Does Cellular Metabolism from Primary Fibroblasts and Oxidative Stress in Blood Differ between Mammals and Birds? The (Lack-thereof) Scaling of Oxidative Stress.

As part of mitonuclear communication, retrograde and anterograde signaling helps maintain homeostasis under basal conditions. Basal conditions, however, vary across phylogeny. At the cell-level, some mitonuclear retrograde responses can be quantified by measuring the constitutive components of oxidative stress, the balance between reactive oxygen species (ROS) and antioxidants. ROS are metabolic by-products produced by the mitochondria that can damage macromolecules by structurally altering proteins and inducing mutations in DNA, among other processes. To combat accumulating damage, organisms have evolved endogenous antioxidants and can consume exogenous antioxidants to sequester ROS before they cause cellular damage. ROS are also considered to be regulated through a retrograde signaling cascade from the mitochondria to the nucleus. These cellular pathways may have implications at the whole-animal level as well. For example, birds have higher basal metabolic rates, higher blood glucose concentration, and longer lifespans than similar sized mammals, however, the literature is divergent on whether oxidative stress is higher in birds compared with mammals. Herein, we collected literature values for whole-animal metabolism of birds and mammals. Then, we collected cellular metabolic rate data from primary fibroblast cells isolated from birds and mammals and we collected blood from a phylogenetically diverse group of birds and mammals housed at zoos and measured several parameters of oxidative stress. Additionally, we reviewed the literature on basal-level oxidative stress parameters between mammals and birds. We found that mass-specific metabolic rates were higher in birds compared with mammals. Our laboratory results suggest that cellular basal metabolism, total antioxidant capacity, circulating lipid damage, and catalase activity were significantly lower in birds compared with mammals. We found no body-size correlation on cellular metabolism or oxidative stress. We also found that most oxidative stress parameters significantly correlate with increasing age in mammals, but not in birds; and that correlations with reported maximum lifespans show different results compared with correlations with known aged birds. Our literature review revealed that basal levels of oxidative stress measurements for birds were rare, which made it difficult to draw conclusions.

Alloprimed CD8(+) T cells regulate alloantibody and eliminate alloprimed B cells through perforin- and FasL-dependent mechanisms.

While it is well known that CD4(+) T cells and B cells collaborate for antibody production, our group previously reported that CD8(+) T cells down-regulate alloantibody responses following transplantation. However, the exact mechanism involved in CD8(+) T cell-mediated down-regulation of alloantibody remains unclear. We also reported that alloantibody production is enhanced when either perforin or FasL is deficient in transplant recipients. Here, we report that CD8(+) T cell-deficient transplant recipient mice (high alloantibody producers) exhibit an increased number of primed B cells compared to WT transplant recipients. Furthermore, CD8(+) T cells require FasL, perforin and allospecificity to down-regulate posttransplant alloantibody production. In vivo CD8-mediated clearance of alloprimed B cells was also FasL- and perforin-dependent. In vitro data demonstrated that recipient CD8(+) T cells directly induce apoptosis of alloprimed IgG1(+) B cells in co-culture in an allospecific and MHC class I-dependent fashion. Altogether these data are consistent with the interpretation that CD8(+) T cells down-regulate posttransplant alloantibody production by FasL- and perforin-dependent direct elimination of alloprimed IgG1(+) B cells.

Fast-food consumption and educational test scores in the USA.

BACKGROUND: Children in the USA are experiencing obesity and overweight at epidemic rates. Schools have started to make policy decisions based on a popularly presumed connection between nutrition and academic achievement. This study aimed to determine whether such a relationship exists, and if so, its nature. METHODS: Data from the Food Consumption Questionnaire administered to approximately 12 000 fifth graders as part of the nationally representative Early Childhood Longitudinal Study-Kindergarten Cohort was analysed using regression analysis. The analysis used propensity score matching to examine the relationship between students' reported fast-food consumption and their test scores in reading and mathematics. Propensity score matching attempts to control for a host of background characteristics that might be correlated with both fast-food consumption and test scores. RESULTS: Standard ordinary least squares regression showed that test scores decreased as reported fast-food consumption increased. In the propensity-score-matched analysis, which controlled for 25 student background characteristics, higher-than-average fast-food consumption ('four to six times in the last 7 days' or more) was associated with significantly lower test scores in both reading (-11.15 points or 0.48 SD) and math (-11.13 points or 0.52 SD), even when teacher experience, school poverty level and school urbanicity were also included in the model. CONCLUSIONS: Although this study is preliminary, its results indicate that the relationship between poor nutrition and test scores may in fact be quite negative, strengthening the impetus for schools to consider policies that support students' healthy eating. In order to strengthen these findings and investigate possible mechanisms through which poor nutrition might affect test scores, there is a need for further research.

Treatment of cardiac risk factors in diabetic patients: How well do we follow the guidelines?

BACKGROUND: Diabetic patients are at increased risk for both macrovascular and microvascular disease compared with nondiabetic patients. METHODS: We conducted a prospective observational study to assess the control of multiple predetermined cardiovascular risk factors in 235 treated diabetic patients undergoing elective cardiac catheterization at our institution between December 20, 1997, and February 15, 2000. The following parameters were used to define optimal treatment in these patients: hemoglobin (Hgb) A1c <7%, low-density lipoprotein cholesterol (LDL-c) <100 mg/dL, high-density lipoprotein cholesterol (HDL-c) >/=45 mg/dL for men and >/=55 mg/dL for women, triglyceride (TG) level <200 mg/dL, blood pressure (BP) <130/85 mm Hg, body mass index (BMI) <25, daily aspirin therapy, and current nonsmoking status. The use of b-blockers and angiotensin-converting enzyme inhibitors was also evaluated. RESULTS: The average patient age was 64 +/- 11 years; 155 (65%) were male. One hundred ninety-one (81%) patients had documented coronary artery disease at cardiac catheterization. The mean Hgb A1c level for all diabetic patients was 8.2% +/- 1.6%. Overall, 49 (21%) had an Hgb A1c level <7%. The fasting cholesterol panel for all patients revealed a mean LDL-c level of 103 +/- 41 mg/dL, a mean HDL level of 39 +/- 11 mg/dL, and a mean TG level of 164 +/- 128 mg/dL. One hundred sixteen (52%) patients had an LDL-c <100 mg/dL. Only 32 of 147 (22%) male patients and 14 of 80 (18%) female patients achieved an HDL-c >/=45 mg/dL or >/=55 mg/dL, respectively. One hundred seventy-seven of 232 (76%) patients had a TG level <200 mg/dL. Only 23 of 233 (10%) diabetics were controlled to a BP of <130/85 mm Hg, and 25 (11%) achieved a BMI <25. Only one patient (0.4%) had optimal control of all modifiable risk factors. CONCLUSIONS: These data demonstrate the poor control of numerous cardiovascular risk factors in treated diabetics undergoing elective cardiac catheterization.

In situ imaging of microorganisms in geologic material.

In order to fully delineate the interactions of microorganisms with geological substrates, unequivocal identification of intact microbial cells within geologic samples is required without the disruption of either the rock texture or the relationship of the microorganisms to the mineral fabric. To achieve this objective we developed a protocol that enables the visualization of intact microbial cells in petrographic thin sections, avoids detaching the cells from their host mineral surfaces and avoids microbial contamination during the lapidary process. Propidium iodide and POPO-3, nucleic acid stains that specifically target double-stranded DNA and RNA were utilized for in situ visualization of cells in surface and subsurface basalts from northeastern Idaho. Additionally, examination of samples incubated with acetic acid-UL-14C via phosphor imagining facilitated the in situ visualization of 14C labeled biomass. Biomass observed was low (<10(7) cells/g). These observations indicate that the microbial distribution in these rocks exhibits a high degree of spatial heterogeneity at the sub-centimeter scale.

A prospective randomized trial of prevention measures in patients at high risk for contrast nephropathy: results of the P.R.I.N.C.E. Study. Prevention of Radiocontrast Induced Nephropathy Clinical Evaluation.

OBJECTIVES: This study was done to test the hypothesis that a forced diuresis with maintenance of intravascular volume after contrast exposure would reduce the rate of contrast-induced renal injury. BACKGROUND: We have previously shown a graded relationship with the degree of postprocedure renal failure and the probability of in-hospital death in patients undergoing percutaneous coronary intervention. Earlier studies of singular prevention strategies (atrial natriuretic factor, loop diuretics, dopamine, mannitol) have shown no clear benefit across a spectrum of patients at risk. METHODS: A prospective, randomized, controlled, single-blind trial was conducted where 98 participants were randomized to forced diuresis with intravenous crystalloid, furosemide, mannitol (if pulmonary capillary wedge pressure <20 mm Hg), and low-dose dopamine (n = 43) versus intravenous crystalloid and matching placebos (n = 55). RESULTS: The groups were similar with respect to baseline serum creatinine (2.44+/-0.80 and 2.55+/-0.91 mg/dl), age, weight, diabetic status, left ventricular function, degree of prehydration, contrast volume and ionicity, and extent of peripheral vascular disease. The forced diuresis resulted in higher urine flow rate (163.26+/-54.47 vs. 122.57+/-54.27 ml/h) over the 24 h after contrast exposure (p = 0.001). Two participants in the experimental arm versus five in the control arm required dialysis, with all seven cases having measured flow rates <145 ml/h in the 24 h after the procedure. The mean individual change in serum creatinine at 48 h, the primary end point, was 0.48+/-0.86 versus 0.51+/-0.87, in the experimental and control arms, respectively, p = 0.87. There were no differences in the rates of renal failure across six definitions of renal failure by intent-to-treat analysis. However, in all participants combined, the rise in serum creatinine was related to the degree of induced diuresis after controlling for baseline renal function, r = -0.36, p = 0.005. The rates of renal failure in those with urine flow rates greater than 150 ml/h in the postprocedure period were significantly lower, 8/37 (21.6%) versus 28/61 (45.9%), p = 0.03. CONCLUSIONS: Forced diuresis with intravenous crystalloid, furosemide, and mannitol if hemodynamics permit, beginning at the start of angiography provides a modest benefit against contrast-induced nephropathy provided a high urine flow rate can be achieved.

Validation of a decision support tool for the evaluation of cardiac arrest victims.

BACKGROUND: There is currently no well-accepted model for early and accurate prediction of neurologic and vital outcomes after cardiac arrest. Recent studies indicate that individuals with acute myocardial ischemia as the etiology for the arrest may benefit from early revascularization. HYPOTHESIS: This study was undertaken to examine whether the cardiac arrest score is valid for predicting outcomes upon arrival at the emergency department. METHODS: We previously developed a cardiac arrest score based on time to return of spontaneous circulation, initial systolic blood pressure, and level of neurologic alertness in 127 patients (derivation set). This score was prospectively applied to 62 patients with similar clinical profiles (validation set). Utility of the score was evaluated by the area under the receiver operator characteristic curves (C) for both sets. Consistency was measured by using the alpha statistic applied to the cumulative survival at each ascending level of the score. RESULTS: The derivation and validation sets were similar with respect to baseline characteristics and proportions at each level of score. The survival to discharge was 41.7 and 53.2% for the two sets, respectively. The value of C was 0.89 +/- 0.03 and 0.93 +/- 0.03 for neurologic recovery and 0.81 +/- 0.04 and 0.92 +/- 0.04 for survival to discharge in the two sets, respectively. The level of agreement between the sets across the levels of the score was 0.98 and 0.99 (both p < 0.0001) for the two outcomes. CONCLUSIONS: The cardiac arrest score is a valid decision support tool in the evaluation of cardiac arrest victims. Patients with the most favorable scores may be considered for early angiography and revascularization if myocardial ischemia is the etiology of the arrest.