Background: Glioblastoma (GBM) highly expresses Src tyrosine kinase involved in survival, proliferation, angiogenesis and invasiveness of tumor cells. Src activation also reduces reactive oxygen species (ROS) generation, whereas Src inhibitors are able to increase cellular ROS levels. Methods: Pro-oxidative effects of two pyrazolo[3,4-d]pyrimidine derivatives—Src tyrosine kinase inhibitors, Si306 and its prodrug pro-Si306—were investigated in human GBM cells U87 and patient-derived GBM-6. ROS production and changes in mitochondrial membrane potential were assessed by flow cytometry. The expression levels of superoxide dismutase 1 (SOD1) and 2 (SOD2) were studied by Western blot. DNA damage, cell death induction and senescence were also examined in GBM-6 cells. Results: Si306 and pro-Si306 more prominently triggered ROS production and expression of antioxidant enzymes in primary GBM cells. These effects were followed by mitochondrial membrane potential disruption, double-strand DNA breaks and senescence that eventually led to necrosis. Conclusion: Src kinase inhibitors, Si306 and pro-Si306, showed significant pro-oxidative potential in patient-derived GBM cells. This feature contributes to the already demonstrated anti-glioblastoma properties of these compounds in vitro and in vivo and encourages clinical investigations.

Glioblastoma (GBM), as the most aggressive brain tumor, displays a high expression of Src tyrosine kinase, which is involved in the survival, migration, and invasiveness of tumor cells. Thus, Src emerged as a potential target for GBM therapy. The effects of Src inhibitors pyrazolo[3,4-d]pyrimidines, Si306 and its prodrug pro-Si306 were investigated in human GBM cell lines (U87 and U87-TxR) and three primary GBM cell cultures. Primary GBM cells were more resistant to Si306 and pro-Si306 according to the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. However, the ability of all GBM cells to degrade the extracellular matrix was considerably compromised after Si306 and pro-Si306 applications. Besides reducing the phosphorylation of Src and its downstream signaling pathway components, both compounds decreased the phosphorylated form of focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) expression, showing the potential to suppress the aggressiveness of GBM. In vivo, Si306 and pro-Si306 displayed an anti-invasive effect against U87 xenografts in the zebrafish embryo model. Considering that Si306 and pro-Si306 are able to cross the blood–brain barrier and suppress the spread of GBM cells, we anticipate their clinical testing in the near future. Moreover, the prodrug showed similar efficacy to the drug, implying the rationality of its use in clinical settings.

INTRODUCTION Cauda equina syndrome from lumbar disc herniation accounts for up to 2-3% of all disc herniations. The aim of this study was to investigate whether recovery of bladder function after surgery depends on preoperative duration of disease. Patients and methods This retrospective study included 47 patients who underwent surgery for cauda equina syndrome due to a herniated disc in the period between 1997 and 2002. Eleven patients were female and 36 male, with a mean age of 43 years (range 23-67). All presented with sciatica and saddle hypoesthesia, whereas 13 presented with motor weakness of legs. All patients had been catheterized at the time of admission to the Neurosurgical unit. Levels of herniation were L4-L5 in 27 (57%), L5-S1 in 14 (30%), and L3-L4 in 6 (13%) patients. In 7 (15%) patients, surgery was performed within 48 hours of the cauda equina syndrome onset. None underwent surgery within 24 hours. 13 (28%) patients were operated between the 2nd and 7th day and 27 (57%) after 7th day of the cauda equina onset. The role of preoperative duration of symptoms in recovery of bladder function was examined (chi 2 analysis). RESULTS The follow-up ranged from 15 to 74 months (mean 24.2 months). In 33 patients (70%) excellent result were achieved, in 9 (19%) patients good results and 5 (11%) patients presented with poor results. There was no statistically significant difference concerning the time between the onset of symptoms and surgical decompression and subsequent recovery of bladder function (p>0.05). CONCLUSION After accurate diagnosis and adequate operative treatment, postoperative results of cauda equina syndrome due to lumbar disc herniation appear satisfactory regardless of the timing of surgery.

Introduction. Natural course of aneurysms that occur on blood vessels of the brain singles out the need for understanding the mechanism of the occurrence of aneurysm wall rupture and identification of anatomic characteristics as predictive factors for hemorrhage to occur. Objective. In this study we comparatively present results of our researches and experimental models on animals. Methods. We made a comparative analysis of anatomical characteristics of blood vessels of the brain and aneurysms obtained on the basis of digital subtraction angiography and intraoperative finding. In this article we review recent research in the anatomic characteristics of intracranial aneurysms and parent blood vessels. We present a series of 185 aneurysms (ruptured and unruptured) dissected at the Neurosurgical Clinic of Clinical Center of Serbia in Belgrade. Results. Inclination angle may be considered as the vital predesposing factor for intracranial aneurysm rupture. In aneurysms that ruptured it was 139.748?27.242?, while in unruptured aneurysms it was considerably smaller and amounted to 100.882?22.001? (p<0.01). Conclusion. Inclination angle may be regarded as the vital predisposing factor since it differs considerably in unruptured and ruptured aneurysms. Aneurysms with blood stream angle smaller than 115? have very small probability of rupture, while blood stream angle bigger than 150? presents a high risk of rupture.

Introduction. Intraventricular hemorrhage occurs in almost one fifth of prematurely born children. Due to present complications, such as hydrocephalus and neurological deficit, it endangers the child’s life, therefore there is the need for understanding and prevent risk factors as well as the need for finding most optimal methods of treatment. Objective. The aim of the study was to point out the current therapeutic modalities of the treatment of posthemorrhagic hydrocephalus in prematurely born children. Methods. The study included 60 patients divided into two groups of 30 patients treated at the University Children’s Hospital of Belgrade in the period 2003-2008. Results. Treatment outcome of the control group of patients treated by standard methods was influenced by gestational age (p=0.024), head circumference on birth (p=0.043), body mass on birth (p=0.006), Apgar score on birth (p<0.001), peripartum asphyxia (p<0.001), cardiorespiratory arrest (p<0.001), respiratory distress (p=0.002) and intraventricular hemorrhagic grade (p<0.001). As statistically significant predictors of the poor treatment outcome of the experimental group of patients treated by using Ommaya reservoir were identified: low body mass on birth (p<0.05), low Apgar score (p<0.05), prolonged number of days on assisted ventilation (p<0.05), presence of peripartum asphyxia (p<0.05) and cardiorespiratory arrest (p<0.05). Conclusion. No statistically significant difference was detected in the outcome between the patients treated by the standard method and those with installed Ommaya reservoir. However, the difference of 10% in mortality between the two groups may be clinically significant so that further studies of larger samples are necessary.

Intracranial aneurysm rupture is followed by high mortality and morbidity. In order to understand the aneurysm's natural course, it is necessary to recognize the predisposing factors for the rupture.