Objectives: Tuberculosis is still a major public health problem in developing world and in Bosnia and Herzegovina. Treatment of tuberculosis requires a “standard” combination of antituberculotics for a 6-month period. Prolonged use of isoniazid and rifampicin is associated with hepatotoxicity. The pathophysiology of hepatotoxicity is not yet elucidated, and suggested mechanism is oxidative stress. Isoniazid metabolite is considered to be responsible for the tissue damage through formation of free radicals. Methods : Twenty one adult male Wistar rats (210-280 g) were randomized into two groups. In group I (14 rats) animals received rifampicin (50 mg/kg) and isoniazid (50 mg/kg) dissolved in 4 ml/kg isotonic saline. Group II (7 rats) served as control and the animals received 4 ml/kg isotonic saline. The administration was performed intraperitoneally, during 21 days. The animals were sacrificed at the end of that period. Blood samples were obtained for biochemical analysis and liver tissue was processed by histotechnological method. Liver tissue was stained with H&E and PAS method and qualitative histological analysis was performed using light microscopy. Results : Our study revealed changes in liver tissue in the isoniazid-rifampicin treated group including enlargement and swelling of hepatocytes with vacuolization in centrilobular area, dilatation of sinusoids and mononuclear infiltration in portal space. Biochemical analysis of liver enzymes did not show significant difference between groups. Conclusion : In the isoniazid-rifampicin treated group of animals qualitative histological analysis revealed mild changes in liver tissue. Keywords : liver injury, isoniazid, rifampicin, rats, histology

Objectives: Two main and the most common types of congenital abdominal wall defects are omphalocele and gastroschisis. According to the literature, the frequency of omphalocele is generally stable, the rate of gastroschisis has increased lately, and cloacal exstrophy is a very rare birth defect. Methods: A retrospective study was performed on the basis of clinical records for the period January 2000. to December 2008. and the standard methods of descriptive statistics were performed for the data analysis. Investigation was carried out to obtain the frequency and gender distribution of congenitalabdominal wall defects among patients surgically treated in the Clinic for Children’s Surgery, Clinical Center University of Sarajevo,Bosnia and Herzegovina. Results: A register-based data show that total of 26 abdominal wall defect cases were surgically treated in the investigated period. Out of that number 15 (60%) were male patients, while 11 (40%) were female patients; sex ratio – 1.5:1. Twenty patients had gastroschisis, five omphalocele and one patient were with cloacal exstrophy. Anomalies associated with abdominal wall defects were present in total of six patients (23%), four male (15%) and two female (8%) patients. Conclusion: The study allows the conclusion that abdominal wall defects are generally rare congenital anomalies of which cloacal exstrophy is the rarest, the gastroschisis is on the rising trend and omphalocele is generally stable. Keywords: omphalocele, gastroschisis, cloacal exstrophy, frequency

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.

Research in this study had the character of retrospective study for which we used 24 adult female Wistar rats, who we reared under standardized laboratory conditions and divided into two groups: experimental and control. The experimental group consisted of a total of 12 animals who were classified into 2 subgroups: Z1 and Z2. The control group consisted of 12 untreated animals who were divided into 2 subgroups: K1 and K2. Once a day at regular intervals we applied by the gastric probe mycotoxin zearalenone previously dissolved in sunflower oil. To the animals in the control group we applied sunflower oil only. Dose of toxin administered was 0,5 mg/kg body weight, and a period of observation spanned two different time intervals-14 and 28 days. After completing the application of toxins, the animals were sacrificed under the general ether anesthesia and by the rules of autopsy techniques. Taken ovaries were prepared for histological and stereological analysis. Structural changes in the ovaries of treated animals were observed as degenerative changes, primarily at the level of the ovarian follicles and corpora lutea. The apparent findings in the stroma were in terms of its hipercelularity and marked hyperemia of the blood vessels. The longer the application period, the more pronounced the changes. The resulting qualitative histological changes in the ovaries of treated rats were objectified quantitatively - by stereology. We found changes in terms of decreasing volume density of functional elements of the parenchyma (ovarian follicles and corpora lutea), and increased volume density of ovarian stroma with blood vessels. Key words: zearalenone, rat, ovary, qualitative changes, stereology

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.

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.

Background:  Inadvertent intraneural injection of local anesthetics may result in neurologic injury. We hypothesized that an intraneural injection may be associated with higher injection pressures and an increase in the risk of neurologic injury.

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.

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.

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.

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.

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.

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.