[Phytoprophylaxis of complications after extracorporeal lithotrips].

AIM: To evaluate the efficiency of the drug phytolysin (capsules) in the prevention of complications after extracorporeal lithotripsy. MATERIALS AND METHODS: A total of 15 patients diagnosed with urolithiasis and chronic pyelonephritis in the latent phase were treated. The predominant localization of radiopaque stones no larger than 20 mm in size was the collecting system. The piezoelectric lithotripsy (1-2 sessions) was performed, followed by the administration of the herbal drug Phytolysin in the dosage form of a capsule. The follow-up was carried out after 14- and 30-days using laboratory, ultrasound and x-ray methods. RESULTS: In the postoperative period, there were no cases of the pyelonephritis, which may result from a short-term disturbance of the upper urinary tract urodynamics due to the passage of stone fragments. The antibacterial, antispasmodic, diuretic and anti-inflammatory effects of Phytolysin ensured positive changes in laboratory and bacteriological tests, contributed to the prevention of postoperative complications after extracorporeal lithotripsy (renal colic, pyelonephritis), and contributed to maintaining renal blood flow within normal limits and significantly reduced the time to stone-free status. CONCLUSIONS: Our results justify the feasibility of using phytolysin in capsules in patients with urolithiasis after extracorporeal lithotripsy. The dosage form in capsules eliminates the undesirable effects associated with the specific smell and taste, that patients noted when using phytolysin in the form of a paste.

[Involvement of p2 receptors in the contractile activity of the bladder in patients with benign prostatic hyperplasia].

AIM: to study the role of P2 receptors in impaired bladder contractility in patients with lower urinary tract obstruction. MATERIALS AND METHODS: in pharmacological studies, tissue samples from the bladder wall of 30 patients were used, obtained during planned surgical interventions for benign prostatic hyperplasia (transvesical simple prostatectomy without placement of cystostomy tube). Based on these tissue, isolated smooth muscle specimens were prepared. Their mechanical activity and the efficiency of ligands of purine P2 and other receptors were evaluated. With this aim, the following P2-receptor agonists were used: adenosine triphosphoric acid (ATP), adenosine diphosphoric acid (ADP), uridine-5'-triphosphoric acid (UTP), alpha, beta-methylene-ATP, 2-methylthio-ADP, as well as antagonists of P2-disulfonate receptors acid (PPADS), suramin, NF023, MRS2500. In addition, the efficiency of ligands of other receptors, including carbacholine, epinephrine, histamine, serotonin, atropine was evaluated. RESULTS: the most effective agonist was alpha-beta-methylene-ATP, while ATP and 2-methylthio-ADP were significantly less active. In our experiments, ADP and UTP did not show an effect on human bladder. The influence of P2 receptor agonists was inhibited by P2 receptor antagonists PPADS and suramin, as well as MRS2500, although to a lesser extent. Carbacholine caused a strong concentration-dependent contractile response of the bladder, which was inhibited by atropine. Histamine resulted in mild bladder contractions only at high concentrations. Epinephrine and serotonin did not cause significant changes in the contractile activity of the bladder. CONCLUSION: The main subtype of P2 receptors involved in the contractile activity of the human bladder is P2X1 receptors. P2Y1 receptors also have some influence on the contraction, while other subtypes of P2 receptors are not detected by pharmacological methods.

Social and Cognitive Impairments in Rat Offspring after Ultrasound-Induced Prenatal Stress.

We studied the possibility of developing an autism model based on chronic prenatal psychological stress caused by variable frequency ultrasound 20-45 kHz. The offspring of female rats stressed during pregnancy demonstrated reduced time of social contacts in the social interaction test, increased anxiety in the open-field test, and memory impairment in the Morris water maze test in comparison with the control (intact) rat offspring. We also found a reducing trend in the BDNF gene expression in the amygdala in males of the experimental group. The results showed the possibility of developing the animal autism model based on prenatal stress.

Chronic Exposure to Ultrasonic Frequencies Selectively Increases Aggression in Rats.

We studied aggression in male Sprague-Dawley rats in a model of a depressive-like state induced by unpredictable treatment with ultrasonic waves with the frequencies of 20-45 kHz for 1, 2 or 3 weeks. We did not find any increase in the number of animals exhibiting aggression in the "resident-intruder" test after the treatment of any selected duration. However, the aggressive animals exposed to ultrasound exhibited the substantially increased number of attacks and their total duration as well as decreased latency of the first attack compared to the respective indices in the animals of the control group. Taking this into account, it is possible to suggest that the initial level of aggression increases in a model of ultrasonic chronic stress.

Post-Weaning Social Isolation Disturbs Gene Expression in Rat Brain Structures.

Post-weaning social isolation of male Wistar rats for 10 weeks led to an increase of their aggressiveness, sensorimotor reactivity, and cognitive deficiency, manifesting in training disorders evaluated by the acoustic startle response (amplitude of the response decreasing). Expression of gene encoding serine protease prolyl endopeptidase (EC 3.4.21.26) in the frontal cortex was higher than in control rats kept in groups, while the level of mRNA of the gene encoding dipeptidyl peptidase IV (EC 3.4.14.5) did not differ from the control in any of the brain structures. The levels of serotonin transporter gene mRNA in the striatum and hypothalamus were higher than in the control. No appreciable changes in the expression of genes encoding tryptophan hydroxylase-2 and monoaminoxidase A and B in the frontal cortex, striatum, amygdala, hypothalamus, and hippocampus were detected. The data indicated the involvement of genes associated with the serotoninergic system in the mechanisms of mental disorders induced by post-weaning social isolation and suggest the gene encoding prolyl endopeptidase as a candidate gene involved in the pathogenesis of these disorders.

Three-Week Isolation Does Not Lead to Depressive-Like Disorders in Rats.

We studied the effects of social isolation for 1, 2 or 3 weeks on behavioral reactions of male rats. As social isolation is a common model for inducing depressive-like state in rodents, classical tests for depressive-like behavioral features were conducted: Porsolt forced swimming test and tests for anhedonia and social interest. None of the experimental groups showed statistically significant disorders in comparison with the control group kept under standard conditions. Thus, social isolation for up to 3 weeks did not cause behavioral abnormalities in male rats. Single housing can be used in other models of induction of depressive-like states, but the use of this paradigm as an independent model for the development of depressive-like behavior requires longer period of social isolation.

Effect of Electroconvulsive Therapy on Cognitive Functions of Rats with Depression-Like Disorders Induced by Ultrasound Exposure.

We studied the effect of electroconvulsive therapy on cognitive functions in rats with depression-like disorder caused by exposure to ultrasound of varying frequency (20-45 kHz). Object recognition and Morris water-maze tests revealed no negative effects of the therapy on memory. Moreover, positive effect of therapy was demonstrated that manifested in amelioration of memory disturbances in depression-like disorders in these behavioral tests. The results of this study do not support the idea about side effects of electroconvulsive therapy, in particular, development of transient amnesia, and are a prerequisite for a more thorough study of internal mechanisms of the effect of the therapy on cognitive sphere.

Effects of Chronic Exposure to Ultrasound of Alternating Frequencies on the Levels of Aggression and Anxiety in CBA and BALB/c mice.

Stress-induced changes in the behavior of CBA and BALB/c mice were studied after 3-week ultrasound exposure (22-45 kHz). The mice of both lines demonstrated increased aggression in the resident-intruder and social interest paradigms and reduced number of social interactions in the social interest test. Elevated plus maze test showed a decrease in anxiety level in CBA mice and an increase in this parameter in BALB/c mice. Chronic exposure to ultrasound induced an increase in aggression level in mice of both lines that was not directly related to changes in anxiety level.

Dynamics of the Development of Depressive-Like State in Rats Stressed by Chronic Exposure of Ultrasound of Variable Frequency.

We studied the effect of ultrasonic waves with a frequency of 20-45 kHz on behavioral reactions of rats after 7, 14 and 21 days of continuous exposure. A decrease in the number of social contacts in the social interest test was recorded in all groups, while lengthening of immobility time in Porsolt test was found only in the groups exposed to ultrasound for 2 and 3 weeks. Memory impairment in the new object recognition test was recorded only after 21 days of stressing. Chronic exposure to ultrasound of variable frequencies leads to the development of a depressive-like state in rats and the duration of exposure affects the specificity of the observed disorders. Different protocols of using of this model help to determine the stages of depressive-like condition in rats that can serve as a basis for the development of new methods of depressive disorders treatment.

[Genetic aspects of schizophrenia]. / Geneticheskie aspekty shizofrenii.

Schizophrenia is a disease with a complex non-Mendelian inheritance mechanism in most cases involving the combined action of a large number of genes. Identifying of genomic variations associated with schizophrenia endophenotypes has a great potential. This review describes genetic markers of the disease, current methods of their analysis, including genome-wide association study (GWAS). Certain genes with mutations that increase the risk of schizophrenia are described. Functional polymorphisms with phenotypic expression, which are significantly associated with clinical manifestation of schizophrenia, can serve as useful genetic markers. The authors highlight that currently there are no certain susceptibility genes. Further global research and search for markers in different population groups are needed.

[Behavioral Phenotype of Mice with Alkali Sensor IRR Gene Knockout].

Receptor-like tyrosine kinase IRR (the insulin receptor-related receptor) can be activated by extra- cellular alkaline media. IRR is found in organs that come in contact with liquids of extremal pH, and also in specific cells of the nervous systems where its function is not known. In this study, we analyzed the phenotype of IRR knockout mice in a series of behavioral tests. In control experi- ments, null-mutation littermate mice were analyzed. In the "Social interaction" test, the knockout animals showed a reduced number of social contacts. No statistically significant differences in im- mobility time were revealed in the "Forced swim" test, yet the number of animals that showed pro- longed immobility time, was higher in the group of knockout mice. In the "Resident-intruder" test, wild-type mice demonstrated their typical aggressive behavior whereas 7 out of 16 knockout animals stayed inert and, in contrast, attacked by the intruder. The obtained data suggest that the IRR gene inactivation results in disturbances of the aggressive-defensive behavior typical of the parental mouse strain.

Expression of genes encoding serotonin receptors and SERT in various brain structures of stressed rats after chronic exposure to ultrasound.

The expression of genes encoding serotonin receptors and serotonin transporter in emotiogenic structures of rat brain was shown to change after chronic stress with ultrasonic waves of varying frequencies. A QPCR-RT study revealed the increased expression of genes for SERT and 5-HT1B receptor and decreased expression of the 5-HT2A receptor in the prefrontal cortex of rats after chronic exposure to ultrasonic waves of varying frequencies. Gene expression was increased for SERT, but decreased for 5-HT1B, 5-HT2A, and 5-HT2B receptors in the midbrain of animals. The hippocampus was characterized by an increased expression of genes encoding SERT and 5-HT1A, 5-HT2A, and 5-HT2B receptors. Our results indicate that the exposure to this type of stress is followed by dysregulation in the serotoninergic system of the brain.

Effects of prenatal exposure to antibodies against brain-specific anion transporter on cognitive functions in rats.

We studied the effects of single intravenous injection of antibodies to brain-specific transmembrane anion transporter (BSAT1; 5 mg/kg) to pregnant rats (gestation day 10) on cognitive functions and behavior of their progeny. One of major functions of BSAT1 (or Oatp1c1) is specific transport of thyroxin across the blood-brain barrier. Female rats of two control groups were injected with non-specific Ig and 0.9% NaCl. The progeny of rats receiving monoclonal antibodies to BSAT1 demonstrated memory impairment in the Y-maze, novel object recognition test, passive avoidance test, and Morris water maze test in comparison with the control group. Our findings suggest that single injection of monoclonal antibodies to BSAT1 during the prenatal period was followed by cognitive impairments, which were probably related to thyroxin deficiency in the nervous tissue.

[Suprapubic transvesical adenomectomy of external glands of prostate with blind suture of bladder].

The article presents the experience of 524 open suprapubic transvesical prostatectomies with blind suture of bladder and hemostasis of adenoma bed by removable catgut ligatures. The advantages of this type of operation include early recovery of urethral urination (2 to 4th day), the normalization of urodynamic parameters, the restoration of anatomical and functional status of the upper urinary tract (91% of patients), rapid epithelialization of adenoma bed and low incidence of inflammatory and obstructive complications.

Effect of ultrasonic irradiation on the development of symptoms of depression and anxiety in rats.

Behavioral reactions of rats were studied under conditions of constant exposure to ultrasonic irradiation at a frequency of 20-45 kHz for 21 days. In rats subjected to ultrasound, impaired behavior in the social interest test and Porsolt forced swimming test was observed; the development of anhedonia in the sucrose preference test was revealed (manifested in the symptoms of depression). The effects of ultrasonic irradiation were abolished by an antidepressant fluoxetine, a selective serotonin reuptake inhibitor. Our results indicate that chronic exposure to ultrasonic radiation produces a modulatory effect on depressive symptoms in rats. These changes satisfy the requirements for experimental animals, which are used as a model of psychopathological processes.

The role of 5-HT2A receptor and 5-HT2A/5-HT1A receptor interaction in the suppression of catalepsy.

In the present study, the 5-HT(2A) and 5-HT(1A) receptors functional activity and 5-HT(2A) receptor gene expression were examined in the brain of ASC/Icg and congenic AKR.CBAD13Mit76C mouse strains (genetically predisposed to catalepsy) in comparison with the parental catalepsy-resistant AKR/J and catalepsy-prone CBA/Lac mouse strains. The significantly reduced 5-HT(2A) receptor functional activity along with decreased 5-HT(2A) receptor gene expression in the frontal cortex was found in all mice predisposed to catalepsy compared with catalepsy-resistant AKR/J. 5-HT(2A) agonist DOI (0.5 and 1 mg/kg, i.p.) significantly reduced catalepsy in ASC/Icg and CBA/Lac, but not in AKR.CBAD13Mit76C mice. Essential increase in 5-HT(1A) receptor functional activity was shown in catalepsy-prone mouse strains in comparison with catalepsy-resistant AKR/J mice. However, in AKR.CBAD13Mit76C mice it was lower than in ASC/Icg and CBA/Lac mice. The inter-relation between 5-HT(2A) and 5-HT(1A) receptors in the regulation of catalepsy was suggested. This suggestion was confirmed by prevention of DOI anticataleptic effect in ASC/Icg and CBA/Lac mice by pretreatment with 5-HT(1A) receptor antagonist p-MPPI (3 mg/kg, i.p.). At the same time, the activation of 5-HT(2A) receptor led to the essential suppression of 5-HT(1A) receptor functional activity, indicating the opposite effect of 5-HT(2A) receptor on pre- and postsynaptic 5-HT(1A) receptors. Thus, 5-HT(2A)/5-HT(1A) receptor interaction in the mechanism of catalepsy suppression in mice was shown.

Chronic actions of thyroxine on behavior and serotonin receptors in mouse strains with contrasting predispositions to catalepsy.

The studies reported here addressed the effects of chronic administration of thyroxine (2 mg/liter for 60 days) on catalepsy and the functional activity and expression of the 5-HT(1A) and 5-HT(2A) receptor genes in the brains of adult male mice of the cataleptic ASC strain and the catalepsy-resistant AKR strain. Thyroxine induced cataleptics in AKR mice but had anticataleptic activity in ASC animals. Chronic thyroxine administration increased the functional activity and expression of 5-HT(2A) receptors in the frontal cortex in AKR mice but not in ASC mice. In ASC mice, the hormone significantly weakened the hypothermic effect of the 5-HT(1A) receptor agonist 8-OH-DPAT, though it did not alter the expression of these receptors. These results suggest that 5-HT(2A) receptors are involved in the cataleptogenic while 5-HT(1A) receptors are involved in the anticataleptic effects of the hormone in mice.

Effect of thyroxin on behavior of mice with inherited difference in predisposition to catalepsy.

We studied effects of chronic thyroxin administration (2 mg/l, for 60 days) on motor activity, anxiety and depression-like behavior in cataleptic (ASC/Icg) and non-cataleptic (AKR/J) strains of mice. No effects of thyroxin on anxiety indicators in "open field" and "light/dark" tests were revealed in mice of the strains under study. At the same time, thyroxin increased moveability in the "open field" test in AKR/J mice and produced an antidepressant effect in the "forced swimming" test in animals from ASC/Icg strain. Obtained results are indicative of the role of inherited predisposition to catalepsy in determining the sensitivity to thyroid hormones.

[Chronic effect of thyroxine on behavior and brain serotonin receptors in mice with the sharp difference in predisposition to catalepsy].

Effects of chronic thyroxine treatment (2mg/l, 60 days) on catalepsy, functional activity and expression of 5-HT(1A) and 5-HT(2A) receptors genes in the brain were studied in adult males of catalepsy-prone ASC and catalepsy-resistant AKR mouse strains. Thyroxine caused an appearance of cataleptics in AKR, but produced an anticataleptic effect on ASC mice. Chronic thyroxine treatment increased the functional activity and expression of 5-HT(2A) receptors in the frontal cortex in AKR, but not in ASC mice. Hormone markedly attenuated hypothermic effect of 8-OH-DPAT, 5-HT(1A) receptor agonist, but did not affect the expression of 5-HT(1A) receptors in ASC mice. The results suggest the involvement of the 5-HT(2A) receptors in the cataleptogenic and the 5-HT(1A) receptors in the anticataleptic effects of hormone.

Chronic thyroxine treatment activates the 5-HT2A serotonin receptor in the mouse brain.

Chronic thyroxine administration (2.0 mg/l, 60 days) significantly increases the 5-HT2A serotonin receptor gene mRNA level in the frontal cortex and augments the frequency of head twitches induced by the receptor agonist DOI (1.0 mg/kg, i.p.) in AKR mice. The result indicates thyroid hormones involvement in 5-HT2A receptor regulation in adult brain.