Annaswamy Raja

Role of antioxidant enzymes in brain tumours

Erythrocyte antioxidant enzymes were analysed in 100 patients with intracranial neoplasm and in 47 controls. There was a significant decrease in RBC glutathione reductase (GRx) and superoxide dismutase (SOD) activity in most types of brain tumor cases. Patients with acoustic neurinoma showed a significant reduction in selenium-dependent glutathione peroxidase (Se-GPx) activity. A decrease in catalase (CT) activity was seen in most of the brain tumor patients but remained statistically insignificant when compared to controls. A significant increase in plasma ceruloplasmin concentration was observed in patients with glioma. These enzymes were also studied in 27 post-treatment cases. GRx activity returned to normal levels in these patients. RBC SOD and plasma ceruloplasmin levels showed a tendency to return to normal. Hence, a marked decrease in the antioxidant enzymes may have a role in the genesis of considerable oxidative stress in patients with brain tumors.

Relationship between neurological outcome and early oxidative changes in erythrocytes in head injury patients.

Abstract Background: Experimental data indicate that destructive oxidative events reach their peak within the first 24 h after trauma in head injury (HI) and that brain damage occurring due to this impact can be the cause of death or irreversible permanent disabilities in affected patients. Methods: Venous blood samples were obtained from 50 HI patients within 24 h of trauma onset and from 30 age- and sex-matched normal controls (NC). Patients were divided into three different neurological outcome groups: those who died within 10 days of trauma (D), and those with severe neurological deficits (SD) or mild/no neurological deficits (MD) at 90 days after trauma. Early oxidative changes in erythrocytes were assessed by estimating an indicator of lipid peroxidative damage – thiobarbituric acid-reactive substances (TBARS) – and antioxidants [reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity]. Results: In the D group, erythrocyte TBARS levels were significantly higher compared to the NC, SD and MD groups (p<0.001); GSH levels were significantly lower compared to the NC (p<0.001) and MD (p<0.01) groups and SOD activity was significantly higher than in the NC (p<0.01) and MD (p<0.01) groups. In the SD group, TBARS levels were significantly higher than in the NC (p<0.001) and MD (p<0.05) groups; GSH levels were significantly lower than in the NC (p<0.001) and MD (p<0.01) groups and SOD activity was higher compared to the NC and MD (p<0.01) groups. In the MD group, TBARS levels were significantly higher and GSH levels significantly lower compared to the NC group (p<0.001). However, we did not observe any significant change in SOD activity compared to the NC group. Conclusions: These findings indicate that early oxidative changes may reflect the severity of neurological insult and provide an early indication of patient outcome in traumatic HI. Clin Chem Lab Med 2007;45:629–33.

Erythrocyte indicators of oxidative changes in patients with graded traumatic head injury

CONTEXT Acute oxidative stress following a traumatic head injury (HI) has been implicated in inducing severe secondary brain damage and influencing the clinical outcome of HI patients. AIMS This study was performed to evaluate and compare the oxidative changes in patients with varying severity of HI in the early posttraumatic period using erythrocyte indicators. SETTINGS AND DESIGN Head injury patients were divided into two groups based on their Glasgow Coma Scale (GCS) scores recorded at admission to the hospital on the day of trauma itself. Accordingly, the study included 30 severe HI (SHI, GCS scores 8 or less) and 25 Mild HI (MHI, GCS scores more than 8) patients. Thirty age and sex-matched healthy individuals were included in this comparative study as controls. MATERIALS AND METHODS Blood samples were obtained from controls and HI patients (within 24 h of trauma onset). Erythrocyte oxidative changes were studied by estimating thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD) and glutathione reductase (GR). RESULTS Erythrocyte TBARS levels were significantly higher and GSH levels were significantly lower in SHI and MHI patients as compared to controls. The SOD activity was significantly increased only in SHI patients and remained unchanged in MHI patients as compared to controls. As compared to MHI patients, erythrocyte TBARS levels were significantly higher, GSH levels were significantly lower and SOD activity was markedly elevated in SHI patients. Erythrocyte GR activity did not show significant changes in both groups of patients as compared to controls. CONCLUSION Oxidative stress is evident in both SHI and MHI patients in the early posttraumatic period as reflected by their erythrocyte indicators, but the severity of oxidative stress has varied relatively with the severity of head injury. The present findings provide indications that early oxidative changes could influence the neurological recovery of HI patients.

Time-level relationship between indicators of oxidative stress and Glasgow Coma Scale scores of severe head injury patients

Abstract Background: Oxidative stress is said to strongly influence the neurological recovery of patients following a severe head injury. Estimation of the markers of oxidative stress in the blood of such patients can hence aid in predicting the prognosis of head injury. Methods: Erythrocyte thiobarbituric acid-reactive substances (TBARS) and plasma ceruloplasmin (CP) levels were estimated in 24 severe head-injury patients on days 1, 7 and 21 of the post-traumatic period and compared with levels in 25 healthy age- and sex-matched controls. These parameters reflecting oxidative stress status were related to the Glasgow Coma Scale (GCS) scores of patients noted at the same time points of the study period. Results: Lipid peroxidation as indicated by increased levels of erythrocyte TBARS remained significantly elevated in severe head injury patients compared to controls on day 1 (p<0.001), day 7 (p<0.001) and 21 (p<0.001) of the post-traumatic period. Plasma CP levels remained significantly elevated (p<0.001) at these three time points compared to controls. The significant decrease in lipid peroxidation products (p<0.01) and significant increase in CP levels (p<0.001) on day 21 compared to day 1 in head injury patients correlated well with the significant improvement in GCS scores of patients on day 21 compared to day 1 (p<0.05). Conclusion: The above results could account for the adaptation of the study patients to severe oxidative stress, as evidenced by their clinical recovery trend during the study period.

Time-relative changes in the erythrocyte antioxidant enzyme activities and their relationship with Glasgow Coma Scale scores in severe head injury patients in the 21-day posttraumatic study period.

BACKGROUND Reactive oxygen species are indicated to play a prime role in the pathophysiology of brain damage following a severe head injury (SHI). AIM The current study was designed to understand the time-relative changes and relationship between erythrocyte antioxidant enzyme activities and Glasgow Coma Scale (GCS) scores of SHI patients in the 21-day posttraumatic study period. SETTINGS AND DESIGN The study included 24 SHI patients and 25 age- and sex-matched normal controls (NC). Activities of superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) were assayed in these patients and controls. The GCS scores of these patients were also recorded for the comparative study. MATERIALS AND METHODS Venous blood samples were collected on day 7 (D7) and D21 from SHI patients and NC for the assay of SOD, GR and GSH-Px activities. These changes were correlated with age and changes in GCS scores of patients. STATISTICAL ANALYSIS A one-way analysis of variance (ANOVA) was used to compare mean values of each parameter between group 1 (NC), group 2 (D7 changes in SHI patients) and group 3 (D21 changes in SHI patients). ANOVA was followed by Bonferroni post hoc tests. The Pearson correlation was applied to correlate between the antioxidant parameters and age and GCS scores of these patients. RESULTS A significant increase in erythrocyte SOD and GSH-Px activities was observed in group 3 as compared to groups 1 and 2. The increase in GSH-Px activity was significant in group 2 as compared to group 1. Although not significant, there was an increase in mean GR activity in groups 2 and 3 as compared to group 1. CONCLUSION These findings indicate that SHI patients have shown significantly enhanced erythrocyte SOD and GSH-Px activities during the 21-day posttraumatic study period.

Cystic cervical intramedullary schwannoma with syringomyelia.

We report a case of cervical intramedullary cystic schwannoma associated with segmental syrinx in a young adult without evidence of neurofibromatosis. The relevant literature is reviewed.

Urinary Excretion of 6-Hydroxymethylpterin in Brain Tumours

The urinary 6-hydroxymethylpterin(Pt-6-CH2OH) excretion was determined in 87 patients with brain tumours and in 50 control patients. The Pt-6-CH2OH levels were significantly elevated in all patients with tumours. No difference was observed when malignant tumours were compared with benign neoplasms. Following therapy, the Pt-6-CH2OH levels were partially reduced when compared with control patients and their pre-operative values.

Plasma protein oxidation in patients with brain tumors

Abstract Objective: Proteins can undergo numerous covalent changes on exposure to oxidants. Oxidative modification of protein in vivo may affect a variety of cellular functions. Protein oxidation in vivo is a natural consequence of aerobic life. Oxygen radicals and other activated oxygen species generated as byproducts of cellular metabolism or from environmental sources cause modifications to the amino acids of proteins that generally result in loss of protein function/enzymatic activity. It is now well known that reactive oxygen species (ROS) play a key role in human cancer development. Moreover, the brain is especially vulnerable to ROS mediated injury. Method: Therefore, in the present study, protein oxidation was assessed in the plasma of 17 patients with brain tumors and 16 age and gender-matched controls by measuring protein thiols and protein carbonyls spectrophotometrically. Results: There was a significant decrease in protein thiols and carbonyls in malignant cases of brain tumors when compared with the control group. No significant change in protein thiols was noted in benign cases compared to controls. A comparison of levels in benign and malignant cases for both the parameters also showed no significant difference. Discussion: Thus, free radical toxicity does lead to protein oxidation in patients with brain tumors.

Assessment of total sialic acid and lipid-bound sialic acid in management of brain tumors

Background: Glycoconjugate molecules expressed at the plasma membrane of mammalian cells have been reported to be associated with tumor progression. The measurement of total sialic acid (TSA) and lipid-bound sialic acid (LBSA) in the cerebrospinal fluid (CSF) is suggested to be useful for the diagnosis of brain tumors. But there are very few reports available on the serum glycoconjugate levels in patients with brain tumors. Objective: The objective of this study is to check the feasibility of using serum glycoconjugates such as TSA and LBSA as tumor markers in brain tumor patients. Materials and Methods: Colorimetric estimation of TSA using diphenylamine was done on 100 patients with intracranial tumors; follow-up study was carried out in 24 cases. The LBSA fraction was isolated from the serum of 68 brain tumor patients and evaluated using phosphotungstic acid and resorcinol; follow-up study was done on 23 patients. The various types of brain tumors included in this study were glioma, meningioma, and acoustic neurinoma as well as some other types such as medulloblastoma, secondary tumors, and craniopharyngioma. Results: There was no significant difference between the TSA and LBSA concentrations seen in pretreatment or post-treatment cases and that seen in control subjects. Discussion: TSA and LBSA do not have the ability to discriminate between benign and malignant brain tumors. TSA and LBSA appear to be tumor markers of very limited value in patients with brain tumors.

Relationship between markers of lipid peroxidation, thiol oxidation and Glasgow coma scale scores of moderate head injury patients in the 7 day post-traumatic period

Abstract Objective: Epidemiologic works reveal that moderate head injury (MHI) is more frequent and a substantial number of these patients develop complications resulting in neurological disabilities. Reactive oxygen species (ROS) play a major role in post-traumatic neuronal damage following traumatic head injury. Thus, the current study analysed the post-traumatic changes in the erythrocyte markers of oxidative damage and the relationship between these parameters and Glasgow coma scale (GCS) scores of MHI patients during the 7 day study period. Methods: Peripheral venous blood samples were taken at the time of hospital admission (d1 of injury) and on d7 from 25 MHI patients (admission GCS score>8). These were compared with samples from 25 healthy individuals (normal controls, NC). GCS scores were recorded at the same time points of the study period. Erythrocyte lipid peroxidation (LP) and thiol oxidation levels were estimated and compared with that of NC. The relationship between GCS scores and erythrocyte markers were also studied. Results: Erythrocyte thiobarbituric acid reactive substance (TBARS) levels reflecting lipid peroxidative damage remained significantly elevated at both time points of the study period in MHI patients as compared to NC (p<0.001). There was a significant decrease in the level of non-protein thiols in MHI patients as compared to NC (p<0.01) at the same time points of the study. However, on d7 there were no further significant changes in the markers of oxidative damage in MHI patients as compared to on d1. Conclusion: These findings suggest that a condition of oxidative stress occurs during the entire post-traumatic period in MHI patients and the utility of markers of oxidative damage in the prognosis of head injury needs to be addressed in further works.