[Molecular docking study and experimental evaluation of potential CTLA-4 binding peptides]. / Molekuliarnyi doking i éksperimental'naia otsenka peptida, vzaimodeistvuiushchego s CTLA-4.

Current advances in research of immune checkpoints CTLA-4, PD-1, PD-L1, opened new possibilities for effective cancer immunotherapy using monoclonal antibodies. However, antibodies have a number of limitations for clinical use, which provides a basis for the search for low molecular weight compounds capable of regulating (blocking) molecules that inhibit the immune response. This paper presents the results of molecular docking and evaluation of synthetic peptide interaction with a CTLA-4 molecule. Using mathematical modeling, it was shown that peptides interacted with the 99MYPPPY104 loop of the CTLA-4 protein and could potentially block the interaction of the CTLA-4 receptor with its natural ligand B7-1. The specificity of the interaction between the identified peptide and recombinant chimeric CTLA-4 protein was evaluated. The detected synthetic peptide can be used for the development of immunomodulatory drugs for therapy of cancer or autoimmune diseases.

Activation of P-450-Dependent Monooxygenases Modulates the Diuretic Effect of Histochrome in Rats.

We studied the role of the liver monooxygenase system in pharmacological activity of histochrome, a pharmaceutical form of echinochrome A. In experiments on rats, benzonal, an inductor of the monooxygenase system of phenobarbytal type, significantly potentiated the diuretic effect of histochrome. Benzonal withdrawal was followed by a natriuretic reaction. In view of the known inverse relation between the biological effect of the drug and the rate of its metabolism, our findings suggest that the effects of echinochrome A on some kidney excretory function parameters are produced not by native agent, but one of its metabolites.

[Identification of histochrome metabolism products in urine for studying drug pharmacokinetics].

Histochrome is the medicinal form of echinochrome (2,3,5,6,8-pentahydroxy-7-ethyl-1,4-naphthoquinone). The drug pharmacodynamics and its relationship with metabolism, which was revealed in previous investigations, predetermined the aim of this work: to study excretion of echinochrome and its possible metabolites in urine of rats. Histochrome was introduced to Wistar rats (n = 10) subcutaneously in a dose of 10 mg/kg. Naphthoquinone derivatives were extracted from the acidified urine by ethyl acetate and analyzed by high performance liquid chromatography with UV detection (HPLC/UV) and mass-spectrometric detection (HPLC/MS). It was established that histochrome is completely metabolized in an organism and excreted by kidneys in the form of 3-methoxy-2,5,6,8-tetrahydroxy-7-ethyl-1,4-naphthoquinone and 2-metoxy-3,5,6,8-tetrahydroxy-7-ethyl-1,4-naphthoquinone.

Expression of renal crystallization inhibitors in experimental nephrolithiasis.

The expression of renal inhibitors of crystallization (Tamm-Horsefall protein, osteopontin, bikunin) in experimental nephrolithiasis was studied in rats receiving 1% ethylene glycol solution for drinking for 3 weeks. The expression of Tamm-Horsefall protein increased, while osteopontin and bikunin expression decreased in experimental nephrolithiasis.

[Anti-lithogenic effect of meloxicam in experimental nephrolithiasis].

Experiments performed on 23 male rats, were divided into 2 groups. Animals in the control received group 1% solution of ethylene glycol (EG) as a drink during 6 weeks. In the test group, EG was also introduced for 6 weeks, and meloxicam was administered in a dose of 2.5 mg/kg from the 4th week. Every 7 days, daily urine was analyzed for the concentrations of oxalate, phosphate, and calcium and for the activity of urothelium injury marker enzymes includng lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and N-acetyl-beta-D-glucose aminidase (NAG). In addition, sections of the rats kidney were used to detect calcium deposits by histochemical Van Koss method. The treatment of experimental nephrolithiasis by meloxicame led to simplification of pathology, as indicated by a significant reduction in the urine oxalate and calcium concentrations and a pronounced decrease in the activity of all marker enzymes (LDH, GGT, NAG).This was confirmed by morphological studies, which detected very significant reduction in both number and size of calcium deposits.

[Effects of water drinking regimens on crystallization intensity in experimental nephrolithiasis].

We studied effects of water regimens on crystallization efficacy in experimental nephrolithiasis on 3 groups of Wistar male rats with initial experimental nephrolithiasis (ethylene glycol model). The animals were on free, limited and supernormal liquid intake regimen. For 3 weeks each 3-4 days we estimated 24-h diuresis, urine concentration of calcium, phosphate and oxalate ions. After 3 weeks we made a morphological examination of the kidneys. We found that limited drinking leads to an increase in urinary concentrations of oxalate- and phosphate ions which stimulate enhanced formation of calcium-containing concrements. More water intake considerably reduces oxalate and phosphate concentrations in the urine resulting in reduction of the number and size of calcium deposits in renal tissue. Thus, low liquid intake leads to intensification of urine oversaturation causing formation of renal concrements. Much liquid intake weakens oversaturation and reduces the number and size of calcium deposits in the kidneys.

[A new technique for urinary oxalate ion determination].

The authors propose a technique for the determination of urinary oxalate ions by high performance liquid chromatography, which may be used for clinical and scientific purposes.

[Features of the pharmacodynamics and pharmacokinetics of furosemide upon long-term administration in rats].

Long-term administration of furosemide in rats (single daily dose, 20 mg/kg for 7 days) was accompanied by a decrease in the diuretic, natriuretic, and kaliuretic effects, which was related to a decrease in the rate of renal metabolism and excretion. It was found that more than 85% of the daily excretion of sodium takes place within the first 6 h after furosemide administration (on the background of comparable excretion of the drug), while the elimination of potassium and water during one day is more uniform. It is established that the long-term administration of furosemide leads to a decrease in the drug excretion during the first 6-h period, followed by a growth in the subsequent 18-h period of time. These changes in the daily dynamics of drug excretion account for the analogous trends in the elimination of water and electrolytes.

[The effect of microsomal enzyme inducers on the renal transport of iodamide]. / Vliianie induktorov mikrosomal'nykh fermentov na pochechnyi transport iodamida.

On the 3rd day after the last administration of phenobarbital (50 mg/kg orally, 4 days), benzonal (35 mg/kg orally, 4 days), zixorine (200 mg/kg orally, 4 days) and 3-methylcholanthrene (20 mg/kg subcutaneously, 2 days) the rats exhibited a decrease of iodamide secretion in the kidneys. The administration of zixorine to the dog (200 mg orally, 6 days) led to a significant decrease of iodamide transport in the first two weeks after discontinuation of the drug administration.

[The effect of microsomal enzyme inducers on the renal transport of verografin (triombrast)]. / Vliianie induktorov mikrosomal'nykh fermentov na pochechnyi transport verografina (triombrasta).

In experiments on rats and dogs it was shown that administration of phenobarbital (20 and 50 mg/kg orally, 4 days), benzonal (35 mg/kg, orally, 4 days), zixorine (200 mg/kg orally, 4 days) and 3-methylcholanthrene (20 mg/kg subcutaneously, 2 days) caused on the 3rd day following the last administration of the drug a reduction of verografine secretion in the kidneys. After administration of phenobarbital to dogs (20 mg/kg orally, 4 days) a decrease of renal transport of verografine within 4-5 weeks was observed.

[The effect of inducers of microsomal enzymes on glucose transport in the kidneys]. / Vliianie induktorov mikrosomal'nykh fermentov na transport gliukozy v pochkakh.

Phenobarbital (50 mg/kg), benzonal (35 mg/kg) and zixorine (100 mg/kg) administered orally for 4 days and 3-methylcholanthrene (20 mg/kg) administered subcutaneously for 2 days decreased the maximal tubular transport of glucose in rats. Phenobarbital (10 mg/kg) given orally for 8-10 days reduced the tubular reabsorption of glucose in dogs. An increase of phenobarbital dose enhanced and prolonged its effect on the renal tubular transport of glucose.

[The renal transport of cardiotrast, verografin and iodamide]. / Pochechnyi transport kardiotrasta, verografina i iodamida.

In chronic experiments on dogs it was shown that verografin and iodamide are excreted from the body not only by filtration but by tubular excretion as well. The maximal transport of verografin and iodamide is significantly lower than that of cardiotrast. In experiments on rats similar results were obtained. Concurrent administration of verografin and iodamide with cardiotrast decreases their excretion in the urine in rats that is probably due to competition for the common transport system in the epithelium of renal tubules.

[Effect of 5-hydroxymethyluracil and dimephosphon on the tubular secretion of xenobiotics in the kidney]. / Vliianie 5-oksimetiluratsila i dimefosfona na kanal'tsevuiu sekretsiiu ksenobiotikov v pochke.

The effect of 5-hydroxymethyluracyl and dimephosphon on the tubular secretion of cardiotrast was studied on rats. The both drugs were shown to increase the tubular transport of xenobiotics.

[Induction of the monooxygenase system and the transport of xenobiotics in the kidney]. / Induktsiia monooksigenaznoi sistemy i transport ksenobiotikov v pochke.

Phenobarbital (50 mg/kg) and benzonal (35 mg/kg) orally for 4 days and 3-methylcholanthrene (20 mg/kg) subcutaneously increased the excretion and tubular maximal transport of cardiotrast (diodrast) in rats. The inductors of the monooxigenase system seem to stimulate the renal transport of xenobiotics.