Rush University Medical Center

About: Rush University Medical Center is a healthcare organization based out in Chicago, Illinois, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 13915 authors who have published 29027 publications receiving 1379216 citations. The organization is also known as: Rush Presbyterian St. Luke's Medical Center.

Nitric oxide–mediated chondrocyte cell death requires the generation of additional reactive oxygen species

Abstract: Objective Chondrocyte cell death, possibly related to increased production of endogenous nitric oxide (NO), has been observed during the pathogenesis of osteoarthritis and rheumatoid arthritis. The purpose of this study was to investigate the potential role of NO in causing chondrocyte cell death and to determine the contribution of other reactive oxygen species (ROS). Methods Cell death and cytotoxicity were evaluated in human articular chondrocytes in response to various NO donor compounds with and without agents that stimulate or inhibit the production of additional ROS using both the alginate bead and the monolayer culture systems. Cell death was quantified by a total cell count with fluorescent labels, and cytotoxicity was measured as a function of cellular NADH- and NADPH-dependent dehydrogenase activity. To determine if the redox status of the chondrocyte could influence the observed effect of NO, cells were preincubated for 24 hours in L-cystine– and glutathione (GSH)–depleted media to reduce intracellular GSH levels, a major defense mechanism against oxidative stress. Apoptosis was analyzed with the quantification of histone-associated DNA fragments. Results Treatment of chondrocytes with peroxynitrite (ONOO−), 3-morpholinosydnonimine (SIN-1), and sodium nitroprusside (SNP) resulted in apoptotic cell death at concentrations of 0.5 mM, 1.0 mM, and 0.5 mM, respectively. In contrast, treatment of chondrocytes with diazeniumdiolates (or the “NOC” compounds, NOC-5 and NOC-12) at concentrations as high as 2.0 mM did not cause cell death. Furthermore, NOC-5 and NOC-12, at all concentrations tested (0.125–2.0 mM), could prevent cell death caused by oxidative stress. Selective ROS scavengers protected against cell death caused by either SIN-1 or ONOO−; however, no protection could be afforded against the cytotoxicity of SNP with any of the ROS scavengers tested. Conclusion These results show that NO by itself is not cytotoxic to cultured chondrocytes and can even be protective under certain conditions of oxidative stress. Chondrocyte cell death from NO occurs under conditions where other ROS are also generated.

The Feasibility and Perioperative Complications of Outpatient Knee Arthroplasty

Abstract: The duration of hospitalization and subsequent length of recovery after elective knee arthroplasty have decreased. We hypothesized same-day discharge following either a unicompartmental (UKA) or total knee arthroplasty (TKA) in an unselected group of patients would not result in a higher perioperative complication rate than standard-length hospitalization when following a comprehensive perioperative clinical pathway, including preoperative teaching, regional anesthesia, preemptive oral analgesia, preemptive antiemetics, and a rapid rehabilitation protocol. We prospectively followed 111 of all 121 patients who had primary knee arthroplasty completed by noon and who agreed to be followed prospectively; 25 had UKA and 86 TKA. Of the 111 patients, 104 (94%, 24 with UKA and 80 with TKA) met discharge criteria and were discharged directly to home the day of surgery. Nausea requiring additional treatment before discharge was the most common reason for a delay in discharge. There were four (3.6%) readmissions (all with TKA) and one emergency room visit without readmission (in a patient with a TKA) within the first week after surgery, while there were four subsequent readmissions (3.6%) and one additional emergency room visit without readmission within three months of surgery, all among patients undergoing TKA. There were no deaths, cardiac events, or pulmonary complications during this study. Outpatient knee arthroplasty surgery is feasible in a large percentage of patients yet early readmissions may be decreased with a prolonged hospitalization.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead

Abstract: Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.