reduce the risk of remote infectious and functional urinal complications after radiotherapy is the most priority for the implementation of irradiation of any required volume in patients with cancer of the female genital organs.

[Radioprotective Properties of NO-synthase Inhibitor T1023: II. The Ability for Selective Protection of Normal Tissues During Radiotherapy of Tumors].

We studied the effect of T1023, NO-synthase inhibitor, N-acyl-S-alkyl-isothiourea in a single administration at a dose of 75 mg/kg on the growth of transplantable rat sarcoma M-1 and the development of acute skin reactions after the local impact of γ-radiation at the doses of 32 and 36 Gy. The results showed that the T1023 at a single dose had no effect on the growth of sarcoma, and did not modify the radiosensitivity of the tumor and anti-tumor efficacy of γ-rays. However, at both doses T1023 significantly reduced the severity of acute radiation skin reactions.