Effects of Electrolyte Replacement Protocol Implementation in a Medical Intensive Care Unit.

PURPOSE: To evaluate the effects of electrolyte replacement protocol (ERP) implementation in the medical intensive care unit (MICU) setting. We hypothesized that a protocol would reduce the time of replacement dose administration and increase provider satisfaction with the process of electrolyte replacement. METHODS: This was a retrospective review of electronic medical record data before and after implementation of a standardized ERP in an 18-bed military tertiary care MICU. RESULTS: Median time from abnormal laboratory result to time of documented dose administration for potassium decreased from 180 to 98 minutes ( P < .01), phosphorus decreased from 190 to 135 minutes ( P < .01), calcium decreased from 95 to 61 minutes ( P < .01), and magnesium decreased from 155 to 149 minutes ( P < .01). Overall, there was a significant reduction in time to electrolyte repletion from 146 to 98 minutes ( P < .01) for all electrolytes. Nursing satisfaction for autonomy, timeliness, effectiveness, and the need to seek orders was all improved ( P < .01), and physicians saved 4.4 minutes/patient/day ( P = .04). CONCLUSIONS: Electrolyte replacement protocols can be safely implemented in the MICU and reduce the time from abnormal laboratory result to electrolyte replacement dose administration. They can improve provider satisfaction and reduce physician time with the process of electrolyte replacement.

Proline oxidase promotes tumor cell survival in hypoxic tumor microenvironments.

Proline is a readily released stress substrate that can be metabolized by proline oxidase (POX) to generate either reactive oxygen species (ROS) to induce apoptosis or autophagy or ATP during times of nutrient stress. However, the contribution of proline metabolism to tumorigenesis in hypoxic microenvironments has not been explored. In this study, we investigated the different functions of POX under hypoxia and glucose depletion. We found that hypoxia induced POX expression in cancer cells in vitro and that POX upregulation colocalized with hypoxic tissues in vivo. In addition, the combination of hypoxia and low glucose showed additive effects on POX expression. Similar to conditions of low glucose, hypoxia-mediated POX induction was dependent on AMP-activated protein kinase activation but was independent of HIF-1α and HIF-2α. Under low-glucose and combined low-glucose and hypoxic conditions, proline catabolized by POX was used preferentially for ATP production, whereas under hypoxia, POX mediated autophagic signaling for survival by generating ROS. Although the specific mechanism was different for hypoxia and glucose deprivation, POX consistently contributed to tumor cell survival under these conditions. Together, our findings offer new insights into the metabolic reprogramming of tumor cells present within a hostile microenvironment and suggest that proline metabolism is a potential target for cancer therapeutics.

New evidence for the role of heterochrony in the repeated evolution of cichlid opsin expression.

SUMMARY Lake Malawi (LM) cichlids have undergone heterochronic shifts in the expression of their cone opsin genes, the genes responsible for color vision. These shifts have generated species with short-, middle-, and long-wavelength-sensitive cone photoreceptors and visual systems. However, it is unclear when during the evolution of African cichlids these shifts occurred, or whether they could account for similar short- and middle-wavelength-sensitive profiles among unrelated cichlids in Lake Tanganyika (LT). To address these questions, we surveyed opsin expression in developing fry of two African cichlids, Astatotilapia burtoni from LT and Melanochromis auratus from LM. We found that A. burtoni expresses a series of three different single-cone opsins over the course of development, while M. auratus exhibits variation in the expression of only two. Neither A. burtoni nor M. auratus exhibits much variation in the expression of its double-cone opsins. These patterns reveal that A. burtoni exhibits progressive development in the sensitivity of its single-cone photoreceptors, but direct development in the sensitivity of its double-cone photoreceptors. M. auratus exhibits neotenic development in the sensitivity of both photoreceptor sets. Given the intermediate phylogenetic placement of A. burtoni between cichlids from LT and LM, our results suggest that the ancestor of LM's cichlids exhibited a progressive developmental pattern of opsin expression. These results indicate that the heterochronic shifts which produced the short- and middle-wavelength-sensitive profiles of LM's cichlids occurred recently, and suggest that the presence of similar profiles among LT's cichlids are due to parallel heterochronic shifts.

Intraspecific cone opsin expression variation in the cichlids of Lake Malawi.

The expression of cone opsin genes is a primary determinant of the characteristics of colour vision. Interspecific variation in opsin expression is common in African cichlids. It is correlated with foraging among cichlids from Lake Malawi, and with ambient light environment among cichlids from Lake Victoria. In this study, we tested whether gene expression varied within species such that it might be important in contributing to divergence. We hypothesized that light attenuation with depth would be correlated with predictable changes in gene expression in Lake Malawi, and that this variation would tune visual sensitivities to match the ambient light environment. We observed significant differences in cone opsin expression in three different comparisons among populations of the same species. Higher LWS expression was found in shallow versus deep Copadichromis eucinostomus. In Metriaclima zebra, individuals from Zimbawe Rock expressed significantly more SWS2B than those from Thumbi West Island, although these locales have similar ambient light environments. Finally, Tropheops gracilior from deeper water had significantly more variation in expression than their shallow counterparts. These results support that gene expression varies significantly between populations of the same species. Surprisingly, these results could not be explained by predicted visual performance as models predicted that differential expression patterns did not confer sensitivity advantages at different depths. This suggested that expression variation did not confer a local sensitivity advantage. Therefore, our findings were contrary to a primary requirement of the sensory bias hypothesis. As such, other explanations for intraspecific gene expression variation need to be tested.

Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy.

Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy.