Clearance of Subarachnoid Hemorrhage from the Cerebrospinal Fluid in Computational and In Vitro Models.

Subarachnoid hemorrhage (SAH) mostly occurs following the rupture of cerebral aneurysm causing blood to leak into the cranial subarachnoid space (SAS). Hemorrhage volume has been linked to the development of secondary vasospasm. Therefore, eliminating blood contaminants from the cerebrospinal fluid (CSF) space after the initial hemorrhage could improve patient outcomes and prevent the development of vasospasm. A number of clinical trials demonstrate that lumbar drainage effectively clears hemorrhagic debris from the cranial compartment. The benefits of optimal lumbar drainage rate and patient orientation are difficult to determine by trial-and-error in live patients, because of the invasive nature, limited subject availability and ethical considerations. Therefore, there is a lack of consensus about clinical guidelines for the use of continuous lumbar drainage following the ictus of SAH. A realistic bench-top model which reproduces the anatomy and CSF dynamics of the human central nervous system (CNS) was built to experimentally study contaminant clearance scenarios under lumbar drainage. To mimic a hemorrhagic event, porcine blood was injected at the basal cistern level of the bench-top model and the efficacy of lumbar drains was assessed experimentally for different drainage rates and patient orientations. In addition, the efficacy of blood clearance was predicted with a computational fluid dynamics (CFD) model. Bench-top experiments and CFD simulations identify body position and drainage rates as key parameters for effective blood clearance. The study findings suggest the importance of treatment in upright position to maximize contaminant diversion from the cranial CSF compartment. The bench-top CNS model together with the validated CFD predictions of lumbar drainage systems can serve to optimize subject-specific treatment options for SAH patients.

Insect antifeedant and growth-regulating activities of Salannin and other c-seco limonoids from neem oil in relation to Azadirachtin.

The antifeedant and insect growth-regulating activities of salannin, nimbin, and 6-deacetylnimbin, in comparison with azadirachtin-A, have been studied againstSpodoptera litura, Pericallia ricini, andOxya fuscovittata. Salannin deterred feeding, delayed molt by increasing larval duration, caused larval and pupal mortalities, and decreased pupal weights in the two lepidopterans. Salannin also caused molt delays and nymphal mortalities inOxya fuscovittata. The role of salannin and other compounds in conferring bioactivity, along with azadirachtin-A, to neem oil/neem seed extracts is emphasized.

Structure-related insect antifeedant and growth regulating activities of some limonoids.

Insect antifeedant and growth-regulating activities of 22 limonoids (both natural and their derivatives) againstSpodoptera litura were studied to understand the structure-related bioactivities of the limonoids. The C-seco limonoids (azadirachtins A, B, D, H, and I) were the most effective compounds as a group, while the intact limonoids (cedrelone and its derivatives) were the least effective. The cyclohexenone A ring and theα-hydroxy enone group in the B ring appear to be important for antifeedant activity. The presence of a cyclohexenone or 1,2-epoxide in the A ring coupled with anα-hydroxy enone in the B ring correlated well with growth regulatory activity. An acetoxy at C-7 instead ofα-hydroxy enone and perhaps the carbonyl at C-16 increase growth regulatory activity. Absence of 14-15 epoxide may not drastically reduce antifeedant activity and growth regulatory activity.