Antioxidant defense and oxidative damage vary widely among high-altitude residents.

OBJECTIVES: People living at high altitude experience unavoidable low oxygen levels (hypoxia). While acute hypoxia causes an increase in oxidative stress and damage despite higher antioxidant activity, the consequences of chronic hypoxia are poorly understood. The aim of the present study is to assess antioxidant activity and oxidative damage in high-altitude natives and upward migrants. METHODS: Individuals from two indigenous high-altitude populations (Amhara, n = 39), (Sherpa, n = 34), one multigenerational high-altitude population (Oromo, n = 42), one upward migrant population (Nepali, n = 12), and two low-altitude reference populations (Amhara, n = 29; Oromo, n = 18) provided plasma for measurement of superoxide dismutase (SOD) activity as a marker of antioxidant capacity, and urine for measurement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker of DNA oxidative damage. RESULTS: High-altitude Amhara and Sherpa had the highest SOD activity, while highland Oromo and Nepalis had the lowest among high-altitude populations. High-altitude Amhara had the lowest DNA damage, Sherpa intermediate levels, and high-altitude Oromo had the highest. CONCLUSIONS: High-altitude residence alone does not associate with high antioxidant defenses; residence length appears to be influential. The single-generation upward migrant sample had the lowest defense and nearly the highest DNA damage. The two high-altitude resident samples with millennia of residence had higher defenses than the two with multiple or single generations of residence.

Septic transfusion reactions during blood transfusion via indwelling central venous catheters.

BACKGROUND: Transfusion of blood products requires a vascular port. Use of an indwelling central venous catheter (CVC) provides this port readily and safely in general; however, potential risks require assessment. STUDY DESIGN AND METHODS: The objective was to examine septic reactions to blood transfusions performed via CVCs owing to subclinical microbial catheter colonization. All transfusion reactions that occurred from 2007 to 2011 at The University of Texas MD Anderson Cancer Center were analyzed and correlated with microbiology culture results. Data on the reactions, including vascular access via a catheter or peripheral venipuncture, were collected prospectively. RESULTS: A total of 999 reactions were reported, with an incidence of two per 1000 transfusion events. A total of 738 reactions occurred in 642 patients during transfusion through a CVC. Among them, 606 reactions occurred in patients that had cultures of blood samples drawn within 7 days before or after reaction. Sixty of these (9.9%) had at least one significant microorganism isolated from their catheters and/or peripheral blood. The blood culture results and timing suggested that these patients likely had catheter-related bloodstream infections caused by transfusion through a CVC with subclinical microbial colonization. Fever and chills occurred in 35 of these patients (58%), which resembled febrile nonhemolytic transfusion reactions. Culture results of the transfused blood products, although not performed in all cases, were mostly negative in these CVC-related reactions. CONCLUSION: Blood transfusion through an indwelling CVC may lead to septic reaction owing to subclinical microbial colonization. This risk should be considered before transfusion and during investigation of transfusion reactions.

Therapeutic plasma exchange in liver failure.

The multi-organ failure syndrome associated with acute and acute-on-chronic liver failure (ACLF) is thought to be mediated by overwhelming systemic inflammation triggered by both microbial and non-microbial factors. Therapeutic plasma exchange (TPE) has been proven to be an efficacious therapy in autoimmune conditions and altered immunity, with more recent data supporting its use in the management of liver failure. Few therapies have been shown to improve survival in critically ill patients with liver failure who are not expected to survive until liver transplantation (LT), who are ineligible for LT or who have no access to LT. TPE has been shown to reduce the levels of inflammatory cytokines, modulate adaptive immunity with the potential to lessen the susceptibility to infections, and reduce the levels of albumin-bound and water-bound toxins in liver failure. In patients with acute liver failure, high volume TPE has been shown to reduce the vasopressor requirement and improve survival, particularly in patients not eligible for LT. Standard volume TPE has also been shown to reduce mortality in certain sub-populations of patients with ACLF. TPE may be most favorably employed as a bridge to LT in patients with ACLF. In this review, we discuss the efficacy and technical considerations of TPE in both acute and acute-on-chronic liver failure.

Detrimental effects of environmental tobacco smoke in relation to asthma severity.

BACKGROUND: Environmental tobacco smoke (ETS) has adverse effects on the health of asthmatics, however the harmful consequences of ETS in relation to asthma severity are unknown. METHODS: In a multicenter study of severe asthma, we assessed the impact of ETS exposure on morbidity, health care utilization and lung functions; and activity of systemic superoxide dismutase (SOD), a potential oxidative target of ETS that is negatively associated with asthma severity. FINDINGS: From 2002-2006, 654 asthmatics (non-severe 366, severe 288) were enrolled, among whom 109 non-severe and 67 severe asthmatics were routinely exposed to ETS as ascertained by history and validated by urine cotinine levels. ETS-exposure was associated with lower quality of life scores; greater rescue inhaler use; lower lung function; greater bronchodilator responsiveness; and greater risk for emergency room visits, hospitalization and intensive care unit admission. ETS-exposure was associated with lower levels of serum SOD activity, particularly in asthmatic women of African heritage. INTERPRETATION: ETS-exposure of asthmatic individuals is associated with worse lung function, higher acuity of exacerbations, more health care utilization, and greater bronchial hyperreactivity. The association of diminished systemic SOD activity to ETS exposure provides for the first time a specific oxidant mechanism by which ETS may adversely affect patients with asthma.

Correlation of systemic superoxide dismutase deficiency to airflow obstruction in asthma.

RATIONALE: Increased oxidative stress and decreased superoxide dismutase (SOD) activity in the asthmatic airway are correlated to airflow limitation and hyperreactivity. We hypothesized that asthmatic individuals with higher levels of oxidative stress may have greater loss of SOD activity, which would be reflected systemically in loss of circulating SOD activity and clinically by development of severe asthma and/or worsening airflow limitation. METHODS: To investigate this, serum SOD activity and proteins, the glutathione peroxidase/glutathione antioxidant system, and oxidatively modified amino acids were measured in subjects with asthma and healthy control subjects. RESULTS: SOD activity, but not Mn-SOD or Cu,Zn-SOD protein, was lower in asthmatic serum as compared with control, and activity loss was significantly related to airflow limitation. Further, serum SOD activity demonstrated an inverse correlation with circulating levels of 3-bromotyrosine, a posttranslational modification of proteins produced by the eosinophil peroxidase system of eosinophils. Exposure of purified Cu,Zn-SOD to physiologically relevant levels of eosinophil peroxidase-generated reactive brominating species, reactive nitrogen species, or tyrosyl radicals in vitro confirmed that eosinophil-derived oxidative pathways promote enzyme inactivation. CONCLUSION: These findings are consistent with greater oxidant stress in asthma leading to greater inactivation of SOD, which likely amplifies inflammation and progressive airflow obstruction.