Arctigenin, a Potent Ingredient of Arctium lappa L., Induces Endothelial Nitric Oxide Synthase and Attenuates Subarachnoid Hemorrhage-Induced Vasospasm through PI3K/Akt Pathway in a Rat Model.

Upregulation of protein kinase B (PKB, also known as Akt) is observed within the cerebral arteries of subarachnoid hemorrhage (SAH) animals. This study is of interest to examine Arctigenin, a potent antioxidant, on endothelial nitric oxide synthase (eNOS) and Akt pathways in a SAH in vitro study. Basilar arteries (BAs) were obtained to examine phosphatidylinositol-3-kinase (PI3K), phospho-PI3K, Akt, phospho-Akt (Western blot) and morphological examination. Endothelins (ETs) and eNOS evaluation (Western blot and immunostaining) were also determined. Arctigenin treatment significantly alleviates disrupted endothelial cells and tortured internal elastic layer observed in the SAH groups (p < 0.01). The reduced eNOS protein and phospho-Akt expression in the SAH groups were relieved by the treatment of Arctigenin (p < 0.01). This result confirmed that Arctigenin might exert dural effects in preventing SAH-induced vasospasm through upregulating eNOS expression via the PI3K/Akt signaling pathway and attenuate endothelins after SAH. Arctigenin shows therapeutic promise in the treatment of cerebral vasospasm following SAH.

Progesterone attenuates experimental subarachnoid hemorrhage-induced vasospasm by upregulation of endothelial nitric oxide synthase via Akt signaling pathway.

Cerebral vasospasm is the leading cause of mortality and morbidity in patients after aneurysmal subarachnoid hemorrhage (SAH). However, the mechanism and adequate treatment of vasospasm are still elusive. In the present study, we evaluate the effect and possible mechanism of progesterone on SAH-induced vasospasm in a two-hemorrhage rodent model of SAH. Progesterone (8 mg/kg) was subcutaneously injected in ovariectomized female Sprague-Dawley rats one hour after SAH induction. The degree of vasospasm was determined by averaging the cross-sectional areas of basilar artery 7 days after first SAH. Expressions of endothelial nitric oxide synthase (eNOS) and phosphorylated Akt (phospho-Akt) in basilar arteries were evaluated. Prior to perfusion fixation, there were no significant differences among the control and treated groups in physiological parameters recorded. Progesterone treatment significantly (P < 0.01) attenuated SAH-induced vasospasm. The SAH-induced suppression of eNOS protein and phospho-Akt were relieved by progesterone treatment. This result further confirmed that progesterone is effective in preventing SAH-induced vasospasm. The beneficial effect of progesterone might be in part related to upregulation of expression of eNOS via Akt signaling pathway after SAH. Progesterone holds therapeutic promise in the treatment of cerebral vasospasm following SAH.

Qualitative analysis of the fluorophosphonate-based chemical probes using the serine hydrolases from mouse liver and poly-3-hydroxybutyrate depolymerase (PhaZ) from Bacillus thuringiensis.

The serine hydrolase family consists of more than 200 members and is one of the largest enzyme families in the human genome. Although up to 50 % of this family remains unannotated, there are increasing evidences that activities of certain serine hydrolases are associated with diseases like cancer neoplasia, invasiveness, etc. By now, several activity-based chemical probes have been developed and are applied to profile the global activity of serine hydrolases in diverse proteomes. In this study, two fluorophosphonate (FP)-based chemical probes were synthesized. Further examination of their abilities to label and pull down serine hydrolases was conducted. In addition, the poly-3-hydroxybutyrate depolymerase (PhaZ) from Bacillus thuringiensis was demonstrated as an appropriate standard serine hydrolase, which can be applied to measure the labeling ability and pull-down efficiency of FP-based probes. Furthermore, mass spectrometry (MS) was used to identify the serine residue that covalently bonded to the active probes. Finally, these FP-based probes were shown capable of establishing the serine hydrolase profiles in diverse mouse tissues; the serine hydrolases pulled down from mouse liver organ were further identified by MS. In summary, our study provides an adequate method to evaluate the reactivity of FP-based probes targeting serine hydrolases.

Hydrocephalus following decompressive craniectomy for malignant middle cerebral artery infarction.

OBJECTIVE: The aim of this study was to evaluate the incidence of hydrocephalus and understand the influence of hydrocephalus on the functional outcome of patients undergoing decompressive craniectomy for malignant middle cerebral artery (MCA) infarction. METHODS: We retrospectively analyzed data of consecutive patients who underwent decompressive craniectomy for malignant MCA infarction. Clinical and imaging data were reviewed to confirm the incidence of hydrocephalus and evaluate the impact of hydrocephalus on functional outcome. The functional outcomes of patients were estimated with the Glasgow outcome score at 1year after stroke onset. RESULTS: Seventeen patients who received decompressive craniectomy for malignant MCA infarction from January 2003 to December 2006 were enrolled. Persistent hydrocephalus developed in 5 patients. The functional outcomes in these patients were uniformly poor regardless of cerebrospinal fluid diversion surgery. Our data revealed that functional outcome was related to patient age and the duration from infarction to craniectomy. CONCLUSIONS: Persistent hydrocephalus is common in patients who receive decompressive craniectomy for malignant MCA infarction. However, the shunt procedure does not significantly improve the patient's clinical condition. The timing of operation in relation to the functional outcome may be critical.

Divergent synthesis of unsymmetrical annulated biheterocyclic compound libraries: benzimidazole linked indolo-benzodiazepines/quinoxaline.

Diversity-oriented synthesis of novel benzimidazole linked indolo-benzodiazepine/quinoxaline ring systems using poly(ethylene glycol) as soluble polymer support is described. Commercially available 4-fluoro-3-nitrobenzoic acid and indoline were utilized for the construction of these annulated biheterocyclic compound libraries having multiple privileged structures with three-point structural diversity. A reagent based diversification approach coupled with the Pictet-Spengler-type condensation was used to construct the tetracyclic indolo-benzodiazepines/quinoxalines on substituted benzimidazoles.

Foramen ovale cannulation guided by intra-operative computed tomography with integrated neuronavigation for the treatment of trigeminal neuralgia.

BACKGROUND: Radiofrequency rhizotomy of the Gasserian ganglion for the treatment of trigeminal neuralgia via percutaneous cannulation of the foramen ovale is facilitated by various localization modalities. In our preliminary study, we described the feasibility of computed tomography (CT) using an integrated neuronavigation system to cannulate the foramen ovale. METHODS: Analysis was performed on 42 consecutive patients who underwent cannulation of the foramen ovale for radiofrequency trigeminal rhizotomy guided by CT using an integrated neuronavigation system. The reproducibility and safety of the neuronavigation-guided procedure were evaluated. RESULTS: Overall, the average dimension of the foramen ovale was 7.1 (1.5) × 4.7 (1.1) mm, and it was successfully cannulated by neuronavigation guidance in 31 (73.8%) patients with a mean cannulation time of 3.1 (0.7) min and an overall procedure time of 68.2 (16.4) min. The remaining 11 (26.2%) patients required subsequent CT guidance for successful puncture of the foramen ovale. CONCLUSIONS: These data demonstrate that neuronavigation-guided cannulation of the foramen ovale can be executed both quickly and safely on an outpatient basis. Additionally, the use of CT with integrated neuronavigation technology provides superior visual-spatial information compared to conventional fluoroscopy, the process of CT scanning, object planning, and neuronavigation-guided intervention can be completed in the same locale, and its application is easy to master and has the potential to enhance procedure tolerability of awake patients.

Thymic squamous cell carcinoma with multiple brain metastases.

Thymic carcinomas are rare epithelial malignancies with marked invasive tendency which can metastasize to distant organs, most commonly to the lung, bone, liver, kidney and extra-thoracic lymph nodes. Central nervous system metastasis is extremely rare and only 45 such cases have been reported in the English literature. We reported a 42-year-old male with thymic squamous cell carcinoma and lung and bones metastases. He underwent thymomectomy and pulmonary lobectomy with concurrent chemo-radiotherapy. Based on the clinical symptoms of severe headache and vomiting and the results of brain computed tomography and magnetic resonance imaging scans, 2 metastatic tumors with a cystic component were diagnosed. We resected the metastatic tumors and the signs of increased intracranial pressure subsided immediately after the operation. The patient underwent continuous chemotherapy systemically and whole brain irradiation for disease control. This presentation suggests that surgical resection with concurrent chemo-radiotherapy is the treatment of choice for thymic carcinomas with brain metastases.

Brain protection by methylprednisolone in rats with spinal cord injury.

Traumatic spinal cord injury is clinically treated by high doses of methylprednisolone. However, the effect of methylprednisolone on the brain in spinal cord injury patients has been little investigated. This experimental study examined Bcl-2 and Bax protein expression and Nissl staining to evaluate an apoptosis-related intracellular signaling event and final neuron death, respectively. Spinal cord injury produced a significant apoptotic change and cell death not only in the spinal cord but also in the supraventricular cortex and hippocampal cornu ammonis 1 region in the rat brains. The treatment of methylprednisolone increased the Bcl-2/Bax ratio and prevented neuron death for 1-7 days after spinal cord injury. These findings suggest that rats with spinal cord injury show ascending brain injury that could be restricted through methylprednisolone management.

Parallel synthesis of 2-sulphanylated bis-benzimidazoles on soluble polymer support.

A well-sustained multistep synthetic protocol has been designed for the PEG-functionalized aromatic acid amide to generate a molecular library of 2-alkylthio bis-benzimidazoles. An attempted synthesis of benzimidazole-2-thiol in dichloromethane has led to S-chloromethyl methyl sulfides, mimicking bacterial enzymatic systems. Regioselective S-alkylation was brought about under controlled conditions using a mild base at room temperature. The polymer-free compounds, 2-sulfanylated bisbenzimidazoles, were obtained in high yields and high purities. Chemical shift changes in proton and carbon NMR have been employed to monitor the progress of the reaction steps and to prove the site of S-alkylation, respectively.

Scaffold-directed traceless synthesis of tetrahydro-beta-carbolinehydantoins.

Pharmacologically interesting tetrahydro-beta-carbolinehydantoins have been prepared through four-step traceless synthesis by a combinatorial approach. Two-arm PEG 1 (MW approximately 4000) was used as a soluble polymer support and reacted with Fmoc-protected L-tryptophane 2 to form bis-ester 3. The resulting polymer-supported amino ester 3 was deprotected, and amino ester 4 underwent Pictet-Spengler reaction with varoius ketones to form tricyclic indoles 5. The nucleophilic piperidine in the tricyclic indole reacted with isocyanate to generate the urea intermediates and simultaneously intramolecular cyclization to release the target compounds 7 from the support in good yields.