Australindolones, New Aminopyrimidine Substituted Indolone Alkaloids from an Antarctic Tunicate Synoicum sp.

Five new alkaloids have been isolated from the lipophilic extract of the Antarctic tunicate Synoicum sp. Deep-sea specimens of Synoicum sp. were collected during a 2011 cruise of the R/V Nathanial B. Palmer to the southern Scotia Arc, Antarctica. Crude extracts from the invertebrates obtained during the cruise were screened in a zebrafish-based phenotypic assay. The Synoicum sp. extract induced embryonic dysmorphology characterized by axis truncation, leading to the isolation of aminopyrimidine substituted indolone (1-4) and indole (5-12) alkaloids. While the primary bioactivity tracked with previously reported meridianins A-G (5-11), further investigation resulted in the isolation and characterization of australindolones A-D (1-4) and the previously unreported meridianin H (12).

Identification of Potential Antiseizure Agents in Boswellia sacra using In Vivo Zebrafish and Mouse Epilepsy Models.

The resin of the tree Boswellia sacra Flueck. (synonym: B. carterii; Burseraceae), also known as "frankincense", is a traditional remedy used for central nervous system disorders in East Africa. Here we report the evaluation of its antiseizure activity in zebrafish and mouse epilepsy models to identify novel antiseizure compounds. The resin was extracted by solvents of increasing polarity. The hexane extract demonstrated the strongest antiseizure activity and was therefore subjected to bioactivity-guided isolation, which leaded to the isolation of eight terpene derivatives. A new prenylbicyclogermacrene derivative (2) was isolated along with seven other compounds (1, 3-8). Among them, the triterpene ß-boswellic acid (5) showed the strongest activity and reduced 90% of pentylenetetrazole (PTZ)-induced seizures at 100 µg/mL. In parallel to B. sacra, a commercial extract of Boswellia serrata was also evaluated and showed moderate bioactivity (45% reduction at 30 µg/mL). The extract of B. serrata was subjected to targeted isolation of other boswellic acid derivatives (9-13), which were evaluated for antiseizure activity in comparison with 5. In the whole series, ß-boswellic acid (5) was the most active (60% reduction at 200 µM), and its potency was also confirmed with its purchased standard (S5). Pure nanoparticles of S5 and a commercially formulated extract of B. serrata were tested in a PTZ-kindling mouse seizure model. This notably revealed that the S5 administration reduced seizures by 50% in this mouse model, which was consistent with its detection and quantification in plasma and brain samples. This study and the preclinical evaluation performed indicate that ß-boswellic acid, common to various species of Boswellia, has some potential as an antiseizure agent.

Intraoperative consultation of central nervous system lesions. Frozen section, cytology or both?

OBJECTIVE: Frozen section is the traditional method of assessing central nervous system (CNS) lesions intraoperatively. Our aim is to determine the diagnostic accuracy of frozen section and/or cytological evaluation of CNS lesions in our center. STUDY DESIGN: A total of 157 patients with CNS lesions underwent open surgical biopsy or excision in our center during a period of 2 years (2012-2013). All specimens were studied cytologically; of these specimens, 146 cases were also examined by frozen section. Cytology and frozen section slides were studied separately by two general pathologists who were blind to final diagnoses. The final diagnoses were based on permanent sections and IHC studies. RESULTS: The accuracy rates of frozen section analysis and cytological evaluation were 87% and 86%, respectively. If the two methods were considered together, the accuracy rate improved to about 95%. CONCLUSIONS: Cytological evaluation is an acceptable alternative to frozen section analysis and also a great supplement to the diagnosis of CNS lesions.