Changes in cerebral hemodynamics in patients with posttraumatic diffuse brain swelling after external intraventricular drainage.

PURPOSE: To investigate the changes of cerebral hemodynamics pre- and post-ventricular drainage in patients with posttraumatic acute diffuse brain swelling. METHODS: Twenty-four cases of traumatic diffuse brain swelling were analyzed retrospectively. Patients in nonsurgical group were treated by medicine therapy. Patients in surgical group were treated by external ventricular drainage plus medicine therapy. The first CT perfusion scan was completed within 4-5 h after trauma and scanned again after 7 days. The changes of perfusion parameters in area-of-interest in two groups were analyzed and compared before and after treatment. RESULTS: Compared with the nonsurgical group, the value of cerebral blood volume, cerebral blood flow and mean transit time in bilateral frontal temporoparietal grey matter, basal ganglia, cerebellum, and brain stem at pre- and post-therapy were increased significantly (p < 0.05) in surgical group, and consequently the prognosis of patients undergoing surgery was also better than that of nonsurgical group. CONCLUSION: External ventricular drainage can improve cerebral perfusion and increase survival quality for the patients with posttraumatic acute diffuse brain swelling.

Controlled decompression for the treatment of severe head injury: a preliminary study.

AIM: Fast direct decompression surgery for treatment of severe head injury often results in intraoperative and postoperative complications. Controlled decompression may help prevent these complications. This preliminary study aims to compare the effects of controlled and conventional decompression in patients with severe head injury. MATERIAL AND METHODS: A total of 128 patients with severe head injury were included. Patients were allocated to receive either controlled decompression surgery (n = 64) or conventional decompressive craniectomy (n = 64). Controlled decompression comprised controlled ventricular drainage and controlled hematoma evacuation. The occurrence of delayed hematoma, acute brain swelling, and postoperative cerebral infarction were recorded. RESULTS: Significantly lower proportion of patients in the controlled decompression group had intraoperative acute brain swelling compared to patients in the decompressive craniectomy group (9.4% vs 26.6%, P = 0.011). Intraoperative acute encephalocele occurred in 3 of 13 patients (23.1%) who had delayed hematoma in the controlled decompression group compared with 11 of 18 patients (61.1%) in the decompressive craniectomy group. There was no significant between group difference in the incidence of delayed hematoma or postoperative cerebral infarction. CONCLUSION: Controlled decompression may reduce or delay intraoperative acute brain swelling by delaying hematoma formation in patients with severe head injury.

Microarray-based analysis of gene regulation by transcription factors and microRNAs in glioma.

Transcription factor (TF) and microRNA (miRNA) are two best characterized gene regulators that have been found to play an important role in gene regulation. However, high throughput screening the interaction relationships between transcription factors, microRNAs, and target genes in gliomas remains rare. Using GSE16666 and GSE13091 datasets downloaded from Gene Expression Omnibus data, we first screened the differentially expressed genes in gliomas. We explored the regulation relationship among TFs, miRNAs and target genes by different algorithms. The underlying molecular mechanisms of these crucial target genes were investigated by Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Our study has developed three regulation relationships between two TFs and three miRNAs, including TP53/hsa-mir-155, TP53/hsa-mir-125b, and KLF2/hsa-mir-126. In addition, we also constructed a regulation network of the target genes by transcription factors and miRNAs. Some of them had been demonstrated to be involved in glioma progression via various pathways. For example, ATP2B2 target gene could be regulated by has-mir-181a to involve in calcium signaling pathway. RB1 could be regulated by has-miR-26a to participate in pathways in cancer. Smad7 could be regulated by has-miR-21 via intracellular TGF-ß signal transduction. We constructed a comprehensive regulatory network which was found to play an important role in gliomas progression.

Overexpression of Golgi phosphoprotein-3 (GOLPH3) in glioblastoma multiforme is associated with worse prognosis.

Golgi phosphoprotein-3 (GOLPH3), an important protein in mammalian target of rapamycin (mTOR) signaling, is overexpressed in and correlates with the pathological grade of glioma. However, the potential correlation between GOLPH3 and clinical outcome in patients with glioblastoma multiforme (GBM) remains unknown. In this study, we examined GOLPH3 expression in GBM by tissue microarray and correlated this measure to patient outcome. GOLPH3 expression in tumor tissue from 97 primary GBM patients was examined by tissue microarray and immunohistochemistry. Potential effects of GOLPH3 on tumor growth were also examined in representative cell lines (U251 and U87) by downregulating GOLPH3 with RNA interference. For this cohort, the median overall survival (OS) was 12 months [95 % confidence interval (CI): 10.31-13.69 months], and the median progression-free survival (PFS) was 10 months (95 % CI: 7.33-12.67 months). Tissue microarray analysis revealed high GOLPH3 expression in 40 patients (40/97, 41.2 %) and low GOLPH3 expression in the remaining 57 patients (57/97, 58.8 %). Log-rank test showed that patients with low GOLPH3 expression had significantly longer median OS (15 versus 10 months in patients with high GOLPH3 expression, p = 0.009) and median PFS (12 versus 7 months, p = 0.015). Univariate and Cox analysis indicated that GOLPH3 was an independent prognostic factor for OS and PFS. In in vitro experiments, GOLPH3 downregulation by small interfering RNA (siRNA) suppressed proliferation and clonogenic growth in cultured cell lines. These findings demonstrate that high GOLPH3 expression is associated with poor outcome of GBM patients.

Endoscopy-assisted cerebral falx incision via unilateral approach for treatment of dissymmetric bilateral frontal contusion.

OBJECTIVE: To investigate the clinical features and treatment strategy of dissymmetric bilateral frontal contusion, and to summarize our experience in treating these patients by minimally invasive surgery. METHODS: Over the past 3 years, we have treated a total of 31 patients with dissymmetric bilateral frontal contusion using endoscopy-assisted unilateral cerebral falx incision. Other 30 patients treated by routine bilateral approaches within the same period were taken as control. RESULTS: Seventeen cases (54.8%) in the unilateral operation group survived and were in good condition, 8 (25.8%) had moderate disability, 4 (12.9%) had severe disability, 1 (3.2%) was in vegetative state, and 1 (3.2%) died. Compared with the control group, the Glasgow Outcome Scale score was not significantly different in the unilateral operation group, but the operation time, blood transfusion volume, the length of hospital stay, the incidences of mental disorder and olfactory nerve injury were greatly reduced in the unilateral operation group. CONCLUSIONS: Endoscopy-assisted unilateral cerebral falx incision can shorten the operation time, reduce surgical trauma and complications in treatment of patients with dissymmetric bilateral frontal contusion. It can obviously diminish the chance of delayed intracerebral hematoma and subsequently minimize the incidences of subfalcial and centrencephalic herniation.

Intracranial pressure monitoring for special patterns of frontal lobe contusions.

OBJECTIVE: To study the effect and indications of intracranial pressure (ICP) monitoring for frontal lobe contusion patients. METHODS: During January 2005-December 2008, 34 cases of frontal lobe contusion received ICP monitoring in our department (monitoring group). Different treatment protocols were adopted according to the results of ICP. Meanwhile 46 cases of same type of head-injured patients who did not undergo ICP monitoring served as control group. RESULTS: We found that ICP elevated dramatically within 24 hours after head injury if the contusions were located in frontal longitudinal dehiscence, bilateral undersurface of frontal lobe or dispersed in bilateral lobe. After half a year follow-up and on the basis of Glasgow Coma Scale assessment, the monitoring group showed better outcome than the control group with good recovery in 24 cases (70.6%) , moderate disability in 7 cases (20.6%), severe disability in 2 (5.88%) and death in 1 (2.94%). The outcome of control group displayed good condition in 25 cases (54.3%), moderate disabilities in 8 (17.4%), severe disability in 7 (15.2%), and death in 6 (13.0%). CONCLUSIONS: Frontal lobe contusions are vulnerable and complex head injuries, especially when the contusions are located in frontal longitudinal dehiscence, bilateral undersurface of frontal lobe or diffused in bilateral lobes. These patients should undergo ICP monitoring regardless of their consciousness status. If ICP elevates over 25 mm Hg, the craniotomy is mandatory and will markedly reduce the mortality and disability of these patients.

Synthesis and antiviral bioactivities of 2-cyano-3-substituted-amino(phenyl) methylphosphonylacrylates (acrylamides) containing alkoxyethyl moieties.

An efficient reaction under microwave irradiation has been developed for the synthesis of a series of novel 2-cyano-3-substituted-amino(phenyl) methylphosphonylacrylates (acrylamides) II. The products obtained in shorter reaction time with moderate yields are fully characterized by elemental analysis, IR, (1)H, (13)C, and (31)P NMR spectral data. The role of introducing various substituents and the effect of incorporating alpha-aminophosphonates with an alkoxyethyl moiety into the parent cyanoacrylate (acrylamide) structure are investigated. Among the studied compounds, both II-17 and II-24 displayed good in vivo curative, protection, and inactivation effects, which were comparable to those of the commercial reference ningnanmycin (inhibitory rates of 58.8, 60.2, 78.9% and 60.0, 58.9, 85.5%, respectively, at 500 mg/L against TMV). To the best of the authors' knowledge, this is the first report on the synthesis and antiviral activity of the title compounds II.

Synthesis and antiviral activities of chiral thiourea derivatives containing an alpha-aminophosphonate moiety.

Starting from benzaldehyde 1, the title compounds 8 were synthesized in six steps. Benzaldehyde 1 was reacted with ammonium hydroxide, and the resulting imine was then treated with dialkyl phosphite 3 to give dialkyl N-(arylmethylene)-1-amino-1-aryl methylphosphonates 4. Phosphonates 4 were then easily hydrolyzed to give dialkyl 1-amino-1-aryl-methylphosphonates 6, which on treatment with triethylamine, carbon disulfide, and phosphorus oxychloride provided 7. Target compounds 8 were then prepared by the reaction of 7 with substituted chiral amine. The structures were clearly verified by spectroscopic data (IR, (1)H, (13)C, and (31)P NMR, and elemental analysis). The bioassay of these compounds revealed them as antivirally active. It was found that title compounds 8g, 8e, 8k, and 8m had the same curative effects of TMV (inhibitory rate = 54.8, 50.5, 50.4, and 50.4%, respectively) as the commercial product Ningnanmycin (56.2%). This would appear to be the first report of the synthesis and antiviral activity of chiral thiourea derivatives containing an alpha-aminophosphonate moiety.

Synthesis and antiviral activities of pyrazole derivatives containing an oxime moiety.

Target compounds 4a- n were obtained by the reaction of 1-substituted phenyl-3-methyl-5-substituted phenylthio-4-pyrazolaldoximes (3) with chloromethylated heterocyclic compounds (ClCH 2-R 3) under reflux conditions in ethanol. Subsequently, the oxidation of 4a- e with KMnO 4 in HOAc at room temperature afforded eight new compounds, 5a- h. The synthesized compounds were characterized by physical constants, and the structures of the title compounds were confirmed by IR, (1)H NMR, (13)C NMR, and elemental analysis. The bioassay revealed that the compounds possessed antiviral activities. It was found that title compounds 4a and 4g had the same inactivation effects against TMV (EC 50 = 58.7 and 65.3 microg/mL) as the commercial product Ningnanmycin (EC 50 = 52.7 microg/mL). To the best of our knowledge, this is the first report on the antiviral activity of pyrazole derivatives containing an oxime moiety.

Synthesis and antiviral activity of novel pyrazole derivatives containing oxime esters group.

Fourteen title compounds, 1-substituted-5-substitutedphenylthio-4-pyrazolaldoxime ester derivatives 4a-4n, were synthesized from the starting material 1-substitutedphenyl-3-methyl-5-substitutedphenylthio-4-pyrazolaldoximes 3 by treatment with acyl chloride. The synthesized compounds were characterized by physical constants, and the structures of the title compounds were further confirmed by IR, 1H NMR, 13C NMR and elemental analysis. The bioassay results showed that title compounds possessed weak to good anti-TMV bioactivity with 4l showing significant enhancement of disease resistance in tobacco leaves with high affinity for TMV CP.

Simultaneous determination of vancomycin and ceftazidime in cerebrospinal fluid in craniotomy patients by high-performance liquid chromatography.

A simple, accurate and rapid method for simultaneous analysis of vancomycin and ceftazidime in cerebrospinal fluid (CSF), utilizing high-performance liquid chromatography (HPLC), has been developed and thoroughly validated to satisfy strict FDA guidelines for bioanalytical methods. Protein precipitation was used as the sample pretreatment method. In order to increase the accuracy, tinidazole was chosen as the internal standard. Separation was achieved on a Diamonsil C18 column (200 mm x 4.6mm I.D., 5 microm) using a mobile phase composed of acetonitrile and acetate buffer (pH 3.5) (8:92, v/v) at room temperature (25 degrees C), and the detection wavelength was 240 nm. All the validation data, such as accuracy, precision, and inter-day repeatability, were within the required limits. The method was applied to determine vancomycin and ceftazidime concentrations in CSF in five craniotomy patients.

Synthesis and antiviral activities of cyanoacrylate derivatives containing an alpha-aminophosphonate moiety.

Target compounds 8 were obtained by the reaction of alkyl 2-cyano-3,3-dimethylthioacrylate or cyarylamide (7a-7e) and alpha-aminobenzylphosphonate (5a-5e) under reflux condition using ethanol as solvent. Their structures were clearly verified by spectroscopic data (IR and 1H, 13C, and 31P NMR) and elemental analysis. These compounds were shown to be antivirally active in the bioassay. It was found that title compounds 8d and 8e had the same inactivation effect against tobacco mosaic virus (EC 50 = 55.5 and 55.3 microg/mL) as the commercial product ningnanmycin (EC 50 = 50.9 microg/mL). To the best of our knowledge, this is the first report on the synthesis and antiviral activity of cyanoacrylate derivatives containing an alpha-aminophosphonate moiety.

Synthesis and antiviral bioactivities of 2-aryl- or 2-methyl-3-(substituted- benzalamino)-4(3H)-quinazolinone derivatives.

A simple and general method has been developed for the synthesis of various4(3H)-quinazolinone derivatives by the treatment of the appropriate 3-amino-2-aryl-4(3H)-quinazolinone with a substituted benzaldehyde in ethanol. The structures of the compoundswere characterized by elemental analysis, IR, (1)H-NMR and (13)C-NMR spectra. The title 2-aryl- or 2-methyl-3-(substituted-benzalamino)-4(3H)-quinazolinone compounds III-1~III-31 were found to possess moderate to good antiviral activity. Semi-quantitative PCR andReal Time PCR assays were used to ascertain the target of action of compound III-31against TMV. The studies suggest that III-31 possesses antiviral activity due to inductionof up-regulation of PR-1a and PR-5, thereby inhibiting virus proliferation and movementby enhancement of the activity of some defensive enzyme.