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Biomedical subjects

M Mićić

Publications and source records attributed to M Mićić.

At least 19 recordsLinked to original sources

Castration of sexually immature rats affects sympathetic innervation of the adult thymus.

It has been hypothesized that maturational processes within the hypothalamo-pituitary-gonadal (HPG) axis and thymus are reciprocally regulated via neural pathways. To test this hypothesis, in the thymi of adult rats orchidectomized (ORX) at age of 1 (ORX-1), 7 (ORX-7) and 30 days (ORX-30): (i) noradrenaline (NA), dopamine (DA) and serotonin (5-HT) contents and acetylcholinesterase (AChE) activity were measured and (ii) the distribution of monoamine- and AChE-containing nerves and cells was examined by a sucrose phosphate glyoxylic acid (SPG) method and enzyme histochemistry, respectively. In all groups of ORX rats, the thymus weight was significantly increased over that in sham-ORX control rats. In the ORX-1 rats, the increase in the thymus weight was accompanied by a proportional increase in the content of both catecholamines and 5-HT; consequently the concentration of each of them remained unaltered. In these animals, the density of both SPG-stained thymus nerve fibers and cells also remained unchanged. In the ORX-7 rats, the rise in the thymus weight was followed by a proportional increase in the content of all monoamines, except for NA which was reduced. Therefore, in these rats neither the thymus concentrations of DA nor that of 5-HT differed from controls, while the concentration of NA was significantly decreased. The reduction in both NA content and concentration reflected a diminished density of SPG-positive nerve profiles. In the ORX-30 rats, the increase in thymus weight was neither paralleled by a proportional increase in the DA content nor in 5-HT, while the content of NA was decreased. Thus, in their thymi the concentration of both NA and DA, as well as that of 5-HT, were significantly reduced. In parallel with these changes, a decreased density of thymic SPG-positive nerve fibers and cells was found. In all ORX rats, the pattern of intrathymic distribution of SPG-positive fibers and cells remained unchanged. Orchidectomy affected neither the activity of AChE (expressed per gram of tissue) nor the density of AChE-positive nerves and cells in the thymus. As the changes in the density of adrenergic nerve fibers in the thymus from ORX rats were not followed by similar alterations in the density of AChE-containing nerve fibers, it does not seem likely that NA and AChE are colocalized in the thymus nerve fibers. The results also suggest that there is a critical period during ontogenesis when changes within the HPG axis evoked by orchidectomy can affect the sympathetic nerve input to the rat thymus and therefore, most likely, development and function of the organ.

Acetylcholinesterase↗

Effects of estradiol and calcium on gonadotrophic cells in middle-aged female rats.

The effects of multiple treatment with estradiol dipropionate (EDP) or calcium glucoheptonate (Ca) or a combination of the two on gonadotrophic cells in the pituitary pars distalis of middle-aged female rats were examined. The animals were treated daily for two weeks with EDP (0.625 mg i.p./kg body weight) or Ca (11.4 mg/kg body weight) or EDP + Ca. Luteinising (LH) and follicle stimulating hormone (FSH)-producing cells were examined by immunohistochemistry using antisera to the specific (beta) beta-subunits of LH and FSH and a peroxidase-anti-peroxidase immunohistochemical procedure. Plasma levels of FSH and LH were measured by radio-immune assay. A stereological method for determining morphometric parameters in immunopositive FSH and LH cells was used. The number of gonadotrophs per unit area (mm2), their cellular volume and relative volume densities, as well as plasma levels of FSH and LH, were decreased in all treated females in comparison with the controls. The most significant decrease of these parameters was observed in EDP-treated animals. Such changes were also expressed in Ca-treated animals, but the alterations were less distinct. These results demonstrate that multiple EDP or Ca application to middle-aged female rats is able to inhibit, directly or indirectly, the morphofunctional state of gonadotrophic cells in the pituitary pars distalis.

Aging↗

Orchidectomy affects the innervation of the rat thymus.

To assess a putative role of the neural pathways in transfer of information from the gonads to the thymus, adult AO rats were orchidectomized (ORX) or sham ORX (controls); sacrificed 1, 3, 7, or 15 days later and their thymi were analyzed for: (a) the concentrations of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) and distribution of monoamine-containing nerve profiles and (b) the acetylcholinesterase (AChE) activity and distribution of AChE-containing nerve profiles. Three days after the castration, an elevation in the level of both catecholamines, reflecting an increase in the overall intensity of nerve fibers autofluorescence, was found. Seven days post castration neither NA nor DA concentration differed from the appropriate control values, while 15 days after the surgery the concentration of NA was lower than that in the controls, most likely, due to diminished density of noradrenergic nerve profiles. In both the rats sacrificed 7 and 15 days after orchidectomy the concentration of 5-HT was reduced as result of a decrease in the density of 5-HT-containing autofluorescent cells. The activity of AChE was depressed one day after the surgery; then increased, so that 3 days post castration its value was higher than that in the sham ORX. After this increase, AChE activity decreased being, at postoperative day 7 and 15, lower than that in the controls. It seems that this decrease in AChE activity reflected, not only a reduction in the density of AChE-containing nerve fibers, but also a decrease in the density of AChE positive cells. Thus, the results indicate that orchidectomy can evoke changes in the T-cell maturation altering modulatory influences on this process coming via neural route, as well as those coming from the mast cells and AChE positive epithelial cells which constitute important component of the thymus microenvironment.

Acetylcholinesterase↗

Thyroid C cells of middle-aged rats treated with estradiol or calcium.

The structure and function of C cells of middle-aged female rats (14-months old) treated with estradiol dipropionate (EDP), calcium (Ca) or a combination of EDP+Ca were studied. A stereological method was used to determine the volume of calcitonin (CT)-immunoreactive C cells and their nuclei, and the relative volume density and mean number of the C cells per section were calculated. Serum levels of CT, osteocalcin, parathyroid hormone (PTH), and beta-estradiol were also measured. A significant decrease in body weight of the rats treated with EDP or EDP+Ca was observed. These treatments led to a significant decrease in cellular and nuclear volumes, relative volume density, and mean number of C cells per section, in comparison with the corresponding controls. A reduction of the serum level of CT, PTH, and osteocalcin was also recorded in EDP- and EDP+Ca-treated animals. No statistically significant differences between Ca- and vehicle-injected rats, with regard to all morphometric C cell parameters and biochemical values determined, were seen. However, a conspicuous degranulation of the C cells and decreased immunoreactivity for CT in the Ca-receiving group, which could be interpreted as the signs of increased activity of these cells, were noticed. This effect of Ca was also observed in rats injected with EDP and Ca in combination, when the inhibitory effect of EDP on C cell function was less noticeable than in the group treated with EDP alone.

Animals↗

Relationships between monoaminergic and cholinergic innervation of the rat thymus during aging.

The present study has been undertaken in order to investigate whether aging is accompanied by alterations in the thymic autonomic innervation. The results showed that in aged rats compared to young adult rats the density of monoaminergic histofluorescent nerve profiles decreased remarkably, while their pattern of intrathymic distribution remained unchanged. The thymic concentrations of noradrenaline (NA) and dopamine (DA) also significantly decreased between the age of 12 and 18 months. However, the density of thymic autofluorescent cells (afc) markedly increased over the same period, as well as the concentration of 5-hydroxytryptamine (5-HT). The aged rat thymus seemed to be able to maintain its cholinergic innervation in terms of density and pattern of distribution, while the density of cells with intracytoplasmic acetylcholinesterase (AChE) staining even increased. The neurochemical measurement showed an increase in the activity of AChE between the age of 9 to 18 months. The results indicate an altered relation between the components of thymic autonomic innervation of aged rats that might be related to the reduced immunocompetence of their T cells.

Acetylcholinesterase↗

Comparative cephalometric analysis in patients with X-chromosome aneuploidy.

The influence of abnormal sex-chromosome constitution on cranial growth, shape and position of the craniofacial structures was analysed. Reduced cranial growth was found in women with Turner's syndrome (45 XO chromosome constitution) and in men with Klinefelter's syndrome (47 XXY chromosome constitution). Lack of or an extra X chromosome produced opposite effects on cranial-base flexion, jaw displacement and maxillary and mandibular inclination to the anterior cranial base. An extra X chromosome affected deviation in sagittal jaw relation while lack of an X chromosome influenced mandibular shape.

Adult↗

Parasympathetic innervation of the rat thymus during first life period: histochemical and biochemical study.

In the present study we analyzed development of the rat thymus parasympathetic innervation using histochemical determination of distribution and density of acetylcholinesterase (AChE) positive nerve profiles, as well as biochemical measuring of the activity of this enzyme. Rat thymuses from late embryonal to adult periods of life were analyzed. The AChE-positive nerve profiles were found, for the first time, on day 18 of fetal life in capsule and interlobulary septae, but also in the subcapsulary and cortico-medullary areas. The density of these profiles increased during the thymic development. The AChE positive nerve profiles in subcapsulary region were observed mainly in close proximity to the thymic epithelial cells, while in the cortico-medullary region they were found in apposition to the thymocytes. The biochemical analysis showed that the specific AChE activity in rat thymus was high on day 19 of gestation. A significant increase in the activity of this enzyme was measured by the third day of postnatal development, and its activity remained approximately at the same level up to the day 90. The present results suggest that thymus receives parasympathetic innervation relatively early in ontogeny; in addition, these nerve fibers could be involved in the regulation of the organ activity, at least, through action upon the thymocytes and/or by modulation of the thymic epithelial cell activity.

Acetylcholinesterase↗

Testosterone binding sites in the rat thymus during late embryonal and postnatal period.

Using immunoperoxidase staining with anti-testosterone Ab, has been shown that the cells binding testosterone were present in the rat thymus and that these cells are localized in the outer thymic cortex as well as in cortico-medullary region and medulla. Immunoperoxidase staining with that Ab at electron microscopy level showed that thymocytes as well as thymic epithelial cells bind this hormone. Combined immunoperoxidase staining with anti-testosterone Ab and immunofluorescence method with mAbs specific for thymocytes or thymic epithelial cells, revealed that thymocytes binding this hormone are localized mainly in the outer cortex, while thymic epithelial cells binding testosterone were found in cortico-medullary region and medulla. These testosterone binding cells were found, for the first time, in the thymus of 18-day-old fetus. It has also been shown that their density increased markedly by the day 3 of postnatal life and continued to increase up to the adult stage of organ development. These results indicate that testosterone can influence upon function of specific thymic epithelial cells, localized in the corticomedullary region and medulla. Thus, the results also suggest that this hormone can modulate T cell proliferation and/or differentiation, not only directly acting on the T cells localized in the outer thymic cortex, but also indirectly modulating function of the thymic epithelial cells that bind this hormone.

Animals↗

Components of sympathetic innervation of the rat thymus during late fetal and postnatal development: histofluorescence and biochemical study. Sympathetic innervation of the rat thymus.

This study was performed in order to investigate development of sympathetic innervation in the rat thymus. To achieve this aim histofluorescence and biochemical methods were used. The histofluorescence method revealed the presence of sympathetic nervous profiles in this organ for the first time on day 18 of gestation. The density of these profiles and intensity of their fluorescence increased progressively during late embryonal and postnatal development of the organ. In the outer cortex of adult thymus the sympathetic nervous profiles were found mainly in apposition to thymocytes, while in deeper cortex and medulla they were revealed adjacent to thymic epithelial cells. These nervous profiles were also found in close association with thymic autofluorescent cells, which density increased during the thymic postnatal development. Using the fluorometric method the concentrations of neither noradrenaline (NA) and dopamine (DA) nor serotonin (5-HT) were measurable until day 19 of embryogenesis. Their content increased during the postnatal development. The patterns of NA and DA increase during the postnatal development were almost identical, while the pattern of 5-HT increase was quite different. The present results indicate that DA might also be one of the transmitters of the thymic sympathetic nerve supply, as well as that the transmitters of that system can be involved in the regulation of activity of thymic epithelial and autofluorescent cells, but also in the modulation of T cell maturation.

Adrenergic Fibers↗

An extra X chromosome effect on craniofacial morphogenesis in men.

A comparative study of the craniofacial complex in men with an extra X chromosome, and normal male and female individuals was carried out using cephalometric radiography. The anterior cranial base, anterior and posterior facial height, maxillary base and ascending ramus were found to be significantly decreased in men with Klinefelter syndrome when compared to the male control group. Significant differences in the lengths of mandibular base and posterior cranial base were not found. When compared to the female control, all structures examined were significantly increased, except for the maxillary base.

Adult↗

Phenotype of two males with abnormal Y chromosomes.

Two infertile males with sex chromosomal abnormalities and mosaic karyotype, 45,X/46,X,dic(Yq) and 45,X/46,X,ring(Y), had considerably changed physical findings, including tooth sizes and craniofacial dimensions. Spermatogenesis was preserved with abnormal meiotic chromosomal behaviour. Mosaic karyotype and structurally changed Y chromosome in both cases had an influence on physical parameters. Tests were normally developed and spermatogenesis was preserved but depressed in later stages.

Adult↗

Distribution of marker chromosomes in relation to histologic grade in bladder cancer.

Cytogenetic analysis was carried out in 100 tissue specimens from 88 patients with bladder cancer. Using a direct technique of chromosome preparation, analyzable metaphases were obtained in 60 cases. Various chromosomal abnormalities, numerical as well as structural, were found. The frequencies of different marker chromosomes, with the exception of the ring chromosome, increased from grade 1 to grade 3 tumors. The average number of markers per cell was one in G1, four in G2, and eight in G3 tumors. It was possible to make a distinction between structural aberrations occurring in all histologic grades and those specific for the invasive grade 2 and grade 3 tumors.

Chromosome Aberrations↗

Thymic microenvironment in myasthenia gravis.

This study was undertaken to investigate the role of thymic epithelial (TE) cells in the immunopathology of myasthenia gravis (MG). Seventeen thymuses from patients with MG and six normal thymuses were investigated by light and electron microscopy, using a stereologic method. In the myasthenic thymuses the cortex was markedly reduced, while the medulla was hypertrophied and had numerous germinal centers. A subpopulation of cortical TE cells showed a large fibrillar nucleolus and a decreased number of cytoplasmic dense bodies and cysts, indicating decreased function. Medullary TE cells, on the other hand, showed evidence of increased activity with an enlarged euchromatic nucleus and an increased number of cytoplasmic dense bodies. There was a statistically significant negative correlation between the decrease in size of the thymic cortex and the appearance of medullary germinal centers. A significant correlation was also demonstrated between atrophy of cortical TE cells and depletion of cortical thymocytes. Our study shows that both cortical and medullary TE cells are involved in the pathogenesis of MG but have different roles.

Adult↗

Chromosome analysis in patients with bladder tumor.

Cytogenetic analysis was performed in 80 patients with bladder tumor. The mitotic activity in patients with tumor G1, G2 and G3 degree of differentiation was not significantly different among them. Most of the patients with noninvasive tumor (G1) had a diploid or nearly diploid chromosome number, but all patients with invasive (G2 and G3) tumor had polyploidy. Marker chromosomes were found in 14 patients and 9 of them developed recurrence very soon. There is a good correlation between the recurrence rate and numerical or structural chromosomal abnormalities. This study emphasizes the importance of the chromosome analysis in the evaluation of therapy and prognosis for patients with bladder tumors.

Adult↗

Spermatogenesis and meiotic chromosomal behaviour in aged men.

Spermatogenesis and meiotic chromosomal behaviour was analysed in a group of males aged 60-80 years. Decreased spermatogenesis was found in most of these aged men although individual differences existed. Chromosomal analysis of cells undergoing diakinesis showed significantly lower chiasma frequency in elderly men, compared with a group of younger control males and also with infertile males.

Adult↗