[HYGIENIC SUBSTANTIATION OF THE DEVELOPMENT AND USE OF POLYGUANIDINES AS ANTIMICROBIAL PROPHYLACTIC MEANS OF THE INNOVATIVE CLASS].

In the article there are presented data of the system analysis of hygienic properties of polyguanidines (PAG) as an innovative class of domestic microbicidal chemical long-acting compounds synthesized in the domestic scientific institution--Institute ofenvironmental and technological problems, and also delivered on their base new disinfectants. Submitted proceedings of microbiological studies indicate to the antimicrobial action of PA G against Gram-negative and Gram-positive bacteria, viruses, dermatophytes, yeasts, fungi, including pathogens, as well infectious agent of swine and legionellosis. The data of toxicological studies of PAG and a number of derivative disinfectants justify their hygienic safety in dependence on the chemical nature of the used anion (A), the composition and structure of the polymer chain and also the content of residual monomers. All this characterizes PAG as a very promising group of compounds for the use in the form of independent disinfectants and as antimicrobial additives and auxiliaries in such means for different purposes.

[Somatic pain sensitivity of conscious rats with chronic gastric ulcers].

The aim of the study was to investigate the effect of gastric ulcers on somatic nociception in conscious rats. The formation of kissing gastric ulcers was induced by luminal application of 60% acetic. Somatic pain sensitivity was tested by tail flick latency. Application of acetic acid resulted in gastric ulcer formation, somatic hyperalgesia and the appearance of typical signs of chronic stress (a long-lasting increase of plasma corticosterone level, adrenal gland hypertrophy and thymus gland involution). Natural healing of gastric ulcers was accompanied by restoration of pain sensitivity and attenuation of typical signs of chronic stress. Both natural healing of gastric ulcers and restoration of pain sensitivity were prevented by daily indomethacin administration. The results suggest that the formation of chronic gastric ulcers may trigger somatic hypersensitivity.

The role of the hormones of the hypothalamo-hypophyseal-adrenocortical system in the analgesic effect of corticotropin-releasing hormone.

Experiments on anesthetized male rats were performed to study the role of the hormones of the hypothalamo-hypophyseal-adrenocortical system (HHACS) in analgesia induced by central or systemic administration of corticoliberin-releasing hormone (CRF). Studies of the contribution of HHACS hormones were performed by blocking HHACS function by administration of hydrocortisone at a pharmacological dose one week before experiments started. Blockade of HHACS function, resulting in the inability of the system to increase hormone levels, resulted in a decrease in the analgesic effect resulting from systemic administration of CRF and completely abolished the analgesic effect after central administration of CRF. These data lead to the conclusion that there are two components involved in increasing the pain sensitivity threshold in response to administration of CRF: 1) a component dependent on HHACS hormones in central and systemic administration of CRF; 2) a component independent of HHACS hormones on systemic administration of CRF.

Analgesic effect of corticotropin-releasing hormone: involvement of the hypothalamic-pituitary-adrenocortical axis into its realization.

Involvement of hypothalamic-pituitary-adrenocortical axis into the analgesic effect of corticotropin-releasing hormone after its systemic administration was studied in experiments on rats. Pharmacological blockade of the hypothalamic-pituitary-adrenocortical axis decreased the duration and degree of the analgesic effect of corticotropin-releasing hormone. This analgesic effect can be mediated via two pathways: related to hormones of the hypothalamic-pituitary-adrenocortical axis and independent of these hormones.

[The role of hormones of hypothalamic-pituitary-adrenocortical system in analgesic effect of corticotropin-releasing hormone].

The role of hypothalamic-pituitary-adrenocortical system (HPAS) in analgesic effect induced by central or systemic corticotrophin-releasing hormone (CRH) was studied on anaesthetized male rats. Blockade of the HPAS functional activity by hydrocortisone in pharmacological dose one week before the experiment was used as approach to investigate the contribution of the HPAS hormones in CRF-induced analgesia. Elimination of the hormones rise in the blood plasma by hydrocortisone resulted in decrease of analgesic effect induced by systemic CHR and complete disappearance of analgesic effect induced by central CRH. The results suggest that CRH-induced elevation of pain threshold is provided by two components: 1) depending on the HPAS hormones after central and systemic injection of CHR; 2) not depending on the HPAS hormones after systemic injection of CHR.

The role of adrenocorticotropic hormone in the inhibition of pain reactions in conscious rats.

Experiments on conscious male Sprague-Dawley rats were performed to study the effects of adrenocorticotropic hormone (ACTH) on pain reactions. Pain sensitivity was assessed in terms of the latent period of tail withdrawal in response to heat. Systemic administration of ACTH and glucocorticoids to animals with normal levels of hormone production led to increases in the latent period of the tailflick reaction. The roles of glucocorticoids and opioid peptides in ACTH-induced analgesia were addressed in experiment on animals with deficient glucocorticoid production and animals in which opiate receptors were blocked with naltrexone. Deficiency in glucocorticoid production had no effect on ACTH-induced increases in the latent period of the tailflick reaction, while blockade of opiate receptors completely eliminated this effect of ACTH. ACTH-induced analgesia in conscious rats is mediated by opiate receptors and not by glucocorticoids.

Mechanisms of the effects of adrenocorticotropic hormone on pain sensitivity in rats.

Experiments on anaesthetized male Sprague-Dawley rats were performed to study the effects of adrenocorticotropic hormone (ACTH) on pain sensitivity. Systemic administration of ACTH to animals with normal hormone production induced rapidly developing (starting at 3 min) and prolonged (30 min) increases in pain response thresholds. Blockade of opiate receptors led to suppression of the initial stage of the analgesic effect of ACTH: the response was seen only from 15 to 30 min. In animals with deficient glucocorticoid production, the duration of the analgesic action of ACTH decreased to 15 min. Analgesia was completely eliminated by the combination of suppression of glucocorticoid production and blockade of opiate receptors. The analgesic effect of ACTH was mediated by two mechanisms: 1) a rapidly-acting (from 3 to 15 min) mechanism associated with opiate receptors and not related to glucocorticoids, and 2) a delayed (from 15 to 30 min) mechanism associated with glucocorticoids but not opiate receptors.

[The role of adrenocorticotropic hormone in inhibition of pain reaction in awake rats]. / Rol' adrenokortikotropnogo gormona v tormozhenii bolevoi reaktsii u bodrstvuiushchikh krys.

The effect of hormones of hypothalamic-pituitary-adrenocortical system on pain sensitivity were studied in experiments on awake Sprague-Dawley males rats. Pain sensitivity was tested by tail flick reaction induced by thermal stimuli. Systemic glucocorticoids and ACTH injection increased the tail flick latency. The ACTH-induced analgesic effect was unaffected by deficiency of glucocorticoids production in pretreatment with pharmacological dose of cortisol but was fully eliminated by pretreatment with opiate antagonist naltrexone. These findings suggest that ACTH-induced analgesic effect is mediated by opiate receptors but not by glucocorticoids released in response to ACTH injection.

[Healing of gastric mucosal erosions induced by indomethacin and restoration of glucocorticoids levels in the blood of rats]. / Zavisimost' protsessa zazhivleniia érozii slizistoi obolochki zheludka, vyzvannykh indometatsinom, ot soderzhaniia gliukokortikoidov v krovi krys.

The study was made of the effects of low production of glucoorticoids and subsequent replacement with these hormones on healing of hemorrhagic erosions of rat gastric mucosa emerging 4 hours after administration of indomethacin (25 mg/kg percutaneously). Corticosteroid deficiency was produced by adrenalectomy or blocking function of the hypothalamo-hypophyseo-adrenocortical system by introduction of supraphysiological dose of hydrocortisone i week before indomethacin administration. Replacement therapy was conducted 4 hours after indomethacine administration by subcutaneous injection of corticosterone in a dose of 4 mg/kg. Healing was evaluated by changes in the area of damaged surface of gastric mucosa for 2 days after indomethacin administration. Plasma levels of corticosteroids were controlled. It was found that animals with corticosteroid deficiency had a larger area of mucosal lesion and slow healing vs control rats. Administration of corticosterone in physiological dose to animals with deficient production of corticosteroids stimulated healing of gastric mucosa erosions.

[Mechanisms of effect of adrenocorticotropic hormone on the rat pain sensitivity]. / Mekhanizmy vliianiia adrenokortikotropnogo gormona na bolevuiu chuvstvitel'nost' krys.

The mechanisms of effect of adrenocortricotropic hormone on pain sensitivity were studied in anaesthetized Sprague-Dawley male rats. Systemic ACTH administration increased the pain thresholds (from 3 min up to the 30 min after injection) in rats with normal production of hormones. The initial stage of ACTH analgesic effect was fully eliminated by blockade of opiate receptors, ACTH-induced reaction was observed only from 15 up to 30 min after injection. In rats with deficiency of glucocorticoids production, the duration of ACTH-induced analgesic effect decreased to 15 min. The analgesic effect was completely prevented by combination of blockade of glucocorticoids production and blockade of opiate receptors. Thus the ACTH-induced analgesic effect is provided at least by two mechanisms: 1) appearing during the first minutes after injection (from 3 min up to 15 min) and mediated by opiate receptors rather than glucocorticoids, and 2) appearing from 15 min up to 30 min after injection and mediated by glucocorticoids but not opiate receptors.

Effect of ACTH on pain sensitivity in rats.

Systemic administration of ACTH to rats with normal hormone production induced a rapid (started 3 min postinjection) and long-term (persisted 30 min) elevation of pain threshold. Complete inhibition of glucocorticoid production shortened the duration of ACTH-induced analgesia to 15 min. The biphasic effect of ACTH on pain sensitivity is probably mediated by short-term glucocorticoid-independent and long-term glucocorticoid-dependent mechanisms.

[The role of glucocorticoids in healing of indomethacin-induced lesions in the rat gastric mucosa]. / Rol' glukokortikoidov v zazhivlenii érozii slizistoi obolochki zheludka, vyzvannykh indometatsinom, u krys.

Pretreatment with a single large dose of cortisol a week before indomethacin administration, or an adrenalectomy induced a glucocorticoid production deficiency in rats. The area of gastric erosions in these rats was considerably larger than in the control animals in 4, 24, and 48 hours after the indomethacin administration. Administration of corticosterone noticeably prompted the healing of the erosions in the rats with glucocorticoid deficiency. The findings suggest a gastroprotective effect of glucocorticoids in healing of indomethacin-induced mucosal injury.

[The role of corticosteroids in analgesic effect caused by stimulation of the periaqueductal gray matter of the midbrain in rats]. / Rol' kortikosteroidov v obespechenii anal'geticheskogo éffekta, vyzvannogo stimuliatsiei tsentral'nogo serogo veshchestva srednego mozga u krys.

The effects of stimulation of periaqueductal gray matter on pain threshold and blood corticosterone level were studied in anesthetized rats. The stimulation resulted in a alteration of analgesia and corticosterone level. Stimuli-induced analgesia was decreased by adrenalectomy. Corticosterone implantation (50 micrograms) in periaqueductal gray matter resulted in the increase of analgesia. Pretreatment with naloxone (1 mg/kg) failed to modify the effect of stimulation of periaqueductal gray matter on analgesia and corticosterone level. Our results indicate the involvement of corticosterone in the analgesia induced the stimulation of periaqueductal gray matter.

Stress-induced analgesia. The role of hormones produced by the hypophyseal-adrenocortical system.

Experimental studies on the effects of stress on blood corticosteroid levels and the appearance of analgesia were carried out on rats anesthetized with Nembutai (4 mg/100 g). Stress, consisting of stimulation of the hind footpad with a current at 0.7 mA, produced parallel changes in plasma corticosteroid concentrations and the threshold of a pain response. Functional blockade of the hypophyseal-adrenocortical system, produced by systemic administration of hydrocortisone (15 mg/100 g) or by implantation of dexamethasone (200 micrograms) above the paraventricular nucleus of the hypothalamus, resulted in reductions in stress-induced analgesia. Dosage with naloxone (1 and 10 mg/kg) had no effect on the level of analgesia or corticosteroid concentrations. It is concluded that stress-induced analgesia not mediated by opioids is corticosteroid-dependent.

[The adaptation-protective effect of corticosteroids on the rat gastric mucosa and its mechanism]. / Adaptatsionnyi zashchitnyi éffekt kortikosteroidov na slizistuiu obolochku zheludka krys i ego mekhanizm.

The influence of stress-induced corticosteroid production on gastric ulceration, blood flow velocity in gastric microvessels and blood pressure was studied in rats. The role of plasma corticosteroids was investigated by means of blockade of the pituitary-adrenocortical system (PACS) and following corticosterone replacement therapy (400 mu/100 g b.w.). The blockade which was induced by Fi. hydrocortisone administration (7 days before stress, 30 mg/100 g b. w.) resulted in an insufficient corticosteroid production. To evaluate the influence of corticosteroids on blood flow velocity in gastric microvessels of muscular, submucosal and mucosal coats it was used intravital microfilming by means of a dark-field contact epiobjective. Stress (water immersion + restraint) induces an ulceration, a decrease in the systemic arterial blood pressure (3 h after stress onset) and a decrease in blood flow velocity in the gastric microvessels (3 h after stress onset). In rats with insufficient corticosteroid production stress-induced ulceration, a decrease in blood pressure and gastric blood velocity were more greater than in rats with intact PACS. Replacement corticosterone therapy corrected all parameters. The results revealed that antiulcerogenic effect of stress-induced glucocorticoid production is realised owing to normalisation of gastric blood supply which is provided by an increase in systemic blood pressure.

[Stress-induced analgesia. The role of corticosteroids]. / Stress-vyzvannaia analgeziia. Rol' kortikosteroidov.

Non-opioid stress-induced analgesia was studied in anesthetized rats, which were treated with electroshock (0.7 mA, 15 sec on, 15 sec off, 3 min duration) delivered through fixed hind limb electrodes. Tail-flick threshold of electroshock stimulation of the tail was used as a measure of analgesia. Stress-induced analgesia was decreased by adrenalectomy. Medullectomy did not block analgesic effect of stress. These results suggest that corticosteroids, but not enkephalins of adrenal medulla, provide the analgesia induced by short-term stress.

[Stress-induced analgesia. The role of the hormones of the hypophyseal-adrenocortical system]. / Stress-vyzvannaia analgeziia. Rol' gormonov gipofizarno-adrenokortikal'noi sistemy.

The effect of stress on pain threshold and blood corticosteroids was studied in anesthetised rats. The stress stimulation resulted in a parallel changes of analgesia and blood corticosteroids. Stress-induced analgesia were decreased after blocking of the pituitary-adrenocortical system by means of dexamethasone implantation (200 micrograms) in paraventricular nucleus of hypothalamus or i. v. administration of hydrocortisone (15 mg/100 g b. w.). Naloxone administration (1, 10 mg/kg) does not block analgetic effect and corticosteroid level. These results suggest that pituitary-adrenocortical axis provide non opioid stress-induced analgesia.

[The circadian rhythm of the content of corticosteroids and of pain sensitivity in humans and rats]. / Tsirkadiannyi ritm soderzhaniia kortikosteroidov i bolevoi chuvstvitel'nosti u liudei i krys.

The circadian relationships between blood corticosteroids and latent period of pain reaction to hot stimulation were investigated in man and rats. There were no correlation of blood corticosteroids levels and pain latent period but the latent period increased during those time of day when the corticosteroids levels were higher in total: man--morning and day, rats--evening and night.