Effect of a lesion of the hypothalamic nuclei on the morphofunctional state of the hypothalamo-hypophyseal system and the development of experimental atherosclerosis]

Injury of individual nuclei of the anterior and the middle portions of the hypothalamus in rabbits by electrocoagulation through the preliminarily implanted electrodes was accompanied by the change in the morpho-functional condition of the hypothalamo-hypophysial neurosecretory system (HHNS). The nearer the focus of injury to the region of the supraoptic nuclei -- the greater the functional activity of the HHNS. In combining the injuries of individual hypothalamic nuclei with the atherogenic diet there occurred marked morpho-functional changes both in the HHNS and in the adrenal glands; as to animals with experimental atherosclerosis, it acquired under these conditions a more severe form than in the animals on the atherogenic diet alone. Results of investigations pointed to the presence of a close association of the genesis of the atherosclerotic process with the neurogenic factors.     

The hypothalamo-hypophysial system of the lemming Dicrostonyx torquatus Pallas. IV. Influence of experimental animal cooling on the ultrastructure of the hypothalamo-posthypophysial neurosecretory system

The reaction of the hypothalamo-hypophysial neurosecretory system (HHNS) of lemmings to cold (+4 degrees C) was studied by the method of electron microscopy. The animals were kept in cages with nest, but with no wheel to allow running; in cages with a wheel, but with no nest; in cages with no nest and no wheel. No changes in the HHNS reaction were revealed under cold stimulation, if the animals were not deprived of motor activity (running in a wheel), or could hide in a nest. In case of no nest and restricted motor activity exposition to low temperature led to a progressive activation of neurosecretory cells of the supraoptic and paraventricular nuclei, and finally to their exhaustion and degeneration. The intensity of the HHNS reaction to cold is shown to depend on the initial state of the system which varies according to the stages of population cycle. The present study gives grounds to put forward the hypothesis that the adaptation of the Dicrostonyx torquatus Pallas to cold is made possible due to maximal utilization of ecological conditions and behavioral reactions.     

Morphofunctional state of hypothalamic and epiphyseal structures in relatively wild and domesticated silver foxes during estrus

Histochemical and cytometric analyses of the hypothalamo-hypophysial neurosecretory system (HHNS), suprachiasmatic and arcuate nuclei, as well as the pineal gland in mature female silver foxes during oestrus revealed activation of peptidergic and monoaminergic neurosecretory units alongside with activation of the glial and vascular components. The increase of the secretory activity of the HHNS and pineal gland was more evident in domesticated animals. The data obtained show more intense production and excretion of neurohormones which are involved in regulation of reproduction, in domesticated foxes. These peculiarities may account for changes in the oestral cycle in domesticated animals.     

State of the hypothalamo-hypophyseal neurocirculatory system of the gerbil, Rhombomys opimus, during dehydration

Big gerbils, inhabitants of desert, were found to have indices of an increased functional activity of HHNS: low content of neurosecretory material all over the system, relatively large volumes of neurosecretory cell nuclei and nucleoli, hyperemia. Under the condition of a seven-day dehydration, the neurosecretory material reduction in all links of HHNS, enlargement of neurosecretory cell nuclei and nucleoli, intensification of hyperemia were found. With the increase in dehydration time to 23 days a progressive reduction of neurosecretory material in cell processes and hypophysis are seen. However, the decrease in nuclear size takes place under the condition of continuing increase in nucleolar size both in supraoptic and paraventricular nuclei. Extremely intensive hyperemia of all regions of HHNS is seen. The activation of HHNS under the water-salt regime change, seen in big gerbils, is not as pronounced as in albino rats. This is, evidently, due to a specificity of the function and their osmoregulating system.     

The hypothalamo-hypophysial system in the ground squirrel,Citellus erythrogenys Brandt

Summary Monthly observations of the Gomori-positive hypothalamo-hypophysial neurosecretory system (HHNS) of the ground squirrel, Citellus erythrogenys Brandt, were carried out light microscopically using several quantitative methods. From the beginning of hibernation, formation of neurosecretory material (NSM) in the neurosecretory cells (NSC) progressively decreases and release of neurohormones from the HHNS is almost fully inhibited. A maximal accumulation of NSM in the perikarya of the NSC and in the posterior pituitary (PP) is found in December. By this time the volume of the cell nuclei and nucleoli is at a minimum. Signs of activation of the HHNS appear and become more conspicuous as the time of arousal from torpor approaches. The amount of NSM in the NSC and the PP decreases simultaneously with the increase in volume of the NSC. Hyperemia and activation of glial elements is visible throughout the HHNS. The morphological signs of activation reach their peak in March. After reproduction is completed (April to beginning of May), the NSC and the PP are almost devoid of NSM. Beginning with June and during the summer and autumn months a progressive accumulation of NSM in the NSC and the PP parallels gradual diminution in the volume of the NSC structures and the glial cells. Mechanisms and effector pathways by which the HHNS influences seasonal adaptation of the organism and reproduction are discussed.     

The hypothalamo-hypophysial system of the lemming, Dicrostonyx torquatus Pallas. III. Population aspects of neuroendocrine regulation

The structure and ultrastructure of the following regions of the hypothalamo-hypophysial neurosecretory system (HHNS) in the population cycle of lemming were studied: supraoptic (SON), paraventricular (PVN) and arcuate nuclei (AN), the median eminence (ME) and posterior pituitary (PP). Being compared to the state of endocrine glands and gonads, and the level of reproduction stress in the population cycle of the lemming described earlier, the obtained data revealed a certain regularity. First, at the stages of decrease, increase and in the first period of the stage of population peak the activity of the SON-PP complex and AN is gradually increased. This coincides with intensified reproduction, intensified functioning of the thyroid gland and adrenal cortex. Second, while the population is decreasing, all the above functions become depressed, except that of the thyroid gland which, on the contrary, becomes active. In the second period of the stage of population peak, when reproduction stops abruptly, this regularity, however, does not hold, the activity of SON-PP complex and AN is sharply lowered, whereas that of PVN becomes very high. The structure of the thyroid damaged as a result of previous hyperfunction, is restored, and the adrenal cortex shows signs of hypercorticism. The present work is devoted to specificity of the HHNS functioning at the stage of population peak, referred to as crucial, and the pathways and mechanisms by which neurohormones produced by this system can affect the endocrine glands. In addition, the causes likely to lead to the mass death of animals at this stage, and biological significance of this fact are also given attention to.     

The hypothalamo-hypophysial system in the ground squirrels, Citellus erythrogenys Brandt and Citellus undulatus Pallas. I. Microanatomy and cytomorphology of the gomori-positive neurosecretory system with special reference to its state during hibernation.

Microanatomy of the peptidergic hypothalamo-hypophysial neurosecretory system in the ground squirrels, C. erythrogenys and C. undulatus, is similar to that of other rodents, but differs in details. Bundles of neurosecretory fibres with single neurosecretory cells along their course connect the hypothalamic neurosecretory centers into the one system. The dorso-caudal portions of the NPV reach the level of the columna fornix. The NPO is a special indepedent formation and appears to have some specific functions in the HHNS. The infundibular recess penetrates deeply ihto the hypophysial stem, but does not reach the posterior pituitary. The glandular epithelium of the tuberal portions of the adenohypophysis surrounds the median eminence and a considerable part of the lateral surface of the tuber cinereum. Different functional types of neurosecretory cells reflect certain phases of their secretory cycle. Correlations between their size, structure and the content of NSM are found. A low activity of the HHNS is observed in both C. erythrogenys and C. undulatus during December-January. A higher activity of the HHNS in torpid C. undulatus than in C. erythrogenys is established. This correlates with a difference in deepness of torpor in C. erythrogenys and C. undulatus. An important role of the HHNS in hibernation, i.e. in realization of adaption of species in ontogenesis is suggested.     

Changes of impulse activity recorded from the rat vagus nerve during short-lasting total cooling

Gradual cooling of anesthetized rats followed by a drop in rectal temperature (RT) increased the frequency of efferent impulses and decreased the frequency of afferent impulses in the vagus nerves. Preliminary short-lasting (5 h) moderate cooling of the animals in a thermochamber to +5°C (RT did not change), or intensive cooling to −20°C (RT dropped to 32°C) changed the response of efferent nerve fibers to cooling of the body. Under these conditions, a drop in RT to 29°C was followed by a significant increase in efferent discharges in the vagus nerve after additional cooling throughout the experiment, while an initial cooling phase (RT was equal to 35-30°C) was followed by some inhibitory effect. At the same time, the changes in the afferent link were different. As in the control, gradual cooling decreased frequency of afferent impulses, although the intensity of the effects was different. The involvement of the vagus nerve system in the maintenance of temperature homeostasis during body cooling has been discussed.     

Effect of overheating on spermatogenesis in mice and the value of heat training in adapting sex cells to the effects of high temperatures]

A single, 10-minute, stay of albino mature mice in a thermochamber at a temperature of 43 degrees C and a relative humidity of 65% caused destruction of the spermatogenic epithelium expressed in degeneration and desquamation of the sexual cells in 55% of the seminiferous tubules. Preliminary 10-day thermal training caused only an intensification of the physiological degeneration of the spermatogenic cells in 16% of the seminiferous tubules; this could point to the adaptation of the sex cells to the action of the high temperature.     

The role of the medial septum in the acoustic trachea of the cricket Gryllus bimaculatus

In the cricket Gryllus bimaculatus, it is demonstrated that the medial septum in the prothoracic trachea of the auditory system plays an important role in shaping the directional sensitivity of the ear.After perforation of the medial septum, the directional characteristic of intact animals, showing a mean right-to-left difference in sensitivity of 14 dB, becomes more omnidirectional with a mean right-to-left difference of only 7 dB. Correspondingly, the rate of change in auditory sensitivity for a sound source moving from frontal to contralateral is reduced to 0.78 dB/10° versus 1.5 dB/10° in intact animals (Figs. 2, 3).A computer simulation of phonotaxis based on these findings predicts a reduction in phonotactic performance in animals with a perforated septum. This prediction is in good quantitative agreement with experimental data (Fig. 4) and emphasizes the importance of an intact septum for effective phonotaxis in crickets.     

Maturation of the human hypothalamo-hypophyseal neurosecretory system in prenatal ontogeny. A light-optical and electron microscopic study

The hypothalamic-hypophysial neurosecretory system (HHNS) was studied in the human foetuses from the age of 8 weeks till birth. The hypothalamus of 8 weeks old foetuses is weakly differentiated, no individual cell groups, so-called nuclei, are identified. The supraoptic (SON) and paraventricular (PVN) nuclei are identified from the age of 12 weeks on. The size of cell nuclei increases with the age. The Homori-positive granules were first found in some SON and PVN cell and in neurohypophysis in the 18 weeks old foetuses. It was shown under the electron microscope that the neurohypophysis of 8 weeks old foetuses consisted mainly of pituicytes with axons among the cytoplasmic processes of the latter. After the age of 10 weeks, the area of parenchyma of the neurohypophysis occupied by axons increased and typical elementary neurosecretory granules appeared in them. The data obtained are discussed with respect to the participation of HHNS in the regulation of water metabolism in the human foetuses.     

Combinatorial effects of the phytoestrogen genistein and of estradiol in uterus and liver of female Wistar rats

The knowledge about safety of phytoestrogens on proliferative endpoints in the endometrium is rather limited, particularly when low amounts of estrogens are present like in postmenopausal women. Therefore, we now studied how genistein (GEN) exposure affects proliferative endpoints in the endometrium in estrogenized animals. We investigated the effects of GEN (10 mg/(kg day) BW) on uterine proliferation and on general uterine response markers in intact female rats and ovariectomized (OVX) female rats co-treated with different doses of estradiol (E2; 1 or 4 μg/(kg day) BW). In parallel we investigated generalized hepatic effects of GEN in this co-stimulatory protocol. In agreement to our previous results, GEN treatment of OVX animals for 3 days results in a faint stimulation of the uterine wet weight. In intact animals and in OVX animals co-treated with E2 no effects of GEN on uterine wet weight were detectable. GEN treatment did not affect the uterine epithelial height in intact animals but resulted in a decrease of the protein and mRNA expression of the proliferation marker PCNA. In OVX animals co-treated with E2, GEN antagonized the E2 stimulated increase of the uterine epithelial height and epithelial PCNA expression. Besides PCNA, GEN effects on the uterine mRNA expression of IGF-1, IGF-1R, Complement C3, estrogen receptor- (ER) and -β (ERβ), as well as progesterone receptor were investigated in intact and OVX co-treated animals. Overall there was a tendency in all combinatorial groups that GEN counteracts E2 function in uterine tissue. Surprisingly, while investigating estrogenic response markers in liver, we observed very strong effects of GEN on hepatic marker gene expression. GEN significantly down-regulated CaBP9K and IGFBP1 mRNA levels in intact animals. In OVX animals hepatic CABP9K and IGFBP1 mRNA levels were not affected by E2 treatment. GEN treatment, even in combination with E2, decreased the hepatic CaBP9K expression below the levels observed in untreated animals. Interestingly co-treatment of OVX rats with low dose E2 and GEN resulted in a significant increase of IGFBP1 mRNA expression. Summarising our results we conclude that (1) GEN treatment in the presence of E2 is safe regarding proliferative responses in the endometrium of adult animals; (2) the observation of differences of the GEN activity in intact and OVX/E2 substituted animals can be taken as a hint that GEN may interact mechanistically with progestins which has to be proven in detail in future investigations and (3) the detection of strong effects of the phytoestrogen GEN on hepatic gene expression may point to the need of future investigations to rule out the possibility of adverse responses in this organ.     

Sensitivity and specificity of bioassay of estrogenicity on mammary gland and uterus of female mice

Young intact (18 days of age) and adult ovariectomized (OV-X, ovariectomized between 21 to 24 days of age) C3H/Di mice were used to measure the estrogenicity on the basis of the growth response of mammary epithelial structures and weight of the uterus. The percentage area of the mammary fat pad occupied by mammary epithelial structures was progressively increased by 17beta estradiol from dose 0.001 microg.d(-1). The maximum effective dose of estradiol was 0.01 microg.d(-1) and the dose 10 microg.d(-1) of estradiol decreased mammary size to control levels (inverted-U-shaped dose-response curve). Progesterone alone progressively stimulated mammary growth in young intact females from dose 125 microg.d(-1), in adult OV-X animals from dose 1000 microg.d(-1). Both in young intact and adult OV-X animals, uterine weight progressively increased during estradiol treatment. Progesterone alone had no effect on uterine weight in young intact animals; in adult OV-X animals, uterine weight was increased starting from dose 250 microg.d(-1). Progesterone acted synergistically with estradiol to produce higher mammary growth than that in females treated with estradiol alone. The effects of a combination of estradiol plus progesterone in the mammary gland were mimicked by norethindrone acetate and inhibited by cortisol in both young intact and adult OV-X animals. Testosterone inhibited estradiol plus progesterone stimulated growth of mammary gland only in OV-X animals, but stimulated uterine weights in both young intact and adult OV-X animals. Spleen weight and size of mammary lymph nodes were not affected by estradiol, progesterone, norethindrone acetate or testosterone, but were decreased by cortisol. Cortisol also decreased the percent area of the mammary fat pad occupied by mammary epithelial structures, but had no effect on weight of the uterus. These results show that bioassay of estrogenicity in females is not specific. Mammary and uterine growth is stimulated not only by estrogens but also by progesterone and testosterone, respectively.     

Localization of beta-endorphin in the rat heart and modulation by testosterone

Chromatographic analysis and radioimmunoassay were used to identify and quantitate beta-endorphin (BE) and beta-lipotropin (B-LPH) in the hearts (devoid of major blood vessels and atria) from intact male rats, castrated male rats, and castrated male rats treated with testosterone propionate (TP). BE and B-LPH in the plasma of these animals were also identified and measured. In comparison to intact animals, castration resulted in a significant elevation in the content of BE in the heart which was reversed by the administration of TP. The content of B-LPH in the heart was not affected by castration or castration in combination with TP. The ratio of BE to B-LPH in the heart of castrated animals was significantly elevated as compared with intact controls. Treatment of castrates with TP returned the ratio of BE to B-LPH to that observed in intact animals. The concentration of BE in the plasma was greater in castrated rats and castrated rats given TP than in intact males, whereas the concentration of B-LPH was diminished in castrated animals given TP. The ratio of BE to B-LPH was greater in castrated animals treated with TP than in castrated and intact animals. The content of BE and B-LPH, as well as the ratios of the two peptides, varied independently in the cardiac tissue and plasma. The present findings indicated that (i) BE and B-LPH are present in cardiac tissue, (ii) the amount of BE and B-LPH in the heart and the ratio of BE to B-LPH appear to be modulated by TP, and (iii) BE and B-LPH detected in the heart was not simply a reflection of the presence of these peptides in the plasma.     

Effects of photoperiod, melatonin implants and castration on molting and on plasma thyroxine, testosterone and prolactin levels in the European badger (Meles meles)

1. The seasonal molt, which lasts six months in the badger, begins in mid-July and ends at the beginning of winter. It occurs under natural long-day conditions, following the seasonal drop in plasma testosterone levels, concomitant with high levels of thyroxine and prolactin. 2. To examine the role of the different factors involved (day length, prolactin, thyroxine, testosterone), different groups of badgers, divided into subgroups of castrated or intact animals, were subjected to the influence of long days (20L: 4D), short days (4L:20D) or the effect of subcutaneous melatonin implants. 3. In all cases, castration resulted in a significantly earlier onset of molting 1-3 months, depending on the group, regardless of the experimental conditions (20L:4D, 4L:20D, melatonin). 4. However, molting started earliest in animals subjected to long days, irrespective of whether they were castrated or intact. 5. In the melatonin-implanted badgers, molting started either early (castrated animals), or late or not at all (intact animals). 6. Lastly, in castrated badgers subjected to experimental photoperiods (short days or long days) or melatonin implants, the period of molting was shortened from 6 months (intact outdoor animals) to 4 months. 7. The advance in shedding was always related to an early drop in testosterone (or an absence of testosterone in the castrated animals) and to a higher or earlier increase in thyroxine levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dynamics of the dendrite and transcallosum potentials in the cerebral cortex in overheating]

Experiments were conducted on awake rabbits placed in a thermochamber at the temperature of 45 degrees C. The dendrite and the transcallosum potentials were examined in dynamics of the hyperthermia and after the restoration of the thermal homeostasis. The influence of high temperature was accompanied by an expressed inhibition of the amplitude of the dendrite potential, although to a lesser degree than of the transcallosum response. The data obtained could testify to a direct inhibitory thermal effect on the neuron elements of various layers of the cortex. Restoration of the cortical neuron function after the high degree hyperthermia occurred twenty-four hours after the body normothermia was reached.     

Decreased resistance of multiresistant mycobacteria to isoniazid during the treatment of experimental tuberculosis with ozone and isoniazid

Mycobacteria (MB) of the clinical strain resistant to streptomycin, isoniazid (IN), rifampicin and kanamycin were injected intravenously into 68 BALB/c mice. The animals were divided into 5 groups: two control groups 0 and 1 (intact and infected without subsequent treatment), group 2 (treated with IN), group 3 (treated with IN and injected intraperitoneally with dissolved ozone, or dO3), group 4 (injected with dO3). The animals started to die by month 4 after the infection. By month 5 all mice died with the exception of intact mice and those treated with dO3). By month 4 the study of MB cultures isolated from the lungs revealed a decrease in their resistance to IN in the groups undergoing treatment with dO3. Hepatic and splenic lesions were observed after treatment with IN only were greater than in the absence of treatment. After the use of IN + dO3 such lesions were the least. The mechanism of a decrease in the medicinal resistance of MB under the action of dO3 and the expediency of the simultaneous use IN and dO3 in cases of the unknown medicinal resistance of MB are discussed.     

Comparison of motor patterns in the intact and deafferented flight system of the locust

Summary The activity of flight interneurons was recorded intracellularly in intact, tethered flying locusts (Locusta migratoria) and after removal of sensory input from the wing receptors. Depolarization patterns and spike discharges were characterized and compared for the two situations.In general, depressor interneurons (n=6) showed only minor changes in their activity as a result of deafferentation (Fig. 1). Exceptions were interneurons 308 and 506 (Fig. 2). By contrast, all but one of the elevator interneurons (n=9) produced distinctly different depolarization patterns in intact locusts and following deafferentation. Three different groups of elevator interneurons were found (excluding the one exceptional neuron, Fig. 6). (i) One group of interneurons (n=4) produced different, superthreshold depolarizations in intact and deafferented animals (Fig. 3). Characteristic, biphasic depolarizations were recorded from these fibres at lower wingbeat frequencies in the intact situation but only single, delayed potentials were recorded after deafferentation. (ii) The second group of interneurons (n=3) exhibited distinct rhythmic activity only in intact animals. After deafferentation their depolarizations were small and often below the threshold for spike initiation (Fig. 4). (iii) One interneuron produced rhythmic flight motor oscillations only after deafferentation. In intact locusts the membrane potential of this neuron showed very small oscillations and remained subthreshold (Fig. 5).Four main conclusions emerge from these data. (i) The activity of elevator interneurons is under greater sensory control than that of the depressors. This confirms the results of our previous electromyographic and motoneuronal analyses, (ii) A considerable portion of elevator activity is generated as a result of phasic sensory feedback. An essential input is from the hindwing tegulae (Table 1; Pearson and Wolf 1988). (iii) The activity of depressor interneurons appears to be determined by central mechanisms to a major extent. (iv) Different sets of central neurons appear to be involved in flight pattern generation in intact and deafferented locusts —although the two sets share many common elements.Abbreviations EMG electromyogram - PSP postsynaptic potential (EPSP excitatory andIPSP inhibitory)     

Evaluation of the role of calcitonin deficiency in ovariectomy-induced osteopenia

Studies were carried out in rats to examine the role of calcitonin deficiency in the pathogenesis of ovariectomy-induced osteopenia. The parathyroid glands of 80 female Wistar rats were autotransplanted to their thigh muscle and the animals divided into 4 groups. Group 1 rats were sham ovariectomized, and thyroidectomized to make them calcitonin deficient; Group 2 rats were thyroidectomized, and ovariectomized to make them deficient in ovarian hormones as well; Group 3 rats were sham thyroidectomized and sham ovariectomized, and Group 4 rats were sham thyroidectomized and ovariectomized. A fifth group of rats were unoperated upon and served as controls. Thyroidectomized animals were maintained on thyroxine replacement and 11 months after ovariectomy all the animals were bled, killed and their femurs dissected out. In both the thyroid intact and thyroidectomized animals, ovariectomy decreased femur density significantly (P less than 0.01). Similarly, ovariectomy resulted in a decrease in femur calcium (P less than 0.01) in both groups of animals, and in a significant decrease in serum calcitonin (P less than 0.05) in the thyroid intact animals. We conclude from these findings that ovarian hormone deficiency can cause bone loss independently of lowering circulating calcitonin levels.     

Study of the immunotropic activity of aminoglycoside antibiotics

The action of some aminoglycoside antibiotics on the immune system was studied on both intact mice and the animals with immune deficiency caused by administration of cyclophosphamide. The following tests were used: local hemolysis (the Herne test), lymphocyte transformation (LT), delayed hypersensitivity to sheep red blood cells and the local graft versus host reaction (GVHR). Amikacin was shown to have no significant action on the activity of lymphocytes in the intact mice and stimulated both cellular (LT and GVHR) and humoral (the Herne test) immunity in the animals with lowered immunological reactivity. Sisomicin had no significant action on the immune system of the animals. Gentamicin suppressed the immune response only in the intact mice. Kanamycin and streptomycin induced inhibition of humoral and cellular immunity in both the intact mice and animals with immune deficiency. On the basis of the results it was concluded that gentamicin, amikacin and sisomicin may be used in the treatment of diseases developing in the presence of immune deficiency whereas streptomycin and kanamycin should be recommended when inhibition of the immunity is needed.