Increased expression of ubiquitin C-terminal hydrolase L1 in astrocytomas of ascending grades.

BACKGROUND: The ubiquitin-proteasome pathway controls the monitoring and degradation of important proteins and is involved in several cellular processes, such as development, differentiation, and transcriptional regulation. Recent evidence has shown that ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), a member of the deubiquitinating enzyme family that removes ubiquitin from protein substrates, is overexpressed in many types of cancer. AIM: This study thus examined the expression of UCH-L1 in human astrocytoma tissues. MATERIAL AND METHODS: Formalin-fixed, paraffin-embedded astrocytoma samples were obtained from 40 patients, after which histopathological examination, typing, and grading were performed. The study group included 10 histologically normal brain tissues, which served as the control group, and 10 WHO grade II, 10 WHO grade III, and 10 WHO grade IV (glioblastoma) samples. Normal brain tissue samples were obtained from the histologically normal, non-tumoral portion of the pathology specimens. UCH-L1 expression was evaluated using quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. RESULTS: Astrocytoma tissues exhibited higher UCH-L1 expression compared to the control group. UCH-L1 overexpression increased significantly together with the increase in astrocytoma grades (from II to IV). CONCLUSION: UCH-L1 could be a good diagnostic and therapeutic marker for determining astrocytoma development and progression.

New Clues in the Malignant Progression of Glioblastoma: Can the Thioredoxin System Play a Role?

AIM: To evaluate and compare the expression of thioredoxin reductase 1 (TrxR1) in primary and secondary glioblastoma samples. MATERIAL AND METHODS: Surgically resected human glioblastoma samples from 40 patients who underwent surgery at our institution were extracted from their histopathological specimens and divided into three groups. Ten histopathologically regular cerebral tissue samples, acquired from the non-neoplastic portion of the specimens, were assigned as the control group. Twenty specimens that included tumoral tissue from each type of glioblastoma (WHO grade IV, primary and secondary) were assigned as the primary and secondary glioblastoma groups. TrxR1 expression was analyzed by using both quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Isocitrate dehydrogenase 1 (IDH1) mutation was analyzed by immunohistochemistry. Ki-67 proliferative index and apoptosis were also analyzed by immunohistochemistry. The differences between the groups were statistically compared and the correlation between these parameters was analyzed. RESULTS: The expressions of TrxR1 and Ki-67 values were significantly higher in primary glioblastoma. IDH1 mutation was significantly higher in secondary glioblastoma. TrxR1 expression was found to be highly correlated with the Ki-67 index. The apoptotic index was similar between primary and secondary glioblastoma. CONCLUSION: This study showed a high TrxR1 expression in primary glioblastoma which could indicate a role of the Trx system in promoting the malignant progression by some complex processes.

Intratumoral hemorrhage-related differences in the expression of vascular endothelial growth factor, basic fibroblast growth factor and thioredoxin reductase 1 in human glioblastoma.

The present study was designed to evaluate the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and thioredoxin reductase 1 (TrxR1) in glioblastoma multiforme (GBM) with and without intratumoral hemorrhage. Surgically resected human GBM samples from 20 patients who underwent surgery at our institute were extracted from the histopathological specimens and divided into two groups. A total of 10 samples from each type of GBM (World Health Organization grade IV, intratumoral hemorrhage-positive or -negative) were included in each group. VEGF, bFGF and TrxR1 expression was analyzed using immunohistochemistry and the results were compared between groups. VEGF and bFGF immunoreactivity was significantly higher in GBMs containing intratumoral hemorrhage. Furthermore, VEGF, bFGF and TrxR1 immunointensity was significantly higher in GBMs containing intratumoral hemorrhage. Thus, the present study demonstrated a higher VEGF, bFGF and TrxR1 expression in GBMs contain intratumoral hemorrhage, indicatiogn a role of VEGF, bFGF and TrxR1 expression in the promotion of tumoral angiogenesis and tumoral growth by complex mechanisms that require further elucidation.

The Role of Fenestration of the Lamina Terminalis on Symptomatic Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Clinical Research.

AIM: To compare the beneficial effects of cisternal blood clot evacuation with or without microsurgical fenestration of the lamina terminalis (LT) on symptomatic vasospasm during the course of aneurysmal subarachnoid hemorrhage. MATERIAL AND METHODS: This was a clinical, retrospective study that included 72 patients with aneurysmal subarachnoid hemorrhage (aSAH). The patient group that underwent aneurysm clipping with only extensive cisternal drainage of the subarachnoid blood clot was defined as the non fenestrated lamina terminalis group (NonFLT group, n=39). The patient group that underwent aneurysm clipping with extensive cisternal drainage of the subarachnoid blood clot combined with microsurgical fenestration of LT was defined as the fenestrated lamina terminalis group (FLT group, n=33). All patients were operated by the same experienced neurovascular surgeon, the senior author of this article (MEU), and his colleagues. New cerebral infarct development was determined with computed tomography, Glasgow Outcome Score (GOS), clinical vasospasm rate and Hunt-Hess scale (H&H) grade before and after surgery and duration of hospital stay of the patients were assessed and compared. RESULTS: A favorable clinical outcome was obtained from 51.2% of the NonFLT group patients and 72.66% of the FLT group patients. And FLT group patients have better GOS and H&H grade. Clinical vasospasm rate and duration of hospital stay were also significantly reduced in FLT group patients. CONCLUSION: Wide fenestration of lamina terminalis as a cerebrospinal fluid diversion technique may be very beneficial in the surgical treatment of aneurysmal SAH.

Telmisartan ameliorates oxidative stress and subarachnoid haemorrhage-induced cerebral vasospasm.

OBJECTIVES: Growing evidence suggests that oxidative stress is one of the factors contributing to subarachnoid haemorrhage (SAH)-induced cerebral vasospasm. SAH-induced cerebral vasospam alters thioredoxin (Trx) cycle enzymes and thioredoxin-interacting protein (TXNIP) as an important endogenous antioxidant system. In this study, we have explored the effects of telmisartan on the vascular morphological changes, endothelial apoptosis, tissue oxidative stress status and the level of Trx cycle enzymes/ TXNIP in a rabbit SAH model. METHODS: Forty male New Zealand rabbits were randomly divided into five groups of eight rabbits each: control group, sham group, SAH group, SAH + vehicle group and SAH + telmisartan group. SAH was created by a single cisterna magna blood injection. SAH + telmisartan group received telmisartan treatment (5 mg/kg intraperitoneal, once daily) for 72 h. The brainstem tissue Trx1, Trx2, Trx reductase (TrxR), TrxR1and TXNIP levels were investigated. Total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA) levels and tumour necrosis factor alpha (TNF alpha) levels were investigated. Basilar artery segments were investigated for cross-sectional area, wall thickness measurements and endothelial apoptosis. RESULTS: Telmisartan treatment restored the lowered level of Trx1, TrxR, TAS and the expression of TrxR1 seen in SAH. Telmisartan treatment also decreased TXNIP expression, TOS, MDA and TNF alpha levels. Morphological changes of cerebral vasospasm were attenuated after treatment. Endothelial apoptosis significantly reduced. DISCUSSION: Treatment with telmisartan ameliorates oxidative stress and SAH-induced cerebral vasospasm in rabbits. These effects of telmisartan may be associated with downregulation of TXNIP and upregulation of Trx/TrxR.

Sellar-Suprasellar Extraventricular Choroid Plexus Papilloma : A Case Report and Review of the Literature.

Choroid plexus papillomas (CPPs) are relatively rare neuroectodermal tumors that develop from choroid plexus epithelial cells and are usually restricted to the ventricles. Extraventricular CPPs are very unusual and can be difficult to diagnose and treat. A 50-year-old male patient was admitted to our clinic complaining of headache and visual deterioration. Neurological examination found no abnormalities except decreased light perception and secondary optic atrophy in the left eye. Endocrine testing revealed normal levels of hormones produced by the pituitary and target glands. Magnetic resonance imaging of the brain revealed a huge regular-shaped lesion in the sellar-suprasellar region occupying the sella turcica and extending into the suprasellar cistern and planum sphenoidale. The lesion was completely excised by microsurgery via an ordinary left-sided pterional approach. Histopathology identified the lesion as a choroid plexus papilloma. Following the case report, literature on the origin, differential diagnosis, and treatment of this rare tumor is reviewed.

Facilitating triple rhomboid flaps for meningomyelocele defect closure using a honeycomb structure as a template.

PURPOSE: Various reconstruction options are available for the soft-tissue coverage of meningomyelocele defects. For small defects, primary closure or local single flaps may be sufficient, while large defects require more complex reconstructive techniques. This study suggests an easy way for surgeons to close large meningomyelocele defects using triple rhomboid flaps. METHODS: The hexagonal structure of a honeycomb was considered when planning for the coverage of large meningomyelocele defects. The intact skin around the defect was imagined as multiple hexagons, which allowed us to plan triple rhomboid flaps correctly and more easily. This technique was used in seven patients with defects ranging from 7 × 5 to 12 × 8 cm in size. RESULTS: No major postoperative complications were seen. Minimal dehiscence was observed in two patients and healed secondarily. CONCLUSIONS: The honeycomb modification for planning triple rhomboid flaps is an easy, practical, and memorable approach for surgeons reconstructing large meningomyelocele defects.

Endoscopic Endonasal Transethmoidal Approach for the Management of a Traumatic Brain Abscess and Reconstruction of the Accompanying Anterior Skull Base Defect.

Skull base endoscopy in the treatment of brain abscesses has been rarely published. Moreover, endoscopic endonasal transethmoidal approach (EETA) for the treatment of brain abscess following a head trauma has been reported only in a few case reports. We report the management of a patient of intracerebral abscess and reconstruction of the accompanying anterior skull base defect through an EETA.Thirty-year-old male with a frontal lobe abscess due to a penetrating skull base trauma was operated via EETA. After drainage of the abscess, dural and bony defects were repaired to prevent any recurrence. Postoperative radiological imaging revealed prominent decrease in abscess size. The patient did not need any further surgical intervention, and antibiotherapy was adequate.EETA is safe and effective in the management of brain abscesses. Skull base endoscopy provides direct visualization of the abscess cavity through a minimal invasive route, facilitates wide exposure of surrounding neurovascular structures within the operative field, and enables concurrent closure of the skull base defect.

Endovascular management of a collateral network aneurysm in a patient with spontaneous internal carotid artery occlusion.

Spontaneous "non-moyamoya" arterial occlusion of the intracranial arteries is very unusual. Progressive occlusion of a major intracranial artery, independently from the etiology, can lead to the development of collateral arterial networks that supply blood flow to distal territories beyond the occlusion. These collateral arteries are typically small and conduct low flows, but the hemodynamic stress within them can lead to aneurysm formation within the collateral network. In this report we present a case of spontaneous internal carotid artery occlusion and collateral network aneurysm for the first time in the literature and discuss the main features of the etiology and endovascular treatment of this rare, challenging aneurysm.

Radiological anatomy of the C7 vertebra: Clinical implications in spine surgery.

CONTEXT: This study was designed to understand and define the special radio-anatomic morphometry of C7 vertebra by using multidetector computed tomography (MDCT). AIMS: The major aim of the study was to detect the gender- and side-related morphometric differences of C7 vertebra among subjects. SETTING AND DESIGN: Our radiology unit database scanned for MDCT sections of the C7 vertebra. MATERIALS AND METHODS: A total of 214 patients (134 men, 80 women) were selected. A detailed morphometric evaluation of C7 was done. STATISTICAL ANALYSIS USED: T test, ANOVA. Lamina length (P < 0.001), pedicle length (P < 0.001), outer cortical (P = 0.01) and inner cancellous pedicle (P < 0.001) width, pedicle angle to sagittal plane (P < 0.001) values were statistically significantly different on the right versus left side. When the results were stratified by gender, lamina length, inner cancellous lamina height, pedicle length, inner cancellous pedicle height, outer cortical pedicle width, lateral mass anteroposterior length, anteroposterior length of C7 corpus, height of C7 corpus (P < 0.001), C6-7 (P = 0.013) and C7-T1disc height (P = 0.04), transverse foramina perpendicular width at C7 (P = 0.046) values were found to be statistically significantly different. Vertebral artery most commonly enters into the transverse foramina at C6 level. CONCLUSIONS: Gender and side differences are important factors for preoperative planning and showed significant differences among subjects. MDCT is a practical option for investigating the exact anatomical features of osseous structures.

High thioredoxin reductase 1 expression in meningiomas undergoing malignant progression.

Thioredoxin (Trx) is a redox active protein that regulates several physiological and biochemical functions, such as growth, apoptosis and cellular defense. The function of Trx itself is regulated by thioredoxin reductase (TrxR). This study was designed to determine the expression of TrxR1 in meningioma tissues of different World Health Organization grades (grade I-III). Meningioma tissues were extracted from the histopathological specimens of 29 patients. These samples included seven histologically normal meningeal tissues that served as a control group and 12 grade I, 12 grade II and 5 grade III meningioma samples. TrxR1 expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunostaining. The proliferative and apoptotic indices of the specimens were investigated by Ki-67 immunostaining and TUNEL assay, respectively. TrxR1 expression, as assessed by qRT-PCR, increased significantly with meningioma grade (p < 0.001). The immunostaining intensity of TrxR1 increased significantly with meningioma grade (p < 0.001). Ki-67 index values increased significantly in accordance with grade progression (p < 0.001). The apoptotic index values were not significantly different in any group (p > 0.05). Trx system seems to be involved in the malignant progression of meningiomas. Further, large studies are required to elucidate the exact role of this system.

Tissue thioredoxin reductase-1 expression in astrocytomas of different grades.

Thioredoxin (Trx) is a redox active protein that regulates several physiological and biochemical functions, such as growth, apoptosis and cellular defense. The function of Trx itself is regulated by thioredoxin reductase (TrxR). Studies performed in a variety of human primary tumors have shown that thioredoxin reductase 1 (TrxR1) is overexpressed in tumoral tissues compared with corresponding normal tissues. This study was designed to determine the expression of TrxR1 in astrocytoma tissues of different World Health Organization (WHO) grades (grade I-IV). The proliferative (Ki-67) and apoptotic indices of the specimens were also investigated for correlation analysis. Astrocytoma tissues were extracted from the histopathological specimens of 40 patients. These samples included seven histologically normal brain tissues that served as a control group and ten tumoral samples for each grade of astrocytoma (grade I-IV). The histologically normal brain tissues were obtained from the non-tumoral portions of the pathological specimens of grade I (2 cases), grade II (2 cases), grade III (2 cases) and grade IV (1 case) astrocytomas. TrxR1 expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunostaining. The proliferative and apoptotic indices of the specimens were investigated by Ki-67 immunostaining and TUNEL assay, respectively. TrxR1 expression, as assessed by qRT-PCR, increased significantly with astrocytoma grade (p = 0.01). The immunostaining intensity of TrxR1 in grade IV astrocytomas was significantly greater than that in the control tissue and all other astrocytoma grades (p < 0.001). Similarly, immunostaining intensity of TrxR1 in the grade III astrocytomas was significantly greater than that in the control group and grade I astrocytomas (p < 0.001). All astrocytoma tissues showed more intense staining in ascending grades, but the differences between grade I and the control, grade II and the control, grades II and I, grades III and II were not statistically significant (p > 0.05). Ki-67 index values increased significant in accordance with grade progression (p = 0.01). The apoptotic index values were not significantly different in any group (p > 0.05); however, the differences between grade IV and the control and between grades IV and I were statistically significant (p < 0.05). Expression of TrxR1, as assessed by both qRT-PCR and immunostaining, correlated highly with both the astrocytoma grade and Ki-67 index.

Endovascular treatment of complex intracranial aneurysms by pipeline flow-diverter embolization device: a single-center experience.

OBJECTIVE: Endovascular coil embolization has become an effective treatment modality for most intracranial aneurysms. However, complex aneurysms including large and giant aneurysms, fusiform shaped aneurysms, wide necked aneurysm, or small aneurysm that are unsuitable for coil embolization are still deterrent to be treated. Flow diversion is a novel concept that is applied in the treatment of these complex intracranial aneurysms. METHOD: We review the results and important features of 25 aneurysms in 24 patients who underwent endovascular treatment by using the pipeline flow-diverter embolization device. RESULT: At 6 month follow-up, all aneurysms (100%) showed total occlusion in our series. Only one patient who had giant vertebrobasilar aneurysm experienced major complication related to endovascular treatment. DISCUSSION: We suggest that parent artery reconstruction via flow diversion with the PED is a valid and safe treatment modality.

Congenital carotid-jugular fistula in a child: a case report.

Congenital carotid-jugular (CJ) fistula of the neck is a very rare clinical entity that has various causes. The CJ fistulas are particularly prone to complications unlike other peripheral arteriovenous fistulas. The aim of this report is to present a case of a CJ fistula between the external carotid and the external jugular vein, which was successfully closed with detachable balloon by an endovascular approach. A 14-year-old child was admitted to our clinic with a pulsatile neck swelling. There was no previous history of trauma. A high-flow fistula between the external carotid and the external jugular vein was determined. The fistula was closed with detachable balloon by an endovascular approach. The postoperative angiogram demonstrated complete resolution of the fistula. Endovascular treatment of CJ fistulas with detachable balloons is a safe and less traumatic technique and may be an effective alternative to the open surgery in selected patients.

The surgical management of traumatic c6-c7 spondyloptosis.

A case of traumatic spondyloptosis of the cervical spine at the C6-C7 level is reported. The patient was treated succesfully with a anterior-posterior combined approach and decompression. The patient had good neurological outcome after surgery. A-51-year-old female patient was transported to our hospital's emergency department after a vehicle accident. The patient was quadriparetic (Asia D, MRC power 4/5) with severe neck pain. Plain radiographs, computerize tomography and spinal magnetic resonance imaging (MRI) showed C6-7 spondyloptosis and C5, C6 posterior element fractures. Gardner-Wells skeleton traction was applied. Spinal alignment was reachived by traction and dislocation was decreased to a grade 1 spondylolisthesis. Then the patient was firstly operated by anterior approach. Anterior stabilization and fusion was firstly achieved. Seven days after first operation the patient was operated by a posterior approach. The posterior stabilization and fusion was achieved. Postoperative lateral X-rays and three-dimensional computed tomography showed the physiological realignment and the correct screw placements. The patient's quadriparesis was improved significantly. Subaxial cervical spondyloptosis is a relatively rare clinical entity. In this report we present a summary of the clinical presentation, the surgical technique and outcome of this rarely seen spinal disorder.

CSF hydrothorax after ventriculoperitoneal shunt without catheter migration: a case report.

Ventriculoperitoneal (VP) shunting is the most common procedure performed for the management of hydrocephalus. VP shunt related complications remain a persistent problem in current clinical practice. Five-year-old female patient was admitted to our hospital with persistent dyspnea complaint. The patient was operated at the age of 3 months and a VP shunt established in a different clinic due to hydrocephalus associated with Dandy-Walker malformation. The patient's chest X-ray revealed right sided pleural effusion. Thorasentesis was performed and the effusion was drained with a chest tube. The discharged liquid was consistent with CSF. Scintigraphic radionuclide shunt analyses were performed and CSF passage from abdomen to chest and lower mediastinal region was determined in the late static images. The patient was operated and the incorporated ventriculoperitoneal shunt was removed. Hydrothorax was completely resolved after early postoperative stage. CSF hydrothorax especially without catheter migration is an unusual but potentially serious-clinical complication.

Primary spinal hydatid cyst in a patient with acquired immunodeficiency syndrome.

Spinal hydatid cyst is a serious and unusual infectious disease. There is little information on infections caused by cestodes in patients with human immunodeficiency virus (HIV) infection. Although infrequent, infections by cestodes constitute a cause of disease in HIV-infected patients, especially in endemic areas. This report presents, for the first time in the literature, primary spinal cyst hydatid in a patient with acquired immunodeficiency syndrome.

N-acetylcysteine prevents vasospasm after subarachnoid hemorrhage.

BACKGROUND: This study investigated the ability of NAC to prevent cerebral vasospasm in a rabbit model of SAH. METHODS: Twenty-one, male New Zealand white rabbits were randomly divided into 3 groups of 7 rabbits each: group 1 (control), group 2 (SAH only), group 3 (SAH + NAC treatment). NAC (150 mg/kg, single dose, IP) was administered just before SAH and continued until 72 hours after SAH in group 3. Animals were killed 72 hours after SAH. Tissue MDA levels, SOD, and GSH-Px activities were measured, and basilar artery cross-sectional areas, arterial wall thickness, and endothelial apoptosis in a cross section of basillary artery were determined in all groups. RESULTS: Intraperitoneal administration of NAC was found to be markedly effective against developing a cerebral vasospasm following a SAH in rabbits. It could significantly reduce elevated lipid peroxidation and increase the level of tissue GSH-Px and SOD enzymatic activities. Also, NAC treatment was found to be effective in increasing the luminal area and reducing wall thickness of the basilar artery. The morphology of arteries in the NAC treatment group was well protected. NAC markedly reduced apoptotic index and protects the endothelial integrity. CONCLUSIONS: This study demonstrates, for the first time, that NAC treatment attenuates cerebral vasospasm in a rabbit SAH model. NAC treatment has significant neuroprotective effect and markedly prevents cerebral vasospasm after SAH. In conclusion, the NAC treatment might be beneficial in preventing cerebral vasospasm after SAH, thus showing potential for clinical implications.

Electrophysiology of papillary muscle in SAH: changes and N-acetylcysteine protection.

BACKGROUND: Although subarachnoid hemorrhage (SAH) serves as a good model to study heart-brain interactions, neither the changes on the single ventricular action potential (SVAP) and contraction nor the effects of possible cardioprotective agents have been investigated. MATERIALS AND METHODS: A total of 18 male rabbits were used for the three experimental groups. SAH was induced by replacing the cerebrospinal fluid (CSF) with fresh autologous blood at the ratio of 1 mL to the 1-kg body mass (N = 6). In the control (CON; N = 6) group, the CSF was replaced with serum physiologic at the same ratio. The treated SAH group (SAH+NAC) received daily intraperitoneal N-acetylcysteine (NAC; 150 mg/kg for 3 days) starting from just before SAH was induced by CSF replacement. On the fourth day, animals were examined for the single action potential and contraction recordings from the left ventricular papillary muscle. RESULTS: At the end of 3 days, the overshoot decreased together with increased time to reach the peak potential. Additionally, the resting membrane potential was depressed and repolarization was slowed during SVAPs. On the other hand, peak tension depressed and time to peak increased. NAC treatment, which protects infarction in the brain, prevented these pathological changes in the cardiac muscle. CONCLUSION: SAH-induced cardiac changes can be attributed to adenosine triphosphate depletion through mitochondrial dysfunction. Pretreatment of NAC to SAH on the other hand had a positive effect on these cardiac changes. But the exact mechanism by which NAC treatment protects the cardiac muscle needs further investigation.