No abstract

Insertion of a VP shunt represents the most frequent method of choice of the surgical treatment of hydrocephalus, but also potentially a highly risky procedure followed by various complications about which parents should be informed when patients are children. Owing to adequate approach in the follow-up of children with implanted VP shunt, large bowel and urinary bladder perforation, examples of severe and potentially fatal complications of this surgical intervention, could be disclosed on time and adequately resolved.

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.

From our data we conclude that SOX3 can promote the malignant behavior of glioblastoma cells.

A mathematical model was developed to estimate the release of gentamicin sulfate from a bioactive textile material as a transdermal system for wound dressing. The gentamicin sulfate released from the antibiotic/ chitosan hydrogel complexes was measured in vitro by the Franz diffusion cell technique. The diffusive transport of gentamicin sulfate through three connected compartments, that is, chitosan hydrogel, membrane, and solution, was considered by the formulation of a model based on Fick's second law. Initially, the total amount of gentamicin sulfate was placed within an already swollen chitosan hydrogel. The value of the diffusivity coefficient of the drug through the chitosan hydrogel was calculated for every initial amount of the active substance. For the initial concentration of gentamicin sulfate, which was lower than 2.81 Â 10 4 lg/mL, the diffusion coefficient was approximately constant. A higher amount of gentamicin sulfate in the hydrogel reduced its own transport as a consequence of an increase in the intensity of the interaction field between the molecules of gentamicin sulfate. The model provides the possibility of optimizing the process of drug release by ensuring a compromise between a higher value of the diffusivity coefficient and a desirable amount of gentamicin sulfate and a constant concentration within the solution over 48 h.

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.

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.

Pheochromocytomas and sympathetic paragangliomas are rare catecholamine-secreting tumours that represent very rare causes of intracerebral haemorrhage in the young, with only a few cases reported. A 32-year-old man presented to our emergency department because of sudden onset of severe headache. He had a six-month history of paroxysmal headache, palpitations, and sweating. During examination he became somnolent and developed left-sided hemiplegia. A computed tomographic (CT) scan of the brain showed a right temporoparietal haematoma. He was admitted to the Clinic for Neurosurgery and the haematoma was evacuated. The patient was comatose, on assisted respiration, with frequent hypertensive crises. An examination for possible secondary causes of hypertension was undertaken. Plasma metanephrine value was elevated (414 pg/mL, reference values < 90 pg/mL). Abdominal CT scans revealed a large mass (6 cm) in the right adrenal gland. After adequate control of the hypertension was achieved with nonselective a-and b-adrenergic blockers the tumour was excised. The histopathologic findings confirmed the diagnosis of pheochromocytoma. The genetic analysis demonstrated a duplication in exon 1 of the VHL gene. We reported a rare, potentially fatal complication of pheochromocytoma-an intracerebral haemorrhage. This case and review of similar rare cases in the literature illustrate the importance of early recognition of the characteristic symptoms of catecholamine excess in young patients with hypertension.