BackgroundVincristine-induced peripheral neuropathy is a major dose limiting side effect and thus effective therapeutic strategy is required. In this study, we investigated the antinociceptive effect of memantine and morphine on a vincristine-induced peripheral neuropathy model in rats.MethodsMale Sprague-Dawley rats weighing 220-240 g were used in all experiments. Rats subsequently received daily intraperitoneal injections of either vincristine sulfate (0.1 ml/kg/day) or saline (0.1 ml/kg/day) over 12 days, immediately following behavioral testing. For assessment of mechanical allodynia, mechanical stimuli using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of N-methyl-D-aspartate receptors antagonist (memantine; 2.5, 5, 10 mg/kg intraperitoneal), opioid agonist (morphine; 2.5, 5, 10 mg/kg intraperitoneal) and vehicle (saline) on vicristine-induced neuropathy were evaluated.ResultsMechanical allodynia developed over the course of ten daily injections of vincristine relative to groups receiving saline at the same time. Morphine abolished the reduction in paw withdrawal threshold compared to vehicle and produced dose-responsiveness. Only the highest dose of memantine (10 mg/kg) was able to increase paw withdrawal threshold compared to vehicle.ConclusionsSystemic morphine and memantine have an antinociceptive effect on the vincristine-induced peripheral neuropathy model in rats. These results suggest morphine and memantine may be an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

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This report compiles 3-D finite element analyses performed to evaluate the stability of Strategic Petroleum Reserve (SPR) caverns over multiple leach cycles. When oil is withdrawn from a cavern in salt using freshwater, the cavern enlarges. As a result, the pillar separating caverns in the SPR fields is reduced over time due to usage of the reserve. The enlarged cavern diameters and smaller pillars reduce underground stability. Advances in geomechanics modeling enable the allowable pillar to diameter ratio (P/D) to be defined. Prior to such modeling capabilities, the allowable P/D was established as 1.78 based on some very limited experience in other cavern fields. While appropriate for 1980, the ratio conservatively limits the allowable number of oil drawdowns and hence limits the overall utility and life of the SPR cavern field. Analyses from all four cavern fields are evaluated along with operating experience gained over the past 30 years to define a new P/D for the reserve. A new ratio of 1.0 is recommended. This ratio is applicable only to existing SPR caverns.

Oil leaks were found in wellbores of Caverns 105 and 109 at the Big Hill Strategic Petroleum Reserve site. According to the field observations, two instances of casing damage occurred at the depth of the interbed between the caprock bottom and salt top. A three dimensional finite element model, which contains wellbore element blocks and allows each cavern to be configured individually, is constructed to investigate the wellbore damage mechanism. The model also contains element blocks to represent interface between each lithology and a shear zone to examine the interbed behavior in a realistic manner. The causes of the damaged casing segments are a result of vertical and horizontal movements of the interbed between the caprock and salt dome. The salt top subsides because the volume of caverns below the salt top decrease with time due to salt creep closure, while the caprock subsides at a slower rate because the caprock is thick and stiffer. This discrepancy yields a deformation of the well. The deformed wellbore may fail at some time. An oil leak occurs when the wellbore fails. A possible oil leak date of each well is determined using the equivalent plastic strain failure criterion. A well grading system for a remediation plan is developed based on the predicted leak dates of each wellbore.

Oil leaks were found in wellbores of Caverns 105 and 109 at the Big Hill Strategic Petroleum Reserve site. According to the field observations, two instances of casing damage occurred at the depth of the interbed between the caprock bottom and salt top. A three-dimensional finite element model, which allows each cavern to be configured individually, was constructed to investigate horizontal and vertical displacements in each well as it crosses the various interbeds. The model contains interfaces between each lithology and a shear zone (fault) to examine the interbed behavior in a realistic manner. This analysis results indicate that the casings of Caverns 105 and 109 failed, respectively, from shear stress that exceeded the casing shear strength due to the horizontal movement of the salt top relative to the caprock and tensile stress due to the downward movement of the salt top from the caprock. The wellbores of Caverns 114 and 104, located at the far end of the field and near the fault, respectively, are predicted to fail by shear stress in the near future. The wellbores of inmost Caverns 107 and 108 are predicted to fail by tensile stress in the near future. The salt top subsides because the volumes of caverns in the salt dome decrease with time due to salt creep closure, while the caprock does not subside at the same rate as the salt top because the caprock is thick and stiff. This discrepancy yields deformation of the well.

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The finite-element shock hydrodynamics code ALEGRA has recently been upgraded to include an X-FEM implementation in 2D for simulating impact, sliding, and release between materials in the Eulerian frame. For validation testing purposes, the problem of long-rod penetration in semi-infinite targets is considered in this report, at velocities of 500 to 3000 m/s. We describe testing simulations done using ALEGRA with and without the X-FEM capability, in order to verify its adequacy by showing X-FEM recovers the good results found with the standard ALEGRA formulation. The X-FEM results for depth of penetration differ from previously measured experimental data by less than 2%, and from the standard formulation results by less than 1%. They converge monotonically under mesh refinement at first order. Sensitivities to domain size and rear boundary condition are investigated and shown to be small. Aside from some simulation stability issues, X-FEM is found to produce good results for this classical impact and penetration problem.4