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Congenital anomalies of the central nervous system (CNS) are common. The prevalence of these anomalies shows considerable geographical variation and female predominance. The aim of this work was to obtain the frequency of different CNS congenital anomalies types and their sex distribution among cases hospitalized in a Department of Neurosurgery, University of Sarajevo Clinics Center, Bosnia and Herzegovina, during the period January 2001 to December 2004. Retrospective study was carried out on the basis of the clinical records. Standard methods of descriptive statistics were performed for the data analysis. A total of 103 cases were surgically treated in the period from 2001 through 2004. Out of that number 56 (54.4%) were female patients, while 47 (46.6%) were male patients. Seven different CNS birth defect types were found in this investigation. These were: spina bifida (42 cases or 40.78%), congenital hydrocephalus (35 cases or 33.98%), arachnoid cyst (15 cases or 14.56%), Dandy-Walker syndrome (5 cases or 4.85%), dermoid cyst (4 cases or 3.88%), one of Arnold-Chiari syndrome (0.98%) and one of encephalocele (0.98%). According to this investigation, CNS congenital birth defects were slightly higher in females (54.4%). The most frequent types were spina bifida (40.78%) both in females (22.33%) and in males (18.45%), hydrocephalus (33.98%) and arachnoid cyst (14.56%). The anomalies of the other organ systems, associated with CNS anomalies obtained in this investigation, were pes equinovarus, cheiloschisis, cardiomegaly and palatoschisis. They were found in six cases (5.82%), equal in both sexes.

Seven days after the application of 2% lidocaine (4 ml doze, the speed of application 3 ml/min, mean application pressure 15 +/- 2.47 kPa) into mesoneurium of adult rabbit sciatic nerve, a nerve segment was intravitally excided from the injection site with a length of 1 cm and qualitatively and quantitatively analyzed. Histological changes at the level of total nerve structures were found, especially of its sheaths. Epi- and interfascicular epineurium were thickened with a hipercellularity of a mononuclear inflammatory process type. On the side of application, occasional delamination of perineurium was registered. Myelinated fibers were sporadically demyelinated, followed by axon degeneration which, in thick fibers, reached a full disintegration. In general, the damages were more severe at the side of application although some zonal differences in the degree of damage (above, below and at the site of application) within individual fasciculi were expressed. A significantly higher volume density of epifascicular and interfascicular connective tissue in comparison to the control, untreted nerves, observed by the stereological analysis, may be considered as an inflammatory-repairing reaction which we identified microscopically. At the same time, we found a significantly higher volume density of endoneurium in lidocaine treated nerves.

S. Aličelebić, Z. Mornjaković, I. Susko, E. Ćosović, Amira Beganović-Petrović

Pineal gland has and antistressogenic role. Its main hormone, melatonin, has radio protective effect on endocrine and other dynamic tissues. In our previous study, we have shown that pinealectomy changes the behavior of suprarenal gland in totally irradiated rats. The aim of this study is to evaluate the effect of exogenous melatonin on suprarenal gland of rats with or without pineal gland. Four months after pinealectomy (experimental group) or shampinealectomy (control group), adult Wistar male rats were daily treated with 0,2 mg of melatonin intraperitoneally, during two weeks. Thereafter, all animals were totally irradiated with 8 Gy of Gamma rays produced from Cobalt 60. Animals who survived were sacrificed on the 17(th) post irradiation day. Qualitative and quantitative characteristics of the suprarenal gland were studied using histological methods. The results show that exogenous melatonin had protective role on suprarenal gland in totally irradiated rats and that those effects were more pronounced in the presence of pineal gland.

Amira Beganović-Petrović, Z. Mornjaković, E. Ćosović, S. Aličelebić, I. Susko

Haloperidol (4'-fluoro-4-[4-Hydroxy-4-p-chlorophenylpiperidino]-Butyrophenone), a neuroleptic, drug is the first choice in the treatment of schizophrenia. Experimental studies on rats show that haloperidol, at female, causes: decreasing of the ovarian weight, inhibition of the ovulation, producing a state of distrust and stimulation of lobuloalveolar development of the mammary glands and increasing of serum prolactin levels in both male and female rats. At male rats haloperidol causes damage of Leydig cells and cells depletion of seminal lineage with sequels on the excretory ducts level and accessory genital glands. Our pilot researches confirm these observations. The aim of this paper is to suggest an attention of the side effects of haloperidol, that's its stricter controlled use.

OBJECTIVES Pineal gland acts as a reley where an anabolic activity be replaced to catabolic and conversely, to adapt a biological rhythm according to the organisme requirement. It is established that pineal extracts stimulate lymphopoiesis in the lymph node and had a radioprotective effects in lymph tissues. Lymph nodes reaction was investigated four weeks after pinealectomy, using qualitative and stereological. METHODS One group of animals ( Wistar rats of both sex) was shame-pinealectomized (chirurgic treatment without pineal extirpation/control) and the other was submitted to surgical ablation of pineal gland.(experimental group). The animals were kept under the same ecologic conditions and they had free access to water supplies. Animals of the same group sacrificed at the same day between 10/14 hour to equal the effects of hormonal rhythm. The paraffin section died with HE (haematoxillin-eosin), PAS/alcian blue and impregnated by Bielschowsky method. For stereological analysis multipurpose M/42 test system was applied. Volume density of nodal structure and relative cellular distribution was evaluated. RESULTS Cortical tissue of lymph nodes of pinealectomized rats was reduced, particularly the paracotical regions. Only in the female rats, decreased number of lymphocytes was observed in the cortex and modularly cords. Stereological analysis confirmed that increased volume density of the medulla is the result of medullar sinus dilatation. Under regressive changes of the cortical structures can be considered the involutary processes in germinal centers and reduction of the younger lymphocyte forms. Macrophage was activated and increased PAS + an inclusion was observed on the cortico/medullary junction and in the modularly cords. Reticular stroma was intensively impregnated and fibrils more coarsed and fragmented. DISCUSSION Established changes in the lymph nodes of pinealectomized a rat was analogous with that observed after treatment with the pineal extracts but in the reverse means. It was evident that the structural dissociation of the reactivity had been established. Really, at one side we have involutive changes in lymphoid population and plasma cells but progressive in phagocytes and reticular cells. It is probably that increased concentration of corticosteroides and gonadal hormones after pinealectomy is responsible for these changes. CONCLUSION Pineal gland-lymph nodes correlations established possibly via hypophyso-adreno-genital axis.

Comparative researches of borderline between telencephalon neuroepithelium and its surrounding mesenchyme in successive early developing stages lack in literature. The aim of this investigation was to carry out systematic morphologic and stereologic analyses of rat telencephalon in early developmental stages. We analysed semithin (1 microm) serial sections of rat embryonic brain from the 12th (E12) to the 15th (E15) day of gestation. The surface densities (SV) of an external mesenchymal surface, an internal mesenchymal surface and a neuroepithelial (ventricular) surface were examined stereologically and compared. The surface density of the external mesenchymal surface was the biggest at E12 (4,05 mm-1) and the least at E15 (1,87 mm-1)-p<0,0005. The surface density of the internal mesenchymal surface was the biggest at E12 (4,02 mm-1) and the least at E15 (2,69 mm-1)-p<0,0005. The surface density of the internal neuroepithelial surface was the biggest at E12 (3,31 mm-1) and the least at E15 (2,01 mm-1)-p<<0,0005. Our stereological examines give objective numerical proof of significant morphogenetic changes in telencephalon shape described by morphologic analyses. The major advantage of stereological methods is the possibility to carry out the estimation procedures in specified, well-defined brain regions or layers.

S. Aličelebić, Zakira Morniaković, I. Susko

Ultrastructural characteristics of ductular parenchyma epithelial and myoepithelial cells were analysed in 18 cases of normal female breast tissue. Different physiological states have been compared and that pre- and postmenopausal. Nuclei and cytoplasm of epithelial and myoepithelial cells have been examined and compared. There were obvious signs of secretion and that apical protein granules, "dense-core" granules and light vesicles and lipid vacuoles and glycogen granules were accumulated in the deeper parts of premenopausal breast epithelial cells cytoplasm. Morphologic equivalents of secretion and accumulated glycogen were presented in the postmenopausal breast epithelial cells. Ultrastructural morphologic characteristics of postmenopausal myoepithelial cells were not different from those in premenopausal breasts.

With regard to intensive morphometric changes, morphometry as a method is mainly used for histogenetic studies of brain development in normal and experimental conditions. The aim of our study was to quantitatively analyse morphological parameters of the rat telencephalon during embryonic development. The investigation was carried out on semithin serial sections of rat brain from embryonic days 12 to 15. The volume densities (VV) of the lateral ventricles, the telencephalic neuroepithelium and the surrounding mesenchyme have been analysed stereologically and compared in examined embryonic stages. The neuroepithelial volume density was the smallest (28%) at E13 and the biggest (44%) at E15 (p<0.0005). The mesenchymal volume density was the smallest (32%) at E13 and the biggest (48%) at E14 (p<0.0005). The volume density of lateral ventricles was the biggest (40%) at E13 and the smallest (14%) at E15 (p<0.0005). Neurostereological methods have been making a very valuable contribution to neuroscience over recent years. We have used unbiased stereological counting methods to obtain objective quantitative parameters which show relations between some parts of rat embryonic telencephalon examined during its normal development.

BACKGROUND AND PURPOSE Developmental process that leads to final forebrain shaping is a result of complex histogenetic and morphogenetic events. Comprehensions about brain development are based on observations carried out on onthogenetic successive stages. Microscopic analysis of brain together with analysis of serial sections gives information about shape the of some forebrain parts and basic relations between them. The aim of this study was to analyse morphogenesis in the earliest stages of rat's forebrain development. MATERIAL AND METHODS Rat brains used in this study were obtained from Fisher inbred rats with accurately timed pregnancies. The investigation was carried out on serial frontal sections of rat embryonic heads from the 12th (E12) to the 16th (E16) day of gestation. Gestation was considered to have begun early in the morning when sperm was found in the vaginal smear. Histological paraffin and plastic sections were systematically inspected with regard to morphogenetic changes of the forebrain parts telencephalon and diencephalon. RESULTS E12: neural tube is completely closed in its cranial part. Rostral part of forebrain shows telencephalons vesicles origins as slightly paired enlargements of neuroepithelial wall. Between telencephalic vesicles origin and in direction to caudal there is an origin of diencephalon. E13: rostral part of forebrain shows well expressed and divided areas of telencephalons vesicles as basal, basolateral, dorsal and medial telencephalon. Central area between paired vesicles is a telencephalon impar. In diencephalon optic vesicles appeared. Epithalamus, thalamus and hypothalamus origins are slight enlargements of its neuroepithelial wall. E14: telencephalic vesicles spread above telencephalon impar into rostral direction and above diencephalon in rostrodorsal direction. Their basolateral parts of are very thickened and become folded. Sulcus telodiencephalicus appears. E15: the main event is the appearance of the origins of plexus choroideus in the area of telencephalon impar as fingerlike processes. E16: all forebrain parts, especially telencephalic vesicles-origin of brain hemispheres and processes of plexus choroideus, are progressively growing and shaping. CONCLUSIONS Our morphologic analysis describes significant morphogenetic changes in the forebrain shape. The forebrain changes from a relatively simple tubular structure with thin walls surrounding a large ventricular system to a thick-walled brain with a highly convoluted but reduced ventricular system.

Melatonin, the major product of the pincal gland, is also synthesized in the retina of several vertebrate species. Retinal melatonin levels show a marked daily variation, with high levels at night and low levels during the light period. Melatonin rhythm generating system includes photodetector, circadian clock and melatonin synthesis machinery and they are located in pincal organ and retina. In both, light regulates daily variations in melatonin secretion by controlling the activity of arylalkylamine N-acetyltransferase (AANAT). In mammals, circadian system is comprised of three major components: the eyes, the hypothalamic suprachiasmatic nucleus (SCN) and the pincal gland. The SCN harbours the endogenous oscillator that is entrained every day to the ambient lighting conditions via retinal input. Among the many circadian rhythms in the body that are driven by SCN output, the synthesis of melatonin in the pincal gland functions as a hormonal message encoding for the duration of darkness. Dissemination of this circadian information relies on the activation of melatonin receptors, which are most prominently expressed in the SCN, and the hypophysical pars tuberalis (PT), but also in many other tissues. Melatonin is essential for rhythmic signaling in the PT. Here, melatonin acts in concert with adenosine to elicit rhythms in clock gene expression. By sensitizing adenylyl cyclase, melatonin opens a temporally-restricted gate and thus lowers the threshold for adenosine to induce cAMP-sensitive genes. This interaction, which regulates gene expression and pituitary output (by endocrine-endocrine interaction) represents general mechanism by which the master clock in the brain synchronizes clock cells in peripheral tissues that require unique phasing of output signals.

BACKGROUND AND PURPOSE The aim of this work was to order quantitative parameters of the proximal convoluted tubules (PCT) in the normal rat kidney cortex. Volume density (VV), both surface and specific surface density toward interstitium (SVi and SVi/VV) and toward lumen (SVl and SVl/VV) and thickness (T) of tubules epithelium have been stereologically ordered. MATERIAL AND METHODS Stereologically were analysed 170 test fields by lattice L36 on the paraffin sections of the three adult male Wistar rats kidney dyeing by PAS-method. RESULTS The mean values of the variables analysed were: VV=76.4 % +/-0.012; SVi=0.056 microm-1 +/-0.004; SVl=0.028 microm-1 +/-0.003; SVi/VV=0.073 microm-1 +/-0.003; SVl/VV=0.037 microm-1 +/-0.005; T=18,26 microm +/-0.897. CONCLUSIONS Stereological methods are making a very valuable contribution to science over recent years. We have used unbiased stereological counting methods to obtain objective quantitative parameters of the PCT epithelium in the normal rats' kidney cortex.

Stereological characteristics of ductular parenchyma epithelial cells are analysed ultrastructurally on 8 cases of normal breast tissue. Different physiological states have been compared and tahat pre- and postovulatory. Volume density (VV), surface density (SV) and specific surface density (SV/VV) of nuclei and epithelial cells cytoplasm have been stereologically examined and compared. Postovulatory, the volume density (VV) and surface density (SV) of nuclei as well as specific surface density (SV/VV) of epithelial cells cytoplasm are much less, while a volume density (VV) of epithelial cells cytoplasm is greater.

The mammary glands of primigravid Wistar rats were investigated by stereological analysis in conditions of lead acetate administration via drinking water. The experiment was made in early summer period when absorbing ability of rat intestinum for lead is highest. Morphological state of glands was observed on 7th, 14th and 21st day of pregnancy. Groups of control animals were drinking deionized water but groups of experimental animals were drinking deionized water with added lead acetate. On paraffin sections coloured by HE method, volume density (VV) of glands structural elements were determined by multipurpose test system M42. Stereological analysis shows that lead diminishes the proliferative capacity of the mammary parenchyma and changes the morphofunctional differentiation of the overall structure in mammary gland during pregnancy. At the same time lead modifies quantitative trait of the mammary gland, i.e. the composition of the volume units in organ, without changing intramammary syncornization between the epithelium and lipocytes.

The late effect of surgical ablation of pineal gland on the morphometric changes in epithelial cells of rat thymus were investigated. The aim of this study is to determine a possible existence of sex-different changes in composition of the epithelial cell component unit long after pinealecotmy what could be important for the subtle understanding of mutual correlation between pincal body and thymus. This article presents results of stereological ultrastructure parameters of thymuscortical and medullar epithelial cells of male and female rats two month after pinealectomy. The experimental animals were divide into two groups: an experimental one (pinealectomized) and the control group (shampinealectomized). Pinealectomized animals were submitted to surgical ablation of pineal gland while the control were undertaken the same surgical treatment but without removal of the pineal gland. Animals were sacrificed 60 th days following the surgery treatment. Parasagital pieces of thymus tissue were fixed by means of immersion in glutaraldehyde and prepared for transmission electron microscopy. Using Weibls multipurpose test system and multilevel sampling technique on electron micrographs the volume and surface density of nucleus (Vu, Sv) and cytoplasm of cortical and medullar thymus epithelial cells were calculated. At the different magnification level were established the volume and surface density of mitochondria (Vvm, Svm) endoplasmic reticulum (Vvr, Svr), vacoule(Vuv) as well as numerical density of mitochondria (Nvm). Our analysis has conformed statistically significant increase in Vv of reticulum and vacuole in both sex of pinealectomized rats. Sv of plasmalema, reticulum and mitochondrial membrane are markedly increased in thymus medullar epithelial cells of pienalectomized rats. Vv of mitochondria is significantly increased in cortical epithelial cells of pienalectomized animals. Results allow us to confirm that mutual correlation between pineal gland and thymus exists but present findings seem to support the concept of sex independent inhibitory action of pineal gland on thymus cortical and medullar epithelial cells.

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