Transitions of care from the womb to the world: Implementation of inpatient neonatal med rec.

BACKGROUND: Medication use during pregnancy is common. Safety of fetal medication exposures is an important consideration for pregnancy and for pharmacologic management and care of newborns. OBJECTIVES: The objective of this study was to describe the impact of implementing a neonatal medication reconciliation service at an acute-care hospital. PRACTICE DESCRIPTION: A neonatal medication reconciliation process was implemented at the University of New Mexico Hospital, a level 4 maternity center in a 500-bed academic medical center. Pharmacy personnel identified inpatient pregnant and postpartum patients who required medication reconciliation. In addition to performing maternal medication reconciliation, clinically significant medication exposures that occurred during pregnancy were recorded for neonates. PRACTICE INNOVATION: Our neonatal medication reconciliation process evaluated prenatal "medication use" via a maternal medication history. We considered our medication reconciliation to be occurring during a "transition" from in utero to being born, which, to the best of our knowledge, has not been commonly reported as a transition of care in which pharmacists may play a role. EVALUATION METHODS: We conducted a retrospective descriptive chart review of patients who had both maternal and neonatal medication reconciliation services performed. We collected demographics, comorbidities, medications, and clinically significant exposures from the medication reconciliation note. RESULTS: A total of 384 charts were included in the final analysis. Of these, 167 medication reconciliations (43.5%) identified at least one medication history problem and 97 medication histories (25.3%) identified at least one potentially clinically significant neonatal medication exposure. PRACTICE IMPLICATIONS: Although several limitations exist, a neonatal medication reconciliation process can be implemented in any inpatient setting with pharmacy staff available to perform and record reconciliation. CONCLUSION: Opportunities for pharmacist involvement in pregnancy, postpartum, and neonatal care are expected to increase. Further research is warranted to more clearly determine the maternal and neonatal benefits of this medication reconciliation process and to link fetal exposures to outcomes.

The role of visfatin and resistin in an in vitro model of obesity-induced invasive liver cancer.

Obesity is associated with the development of liver disease and its progression to hepatocellular carcinoma. This link may be attributed to adipocytokines such as visfatin and resistin which have been shown to promote liver cancer incidence and progression. Studies have yet to determine the role of visfatin and resistin in liver cancer, specifically in the context of obesity. The objective of this study was to investigate the effect of neutralizing visfatin and resistin in obese (OB) or normal weight (NW) sera to determine the contribution of these proteins in obesity-induced invasive liver cancer. Sera from OB or NW males was used to determine the efficacy of neutralizing visfatin and resistin to reduce the obesity-induced liver cancer phenotype. HepG2 and SNU-449 cells were exposed to OB and NW sera ± antibodies for visfatin or resistin. The neutralizing antibodies differentially suppressed invasion, reactive oxygen species production, and matrix metalloproteinase-9 secretion. These changes corresponded with a decrease in phosphorylated extracellular signal-regulated kinases and protein kinase B in HepG2 cells, but differences were not observed in CAP1 or ß-catenin. In conclusion, visfatin and resistin have differential roles in obesity-associated liver cancer and may be potential targets to reverse the impact of obesity on liver cancer progression.

The differential role of resistin on invasive liver cancer cells.

OBJECTIVES: To determine whether inhibition of kinase signaling will suppress resistin-induced liver cancer progression. Resistin is located in monocytes and macrophages of adipose tissue. This adipocytokine is an important link between obesity, inflammation, insulin resistance, and cancer risk. Pathways that resistin is known to be involved include but are not limited to mitogen-activated protein kinases (MAPKs) and extracellular signal-regulated kinases (ERK). The ERK pathway promotes cellular proliferation, migration, survival of cancer cells, and tumor progression. The Akt pathway is known to be up-regulated in many cancers including liver cancer. METHODS: Using an in vitro model, HepG2 and SNU-449 liver cancer cells were exposed to resistin ± ERK, Akt, or both inhibitors. The following physiological parameters were assessed: cellular proliferation, ROS, lipogenesis, invasion, MMP, and lactate dehydrogenase activity. RESULTS: The inhibition of kinase signaling suppressed resistin-induced invasion and lactate dehydrogenase in both cell lines. In addition, in SNU-449 cells, resistin increased proliferation, ROS, and MMP-9 activity. Inhibition of PI3K and ERK decreased phosphorylated Akt and ERK, and pyruvate dehydrogenase. CONCLUSIONS: In this study, we describe the effect of Akt and ERK inhibitors to determine if inhibition suppresses resistin-induced liver cancer progression. Resistin promotes cellular proliferation, ROS, MMP, invasion and LDH activity in SNU-449 liver cancer cells which is differentially mediated by Akt and ERK signaling pathways.

Inhibition of PI3K/Akt and ERK signaling decreases visfatin-induced invasion in liver cancer cells.

OBJECTIVES: Visfatin is found in adipose tissue and is referred to as nicotinamide phosphoribosyltransferase (Nampt). Visfatin has anti-apoptotic, proliferative, and metastatic properties and may mediate its effects via ERK and PI3K/Akt signaling. Studies have yet to determine whether inhibition of kinase signaling will suppress visfatin-induced liver cancer. The purpose of this study was to determine which signaling pathways visfatin may promote liver cancer progression. METHODS: HepG2 and SNU-449 liver cancer cells were exposed to visfatin with or without ERK or PI3K/Akt inhibitor, or both inhibitors combined. These processes that were assessed: proliferation, reactive oxygen species (ROS), lipogenesis, invasion, and matrix metalloproteinase (MMP). RESULTS: Inhibition of PI3K/Akt and combination of inhibitors suppressed visfatin-induced viability. ERK inhibition in HepG2 cells decreased visfatin-induced proliferation. ERK inhibitor alone or in combination with PI3K inhibitors effectively suppressed MMP-9 secretion and invasion in liver cancer cells. PI3K and ERK inhibition and PI3K inhibition alone blocked visfatin's ROS production in SNU-449 cells. These results corresponded with a decrease in phosphorylated Akt and ERK, ß-catenin, and fatty acid synthase. CONCLUSIONS: Akt and ERK inhibition differentially regulated physiological changes in liver cancer cells. Inhibition of Akt and ERK signaling pathways suppressed visfatin-induced invasion, viability, MMP-9 activation, and ROS production.

Characterizing the differential physiological effects of adipocytokines visfatin and resistin in liver cancer cells.

Background Obesity, a major public health concern, increases the risk of developing liver cancer which is the leading cause of cancer-related deaths worldwide. Obesity is associated with increased adiposity and macrophage infiltration both of which promote secretion of adipokines and cytokines in the tumor microenvironment. Specifically, visfatin and resistin have been detected at higher levels in the serum of obese individuals and liver tumors. However, the contribution of these adipocytokines in the progression of liver cancer remains unclear. Materials and methods The objective of this study was to characterize the effects of visfatin and resistin on HepG2, SNU-449 and HuH7 liver cancer cells. Cells exposed to visfatin and resistin were analyzed for fatty acid synthase protein, and phosphorylation of Akt and ERK tumorigenic signaling pathways, cell viability, lipogenesis, reactive oxygen species (ROS), matrix metallopeptidase 9 (MMP-9) enzyme activity and invasion. Results HepG2, SNU-449, and HuH7 liver cancer cells treated with visfatin and resistin increased cell viability, invasion, FASN protein, and Akt and ERK phosphorylation. Visfatin and resistin selectively increased ROS production in HepG2 and SNU-449 cells while there was no statistical difference in HuH7 cells. Visfatin and resistin stimulated lipogenesis in HepG2 cells while visfatin increased lipogenesis in SNU-449 cells, and visfatin nor resistin had an effect on lipogenesis in HuH7 cells. Lastly, visfatin and resistin increased MMP-9 enzyme activity in HepG2 and HuH-7 cells but only visfatin increased MMP-9 activity in SNU-449 cells. Conclusions Future studies are needed to determine if inhibition of ERK and Akt suppresses the visfatin and resistin-induced invasive liver cancer phenotype.