Multi-Injection Pharmacokinetics of Meloxicam in Kemp’s Ridley (Lepidochelys kempii) and Green (Chelonia mydas) Sea Turtles after Subcutaneous Administration

The objective of this study was to determine the pharmacokinetics and safety of multiple injections of meloxicam (MLX) administered subcutaneously (SQ) in Kemp’s ridley (Lepidochelys kempii) and green (Chelonia mydas) sea turtles. Based on results from a previously published single-injection study, a multiple-injection regimen was derived for the Kemp’s ridleys, which consisted of administering MLX at a dose of 1 mg/kg SQ every 12 h for 5 days, and for green turtles at a dose of 1 mg/kg SQ every 48 h for three treatments. Six turtles of each species were used for the study, and blood samples were taken at multiple time intervals. The terminal half-life after the last dose for the Kemp’s ridley sea turtles was calculated at 7.18 h, and for the green sea turtles at 23.71 h. Throughout the multiple injections, MLX concentrations remained above 0.57 µg/mL, a concentration targeted in humans for the analgesic and anti-inflammatory effects. No negative side effects or changes to blood parameters evaluated were observed during the study in either species. The results of this study suggest MLX should be administered SQ to Kemp’s ridley sea turtles at a dosage of 1 mg/kg every 12 h and in green sea turtles at a dose of 1 mg/kg every 48 h. The novelty of this work is that it is a multiple-injection study. Multiple injections were administered and produced concentrations that were considered therapeutic in humans, and the turtles did not have any adverse side effects. Furthermore, there were large differences in the pharmacokinetic values between green and Kemp’s ridley sea turtles.

Compositional Modeling of Carbonate Acidizing Processes with CO2 Evolution in Aqueous Environments

Summary Several modeling studies have been conducted in carbonate acidizing, particularly in the area of aqueous environments. Yet, complete understanding of this complex subsurface process remains elusive. Characterizing the effects of evolved CO2, a product of the chemical reaction between carbonates and HCl (hydrochloric acid), has been ignored to date under the assumption that high operating pore pressures keep CO2 completely dissolved in the surrounding solution. However, the presence of CO2 in the porous media of the formation itself changes fluid-flow dynamics throughout the entire system. This paper describes a numerical simulation study to accurately model the physics of carbonate acidizing. A validation of the model is conducted by replicating experiments described in the published literature and by performing laboratory coreflood experiments of carbonate acidizing. The acid efficiency curve and initial pore pressure variations for single-phase experimental studies from the literature is matched by including the effects of evolved CO2 in the model. Two Indiana limestone cores of 6 in. length and 1.5 in. diameter were used to conduct (1) a tracer-injection study with 5 wt% KCl (potassium chloride) solution and (2) an acid-injection study with 15 wt% HCl solution. The experiments were conducted at 72°F, and 1,180 psi pore pressure. The Indiana limestone cores were characterized via computed tomography (CT) scans, and a detailed, accurate porosity profile of each core was used as input to the numerical model. The tracer fluid was used to characterize the porous environment and mechanical dispersion coefficients, and for subsequent calibration of the simulation model. From the conducted single-phase acidizing coreflood experiment, pressure drop values across the core were closely monitored with time to assess acid breakthrough, and the core effluent samples were collected at regular intervals and analyzed to determine the concentrations of calcium chloride (CaCl2) and HCl. CT scans of each core conducted post-acidizing describe its wormhole pattern. These parameters are accurately matched using the simulation model. A high pore pressure of 1,000 psi and above is not sufficient to keep all the evolved CO2 in solution during carbonate acidizing. The presence of CO2 as a separate phase hinders acid efficiency. Up to 24% by volume of pore space is shown to be occupied by the evolved CO2 that exists as a separate phase, and is located ahead of the acid front during the acidizing process, thus competing for flow with the incoming acid. The modeling of CO2 as a component for simulating the acid coreflood played a key role in acquiring a better match with experimental results, with limited dependency on empirical pore-scale parameters. In addition to wormhole propagation, the current model accurately forecasts effluent concentrations collected and quantity of rock dissolved from the acidized porous media. A new approach to accurately predict carbonate acidizing in porous media for an aqueous environment has been presented via compositional modeling using a reservoir simulator. The presented methodology can be incorporated in large field scale reservoir models.

The Effects of Doxorubicin-based Chemotherapy and Omega-3 Supplementation on Mouse Brain Lipids

Chemotherapy-induced cognitive impairment affects ~30% of breast cancer survivors, but the effects on how chemotherapy impacts brain lipids, and how omega-3 polyunsaturated fatty acid supplementation may confer protection, is unknown. Ovariectomized mice were randomized to two rounds of injections of doxorubicin + cyclophosphamide or vehicle after consuming a diet supplemented with 2% or 0% EPA+DHA, and sacrificed 4, 7, and 14 days after the last injection (study 1, n = 120) or sacrificed 10 days after the last injection (study 2, n = 40). Study 1 whole brain samples were extracted and analyzed by UHPLC-MS/MS to quantify specialized pro-resolving mediators (SPMs). Lipidomics analyses were performed on hippocampal extracts from study 2 to determine changes in the brain lipidome. Study 1 results: only resolvin D1 was present in all samples, but no differences in concentration were observed (P > 0.05). Study 2 results: chemotherapy was positively correlated with omega-9 fatty acids, and EPA+DHA supplementation helped to maintain levels of plasmalogens. No statistically significant chemotherapy*diet effect was observed. Results demonstrate a limited role of SPMs in the brain post-chemotherapy, but a significant alteration of hippocampal lipids previously associated with other models of cognitive impairment (i.e., Alzheimer’s and Parkinson’s disease).