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Öğe Cerebrospinal fluid and serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in patients with severe head injury(Turkish Assoc Trauma Emergency Surgery, 2007) Sanus, Galip Zihni; Tanrıverdi, Taner; Coşkun, Abdurrahman; Hanımoğlu, Hakan; İş, Merih; Uzan, MustafaBACKGROUND The aim of this study is to present time course of insulin like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels in both cerebrospinal fluid (CSF) and serum of patients after severe head injury (SHI) and to compare with controls. METHODS Our trauma and control groups included 11 consecutive patients with isolated SHI and 9 patients with hydrocephalus (one with normotensive and eight with hydrocephalus due to aqueduct stenosis), respectively. Both serum and cerebrospinal fluid levels of IGF-1 and IGFBP-3 were measured during post-traumatic days and we compared the levels with controls. RESULTS Patients and controls showed undetectable levels of both IGF-1 and IGFBP-3 in their CSF. When considering serum levels, patients with SHI had always lower levels of both molecules than that of controls. CONCLUSION Administration of IGF-1 during acute, as well as chronic phase of severe head trauma may provide beneficial effects and may decrease both mortality and morbidity in humans with SHI.Öğe Expression and cellular distribution of multidrug resistance-related proteins in patients with focal cortical dysplasia(W B Saunders Co Ltd, 2007) Ak, Halil; Ay, Bahadır; Tanrıverdi, Taner; Sanus, Galip Zihni; İş, Merih; Sar, Mehmet; Uzan, MustafaRecent arouse of interest indicated that drug resistant proteins are markedly over-expressed in the epileptogenic tissue and they may be responsible for the one-third of the epileptic patients who were refractory to anti-epileptic drugs (AEDs). Since several AEDs may act as substrates for these drug resistant proteins, the enhanced function of such proteins may increase drug extrusion, resulting in inadequate response to drug therapy in patients with epilepsy. We studied expression of the muttidrug resistance protein 1 (MDR1) and muttidrug resistance-associated protein 1 (MRP1) in the epileptic tissues resected surgically in 28 patients with focal cortical dyspLasia (FCD) by immunohistochemistry. The results were compared with 10 normal necropsy brain tissues. Normal brain showed no MDR1 expression in neurons and astrocytes, while MRP1 expression was very weak, which were encountered in a few samples. MDR1 expression was mainly localized on the vascular endothelial cells. In contrast to normal brain, we found intense MDR1 and MRP1 expression in both neurons and reactive astrocytes in the vast majority of dysplastic tissues. The majority of the dysplastic neurons demonstrated moderate to strong MRP1 immunoreactivity. Endothelial cells showed both MDR1 and MRP1 expression in the majority of the specimens studied. Muttidrug transporters are over-expressed in the epiteptogenic zone in patients with FCD. These results are concordant with previous studies, in which over-expression of multidrug proteins were shown in epiteptogenic brain tissue in patients with FCD, that the over-expression of drug transport proteins in tissue from patients with refractory epilepsy may explain one possible mechanism for drug resistant in these pathologies. (c) 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.Öğe High-sensitivity C-reactive protein levels in cerebrospinal fluid and serum in severe head injury: Relationship to tumor necrosis factor-alpha and interleukin-6(Churchill Livingstone, 2007) İş, Merih; Coşkun, Abdurrahman; Sanus, Galip Zihni; Tanrıverdi, Taner; Kafadar, Ali Metin; Hanımoğlu, Hakan; Uzan, MustafaRecent studies have demonstrated the role of high-sensitivity C-reactive protein (hsCRP) in inflammatory diseases; however, it is unclear whether this molecule has a role after severe head injury (SHI). Our aim was to evaluate the levels of hsCRP in both cerebrospinal fluid (CSF) and serum from patients after SHI. The study focused on 11 patients with SHI and evaluated CSF and serum levels of hsCRP, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in a 10-day period following the head trauma. The values were compared with those from nine control patients, who had normal pressure hydrocephalus. In the CSF and serum of the patients after SHI HsCRP was found to be significantly higher, at all times, than in the controls; TNF-alpha and IL-6 levels were also higher in these patients. However, hsCRP levels did not correlate with either TNF-alpha or IL-6. TNF-alpha and IL-6 increased during the period immediately following the SHI and intrathecal levels were always higher than those of the serum. This study demonstrates for the first time that hsCRP reaches high levels in both CSF and serum in patients with SHI, and it may therefore be used as an inflammatory index. This finding suggests a need for further studies in this area, which are larger in scope than the present study. (c) 2007 Elsevier Ltd. All rights reserved.Öğe Intraventricular albumin: an optional agent in experimental post-traumatic brain edema(Taylor & Francis Ltd, 2005) İş, Merih; Uzan, Mustafa; Ünal, Faruk; Kırış, Talat; Tanrıverdi, Taner; Mengi, Murat; Kılıç, NurtenHypothesis: Human albumin may be effective in the treatment of posttraumatic brain edema due to its hyperoncotic features. Therefore, the aim of the experimental stud presented in this paper has two points: the first is to evaluate the efficacy of intraventricular hyperoncotic human albumin on post-traumatic brain edema and the second is to try to show the appropriate posttraumatic time window for albumin administration. Method: Traumatic brain injury and subsequent edema was formed by a model of impact acceleration injury in rats. Human albumin was administered via intraventricular route by using a stereotactic head holder. All animals in each roup were decapitated 24 hours after the procedure and the effect of albumin was evaluate by measurement of tissue specific gravity. Results: Tissue specific gravity decreased in edematous tissue (trauma indicator), increased after albumin administration at the 12th (p<0.001), and both at the 1st and 12th hour of the trauma (edema treatment; p<0.001). On the other hand, albumin administered at the 12th, and at both the 1st and 12th hours in the rats without trauma has caused the formation of the brain edema. Conclusion: We conclude that human albumin is effective in cytotoxic, but not in vasogenic edema and exerts its best anti-edematous effect at the 12th hour of severe head trauma and this study may help future studies that will try to show the effects of albumin with different time modalities after severe head injury.Öğe Lack of association between the IL1A gene (-889) polymorphism and outcome after head injury(Elsevier Science Inc, 2006) Tanrıverdi, Taner; Uzan, Mustafa; Sanus, Galip Zihni; Baykara, Onur; İş, Merih; Özkara, Çiğdem; Buyra, N.Background: Interleukin (IL) I is a proinflammatory cytokine that has been identified as an important mediator of neurodegeneration induced by ischemia or traumatic brain injury. Accumulating evidence to date has suggested that the major cytokine contributing to neurodegeneration after head injury is IL-1 beta rather than IL-1 alpha; however, there is no sufficient data regarding IL-1 alpha in literature, and there may be an association between IL1A gene polymorphism and outcome after head injury. Methods: We performed a prospective clinical study and included a recruited series of 71 patients who had head injury and were admitted to our neurosurgical unit. Severity of initial injury was assessed by the Glasgow Coma Scale. Outcome at 6 months after injury was assessed by means of the Glasgow Outcome Score. Interleukin la genotypes were determined from blood samples by standard methods. Results: Of 40 patients with ILIA*2, 18 (45%) had an unfavorable outcome (dead, vegetative state, or severe disability) compared with 7 (22.5%) of 31 without ILIA*2 (P =.08). Conclusion: Our findings show that there is no genetic association between ILIA gene polymorphism and outcome after head injury. Further clinical studies should be designed to confirm and further evaluate these findings. (c) 2006 Elsevier Inc. All rights reserved.Öğe Pregnancy-Associated Plasma Protein A and High-Sensitivitive C-Reactive Protein Levels in Chronic Subdural Haematoma Patients(Journal Neurological Sciences, 2011) Hanımoğlu, Hakan; Ulu, Mustafa Onur; Biçeroğlu, Hüseyin; Memişoğulları, Ramazan; Coşkun, Abdurrahman; Balak, Naci; Uzan, MustafaObjective: Pregnancy-associated plasma protein A (PAPP-A), a metalloproteinase that regulates insulinlike growth factor-1 bioavailability in vitro, has been suggested to play an active role in the pathophysiology of several conditions involving inflammatory responses. We investigated the values of PAPP-A and high sensitive CRP (hsCRP) levels in chronic subdural haematoma (CSDH) patients and healthy controls. Methods: PAPP-A and hsCRP levels were studied in the serum and subdural haematoma fluid of 20 consecutive patients with CSDHs (M / F: 12 / 8; mean age of 56.7) and in the serum of age matched 16 volunteers (M / F: 10 / 6; mean age: 54,2). Results: The serum PAPP-A [4.15 ng/mL (2.70-12.88)] levels of patients were significantly lower than control group [9.32 ng/mL (6.57 - 17.00)] (p< 0.01) and the hsCRP levels were significantly higher in patient group [4.57 mg/L (1.56 - 12.62)] (p< 0.01). The comparison of PAPP-A values in the serum and subdural haematoma in the patient group revealed significantly very high values in the subdural fluid [204.5 ng/mL (161.1 - 261.4)] than the serum [4.15 ng/mL (2.70-12.88)] (p < 0.0001). The hsCRP values, on the other hand, were significantly lower in the subdural haematoma fluid than the serum in the patient group (p = 0.016). Conclusion: PAPP-A may have an important function in the local inflammatory events and local structural changes associated with CSDH formation and growth. The detection of high peripheral hsCRP levels in the patient group suggests that a systemic inflammatory response follows after the traumatic insult leading to CSDH formation.Öğe Prolonged elevation of magnesium in the cerebrospinal fluid of patients with severe head injury(Taylor & Francis Ltd, 2007) Kafadar, Ali Metin; Sanus, Galip Zihni; İş, Merih; Coşkun, Abdurrahman; Tanrıverdi, Taner; Hanımoğlu, Hakan; Uzan, MustafaObjectives: Several works have investigated the role of serum magnesium (Mg) concentrations in traumatic brain injury. However, there is restricted information about cerebrospinal fluid (CSF) levels of Mg in patients with severe head injury (SHI). We assessed the changes of Mg concentrations in CSF and serum in patients with SHI during the first 10 days after the trauma. Methods: Eleven patients with SHI were studied prospectively on days 1-3, 5 and 10 with analysis of CSF and serum levels of Mg and Ca. The control group consisted of nine patients with hydrocephalus. Results: CSF levels of Mg were significantly higher in patients than controls in the corresponding time points except on days 5 and 10 of trauma. The CSF Mg levels tended to decrease and the highest level was found on day 1 after trauma (2.81 +/- 0.65 mg/dl). In the control group, the CSF level of Mg was 1.95 +/- 0.66 mg/dl. No significant difference can be detected between controls and patients regarding serum Mg and Ca levels. In addition, significantly higher values of Ca in the CSF were observed in all time points after trauma in patients with SHI than in the controls. There was no correlation between the CSF and serum levels of Mg and Ca levels. Discussion: Our study demonstrates that in patients with SHI, CSF levels of Mg and Ca are elevated during the whole observation period. Further works should be designed in order to show the role and importance of CSF levels of ionized Mg in outcome of patients with SHI.Öğe Yings and Yangs of acute ethanol intoxication in experimental traumatic brain injury(Lippincott Williams & Wilkins, 2005) İş, Merih; Tanrıverdi, Taner; Akyüz, Fevzullah; Ulu, Mustafa Onur; Üstündağ, Nil; Gezen, Ferruh; Uzan, MustafaAlthough the deleterious effects of acute alcohol intoxication on traumatic brain injury (TBI) are well known, neuroprotective features of lower doses of ethanol (EtOH) before head trauma have been reported during recent years. Inhibition of N-methyl-D-aspartate receptor (NMDA)-mediated excitotoxicity by lower doses of EtOH has been believed to be responsible for this protection. The aim of this study was to show the neuroprotective effects of low and moderate doses of EtOH and to compare their efficacy in each group. Acute EtOH intoxication at low and moderate doses was induced 40 minutes before trauma. Severe TBI was administered in Sprague-Dawley rats using an impact acceleration model. At 24 hours after trauma, all the rats were decapitated and hippocampi were evaluated under light microscopy. According to our results, red neuron formation and vacuolar degeneration in the CA1 and CA3 sectors of the hippocampi were less prominent in the lowdose and moderate-dose EtOH plus trauma groups than in the trauma only group. In addition, edema formation was less prominent in the EtOH plus trauma group. When comparing the low-dose EtOH Plus trauma and moderate-dose EtOH Plus trauma groups, an almost normal appearance of the hippocampus was noted in the moderate-dose EtOH plus trauma group. EtOH may have a neuroprotective effect when administered at a lower dose, particularly a moderate dose, and this protection may be a result of the inhibition of NMDA receptor-mediated excitotoxicity.
