Liver and peripheral blood concentration ratio (L/P) as a marker of postmortem drug redistribution: a literature review

The liver to peripheral blood (L/P) ratio, based upon review of previously published works, was evaluated as a marker of postmortem redistribution (PMR). Literature supported the proposed model that drugs exhibiting an L/P ratio of less than 5 are prone to little or no PMR, while those with an L/P ratio greater than 20–30 have propensity for significant redistribution. Many antidepressants, including both tricyclic antidepressants and selective serotonin re-uptake inhibitors, were markedly differentiated from drugs previously verified to be free from, or exhibit little, PMR. The magnitude of the liver to blood concentrations also appeared to provide an advantage over the conventional central to peripheral blood ratio model of PMR by demonstrating a wide range of values (1.6–97) for interpretation of drugs’ potential for, and variations in, redistribution.     

Transplantation at the Nexus of Behavioral Economics and Health Care Delivery

The transplant surgeon's decision to accept and utilize an organ typically is made within a constrained time window, explicitly cognizant of numerous health‐related risks and under the potential influence of considerable regulatory and institutional pressures. This decision affects the health of two distinct populations, those patients receiving organ transplants and those waiting to receive a transplant; it also influences the physician's life and their institute's productivity. The numerous, at times nonaligned, incentives established by the complex clinical and regulatory environment, have been derived specifically to influence physicians’ behaviors, and though well intended, may lead to responses that are nonoptimal when considering the myriad stakeholders being influenced. This may compromise the quality of care provided to the population at risk, and has potential to influence the physician–patient relationship. A synergistic collaboration between transplant physicians and economists that is focused on this decision environment may help to alleviate these strains. This viewpoint discusses behavioral economic principles and how they might be applied to transplantation. Specifically, the previous medical decision‐making literature on transplantation will be reviewed and a discussion on how a behavioral model of physician decision making can be utilized will be explored. To date this approach has not been integrated into transplantation decision making.     

IL-1 regulates in vivo C-X-C chemokine induction and neutrophil sequestration following endotoxemia

The influx of neutrophils into tissues in response to inflammatory stimuli involves C-X-C chemokines. Interleukin-1 (IL-1) stimulates chemokine production in vitro, but its role in vivo on chemokine production is not as clearly understood. We hypothesized that IL-1 mediates in vivo tissue C-X-C chemokine production induced by systemic lipopolysaccharide (LPS). IL-1 activity was blocked by IL-1 receptor antagonist (IL-1Ra). Rats were injected with Salmonella typhi LPS (0.5 mg/kg) with and without prior administration of IL-1Ra. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein-2 (MIP-2) protein and mRNA levels, tissue neutrophil accumulation, and indices of organ injury were measured. LPS administration resulted in increased plasma, lung, and liver IL-1beta that was decreased by Il-1Ra. LPS also induced an increase in plasma, lung, and liver CINC-1 and MIP-2 protein and mRNA. However, IL-1Ra had no effect on LPS-induced plasma or lung tissue CINC-1 levels. In contrast, IL-1Ra pretreatment did significantly decrease CINC-1 protein expression in the liver (45% decrease) and MIP-2 protein expression in plasma (100% decrease), lung (72% decrease) and liver (100% decrease) compared to LPS- treated controls. Steady-state mRNA levels by Northern blot analysis of both CINC-1 and MIP-2 in lung and liver were similar to the protein findings. Pretreatment with IL-1Ra also resulted in a 47% and 59% decrease in lung and liver neutrophil accumulation, respectively, following LPS. In addition, indices of both lung and liver injury were decreased in animals pretreated with IL-1Ra. In summary, LPS induces IL-1beta and MIP-2 expression in the lung and liver, both of which are IL-1 dependent. Although lung neutrophil accumulation in both lung and liver after LPS is also IL-1 mediated, lung CINC-1 levels were unaffected by IL-1Ra. These data suggest that IL-1 regulates tissue chemokine expression and neutrophil accumulation after LPS.