Glutamine in critical illness: the time has come, the time is now.

Glutamine (GLN) has been shown to be a key pharmaconutrient in the body's response to stress and injury. It exerts its protective effects via multiple mechanisms, including direct protection of cells and tissue from injury, attenuation inflammation, and preservation of metabolic function. Data support GLN as an ideal pharmacologic intervention to prevent or treat multiple organ dysfunction syndrome after sepsis or other injuries in the intensive care unit population. A large and growing body of clinical data shows that in well-defined critically ill patient groups GLN can be a life-saving intervention.

Discovery and verification of protein differences between Er positive/Her2/neu negative breast tumor tissue and matched adjacent normal breast tissue.

This study was designed to quantify and identify differences in protein levels between tumor and adjacent normal breast tissue from the same breast in 18 women with stage I/II ER positive/Her2/neu negative invasive breast cancer. Eighteen separate difference gel electrophoresis (DIGE) gels were run (1 gel per patient). Relative quantification was based on DIGE analysis. After excision and tryptic digestion, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and peptide mass mapping were used to identify protein spots. Two hundred and forty-three spots were differentially abundant between normal and cancer tissues. Fifty spots were identified: 41 were over abundant and nine were less abundant in cancers than in normal breast tissue. Western blotting provided independent confirmation for three of the most biologically and statistically interesting proteins. All 18 gels were replicated by another technician and 32% of the differentially abundant proteins were verified by the duplicate analysis. Follow-up studies are now examining these proteins as biomarkers in blood.

Effects of pharmaconutrients on cellular dysfunction and the microcirculation in critical illness.

PURPOSE OF REVIEW: A growing body of data has revealed that specific nutrient deficiencies contribute to microvascular and cellular dysfunction following critical illness. Further, targeted administration of these 'pharmaconutrients' may reverse or improve this dysfunction and improve clinical outcome. RECENT FINDINGS: Specific nutrient therapy with glutamine protects cellular metabolism and vascular function via induction of heat shock proteins, which are key proteins found to be deficient following acute illness. Arginine becomes rapidly deficient following trauma and surgery. This leads to significant immunosuppression, which when treated by arginine administration significantly reduces postoperative infection. Omega-3 fatty acids attenuate the inflammatory response and provide for resolution of ongoing inflammatory injury via production of resolvins/protectins. Antioxidants (vitamin C and selenium) and trace elements (zinc) become rapidly depleted in critical illness and replacement appears vital to ensure optimal cellular and microvascular function. Data on targeted metabolic (mitochondrial) therapies (i.e. co-enzyme Q10) show promise to improve myocardial function following cardiac surgery. SUMMARY: These specific nutrients have newly discovered vital mechanistic roles in the optimization of cellular and microcirculatory function in critical illness and injury. A growing body of literature is demonstrating that correction of key nutrient deficiencies via therapeutic administration of these pharmaconutrients can improve clinical outcome in critically ill patients.

Performance-enhancing sports supplements: role in critical care.

Many performance-enhancing supplements and/or drugs are increasing in popularity among professional and amateur athletes alike. Although the uncontrolled use of these agents can pose health risks in the general population, their clearly demonstrated benefits could prove helpful to the critically ill population in whom preservation and restoration of lean body mass and neuromuscular function are crucial. Post-intensive care unit weakness not only impairs post-intensive care unit quality of life but also correlates with intensive care unit mortality. This review covers a number of the agents known to enhance athletic performance, and their possible role in preservation of muscle function and prevention/treatment of post-intensive care unit weakness in critically ill patients. These agents include testosterone analogues, growth hormone, branched chain amino acid, glutamine, arginine, creatine, and beta-hydryoxy-beta-methylbutyrate. Three of the safest and most effective agents in enhancing athletic performance in this group are creatine, branched-chain amino acid, and beta-hydryoxy-beta-methylbutyrate. However, these agents have received very little study in the recovering critically ill patient suffering from post-intensive care unit weakness. More placebo-controlled studies are needed in this area to determine efficacy and optimal dosing. It is very possible that, under the supervision of a physician, many of these agents may prove beneficial in the prevention and treatment of post-intensive care unit weakness.

Genome scan linkage results for longitudinal systolic blood pressure phenotypes in subjects from the Framingham Heart Study.

The relationship between elevated blood pressure and cardiovascular and cerebrovascular disease risk is well accepted. Both systolic and diastolic hypertension are associated with this risk increase, but systolic blood pressure appears to be a more important determinant of cardiovascular risk than diastolic blood pressure. Subjects for this study are derived from the Framingham Heart Study data set. Each subject had five records of clinical data of which systolic blood pressure, age, height, gender, weight, and hypertension treatment were selected to characterize the phenotype in this analysis. We modeled systolic blood pressure as a function of age using a mixed modeling methodology that enabled us to characterize the phenotype for each individual as the individual's deviation from the population average rate of change in systolic blood pressure for each year of age while controlling for gender, body mass index, and hypertension treatment. Significant (p = 0.00002) evidence for linkage was found between this normalized phenotype and a region on chromosome 1. Similar linkage results were obtained when we estimated the phenotype while excluding values obtained during hypertension treatment. The use of linear mixed models to define phenotypes is a methodology that allows for the adjustment of the main factor by covariates. Future work should be done in the area of combining this phenotype estimation directly with the linkage analysis so that the error in estimating the phenotype can be properly incorporated into the genetic analysis, which, at present, assumes that the phenotype is measured (or estimated) without error.