Tripeptides Restore the Number of Neuronal Spines under Conditions of In Vitro Modeled Alzheimer's Disease.

In primary culture of mouse hippocampal neurons, peptide EDR (200 ng/ml) under conditions of amyloid synaptotoxicity (a model of Alzheimer's disease) increased the number of mushroom spines by 71% and returned this parameter to the normal level. Under the same conditions, tripeptide KED (200 ng/ml) increased the number of mushroom spines in hippocampal neurons by 20%. Tripeptide EDR can be recommended for further experimental study as a candidate neuroprotective agent for prevention and treatment of Alzheimer's disease.

[Effect of combined application of ozone therapy and gravitational therapy on the remote results of complex treatment of geriatric patients].

Skin aging is one of the topical issues in modern gerontocosmetology. Application of cosmetic products with short peptides is a promising measure for retardation of skin aging. This research is aimed at investigation of KE (Lys-Glu, Vilon) dipeptide influence on the expression of markers of aging in human skin fibroblasts in vitro. Collagen type I and sirtuin-6 expression in «young¼ and «old¼ skin cell fibroblasts cultures was studied using immunofluorescence confocal microscopy method. The areas of expression of collagen type I and sirtuin-6 are known to decrease in skin fibroblasts with aging by 3,5 and 3,6 times accordingly. KE dipeptide increases collagen type I expression area in «old¼ skin fibroblasts cultures by 83%. KE dipeptide increases expression area of sirtuin-6 in «young¼ and «old¼ skin fibroblasts cultures by 1,6 and 2,6 times correspondingly. Thus, KE dipeptide promotes functional activity of skin fibroblasts and inhibits their aging.

Effects of Vascular Peptide Bioregulator on the Density of Microvascular Network in the Brain Cortex of Aged Rats.

Using a TV unit for microcirculation studies, we studied the density of the entire microvascular network and its arterial compartment in the pia mater of the sensorimotor cortex in intact young and aged rats (2-3 and 22-24 months) and aged rats after a course of vascular peptide bioregulator Slavinorm. The experiments showed that the density of microvascular network in intact animals decreased by 1.6 times with aging. Treatment with the peptide bioregulator 2.5-fold increased the density of the microvascular network in aged rats in comparison with intact animals of the same age, the density of the arterial compartment of the microvascular network in the pia mater increased by 2.8 times.

Molecular aspects of anti-atherosclerotic effects of short peptides.

We studied molecular mechanisms of the vasoprotective effects of tripeptide T-38 and dipeptide RR-1. Short peptides T-38 and the RR-1 activate the processes of cell renewal in organotypic and dissociated cultures of vascular cells during aging by increasing the expression of Ki-67 and reducing the synthesis of p53 protein. T-38 and RR-1 reduce the synthesis of E-selectin, adhesion molecule involved in the formation of atherosclerotic plaques.

Geroprotective effect of ala-glu-asp-gly peptide in male rats exposed to different illumination regimens.

Exposure of male rats to permanent or natural illumination of North-Western Russia accelerated their death in comparison with animals exposed to standard (12 h) light. Permanent illumination promoted the development of spontaneous tumors in comparison with the standard photoregimen. Injection of epithalone (synthetic Ala-Glu-Asp-Gly peptide; subcutaneously 0.1 microg/rat 5 times a week from the age of 4 months until natural death) virtually did not change the mean lifespan of male rats, but was associated with a significant (p<0.05) normalization of population aging rate and hence, time of mortality rate doubling in groups exposed to natural or constant illumination. Epithalone injected to rats exposed to any photoregimen significantly inhibited the development of spontaneous tumors, primarily testicular leydigomas and leukemias.

Comparative analysis of the expression of c-Fos and interleukin-2 proteins in hypothalamus cells during various treatments.

The aim of the present work was to perform a combined analysis of the degree of activation of the anterior hypothalamus of the rat and expression of the interleukin-2 gene during treatments of different types: mild stress ("handling") and adaption to it, as well as intranasal administration of physiological saline and the peptides Vilon (Lys-Glu) and Epitalon (Ala-Glu-Asp-Gly). Changes in the numbers of c-Fos-and IL-2-positive cells in structures of the lateral area (LHA) and anterior (AHN), supraoptic (SON), and paraventricular (PVN) nuclei of the hypothalamus in Wistar rats. Ratios of the quantities of c-Fos-and IL-2-positive cells were determined in intact animals and after activation of brain cells initiated by different treatments; the influences of adaptation to handling on the nature of changes in the expression of these proteins was also studied. Combined analysis of the intensity of expression of these two proteins - c-Fos, a marker of neuron activation and a trans-factor for the IL-2 cytokine gene and other inducible genes, and IL-2 - in intact animals and after various treatments showed that the process of cell activation in most of the hypothalamic structures studied correlated with decreases in the quantity of IL-2-positive cells in these structures; different patterns of changes in the numbers of c-Fos-and IL-2-positive cells were seen in response to different treatments in conditions of stress and adaptation to it.

[Parallel analysis of c-Fos protein and interleukin-2 expression in hypothalamic cells under different influence].

The objective of this work was to perform a parallel analysis of activation of the rat anterior hypothalamus cells as judged by c-Fos protein expression, and of the expression of interleukin-2 (IL-2) under different influences, i. e., mild stress (handling) and adaptation to it, and intranasal administration of saline and the peptides Vilon (Lys-Glu) and Epithalon (Ala-Glu-Asp-Gly). Changes in the counts of cells positive for c-Fos- and IL-2 proteins were studied in structures of the lateral (LHA) area, anterior (AHN), supraoptic (SO) and paraventricular (PVH) nuclei of Wistar rat hypothalamus. Quantity of the interleukin-2-positive and c-Fos-positive cells was calculated. The findings were: a negative correlation between the activation of cells and the amount of IL-2 in the cells in the hypothalamic structures under study, and the specific patterns of changes in the counts of cells positive for c-Fos and IL-2 under stress and adaptation to stress.

Interleukin-2 concentration in hypothalamic structures of rats receiving peptides during mild stress.

The number of hypothalamic IL-2-containing cells changed in rats receiving Vilon and Epithalon during mild stress (handling). The number of IL-2-positive cells in hypothalamic structures decreased 24 h after intramuscular injection of Epithalon and 2 h after intranasal administration of the test peptides. Adaptation of animals to experimental conditions prevented the decrease in the number of IL-2-positive cells in the supraoptic nucleus after intranasal administration of Epithalon.

Synthesis of IL-2 mRNA in cells of rat hypothalamic structures after injection of short peptides.

In situ hybridization on paraffin sections of the rat brain showed that synthetic peptides Vilon, Epithalon, and Cortagen modulated the expression of IL-2 gene in vivo in cells of some hypothalamic structures depending on the terms and routes of administration.

[Effectiveness of prostatylene in the prevention of decompression disease in an experiment]. / Effektivnost' prostatilena v profilaktike dekompressionnoi bolezni v éksperimente.

Works done under elevated environmental pressures present a risk for decompression disease. The use of altitude chambers for its prevention and treatment is technically complex and expensive. The paper presents the results of studies into the effects of the new peptide regulator prostatylene isolated from the bovine prostate. Experiments were conducted on 132 albino noninbred male rats weighing 180-220 g. All the rats were divided into 10 groups by the dose (from 0.5 to 5.0 mg/kg) and frequency of prostatylene administration (1-11 days). The agent was injected in a single intramuscular dose. Altitude exposure was made in a 75-liter chamber provided by a chemical absorbent container. Air temperatures were constant (19-21 degrees C) humidity was no higher than 75%. A compressor was used to pump as high as 0.7 MPa. The duration of compression, isopression, and decompression was 3 min, 1 hour, and 80 sec, respectively. The percentage of rat deaths and the interval from the termination of decompression to death were used as an index for the efficacy of prostatylene. The preset altitude exposure led to 75% death in control rats. A single dose of prostatylene did not affect this index, but thrice preinjection of the agent showed as high as 25% animal death reductions. Its protective properties were shown when the agent was administered in a dose 1 mg/kg for 5 days. It is concluded that the prostate participates in the formation of nonspecific mechanisms of defense when the body is influenced by environmental factors and that prostatic peptides are able to prevent decompression disease in the experiment.

[Rubomycin-induced cardiomyopathy in rats and the potential for therapy with a peptide preparation from the heart]. / Rubomitsinovaia kardiomiopatiia u krys i vozmozhnost' terapii peptidnym preparatom iz serdtsa.

The study has shown the efficiency of heart peptide preparation (HP) in the management of rubomycin cardiomyopathy. HP does not prevent rat mortality if rubomycin doses are very large, but it can improve a state of survived animals. HP affects restoration processes in myocardium improving the myocardial contractibility.

[The protective effect of peptides from the thymus and tracheal mucosa in an experimental respiratory influenzal infection]. / Protektornyi éffekt peptidov timusa i slizistoi obolochki trakhei pri éksperimental'noi respiratornoi grippoznoi infektsii.

To evaluate the possible antiviral activity of a number of peptide bioregulators, an acute influenza infection was induced in developing chick embryos and mice. Four peptide preparations were used: two medicinal peptide preparations of the thymus (thymalin and thymogen) and peptide preparations obtained from the tracheal mucosa (PTM) and lung parenchyma (PLP) of calves according to the technology used for obtaining thymalin. For control, remantadin (for type A virus) and adapromin (for type B virus) were used as antiviral remedies. In experiments on mice, the preparations were introduced 24 hours and 1 hour before and 24, 48 and 72 hours after intranasal challenge. The effectiveness of the preparations was evaluated by the death rate of the animals. In case of type A virus the effectiveness of the preparations was distributed as follows: remantadin > thymogen > thymalin > > PTM. In case of type B virus, adapromin and PTM were found to produce a similar effect, while the preparations of the thymus and PLP had no influence on the death rate of the animals. In experiments on developing chick embryos, none of the peptide preparations under study had any influence on the infection caused by the viruses of both hypes. The results obtained in this investigation are indicative of the absence of direct antiviral activity in the tested peptide preparations. At the same time thymalin, thymogen and PTM significantly enhance the immunological resistance of the body to virus infection, different activity spectra of PTM and the thymus being indicative of the specific nature of their action.

[The effect of erythrocyte polypeptides on the erythron system in experimental anemia]. / Vliianie polipeptidov éritrotsitov na sistemu éritrona pri éksperimental'noi anemii.

The paper reports the action of the polypeptide preparation made of red cells on erythron system in rat toxic anemia. These polypeptides proved more effective as to erythropoiesis stimulation in phenylhydrasine anemia than vitamin B12 or lek. Red cell polypeptides are considered possible regulators of erythropoiesis.

[The interrelationship of doses and the pharmacological effects of cardiac peptides]. / Vzaimosviaz' doz i farmakologicheskikh éffektov peptidov serdtsa.

Low-molecular weight peptides prepared according to an original procedure from a cattle heart possess a protecting effect on the myocardium during ischemia. Peptides in doses of 10(-7) g/ml and less improve the indexes of contractility function of the isolated heart after total ischemia and correct respiration warranting cardiomyocytes survival during hypoxia. However, in different models high doses of heart peptides (5 x 10(-6) g/ml and more) are shown to inhibit contractility, to stop respiration, the action of the peptides increasing with myocardial ischemia degree.

[Effect of a drug isolated from the heart on the bioenergetics of cardiomyocytes in hypoxia and ischemia]. / Vliianie preparata, vydelennogo iz serdtsa, na bioénergetiku kardiomiotsitov v usloviiakh gipoksii i ishemii.

It has been established that cordialin inhibits selectively succinic acid oxidation and intensifies the exudation of a NADH2 substrate which is energetically more advantageous, and in this way has a favorable effect on energy metabolism, evidence of which is increase of the ATP content in the myocardium. Cordialin correction of the biologic energy of cardiomyocytes in hypoxia and ischemia prevents the accumulation of lipid drops in the cells of the peri-infarction zone, which reflects the high intensity of the processes of fatty acids beta-oxidation. As a result of this glycolysis activation is unnecessary (which is confirmed by high glycogen content, both of a qualitative and quantitative character, in the myocardium and low concentrations of glucose and lactate in the blood) and, consequently, the sequelae of acidosis are prevented.

[The mechanism of the therapeutic effect of periodontal cytomedin on the course of experimental periodontitis]. / Mekhanizm terapevticheskogo éffekta tsitomedina iz parodonta na techenie éksperimental'nogo parodontita.

Periodontitis induction causes a drastic elevation of free-radical lipid peroxidation, of ceruloplasmin level, and a reduction of antioxidant enzyme activities. Blood analysis shows hypercoagulation, appearance of paracoagulation products, reduced fibrinolysis, enhanced proaggregation activity of the periodontium, elevated levels of circulating immune complexes; this may by regarded as adaptation failure manifesting by these reactions. Morphologic examinations show foci of destructive changes. Administration of periodontal cytomedin reduced the level of free-radical oxidation, enhanced the activity of antioxidant enzymes, normalized antiaggregation activity of the periodontium and hemostasis and fibrinolysis parameters, and reduced the level of circulating immune complexes. The inflammatory reaction disappears completely, that is seen from reduced ceruloplasmin level and clinically. Morphologic study shows disappearance of foci of destruction. Thus, cytomedin of periodontal tissues may be regarded as an effective agent for the therapy of experimental periodontitis.

[The effect of a polypeptide complex isolated from the animal prostate on thrombus formation]. / Vliianie kompleksa polipeptidov, vydelennykh iz predstatel'noi zhelezy zhivotnykh, na tromboobrazovanie.

The authors studied the effect of polypeptides, which were obtained from the prostate of cattle and were related to the class of cytomedines, on the formation of thrombi in the venules of the mesentery in rats. Thrombosis of the venules was induced by laser irradiation, the thrombogenesis parameters were measured with a TV microscope. Intramuscular injection of the preparation and its local action on the mesenteric vessels reduced the time of growth and the size of the thrombi in the experimental animals as compared to that in the controls. The obtained data are evidenced that the preparation produces an inhibiting effect on the thrombocyte-vascular mechanism of hemostasis by increasing the thromboresistance of the vascular wall.

[The immunocorrective therapy of pyoderma caused by staphylococci multiply resistant to antibiotics]. / Immunokorrigiruiushchaia terapiia piodermii, obuslovlennykh stafilokokkami, polirezistentnymi k antibiotikam.

Examinations of 126 patients with staphylococcal pyodermas have helped detect a relationship between the total antibiotic sensitivity of staphylococci isolated from the involved skin and the patient's immunity status. The total antibiotic sensitivity of staphylococci in directly proportional to the blood level of T-lymphocytes, to the degree of their sensitization to staphylococcus in the leukocyte migration inhibition test, and to the value of IgM/IgG ratio. A new synthetic preparation of thymus, thymogen, had a modulating effect on the lymphocytes of pyoderma patients, manifesting by the increment of the total count of T-lymphocytes and T-helpers. A reduction of the total antibiotic resistance of the agent in foci of skin infection and normalization of the immunologic reactivity parameters were recorded in 23 patients with chronic pyodermas after a course of thymogen therapy. An effective method for the management of chronic pyoderma by a combination of thymogen with antibiotics is suggested.

[The effect of a synthetic thymus peptide (thymogen) on the immune system in candidiasis under immunodepression]. / Vliianie sinteticheskogo peptida timusa (timogena) na immunnuiu sistemu pri kandidoze v usloviiakh immunodepressii.

Experimental candidiasis developing against the background of the secondary immunodeficiency is described. After thymogen injections the course of candidiasis proceeds less severely, this suggesting that thymogen activates the immunocompetent system, including thymus, favouring the disappearance of the fungal infection.