A histological study of the effect of exogenous melatonin on gentamicin induced structural alterations of proximal tubules in rats.

The aim of this research was to assess the reactive changes of rat proximal tubules caused by gentamicin and the effect of relatively low doses of melatonin. 48 adult male Wistar rats were distributed into six groups of equal size which all received one of the following daily intraperitoneal injections: vehicle (5% ethanol in Ringer solution) during 11 days (C); gentamicin (80 mg/kg) during 8 days (G), two groups which concomitantly received gentamicin (80 mg/kg) during 8 days and melatonin in two different test doses (5 or 20 mg/kg) during 11 days (GM1, GM2) and two groups treated only with melatonin in two different doses (5 or 20 mg/kg) during 11 days (M1, M2). Histological analysis included qualitative and semi-quantitative light microscopy analysis of proximal tubules. Exogenous melatonin had no significant effect on the microstructure, independently of dosis. The changes of proximal tubules microstructure induced by gentamicin were expressed in the form of granulovacuolar degeneration, necrosis and desquamation. The grade of proximal tubular changes was smaller in animals who besides gentamicin received melatonin. Melatonin has a dose dependent protective effect on the structural alterations of proximal tubules of the kidney induced by gentamicin.

Heart-type fatty acid-binding protein and its relation with morphological changes in rat myocardial damage model induced by isoproterenol.

We have investigated heart type fatty acid binding protein (H-FABP) rat serum values at different time point following subcutaneous (s.c) isoproterenol (ISO) administration and their correlation with severity of myocardial lesion. Thirty adult, male, Wistar rats were used for this study. Six rats per group were treated with a single dose of either ISO (ISO groups, dose 100 mg/kg, s.c.) at different time point (30', 60', 120', 240') or with saline (control group). Serum H-FABP was determined by enzyme-linked immunosorbent assay (ELISA) and histological analysis was performed by hematoxylin-eosin (HE) method of staining. The first serum H-FABP increase was obtained 30' following ISO administration, but maximal value was reached after 240'. Myocardial histological changes were time-dependent and correlated with serum H-FABP values (p<0.001). The results of the study suggest that H-FABP is sensitive marker for acute rat myocardial injury and its possible inclusion in myocardial injury screening studies in rats.

Time-dependent responses of rat troponin I and cardiac injury following isoproterenol administration.

AIM: To develop a rat model of myocardial infarction induced by isoproterenol (ISO). We investigated a type of histological myocardial changes and cardiac troponin I (TnI) kinetic. METHODS: The study has used adult, male, Wistar strain rats. Rats were distributed in ISO and control groups. Rats treated with ISO were divided into groups according to the time of cTnI and myocardial lesion analyses: ISO I (30'), ISO II (60'), ISO III (120') and ISO IV (240'). We determined cTnI (Life Diagnostics Inc. West Chester PA, USA) in the serum by ELISA method. We performed histological analysis on the specimens of left ventricular wall stained by hematoxillin-eosin (HE) method. RESULTS: The first statistically significant rise of cTnI was noted 30 minutes after the ISO administration. There was no statistically significant difference between cTnI mean values among the ISO groups. Observed myocardial histological changes were time dependent. CONCLUSIONS: This model can be suitable for cardioprotective and cardiotoxicity supstance investigations followed by cTnI measurement in blood. The similarity between induced myocardial lesion on animal model in our study and human myocardial lesion in ischemia give us sufficient impulse for further preclinical researches of new cardiac markers.

Urinary system birth defects in surgically treated infants in Sarajevo region of Bosnia and Herzegovina.

Congenital anomalies of the urinary system are relatively common anomalies. In Bosnia and Herzegovina there is no existent unique evidence of congenital anomalies and registries. The aim of this study was to obtain the frequency of different urinary tract anomalies types and their sex distribution among cases hospitalized in the Department of Pediatric Surgery of the University of Sarajevo Clinics Centre, Bosnia and Herzegovina, during the period from January 2002 to December 2006. Retrospective study was carried out on the basis of clinical records. Standard methods of descriptive statistics were performed for the data analysis. Among 289 patients that were surgically treated 62,37% of the patients were male patients, while 37,63% were female patients. Twenty nine different urinary system anomalies types were found in this study. These were: vesicoureteral reflux (99 cases or 30,75%), hypospadias (62 cases or 19,26%), pelviureteric junction obstruction (42 cases or 13,04%), megaureter (35 cases or 10,87%), duplex pelvis and ureter (16 cases or 4,97%), bladder diverticulum (8 cases or 2,48%), ureterocoele (7 cases or 2,17%), stenosis of the external urethral opening (6 cases or 1,86%), ectopic kidney, duplex kidney and pelvis (each 5 cases or 1,55%), polycystic kidneys and urethral stricture (each 4 cases or 1,24%), multicystic kidney (3 cases or 0,93%), kidney agenesis, ureter agenesis, urethral diverticulum, ectopic ureter, horseshoe kidney and fetal kidney (each 2 cases or 0,62%), renal aplasia, urethral atresia, renal cyst, urachal cyst, epispadias, bladder exstrophy, renal hypoplasia, renal malrotation and Prune-Belly syndrome (each 1 case or 0,31%). According to this study, urinary tract anomalies were more common in male than in female patients (62,37%). Generally, the most frequent anomaly type was vesicoureteral reflux in total number of 99 cases, and in females (66 cases), but hypospadias was the most common anomaly in males (62 cases). The anomalies of other systems associated with urinary system anomalies were found in ten cases. These were: cryptorchidism, congenital inguinal hernia, open inner inguinal ring, uterus bicornis unicollis and one case of multiple anomalies.

Spirulina platensis protects against renal injury in rats with gentamicin-induced acute tubular necrosis.

The present study was carried out to evaluate the renoprotective antioxidant effect of Spirulina platensis on gentamicin-induced acute tubular necrosis in rats. Albino-Wistar rats, (9male and 9 female), weighing approximately 250 g, were used for this study. Rats were randomly assigned to three equal groups. Control group received 0,9 % sodium chloride intraperitoneally for 7 days at the same volume as gentamicin group. Gentamicin group was treated intraperitoneally with gentamicin, 80 mg/kg daily for 7 days. Gentamicin+spirulina group received Spirulina platensis 1000 mg/kg orally 2 days before and 7 days concurrently with gentamicin (80 mg/kg i.p.). Nephrotoxicity was assessed by measuring plasma nitrite concentration, stabile metabolic product of nitric oxide with oxygen. Plasma nitrite concentration was determined by colorimetric method using Griess reaction. For histological analysis kidney specimens were stained with hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stain. Plasma nitrite concentration and the level of kidney damage were significantly higher in gentamicin group in comparison both to the control and gentamicin+spirulina group. Spirulina platensis significantly lowered the plasma nitrite level and attenuated histomorphological changes related to renal injury caused by gentamicin. Thus, the results from present study suggest that Spirulina platensis has renoprotective potential in gentamicin-induced acute tubular necrosis possibly due to its antioxidant properties.

Central nervous system birth defects in surgically treated infants in Sarajevo region of Bosnia and Herzegovina.

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.

Troponin T and histological characteristics of rat myocardial infarction induced by isoproterenol.

In our investigation,we used short-time model of myocardial infarction of rats induced by high dose of isoproterenol (ISP). We investigated cardiac troponin T blood level (cTnT) and histological characteristics of rat myocardium. ISP, single, intraperitoneal dose 250 mg/kg was given to male, adult, Wistar rats (n=12). Rats were distributed depending on their body weight in subgroups: ISP I (BW 260-280g) and ISP II (BW 250-400g).Control group (n=9) was treated with intraperitoneal dose of 0,95% NaCl. Cardiac TnT was measured by electrochemiluminiscence (ECLA) sandwich immunoassay in rat serum 4 hours after ISP application. Rats' hearts were dissected and examined by qualitative histological method (HE). Statistical significance was set at 0,05. There was significant difference in cTnT of ISP II (p=0,0001) vs. control and ISP I (p<0,05) vs. control. Significant difference was between ISP I and ISP II subgroups (p<0.001). The accent of histological changes of myocardium was on nuclei of cell. Cells showed acidophilic changes and nuclei disappearance as signs of coagulative necrosis development. Extensivity of histological changes were different between ISP I and ISP II subgroup. Used dose of ISP induced development of myocardial necrosis in rats. Subendocardial portion of myocardium was more vulnerability than subepicardial portion. Rats of ISP II had more extensive histological changes than these in ISP I. Administered doses of ISP enabled cTnT utilization as a marker of myocardial necrosis.

[Quantification of some qualitative changes of the rabbit sciatic nerve after the application of lidocaine into the mesoneurium]. / Kvantifikacija nekih od kvalitativnih promjena ishijadicnog nerva kunica nakon aplikacije lidokaina u mezoneurijum.

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.

The role of pineal gland and exogenous melatonin on the irradiation stress response of suprarenal gland.

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.

[Early changes in rats cervical lymph nodes after pinealectomy]. / Rane promjene u cervikalnim limfnim cvorovima pacova nakon pinealektomije.

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.

Morphologic findings of the ischemic myocardium.

This study assesses the relation between qualitative and quantitative findings of myocytes and interstitial connective tissue in the ischemic heart disease. Qualitative and quantitative changes of myocytes and interstitial connective tissue were studied on the serial cross myocardial sections from 20 autopsied hearts with ischemic lesions, stained by immunohistochemistry using a monoclonal antibody (von Willebrand factor) and with hematoxylin-eosin method. Myocardial sections included proximal and distal part of occlusion and area of occlusion of coronary vessels. The volume densities (V V) of the cardiac myocytes and interstitial fibrosis in the group with coronary occlusion were examined stereologically and compared with control group. The findings showed a significant reduction in the volume density of myocytes and an increase in the volume density of interstitial fibrosis in patients with coronary occlusion compared with control group. Significant reduction in the volume density of myocytes and an increase in volume density of interstitial fibrosis were greater in the distal part of occlusion and area of occlusion, than in the proximal part of the occlusion. Our stereological results give useful quantitative information's of changes in myocardium parts during coronary occlusion as well as in normal conditions, and represent objective proof of significant changes in ischemic myocardium described by qualitative analyses.

[Haloperidol and its side effects on the reproductive system]. / Haloperidol i njegovi nezeljeni efekti na reproduktivni sistem.

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.

Detection of neurovascular structures using injection pressure in blockade of brachial plexus in rat.

In the last few decades there has been a great development of regional anesthesia; all the postulates are defined and all the techniques of usage are perfected. However, like any other medical procedure, the block of brachial plexus carries a risk of certain unwanted complications, like possible intraneural and intravascular injections. The reason for great discrepancy between the injury of brachial plexus and other periphery nerves while performing the nerve blockade is the frequent usage of this block, but also the specific proximity of neurovascular structures in axilla. The purpose of this work is to determine the values of pressures which appear in para-neural, intraneural and intravascular injection applications of local anesthetic, and to compare those values in order to avoid cases of intraneural and intravascular injections in clinical practice with consequential complications. In experimental study there have been used 12 Wistar rats of both genders. After anesthesia with ether and mid-humoral access to the neurovascular structures in axilla, the injection of 2% lidocaine with epinephrine was performed with the help of automatic syringe charge. The needle was at first placed para-neural, and then also intraneural and intravascular. During every application the pressure values were monitored using the manometer, and then they were analyzed by special software program. All para-neural injections resulted with the pressure between 13,96-27,92 kPa. The majority of intraneural injections were combined with the injection pressure greater than 69,8 kPa, while the intravascular injections were combined with injection pressure less than 6,98 kPa. Based on the available data it can be noticed that so far none of the methods of prevention from unwanted complications of regional anesthesia can insure the avoidance of intraneural and intravascular injection of local anesthetic. Based on our research it is obvious that the measuring of pressure during the nerve blockade is very important in order to decrease the risk of neurological and possible systematic complications. It is also clear that a small, mobile, and financially quite available apparatus for pressure measurement can help in differentiation between para-neural, intraneural and intravascular injection. Avoiding high injection pressure prevents from lodging the needle into intraneural space, while avoiding a very low injection pressure prevents from lodging the needle into intravascular space followed by consequential complications. The usage of this apparatus can find its application in other blockades of periphery nerves, and in other branches of medicine as well.

Topical treatment of standardised burns with herbal remedies in model rats.

Experimental studies of burns require the use of different animal models. The aim of this work was to establish experimental model of thermal injuries and to evaluate the effects of topical agents on healing of the burn wounds. Forty female Wistar rats were randomly classified in 4 groups and isolated for 2 weeks before the onset of experiment. Animals were primarily anaesthetized with pentobarbital-sodium and then shaved (skin area of their back with diameters 5 cm x 5 cm). A round metal stamp with contact area of 5 cm2 and total weight of 100 g was heated up to 80 degrees C and then applied without additional pressure on the depilated skin of the back for 14 seconds. This procedure produced a standardized burn wound. Induced burn wounds were immediately drowned in the 4 degrees C- water for 3 s in order to maintain microcirculation. After the inducement of thermal injures, all rats were treated with 1% silver sulfadiazine cream, herbal topical preparations or were not treated at all. Burn wounds were treated twice a day until the healing completion. The result of treatment application was a significant reduction of burn wound diameters. Herbal topical preparations expressed positive therapeutic effects on the parameters of burn wounds. The efficiency of silver sulfadiazine cream in burn wound healing was significantly more expressed in comparison to healing process in control group of animals (p < or = 0,001). We conclude that herbal topical preparations efficiently caused the completion of burn wound healing process without scar formation.

Histological changes of the sciatic nerve in dogs after intraneural application of lidocaine--relation to the established application pressure.

Histological changes of sciatic nerve in adult dogs 7 days after single application of 2% lidocaine (4 ml dose, speed of injection 3 ml/min) and measurement of the application pressure was studied, with a goal to investigate structural changes of the nerve in relation to the established pressure values. The application pressure was determined by using Bio Bench software. In intrafascicular puncture an average application pressure of 198.23 +/- 52 kPa was found, and in interfascicular puncture its average value was 53.3 +/- 17.9 kPa, with a note that individual differences are regularly present. Seven days after the injection, a nerve dissection was performed and serial sections covering the region of injection's puncture and bordering proximal and distal zones, in the total length of 3 cm, were prepared. The found changed show the presence of nerves' fibers lesions with a strong reactivity of Schwann's cell, as well as the change of interstitial structure concerning hypercellularity and occurrence of cellular extravasation. The covering system of the nerve in the zone of epineurium manifests changes of inflammatory process and in perineurium a decomposition of lamella layers and the alteration of their tinctorial properties were noticed. A comparison of the found nerve reactivities in intra- and interfascicular application showed their one-way alteration, although the lesions were more noticeable in the conditions of intrafascicular application. The damages were mostly expressed in the zone of local application of anesthetic, than distally from it, while the damage to the structure in the proximal part is of the smallest degree.

Combination of intraneural injection and high injection pressure leads to fascicular injury and neurologic deficits in dogs.

BACKGROUND: Unintentional intraneural injection of local anesthetics may cause mechanical injury and pressure ischemia of the nerve fascicles. One study in small animals showed that intraneural injection may be associated with higher injection pressures. However, the pressure heralding an intraneural injection and the clinical consequences of such injections remain controversial. Our hypothesis is that an intraneural injection is associated with higher pressures and an increase in the risk of neurologic injury as compared with perineural injection. METHODS: Seven dogs of mixed breed (15-18 kg) were studied. After general endotracheal anesthesia, the sciatic nerves were exposed bilaterally. Under direct microscopic guidance, a 25-gauge needle was placed either perineurally (into the epineurium) or intraneurally (within the perineurium), and 4 mL of lidocaine 2% (1:250,000 epinephrine) was injected by using an automated infusion pump (4 mL/min). Injection pressure data were acquired by using an in-line manometer coupled to a computer via an analog digital conversion board. After injection, the animals were awakened and subjected to serial neurologic examinations. On the 7th day, the dogs were killed, the sciatic nerves were excised, and histologic examination was performed by pathologists blinded to the purpose of the study. RESULTS: Whereas all perineural injections resulted in pressures < or =4 psi, the majority of intraneural injections were associated with high pressures (25-45 psi) at the beginning of the injection. Normal motor function returned 3 hours after all injections associated with low injection pressures (< or =11 psi), whereas persistent motor deficits were observed in all 4 animals having high injection pressures (> or =25 psi). Histologic examination showed destruction of neural architecture and degeneration of axons in all 4 sciatic nerves receiving high-pressure injections. CONCLUSIONS: High injection pressures at the onset of injection may indicate an intraneural needle placement and lead to severe fascicular injury and persistent neurologic deficits. If these results are applicable to clinical practice, avoiding excessive injection pressure during nerve block administration may help to reduce the risk of neurologic injury.

[Stereologic analysis of renal cortical structures during compensatory hypertrophy in rats]. / Stereoloska analiza kortikalnih struktura bubrega u toku kompenzacijske hipertrofije u stakora.

The qualitative and quantitative study of renal cortical structures was performed seven days after unilateral nephrectomy. Adult Wistar rats (10 male and 10 female) were ether-anaesthetized and the kidneys were removed by dorsolateral approach. Renal hypertrophy was determined by measurement of kidney dry mass. The samples of renal tissue were embedded in paraffin, sectioned at 6 microns and stained by azan and haematoxylineosin methods. The volume densities of renal corpuscles, the epithelium of tubules, luminal space of tubules and cortical interstitial structures were calculated using Weibel's multipurpose test system M 42. The qualitative analysis was performed to determine possible structural sex differences of cortical parenchyma during compensatory hypertrophy. There was no significant difference in volume densities of renal corpuscles and distal tubules between control and hypertrophic kidney. The volume density of the epithelium of proximal tubules and interstitial blood vessels were statistically significant increased in hypertrophic kidney compared to the values determined in control kidney. The volume density of luminal space of proximal tubules and interstitial tissues were statistically significant decreased in hypertrophy compared to control kidney. The data from present studies shows that the increase in epithelial volume of proximal tubules and interstitial blood vessels volume have the primary role in compensatory kidney enlargement after unilateral nephrectomy, while renal corpuscles do not participate significantly.

[Retinal and pineal melatonin--from a circadian signal to therapeutic use]. / Retinalni i pinealni melatonin--od cirkadijalnog signala do terapijske upotrebe.

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.

Morphogenesis of the rat forebrain.

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.