[Possibilities of modern forms of antimicrobial peptides in the treatment of inflammatory pathology of the pharynx]. / Vozmozhnosti sovremennykh form antimikrobnykh peptidov v terapii vospalitel'noi patologii glotki.

Inflammatory diseases of the pharynx occupy one of the leading places in the structure of otorhinolaryngological pathology. Acute and chronic inflammatory processes in the pharynx, as well as exacerbations of the latter, are faced by doctors of a wide range of specialties. Oropharyngeal swab laboratory testing is required to identify a specific pathogen, which takes time. In this regard, of particular interest are local drugs with the necessary spectrum of action, the use of which is possible, both as monotherapy and in combination with systemic therapy. The combination of tyrothricin (tyrothricin), benzalkonium chloride (benzalkonium chloride), and benzocaine (benzocaine) (dorithricin) is highly effective in the treatment of bacterial, viral and fungal infections of the pharynx, and microorganisms consistently demonstrate high sensitivity to the components of the drug.

[Hearing dynamics in acute traumatic perforation of the tympanic membrane after application of blood plasma enriched with platelet growth factors]. / Regeneratsiya barabannoi pereponki i otsenka dinamiki slukha pri ostroi travmaticheskoi perforatsii barabannoi pereponki posle applikatsii plazmy krovi, obogashchennoi trombotsitarnymi faktorami rosta.

OBJECTIVE: The article considers the possibility of treating patients with acute traumatic perforation of the eardrum with a single application of blood plasma enriched with platelet-derived growth factors in the perforation area. As a result of the studies, it was found that the acceleration of its closure and the restoration of hearing. MATERIAL AND METHODS: The study included 43 patients with unilateral acute PBP of various etiologies (Table 1). Patients were divided into 2 groups - the main - 24 patients (10 men and 14 women), the average age - 30±9.7 years and the control - 19 patients (9 men and 10 women), the average age - 26.5±6.37 years. The compared groups did not reliably differ in age, gender, frequency and severity of hearing impairment. RESULTS: Analyzing the results, we can confidently talk about the beneficial effect of blood plasma enriched in platelet-derived growth factors on the speed, completeness of closure of traumatic perforation of the eardrum and the dynamics of restoration of auditory function. The use of blood plasma enriched with platelet growth factors led to a regular reduction in the time and increase in the frequency of cases of early closure of perforated eardrum, as well as improvement and restoration of auditory function according to the results of tonal threshold audiometry and otoacoustic emission in dynamics. CONCLUSION: Being generally available even in outpatient practice, the method of a single application of blood plasma enriched with platelet growth factors in the area of perforation of the tympanic membrane can significantly accelerate the healing process of the tympanic membrane, while improving the quality of life of the patient.

Glutamic Acid Signal Synchronizes Protein Synthesis Kinetics in Hepatocytes from Old Rats for the Following Several Days. Cell Metabolism Memory.

The kinetics of protein synthesis was investigated in primary cultures of hepatocytes from old rats in serum-free medium. The rats were fed mixed fodder supplemented with glutamic acid and then transferred to a regular mixed fodder. The amplitude of protein synthesis rhythm in hepatocytes isolated from these rats increased on average 2-fold in comparison with the rats not receiving glutamic acid supplement. Based on this indicator reflecting the degree of cell-cell interactions, the cells from old rats were not different from those of young rats. The effect was preserved for 3-4 days. These results are discussed in connection with our previous data on preservation of the effect of single administration of gangliosides, noradrenaline, serotonin, and other synchronizers on various cell populations. In contrast to the other investigated factors, glutamic acid is capable of penetrating the blood-brain barrier, which makes its effect possible not only in the case of hepatocytes and other non-brain cells, but also in neurons.

Glutamic Acid as Enhancer of Protein Synthesis Kinetics in Hepatocytes from Old Rats.

Dense cultures of hepatocytes from old rats (~2 years old, body weight 530-610 g) are different from similar cultures of hepatocytes from young rats by the low amplitude of protein synthesis rhythm. Addition of glutamic acid (0.2, 0.4, or 0.6 mg/ml) into the culture medium with hepatocytes of old rats resulted in increase in the oscillation amplitudes of the protein synthesis rhythm to the level of young rats. A similar action of glutamic acid on the protein synthesis kinetics was observed in vivo after feeding old rats with glutamic acid. Inhibition of metabotropic receptors of glutamic acid with α-methyl-4-carboxyphenylglycine (0.01 mg/ml) abolished the effect of glutamic acid. The amplitude of oscillation of the protein synthesis rhythm in a cell population characterizes synchronization of individual oscillations caused by direct cell-cell communications. Hence, glutamic acid, acting as a receptor-dependent transmitter, enhanced direct cell-cell communications of hepatocytes that were decreased with aging. As differentiated from other known membrane signaling factors (gangliosides, norepinephrine, serotonin, dopamine), glutamic acid can penetrate into the brain and thus influence the communications and protein synthesis kinetics that are disturbed with aging not only in hepatocytes, but also in neurons.

Glutamic Acid - Amino Acid, Neurotransmitter, and Drug - Is Responsible for Protein Synthesis Rhythm in Hepatocyte Populations in vitro and in vivo.

Primary cultures of rat hepatocytes were studied in serum-free media. Ultradian protein synthesis rhythm was used as a marker of cell synchronization in the population. Addition of glutamic acid (0.2 mg/ml) to the medium of nonsynchronous sparse cultures resulted in detection of a common protein synthesis rhythm, hence in synchronization of the cells. The antagonist of glutamic acid metabotropic receptors MCPG (0.01 mg/ml) added together with glutamic acid abolished the synchronization effect; in sparse cultures, no rhythm was detected. Feeding rats with glutamic acid (30 mg with food) resulted in protein synthesis rhythm in sparse cultures obtained from the rats. After feeding without glutamic acid, linear kinetics of protein synthesis was revealed. Thus, glutamic acid, a component of blood as a non-neural transmitter, can synchronize the activity of hepatocytes and can form common rhythm of protein synthesis in vitro and in vivo. This effect is realized via receptors. Mechanisms of cell-cell communication are discussed on analyzing effects of non-neural functions of neurotransmitters. Glutamic acid is used clinically in humans. Hence, a previously unknown function of this drug is revealed.

Administration of dopamine to rats disorganizes the rhythm of protein synthesis in hepatocytes.

Dopamine was injected intravenously (9 µg/kg) or intraperitoneally (15 µg/kg) to Wistar rats (3-4 months, 300-400 g). Hepatocytes were isolated 40 min after dopamine injection. Dense cultures were maintained on collagen-coated glasses. By the 5th hour, the circaholarian rhythm of protein synthesis in hepatocytes cultures was absent in the dopamine group, but was present in cultures from animals receiving physiological saline (NaCl). The rhythm-disorganizing effect of dopamine was reversible. The rhythm was observed in cultures of hepatocytes isolated 1 day after dopamine treatment. The effect of dopamine was abolished by melatonin. The protein synthesis rhythm was revealed in 5-h cultures of hepatocytes from rats receiving melatonin (32 ng/kg) 40 min after intraperitoneal injection of dopamine. The results of our in vitro experiments with addition of dopamine into the medium of cultured hepatocytes [1] suggest that dopamine in vivo produces a direct effect on liver cells. The observed changes are discussed taking into account the biochemical mechanisms for a direct cell-cell interaction and previously unknown properties of catecholamines.

Effect of protein synthesis rhythm-organizing signal persists for a day after single administration of melatonin to rat.

Melatonin administered to rat intraperitoneally organizes ultradian rhythm of protein synthesis in hepatocytes that persists for 1 day after exposure to the synchronizing signal. Hepatocytes were isolated 1 day after melatonin administration and cultured on coverslips in a serum-free medium. In 24 h in culture, the kinetics of protein synthesis was analyzed. In our previous experiments, we detected a rhythm in cells isolated in 1.5 h, but not in 3 days after melatonin administration to the rat. We have found that synchronization of oscillations of the protein synthesis intensity in vivo persists over 1 day after rat exposure to melatonin. Phenylephrine, an efficient synchronizer of protein synthesis in vitro, does not organize the rhythm in vivo.

Dopamine disorganizes the rhythm of protein synthesis disrupting self-organization of hepatocytes in vitro.

We studied dense 24-hour cultures of rat hepatocytes in serum-free medium on collagen-coated slides. As before, a circahoralian rhythm of protein synthesis was observed in control cultures in a fresh medium. No rhythm was found after addition of 1-10 µM dopamine to the medium containing such cultures. The rhythm was observed after addition of 0.3 µM ganglioside to pretreated-dopamine cultures. Dopamine is likely to influence the conditioning of intercellular medium with gangliosides. Deficit of this endogenous synchronizing factor in the intercellular medium blocks self-organization of the protein synthesis rhythm. Thus, in contrast to previously studied norepinephrine and serotonin, as well as gangliosides, which organized the population rhythm of protein synthesis, dopamine disorganized the rhythm, impairing direct intercellular interactions.

[Morpho-biophysical research of erythrocytes of intact and vagotomized rats in various terms after the acute hemorrhage].

The acute massive hemorrhage (35-37% of the blood volume) at rats is accompanied by changes of morphological (diameter, the area, polarizations, the form-factor, integrated and specific absorbency) and biophysical (a relief of a surface and microviscosity of a lipid phase of plasmolemma) characteristics of erythrocytes. Thus character and dynamics of response of erythron initially intact and vagotomized (14 days after operation) animals essentially differ: the former demonstrate significant changes in 3-10 h and 240 h and the latter--in 0.5 h and 96 h.

Effect of transplantation of bone marrow monomuclears on angiogenesis in rats.

We studied the effect of non-selective intracoronary transplantation of bone marrow mononuclears on day 30 after acute coronary infarction on angiogenesis in rats. On days 14 and 30 after transplantation of mononuclear cells, stable formation of new vessels was observed. The number of venules considerably increased after transplantation of mononuclear cells, which was seen from increased volume density of blood vessels and their caliber. Stable vascularization after transplantation of mononuclear cells improves blood supply, which is essential for reparation of the myocardium.

Pathways of bone marrow mononuclear cell differentiation after transplantation into postinfarction heart.

We studied homing and differentiation fate of transplanted bone marrow mononuclears after non-selective intracoronary injection on day 30 after acute myocardial infarction in rats. Mononuclear cells migrated to the cicatrix zone where they differentiated into fibroblasts and myofibroblasts. Mononuclear cells did not differentiate into cardiomyocytes, endothelial cells, or smooth muscle cells of vascular media. Stimulation of angiogenesis and reparation of the myocardium was observed under these conditions.

The state of erythrocytes in intact and vagotomized rats of different ages after massive hemorrhage.

Acute massive hemorrhage in rats is accompanied by consistent changes in the morphofunctional characteristics of erythrocytes: diameter, area, polarization, form factor, and integral and specific optical density. Thus, young initially intact rats showed significant increases in the mean diameter, area, and integral optical density at particular time points after hemorrhage, along with increases in erythrocyte polarization and form factor. Vagotomized rats of the same age group responded to hemorrhage only with an increase in the form factor. Initially intact aged rats in these conditions showed increases in the integral optical density and form factor. Aged vagotomized rats showed increases in erythrocyte mean diameter and area. The nature and dynamics of responses to hemorrhage in initially intact and vagotomized (14 days post-operative) animals were significantly different and had age-dependent features. Thus, the most marked changes in young initially intact animals were seen 3-10 h after hemorrhage, while maximum changes were seen at 3 and 96 h in vagotomized animals of the same age. In aged initially intact rats, the greatest changes in study parameters were seen at 3 and 96 h, while the greatest changes were seen in vagotomized rats at 3 and 24 h. The physiological mechanisms of these pathological states are discussed.

Development of differential sensitivity of CaOv ovarian adenocarcinoma cells to antitumor agents under conditions of hypoxia.

We studied the role of VEGF signal pathway in autocrine regulation of tumor cell growth and survival under conditions of hypoxia. Hypoxia-resistant CaOv/H substrain with high level of VEGF-A secretion was obtained by long-term culturing of CaOv ovarian adenocarcinoma cells with CoCl2 (hypoxia inductor). VEGF-A directly participates in autocrine regulation of CaOv cell growth, including the maintenance of cell growth under conditions of hypoxia or cytostatic treatment. On the other hand, CaOv/H cells retain high apoptotic potential and are characterized by high expression of p27Kip1 (cyclin-dependent kinase inhibitor), which attests to possible involvement of this inhibitor into the regulation of apoptotic response of cells under conditions of hypoxia.

Differences in lipid composition and proliferative activity of rat hepatoma-27 depending on the target organ.

Proliferative activity and lipid composition (phospholipids and gangliosides) were studied in rat hepatoma-27 transplanted subcutaneously or intrahepatically (as models for primary and metastasizing tumors). The mitotic index of subcutaneously transplanted hepatoma far exceeded that of the intrahepatically transplanted tumor. The overall amounts of both phospholipids and gangliosides increased appreciably in the subcutaneously growing hepatoma (in contrast to the intrahepatically growing tumor) in comparison to the control hepatic tissue. The ganglioside composition in the tumors differs from that in the liver: ganglioside GD3 appears, whereas gangliosides GD1b and GT1b decrease in amount in the intrahepatic tumor compared to the control liver and disappear in the subcutaneously transplanted hepatoma. In both tumor types, the amounts of both phosphatidylethanolamine and sphingomyelin exceed the control values. Comparison of these results with previously reported data concerning the phospholipid and ganglioside composition in the regenerating rat liver indicates that the difference in the lipid composition between the subcutaneously and intrahepatically growing hepatomas-27 is due to their different proliferative status and also their microenvironment.

Activity of detoxication enzymes in rat hepatoma 27 transplanted in different organs.

Activities of enzymes of active oxygen forms detoxication and phase II xenobiotic metabolism were measured in rat hepatoma 27 cells transplanted to different organs. Activity of phase II xenobiotic metabolizing enzymes was higher in hepatoma cells growing subcutaneously than in those transplanted into the liver, while activity of active oxygen forms detoxication enzymes (except catalase) was higher in cells transplanted into the liver. Benz(a)pyrene induced the enzyme activities in hepatoma growing both subcutaneously and in the liver.