[Protective effects of Ginkgo Terpene Lactones Meglumine Injection on focal cerebral ischemia in rats].

To investigate the protective effects of ginkgo diterpene lactone meglumine injection (GDLMI) on cerebral focal ischemia reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats, and explore its possible mechanism. One hundred and forty male SD rats were randomly divided into sham operation group, model group, ginkgo biloba extract injection (Ginaton, 1.0 mL•kg⁻¹) group, nimodipine (0.4 mg•kg⁻¹) group, and GDLMI (5.2, 2.6, 1.3 mg•kg⁻¹) groups; All of rats received corresponding drugs by tail vein injection 4 days before operation (normal saline in model group and sham operation group). Except the sham operation group, the cerebral ischemic stroke model was established by MCAO method in right brain of the other rats. After 3 h of ischemia, all the animals received intravenous administration again. The neurobehavioral scores of rats after ischemia-reperfusion were evaluated and the infarct rate of brain tissue was observed by TTC staining. The super oxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and lactic acid (LA) contents in brain tissue homogenate and the concentration of Ca2+, glutamate (Glu) and aspartate (Asp), creatine phosphate kinase (CK-BB) and lactate dehydrogenase (LDH) content changes in cerebrospinal fluid were measured. As compared with the sham operation group, the cerebral infarction rate was increased significantly in the model group; the content of MDA and LA in the homogenate of brain tissue was increased, and the content of GSH and SOD was decreased; in cerebrospinal fluid, Ca2+ concentration was decreased, and the content of Glu and Asp, CK-BB and LDH increased significantly. As compared with the model group, the high and medium dose GDLMI groups can significantly reduce the cerebral infarction rate and improve the symptoms of neurological impairment; increase SOD and GSH activity, reduce MDA and LA content in serum; increase Ca2+ concentration in cerebrospinal fluid and decrease the content of neurotransmitter Glu and Asp as well as CK-BB and LDH. GDLMI could obviously improve neurologic impairment in model rats, and the mechanism may be related to recovering the blood brain barrier, scavenging free radicals, decreasing free Ca2+ inflow into the cells and the content of excitatory amino acid in cerebrospinal fluid to improve its protective effect on cerebral ischemia.

Mixtures of receiver operating characteristic curves.

RATIONALE AND OBJECTIVES: Receiver operating characteristic (ROC) curves are ubiquitous in the analysis of imaging metrics as markers of both diagnosis and prognosis. While empirical estimation of ROC curves remains the most popular method, there are several reasons to consider smooth estimates based on a parametric model. MATERIALS AND METHODS: A mixture model is considered for modeling the distribution of the marker in the diseased population motivated by the biological observation that there is more heterogeneity in the diseased population than there is in the normal one. It is shown that this model results in an analytically tractable ROC curve which is itself a mixture of ROC curves. RESULTS: The use of creatine kinase-BB isoenzyme in diagnosis of severe head trauma is used as an example. ROC curves are fit using the direct binormal method, ROCKIT software, and the Box-Cox transformation as well as the proposed mixture model. The mixture model generates an ROC curve that is much closer to the empirical one than the other methods considered. CONCLUSIONS: Mixtures of ROC curves can be helpful in fitting smooth ROC curves in datasets where the diseased population has higher variability than can be explained by a single distribution.

Protective effect of moderate hypothermia on severe traumatic brain injury in children.

This study investigated the safety and neuroprotective effect of moderate hypothermia in children with severe traumatic brain injury (TBI). Twenty-two children suffering from TBI were randomly divided into groups treated with moderate hypothermia (intracranial temperature of 34.5 +/- 0.2 degrees C, maintained for 72 h, n = 12) or normothermia (intracranial temperature of 38.0 +/- 0.5, n = 10). The cerebrospinal fluid levels of neuron-specific enolase (NSE), S-100, brain-specific creatine kinase (CK-BB), and intracranial pressure (ICP) levels were used to assess the protective effects. The variations in pH and electrolyte balance were also examined. The results indicated that the peak ICP level in the normothermia group (26.30 +/- 1.08 mm Hg) was reached 48 h after TBI. The ICP level in the moderate hypothermia group was lower than in the control group at every time point examined (p < 0.01). Furthermore, at 24, 48, and 72 h, the NSE, S-100, and CK-BB levels in the moderate hypothermia group were also lower than that of the normothermia group (p < 0.01). In the moderate hypothermia group, the pH and electrolyte balance at the end of the monitoring period were normal, but the heart rates were lower (p < 0.05). There were a total of three deaths (13.6%) in this study: one in the moderate hypothermia group (8.3%) and two in the normothermia group (20%). In conclusion, moderate hypothermia provided neuronal protection for children with severe TBI, and maintaining the intracranial temperature at 34.5 degrees C for 72 h was safe in this clinical setting.

Cerebrospinal creatinine kinase level in children with meningitis.

BACKGROUND: The aim of this study is to evaluate the diagnostic value of the enzyme creatine kinase (CK) in the cerebrospinal fluid (CSF) of children with meningitis. METHOD: CSF samples were collected from seventy one children suspected of having meningitis. The levels of total CK, CK-BB, Glucose, total protein, WBC counts, and culture were determined in the CSF. The cutoff value for total CK in the CSF was defined as 18 U/L. RESULTS: Three cases (4%) of bacterial meningitis and 11 cases (15%) of aseptic meningitis were confirmed by culture. The sensitivity and specificity of total CK CSF level alone to diagnose bacterial meningitis were found to be 33% and 91% respectively. The positive and negative predictive values were found to be 14% and 98% respectively. On the other hand, the sensitivity and specificity of total CK level in aseptic meningitis were found to be 40% and 98% respectively and the positive and negative predictive values were 86% and 94% respectively. The sensitivity and specificity of total protein and glucose in CSF were also calculated. Streptococcus pneumonia and homophiles influenza were the main types identified in our cases. DISCUSSION AND CONCLUSION: Measuring the total CK level in the CSF may be very useful in diagnosis of meningitis if only combined with other CSF markers. It is not of any much benefit if it is used solely.

The CSF creatine kinase-BB isoenzyme activity in experimental lumbar spinal stenosis model.

STUDY DESIGN: An investigation of creatine kinase (CK)-BB isoenzyme activity in cerebrospinal fluid (CSF) of the rabbits after experimentally induced spinal stenosis. OBJECTIVES: To create a lumbar spinal stenosis (LSS) model at conus medullaris level without laminectomy in rabbits and to investigate the importance of CK-BB isoenzyme activity in CSF associated with electrophysiologic and histopathologic changes in the spinal cord. SUMMARY OF BACKGROUND DATA: LSS is a disorder characterized by leg pain and difficulty of walking. Narrowing of the spinal canal and compression on the spinal cord and nerves are the main features of spinal stenosis. METHODS: Fifteen male albino rabbits were used in this study. A reproducible, subacute LSS model was created in all rabbits, and CSF CK-BB activity was measured above and below the stenosis level. The electrophysiologic evaluation and the histopathologic examination of the conus medullaris were also performed in each rabbit. RESULTS: The CK-BB activity was 71.5% in CSF samples that were obtained below the stenosis. The activity was 44.5% in samples obtained above the stenosis and 43.6% in nonstenotic rabbits. In the electrophysiologic studies, the mean amplitudes were decreased and the latency values were lengthened in all ascending and descending nerve potentials at both sides of the stenosis. The number of the neural cells was decreased and imperception of the nucleolus of neural cells and vacuolar degeneration were observed in the histopathologic examination of conus medullaris. CONCLUSIONS: The activity of CK-BB isoenzyme was increased in CSF of which the circulation was disturbed as a result of neural ischemia, which was accepted in the pathophysiology of LSS.

Relative quantification of proteins in human cerebrospinal fluids by MS/MS using 6-plex isobaric tags.

A new 6-plex isobaric mass tagging technology is presented, and proof of principle studies are carried out using standard protein mixtures and human cerebrospinal fluid (CSF) samples. The Tandem Mass Tags (TMT) comprise a set of structurally identical tags which label peptides on free amino-terminus and epsilon-amino functions of lysine residues. During MS/MS fragmentation, quantification information is obtained through the losses of the reporter ions. After evaluation of the relative quantification with the 6-plex version of the TMT on a model protein mixture at various concentrations, the quantification of proteins in CSF samples was performed using shotgun methods. Human postmortem (PM) CSF was taken as a model of massive brain injury and comparison was carried out with antemortem (AM) CSF. After immunoaffinity depletion, triplicates of AM and PM CSF pooled samples were reduced, alkylated, digested by trypsin, and labeled, respectively, with the six isobaric variants of the TMT (with reporter ions from m/z = 126.1 to 131.1 Th). The samples were pooled and fractionated by SCX chromatography. After RP-LC separation, peptides were identified and quantified by MS/MS analysis with MALDI TOF/TOF and ESI-Q-TOF. The concentration of 78 identified proteins was shown to be clearly increased in PM CSF samples compared to AM. Some of these proteins, like GFAP, protein S100B, and PARK7, have been previously described as brain damage biomarkers, supporting the PM CSF as a valid model of brain insult. ELISA for these proteins confirmed their elevated concentration in PM CSF. This work demonstrates the validity and robustness of the tandem mass tag (TMT) approach for quantitative MS-based proteomics.