Parenteral glutamine increases serum heat shock protein 70 in critically ill patients
ABSTRACT Heat shock protein 70 (HSP-70) is protective against cellular and tissue injury. Increased serum HSP-70 levels are associated with decreased mortality in trauma patients. Glutamine (Gln) administration increases serum and tissue HSP-70 expression in experimental models of sepsis. Gln has been safely administered to critically ill patients and can improve clinical outcomes, but the effect of Gln administration on HSP-70 expression in humans is unknown. We examined whether Gln-supplemented parenteral nutrition (PN) increases serum HSP-70 levels in critically ill patients.
Randomized, controlled, double-blind study in surgical intensive care units (SICU) in a university hospital.
29 patients admitted to the SICU and requiring PN for more than 7 days.
Patients received either Gln-PN (containing alanyl-glutamine dipeptide; 0.5 g/kg per day; n=15) or standard Gln-free PN (control-PN) that was iso-nitrogenous to Gln-PN (n=14). Serum HSP-70 concentrations were measured at enrollment and at 7 days. Clinical outcome measures were also determined.
HSP-70 concentrations were unchanged in control-PN subjects from baseline to day 7. In marked contrast, Gln-PN subjects demonstrated significantly higher (3.7-fold) serum HSP-70 concentrations than control subjects. In Gln-PN patients there was a significant correlation between increases in HSP-70 levels over baseline and decrease in ICU length of stay.
Gln-PN significantly increases serum HSP-70 in critically ill patients. The magnitude of HSP-70 enhancement in Gln-treated patients was correlated with improved clinical outcomes. These data indicate the need for larger, randomized trials of the Gln effect on serum and tissue HSP-70 expression in critical illness and relationship to clinical outcomes.
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ABSTRACT: African American (AA) women are nearly twice as likely as non-Hispanic White (NHW) women to develop atherosclerosis associated with cardiovascular disease. Compelling evidence demonstrates that stress-related biomarkers, such as heat shock protein-70 (HSP70), are associated with increased atherosclerosis risk. Yet little is known about how social factors such as perceived discrimination, subjective social status, and socioeconomic status contribute to the levels of these biomarkers in women with atherosclerosis. The aims of this pilot study were to (1) describe perceived everyday discrimination, subjective social status, perceived stress, and HSP70 level in AA and NHW women diagnosed with coronary or carotid artery disease requiring intervention and (2) determine the extent to which perceived discrimination, subjective social status, and perceived stress are associated with HSP70 level, controlling for age, education, and race. The sample for this cross-sectional, descriptive pilot study consisted of 10 AA and 21 NHW women admitted to the hospital for elective percutaneous cardiac intervention or carotid endarterectomy. Participants completed questionnaires measuring psychosocial variables and provided blood samples for analysis of HSP70. Race, age, education, perceived stress, perceived discrimination, and subjective social status significantly (p = .022) explained 34% of the variance in HSP70 levels. However, only subjective social status (p = .031) and AA race (p = .031) were significant independent predictors of HSP70 levels, with lower subjective social status and AA race associated with higher HSP70. Although larger studies are needed to confirm these results, findings imply that race and subjective social status may play an important role in predicting stress biomarker levels.Biological Research for Nursing 06/2013; 16(3). DOI:10.1177/1099800413491422 · 1.34 Impact Factor
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ABSTRACT: Extracellular heat-shock protein 72 (eHsp72) expression during exercise-heat stress is suggested to increase with the level of hyperthermia attained, independent of the rate of heat storage. This study examined the influence of exercise at various intensities to elucidate this relationship, and investigated the association between eHsp72 and eHsp27. Sixteen male subjects cycled to exhaustion at 60% and 75% of maximal oxygen uptake in hot conditions (40°C, 50% RH). Core temperature, heart rate, oxidative stress, and blood lactate and glucose levels were measured to determine the predictor variables associated with eHsp expression. At exhaustion, heart rate exceeded 96% of maximum in both conditions. Core temperature reached 39.7°C in the 60% trial (58.9 min) and 39.0°C in the 75% trial (27.2 min) (P < 0.001). The rate of rise in core temperature was 2.1°C h(-1) greater in the 75% trial than in the 60% trial (P < 0.001). A significant increase and correlation was observed between eHsp72 and eHsp27 concentrations at exhaustion (P < 0.005). eHsp72 was highly correlated with the core temperature attained (60% trial) and the rate of increase in core temperature (75% trial; P < 0.05). However, no common predictor variable was associated with the expression of both eHsps. The similarity in expression of eHsp72 and eHsp27 during moderate- and high-intensity exercise may relate to the duration (i.e., core temperature attained) and intensity (i.e., rate of increase in core temperature) of exercise. Thus, the immuno-inflammatory release of eHsp72 and eHsp27 in response to exercise in the heat may be duration and intensity dependent.Cell Stress and Chaperones 01/2012; 17(3):375-83. DOI:10.1007/s12192-011-0313-3 · 2.54 Impact Factor
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ABSTRACT: The metabolism of critical illness is characterised by a combination of starvation and stress. There is increased production of cortisol, catecholamines, glucagon and growth hormone and increased insulin-like growth factor-binding protein-1. Phagocytic, epithelial and endothelial cells elaborate reactive oxygen and nitrogen species, chemokines, pro-inflammatory cytokines and lipid mediators, and antioxidant depletion ensues. There is hyperglycaemia, hyperinsulinaemia, hyperlactataemia, increased gluconeogenesis and decreased glycogen production. Insulin resistance, particularly in relation to the liver, is marked. The purpose of nutritional support is primarily to save life and secondarily to speed recovery by reducing neuropathy and maintaining muscle mass and function. There is debate about the optimal timing of nutritional support for the patient in the intensive care unit. It is generally agreed that the enteral route is preferable if possible, but the dangers of the parenteral route, a route of feeding that remains important in the context of critical illness, may have been over-emphasised. Control of hyperglycaemia is beneficial, and avoidance of overfeeding is emphasised. Growth hormone is harmful. The refeeding syndrome needs to be considered, although it has been little studied in the context of critical illness. Achieving energy balance may not be necessary in the early stages of critical illness, particularly in patients who are overweight or obese. Protein turnover is increased and N balance is often negative in the face of normal nutrient intake; optimal N intakes are the subject of some debate. Supplementation of particular amino acids able to support or regulate the immune response, such as glutamine, may have a role not only for their potential metabolic effect but also for their potential antioxidant role. Doubt remains in relation to arginine supplementation. High-dose mineral and vitamin antioxidant therapy may have a place.Proceedings of The Nutrition Society 03/2007; 66(1):16-24. DOI:10.1017/S0029665107005253 · 4.94 Impact Factor