[Biodistribution of the recombinant heat shock protein rhHsp70 in intracranial C6 glioma models in Wistar rats and subcutaneos B16/F10 melanoma in C57BL/6 mice].

For the first time, the biodistribution of recombinant heat shock protein in rhHsp70 rats with grafted intracranial C6 glioma was evaluated. It was assessed using the fluorescent antibody accumulation chaperone rhHsp70 conjugated with fluorochrome Alexa Fluor 555 in tumor cells by intratumoral or intravenous administration. Assessment of the distribution and accumulation of labeled protein was carried out on the model of subcutaneous B16/F10 melanoma in C57BL/6 mice with the use of single-photon emission computer tomography. After 60 minutes after intravenous administration rhHsp70-I123 (20 MBq, 5 mg chaperone) accumulation of the drug mainly in the liver and tumor tissue was showed. The coefficient of the differential accumulation of the labeled protein KDN(tumor/background) was 3.14. It was turned out that comparing the level of fixation of rhHsp70-I123 in the liver and the tumor KDN(tumor/ liver) = 0.76. After 24 hours from the time of injection of rhHsp70-I123 it was observed increase the level of fixation of the labeled protein in the liver and melanoma: KDN(tumor/background) = 3.43; KDN(tumor/liver = 0.78.

[Role of 123-I-metaiodobenzylguanidine imaging as a component in the diagnosis and treatment of neuroblastoma].

Tomoscintigraphy with 123I-metaiodobenzylguanidine reveals function of tumor tissue. It may be used for both primary diagnosis of neuroblastoma, monitoring treatment efficiency and prognosis. Before single photon emission tomography using 123I-metaiodobenzylguanidine is undertaken, MRI by means of computed tomography should be carried out in abdominal area to ensure perfect blending of multimodal images.

[Role of 18F-FDG PET in tumor grading and evaluating effectiveness of therapy in malignant lymphomas].

The report compares the results of (multi-layer spiral computed tomography) (MSCT), 67 Ga citrate lymph scintigraphy and 18FDG PET in patients with Hodgkin's disease. The predictive significance of the latter method exceeded that of MSCT and ultrasound in diagnosing lymph node neoplasia below the diaphragm. As far as peripheral and mediastinal lymph nodes are concerned, the MSCT efficiency of the three procedures was comparable. Advantage was offered by PET in early evaluation of therapeutic effectiveness. Moreover, its practical significance for assessing tumor sensitivity to therapy as well as differentiation between viable tumor tissue and fibrosis was demonstrated.

[Cortical influences on thyroid and sex gland function in neurotic dogs]. / Kortikal'nye vliianiia na funktsiiu shchitovidnoi i polovykh zhelez pri éksperimental'nom nevroze u sobak

Disturbances of higher nervous activity charactetized by the development of an experimental neurosis were elicited in three male dogs by means of functional influences. This was accompanied by an increase, decrease or no change in the level of total thyroxine in the blood with greater fluctuations of its content on different days. An euthyreoid state persisted in the dogs throughout all periods of the neurosis, which is testified by the absence of changes of the free thyroxine coefficient. In the first three to four weeks of the experimental neurosis the testosterone content in the blood plasma was enhanced, its level not correlating with the variations of thyroxine content in the blood.

[The ratio of sex hormone production by the ovaries and the adrenal cortex in different phases of the rat estrous cycle]. / Sootnoshenie produktsii polovykh gormonov iaichnikami i koroi nadpochechnikov v razlichnye fazy éstral'nogo tsikla u krys.

The biosynthesis of estradiol and testosterone was found to occur mainly in the ovaries (4-5 and 10-20 times more than in the adrenals during diestrus and proestrus, resp.). Estron and androstendion were produced equally in both glands. The estrogens and androgens were found to act as synergists in the stimulation of biosynthetic processes in the uterus. Their level in peripheral blood reflects less fully the character of hormonal function of the ovaries than study of these steroids in the incubates of the ovaries. The biosynthesis of progesterone in adrenals exceeds 2-3-fold that in the ovaries. No changes on production of this hormone depending on the cycle phase, were found.

[Gonadotropin releasing activity of different regions of rat brain and the probability of presence of a factor which inhibits it in the suprachiasmatic region]. / Gonadotropin-rilizing aktivnost' razlichnykh otdelov mozga krys i veroiatnost' nalichiia ingibiruiushchego ee faktora v suprakhiazmaticheskoi oblasti.

The amount of gonadotropin-releasing hormone (Gn--RH) was measured in the preoptic area and in some parts of hypothalamus by radioimmunoassay. Maximal level was found in the median eminence next followed by that in the portions containing n. arquatus or retrochiasmatic area. The preoptic area contained less Gn--RH. The quantity of Gn--RH was negligible in the suprachiasmatic area. If tested in both supra- and retrochiasmatic areas simultaneously the amount of Gn--RH was much lower than in the retrochiasmatic area alone. Existence of inhibiting or inactivating factor in the suprachiasmatic fragment is suggested. The amount of Gn--RH was small in hypothalamic areas including n. paraventricularis, n. supraopticus, mamillary bodies. From among all the fragments tested the pineal body showed the lowest Gn--RH. There was no correlation between the serum LH concentration and the amount of Gn--RH in any investigated area except the preoptic one.

[Effect of stimulators of sexual function on the hypothalamo-hypophyseal system and the fertility of androgenized female rats]. / Vliianie stimuliatorov polovoi funktsii na gipotalamo-gipofizarnuiu sistemu i plodovitost' neonatal'no androgenizirovannykh samok krys.

Neonatal androgenization with 15--25 micrograms of testosterone-propyonate makes 43--54% of female rats sterile at puberty. Long-term administration of progesterone, clomiphen, luliberine, prostaglandin E2 induces ovulation but does not improve the fertility. Prostaglandin E2 decreases the amount of luliberine in the median emicnence and arquate nuclei within 30 min and increases the amount of luteinizing hormone in the blood of the control rats, whereas in the androgenized rats prostaglandin E2 is ineffective. According to the authors' hypothesis, a very mobile fraction of luliberine exists in the median emicnence, rapidly released into the portal blood system on stimulation and rather decreased in androgenization. Clomiphen increases the blood level of luteinizing hormone in the evening but its peak is twice as high in normal animals as compared with the androgenized ones.

[Effect of 5,6-hydroxytryptamine and various light schedules on the hypothalamo-hypophyseo-gonadal system of the female rat]. / Vliianie 5,6-oksitriptamina i raznykh svetovykh rezhimov na gipotalamo-gipofizarno-gonadnuiu sistemu samok krys.

Hypothalamic luliberin and plasma lutropin concentration were studied under normal light-darkness cycle or under constant illumination in rats. Some of them were injected with 5,6-dihydroxytryptamine (5,6-HTA) into the lateral brain ventricle. Constant illumination led to a persistent oestrus with a significant drop in plasma lutropin and a decrease in hypothalamic luliberin. Destruction of serotoninergic terminals with 5,6-HTA resulted in an opposite effect and prevented to some extent inhibiting influence of constant illumination. Luliberin synthesis and secretion seem to be suppressed by serotoninergic nerve terminals on the luliberin producing cells as well as by serotonin reaching the hypothalamus from the pineal gland.

[Changes in sexual functioning in the male rat after total or anterior deafferentation of the mediobasal hypothalamus]. / Izmeneniia polovoi funktsii u krys-samtsov posle polnoi ili perednei deafferentatsii mediobazal'nogo gipotalamusa.

After complete deafferentation of the mediobasal hypothalamus in male rats, the luteinizing hormone content increased in the blood which correlated with an increasing of testosterone secretion, weight of seminal glands and additional sexual organs. Half of the operated animals preserve copulating ability. The content of folliculo-stimulating hormone in the blood of animals after the complete deafferentation was decreased, particularly in non-copulating males. After the interior deafferentation of the mediobasal hypothalamus in the rats, the luteinizing hormone and testosterone contents in the blood did not change but the weight of seminal glands and concentration of folliculo-stimulating hormone in the blood decreased. The data obtained suggest different mechanisms of control of the luteinizing and folliculo-stimulating hormones secretion in male rats, the connection of the mediobasal hypothalamus with anterior hypothalamus and preoptic area being necessary for normal secretion of the folliculo-stimulating hormone.

[The content of sex steroid receptors and the activity of marker enzymes of estrogenic action in the uterus of androgen-sterile rats]. / Soderzhanie retseptorov polovykh steroidov i aktivnost' nekotorykh fermentov-markerov éstrogennogo deistviia v matke u androgensteril'nykh krys.

In rats with preserved ovaries, both in normal and in neonatally androgenized, the activity of enzymes kreatinphosphokinase and peroxidase cannot serve as the marker of the estradiol effect upon the uterus. In ovariectomised animals, the dynamics of activity of these enzymes corresponds to uterotropic responses to estradiol. but not to the dynamics of hormone receptor complexes. The data obtained makes doubtful the participation of the hormone receptor complexes in realisation of the estrogens effect upon the uterus.

[Role of catecholamines and serotonin in regulating cyclic and tonic secretion of gonadotropic hormones]. / Znachenie katekholaminov i serotonina v reguliatsii tsiklicheskoi i tonicheskoi sekretsii gonadotropnykh gormonov

In female rats with normal estrous cycle, in the proestrus phase, a significant decrease of the serotonine level was revealed in the anterior and medio-basal parts of the hypothalamus which coincided with ascent of the releasing factor for gonadotropic hormones in the hypothalamus and for gonadotropins in the hypophysis. The dophamine level in the hypothalamic anterior and medio-basal parts changed in different ways attaining during oestrus its maximal values in the anterior and medio-basal parts of the hypothalamus. No regular changes were revealed in noradrenaline content in the course of estrous cycle in any hypothalamic area. For purposes of studying the mechanisms of regulation of the gonadotropins tonic secretion, the same parameters were recorded in androgensterile and ovariectomized rats. Levels of serotonine and noradrenaline revealed no regular connection with changes in the gonadotropins production, while the anterior part of hypothalamis dophamine concentration in the was in reverse proportion to the extent of gonadotropic secretion. Serotonine seemed to participate in regulation of the cyclic but not the tonic secretion of gonadotropins, while dophamine seemed to exert an inhibitory effect on regulation of tonic secretion of gonadotropins.

[The negative and positive phases of the reaction of the hypothalamo-hypophyseal-gonadal system in female rats to the administration of sex hormones]. / Otritsatel'naia i polozhitel'naia fazy reaktsii gipotalamo-gipofizarno-gonadnoi sistemy samok krys na vvedenie polovykh gormonov.

I.m. administration of estradiol benzoat in physiological doses decreased 3-fold the lutropin secretion and follitropin secretion by one third, in ovariectomised rats. The same dose in intact rats decreases the lutropin level in the blood and gonadoliberin contents in the medial eminence by the negative feedback mechanism. In 4-6 hrs after injection the positive effect of estradiol is at its highest level, the lutropin level in the blood increases by 80-100 times, the follitropin--by 2-3 times. Therefore, estradiol plays a decisive role in positive as well as negative effects on the lutropin secretion, whereas its effect upon follitropin secretion is less obvious. The gonadoliberin transport in negative phase of estradiol effect is mainly performed through the medial eminence whereas the positive effect of estradiol needs a participation of organum vasculosum of the lamina terminalis too.

[The synthesis of estradiol and progesterone receptors in relation to the biological effects of sex hormones in ovariectomized rats]. / Sintez retseptorov éstradiola i progesterona v sviazi s biologicheskimi éffektami polovykh gormonov u ovariéktomirovannykh krys.

The concentration of the estradiol and progesterone receptors in cytosol increased within a week after ovariectomy in rats, the nucleic concentration of receptors sharply diminishing. The uterus atrophy following ovariectomy in associated with a reduction of both nucleic and cytosol receptors in the organ. Administration of estradiol (1 mg) restored the organ mass and the character of hormonal reception within a week. Progesterone and clomyphen exerted some uterotropic effect. Ovariectomy reduced the creatinkinase activity by 2.9 times and the peroxydase activity by 13 times. Two types of synthesis of female sex hormones receptors seem to exist in the rat uterus: the constitutional type depending on no hormonal effects and the induced one depending on the sex steroids, estradiol in particular.

[Physiologic mechanisms of the reaction of the reproductive system in female rats to chronic exposure to low doses of toluene]. / Fiziologicheskie mekhanizmy reaktsii reproduktivnoi sistemy samok krys na khronicheskoe vozdeistvie malykh doz toluola.

Chronic inhalation of toluol (2-4 months) did not affect the menstrual cycle in female rats but distorted the mechanisms of the reproduction control. The level of gonadoliberin decreased during dioestrus in preoptic area, the correlation between concentrations of luteinizing and folliculo-stimulating hormones became disordered, and the prolactin secretion increased. Preovular peaks of gonadotropins secretion became lower in proestrus. The cold stress increases the prolactin secretion and decreases the gonadoliberin content in the hypothalamus of control animals. These events do not happen after toluol inhalation. After 4 months of toluol inhalation, the levels of estradiol and progesterone decrease in the blood. However, normal response to gonadotropic stimulation is preserved which suggests a secondary character of hormonal disorders, in response to primary disturbances in the hypothalamo-hypophyseal link of the reproduction control.

[Interrelation of the hormonal indices and the cytologic characteristics of the germ cells]. / Vzaimosviaz' mezhdu gormonal'nymi pokazateliami i tsitologicheskoi kharakteristikoi polovykh kletok.

The analysis of the maturation of follicular oocytes as well as of the state of gametes after induction of ovulation with PMSG or with GnRH in intact and androgenized rats revealed the dependence of the heterogeneity extent (in morphologic and chromosomal damages) of population of germ cells maturing in vivo and in vitro upon the character of gonadotropin regulation disturbances of folliculogenesis. Stable disorder of reproductive function (androgenization) is followed by a significant increase in number of abnormal gametes under its hormonal correction.

[Sexual dimorphism in the content of luliberin following deafferentation of the mediobasal hypothalamus]. / Polovoi dimorfizm v soderzhanii liuliberina posle deafferentatsii mediobazal'nogo gipotalamusa.

Luliberin (LH-RH) was assayed radioimmmunologically in the hypothalamic fragments taken from male and female rats, intact or with isolated mediobasal hypothalamus. An increased amount of LH-RH was found in the fragments containing organum vasculosum of the lamina terminals (OVLT) and taken from intact males. LH-RH amount was negligible in isolated parts of hypothalamic fragments containing arquate nucleus of median eminence. OVLT of females was mu;ch richer with LH-RH than that of the males. The females though were characterized by a lower blood lutropin. The inhibitory influences on the secretion of LH-RH seem to be more obvious in intact males than in females.

[Effect of monoamine levels on gonadotropin releasing hormone concentration in the hypothalamus, pituitary gonadotropic fuction and ovarian ovulatory and hormonal function]. / Vliianie urovnia monoaminov na soderzhanie gonadotropin-rilizing gormona v gipotalamuse, gonadotropunuiu funktsiiu gipofiza, ovuliatornuiu i gormonal'nuiu funktsiiu iaichnikov.

Daily administration of 0.25 mg reserpine during 14 days reduces the noradrenaline and dopamine level in the hypothalamus by 21--47 per cent and the LH level in the blood. The amount of Gn-RH in the supra-and retrochiasmatic portions of the hypothalamus is significantly increased thereby indicating an inhibition of the RH release into the blood of portal vein. The same course of 0.5--0.75 mg reserpine reduces the level of catecholamines by 51--82 per cent, the Gn-Rh content decreasing in the preoptic, supra-and retrochiasmatic areas along with further decrease of LH level in the blood. This is due, probably, to disturbance of both synthesis and release of Gn-RH. Consequently, the catecholamines activate primarily the release and then the synthesis of Gn-RH. The level of gonadotropins in hypophysis undergoes no essential alterations under the influence of reserpine, the animals develop a constant diestrus, great major yellow bodies appearing in the ovaires while the number of folliculi reduces. The hormonal activity of ovaries at that (secretion of estrogens and progesterone) decreases.

[The hypothalamo-hypophyseo-ovarian systems in rats after deafferentiation of the mediobasal hypothalamus]. / Gipotalamo-gipofizarno-ovarial'naia sistema u krys posle deafferentatsii medio-bazal'nogo gipotalamusa.

Complete surgical deafferentation of the medio-basal hypothalamus (MBH) in rats entails suppression of the oestrus cycle as well as a decrease of luteinizing hormone, estrogens and progesterone release into the blood due to a sharp fall of the luliberine content in the median eminence and arquate nuclei. No connection was revealed between the character of oestrus disturbances and the extent of damage or isolation of the arquate, ventromedial, supraoptic and paraventricular nuclei and the amount of Homori-positive neurosecreted in the MBH. In development of permanent diestrus the MBH isolation was more complete than in the preservation of irregular cycle. The luliberine seems to be produced mainly in the anterior hypothalamus of rats whereas the MBH alone fails to maintain even its tonic secretion. Even in complete surgical isolation of the MBH, separate fibers of the luliberinergic cells penetrate into the MBH maintaining there a certain amount of luliberin and preserving synthesis of the luteinizing hormone in the hypophysis with its decreased release into the blood.

[Effect of 6-hydroxydopamine and 5,6-Dihydroxytryptophan on the luliberin and luteinizing hormone levels in female rats under constant illumination]. / Vliianie 6-oksidofamina i 5,6-oksitriptofana na uroven' liuliberina i liuteiniziruiushchego gormona u samok krys pri postoiannom osveshchenii.

Administration of 5,6-oxytryptophan to female rats' 3rd cerebral ventricle, as opposed to 6-oxydopamine, prevents the decrease in the luteinizing hormone contents in the blood occurring under constant illumination. Administration of 6-oxydopamine against the background of desmethylimipramine caused a significant increase of the luliberine contents in the anterior hypothalamus while preserving its normal level in the medio-basal portion.

[Radioimmunologic analysis of steroids. Scientific and practical aspects]. / Radioimmunologicheskii analiz steroidov. Nauchno-prakticheskie aspekty.

Many-year experience of using authors' own systems for steroid radioimmunoassay (RIA) is summarized. Synthesis of natural and anabolic steroid derivatives and their conjugation with bovine serum albumin are considered. Schemes of rabbits immunization with steroid-protein conjugates, and the antisera characteristics are described. Data on comparison of 3H- and 125I-ligands in steroid RIA are presented as well as the characteristics of the RIA systems. The RIA optimization and quality control problems as well as the prospects of the RIA development are discussed.