Levels of Coenzyme Q10 and Several COQ Proteins in Human Astrocytoma Tissues Are Inversely Correlated with Malignancy.

In a previous study, we reported the alterations of primary antioxidant enzymes and decreased citrate synthase (CS) activities in different grades of human astrocytoma tissues. Here, we further investigated coenzyme Q10 (CoQ10) levels and protein levels of polyprenyl diphosphate synthase subunit (PDSS2) and several COQ proteins required for CoQ10 biosynthesis in these tissues. We found that the level of endogenous CoQ10, but not of exogenous α-tocopherol, was higher in nontumor controls than in all grades of astrocytoma tissues. The levels of COQ3, COQ5, COQ6, COQ7, COQ8A, and COQ9, but not of COQ4, were lower in Grade IV astrocytoma tissues than in controls or low-grade (Grades I and II) astrocytomas, but PDSS2 levels were higher in astrocytoma tissues than in controls. Correlation analysis revealed that the levels of CoQ10 and COQ proteins were negatively correlated with malignancy degree and positively correlated with CS activity, whereas PDSS2 level was positively correlated with malignancy. Moreover, lower level of mitochondrial DNA-encoded cytochrome c oxidase subunit 2 was not only associated with a higher malignancy degree but also with lower level of all COQ proteins detected. The results revealed that mitochondrial abnormalities are associated with impaired CoQ10 maintenance in human astrocytoma progression.

Alterations of the levels of primary antioxidant enzymes in different grades of human astrocytoma tissues.

Malignant astrocytoma is the most commonly occurring brain tumour in humans. Oxidative stress is implicated in the development of cancers. Superoxide dismutase 2 (SOD2) was found to exert tumour suppressive effect in basic research, but increased SOD2 protein level was associated with higher aggressiveness of human astrocytomas. However, studies reporting alterations of antioxidant enzymes in human astrocytomas often employed less accurate methods or included different types of tumours. Here we analysed the mRNA levels, activities, and protein levels of primary antioxidant enzymes in control brain tissues and various grades of astrocytomas obtained from 40 patients. SOD1 expression, SOD1 activity, and SOD1 protein level were lower in Grade IV astrocytomas. SOD2 expression was lower in low-grade (Grades I and II) and Grade III astrocytomas than in controls, but SOD2 expression and SOD2 protein level were higher in Grade IV astrocytomas than in Grade III astrocytomas. Although there was no change in SOD2 activity and a lower activity of citrate synthase (CS), the MnSOD:CS ratio increased in Grade IV astrocytomas compared with controls and low-grade astrocytomas. Furthermore, SOD1 activity, CS activity, SOD1 expression, GPX4 expression, and GPX4 protein level were inversely correlated with the malignancy, whereas catalase activity, catalase protein, SOD2 protein level, and the SOD2:CS ratio were positively correlated with the degree of malignancy. Lower SOD2:CS ratio was associated with poor outcomes for Grade IV astrocytomas. This is the first study to quantify changes of various primary antioxidant enzymes in different grades of astrocytomas at different levels concurrently in human astrocytomas.

Clinical Pathway in the Treatment of Nocardial Brain Abscesses following Systemic Infections.

Nocardial infections are commonly encountered in patients with immunocompromised states. Cerebral nocardiosis is an uncommon clinical entity, representing only 2% of all cerebral abscesses. It has a higher mortality rate, especially for multiple cerebral lesions in immunocompromised hosts following systemic infections. However, an optimal treatment policy to deal with these immunocompromised patients in Asia is still lacking. We retrospectively reviewed the subjects with nocardial brain abscesses from 2001 to 2011 at our medical center. All of them had multiple brain abscesses, underlying with immunocompromised state following systemic infections. All cases were under steroid control due to their comorbidities for more than six months. The comorbidities and misdiagnosis often lead to poor prognosis. The change in the environments of the microorganisms caused by immunosuppressive agents and multiple antibiotic uses may play an important role in this critical disorder. Aggressive craniotomy should be performed in time to avoid grievous neurological outcomes. Our conclusion is that early diagnosis and appropriate antibiotic uses should be implemented promptly, and aggressive craniotomy should be performed for nocardial brain abscesses in subjects with systemic infections under an immunocompromised status.

Increased levels of F2-isoprostanes following aneurysmal subarachnoid hemorrhage in humans.

Subarachnoid hemorrhage (SAH) resulting from aneurysmal rupture is the major cause of nontraumatic SAH. We hypothesized that oxidative stress could be increased following aneurysmal SAH due to hemoglobin release and ischemia-reperfusion injury and that may further contribute to poor outcome. We collected plasma and cerebrospinal fluid (CSF) samples from 11 non-SAH controls and 15 aneurysmal SAH patients for up to 10 days after surgery and investigated status of oxidative stress in patients. Results showed that mean or peak levels of F(2)-isoprostanes (F(2)-IsoPs), a specific marker of lipid peroxidation, and total nitrate/nitrite, metabolites of nitric oxide and peroxynitrite, in CSF and plasma were significantly higher in SAH patients than in controls. First-day levels were also higher in CSF, but not in plasma, in SAH patients. Moreover, mean and peak levels of CSF F(2)-IsoPs were positively correlated with poor outcome or severity of clinical conditions in patients. Furthermore, levels of retinol, delta-tocopherol, beta+gamma-tocopherol, lutein, beta-carotene, and coenzyme Q(10) in plasma were significantly lower in SAH patients than in controls. Our results indicate that oxidative damage may play important roles in the severity and complications of aneurysmal SAH and suggest that means to suppress lipid peroxidation may be beneficial in improving the outcome of aneurysmal SAH.

Inducible nitric oxide synthase inhibition potentiates multiple organ dysfunction induced by endotoxin in conscious rats.

This study was designed to investigate the effects of inducible nitric oxide synthase (iNOS) inhibition with S-methylisothiourea (SMT) and L-N-(1-iminoethyl)-lysine (L-Nil) on the endotoxemia induced by intravenous lipopolysaccharide (LPS, 10 mg/kg) in conscious rats. Arterial pressure (AP), heart rate (HR), WBC, platelets, plasma nitrite/nitrate, tumor necrosis factor alpha (TNF alpha), and biochemical factors were measured for 24 hours after LPS with or without iNOS inhibitors. RT-PCR was employed to determine the iNOS and endothelial NOS (eNOS) mRNA. Pathologic examinations of the liver and heart were performed. SMT and L-Nil improved the systemic hypotension and increased the HR after LPS. These agents attenuated the LPS-induced leukocytopenia and thrombocytopenia and the increase in nitrite/nitrate. However, iNOS inhibition aggravated the LPS-induced changes in TNF alpha, all biochemical factors, and the hepatic and cardiac tissue damage. The iNOS mRNA, but not the eNOS, was reduced. Our results in conscious rats indicate that iNOS inhibition enhances the organ dysfunction and tissue damage in sepsis. The discrepancy may be attributed to the method for evaluating the sepsis and the effects of anesthesia. Further investigation is required to ensure the effects of iNOS inhibition on sepsis before iNOS inhibitors can be applied in clinical cases with sepsis.