Novel influenza (H1N1) infection in pediatric renal transplant recipients: a single center experience.

In 2009, novel influenza A H1N1 caused significant morbidity and mortality worldwide, particularly in children. Because they are immunocompromised, pediatric transplant recipients are presumed to be at high risk. This study assessed epidemiological characteristics, presenting symptoms, and clinical course among pediatric renal transplant recipients with confirmed H1N1 infection.

Stress-induced cardiovascular reactivity and atherogenesis in adolescents.

Objective: To examine the association between cardiovascular reactivity to a set of psychological stressors and carotid artery intima-media thickness, a marker of subclinical cardiovascular disease in healthy adolescents.

Methods: Participants were 25 boys and 23 girls age 14.2 ± 0.

Lithium-induced membranous glomerulonephropathy in a pediatric patient.

Lithium-induced glomerular toxicity is an infrequent occurrence in pediatric patients. We report a 13-year-old patient presenting with clinical and laboratory evidence of renal insufficiency after long-term lithium use. Biopsy revealed membranous glomerulonephropathy.

Nutritional status assessment before, during, and after long-duration head-down bed rest.

Introduction: Bed rest is a valuable ground-based model for many of the physiological changes that are associated with spaceflight. Nutritional changes during and after 60 or 90 d of head-down bed rest were evaluated.

Methods: A total of 13 subjects (8 men, 5 women; ages 26-54 yr) participated in either 60 or 90 d of bed rest.

Effects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans.

Spaceflight and bed rest models of microgravity have profound effects on physiological systems, including the cardiovascular, musculoskeletal, and immune systems. These effects can be exacerbated by suboptimal nutrient status, and therefore it is critical to monitor nutritional status when evaluating countermeasures to mitigate negative effects of spaceflight. As part of a larger study to investigate the usefulness of artificial gravity as a countermeasure for musculoskeletal and cardiovascular deficits during bed rest, we tested the hypothesis that artificial gravity would have an effect on some aspects of nutritional status.

Body iron stores and oxidative damage in humans increased during and after a 10- to 12-day undersea dive.

The National Aeronautics and Space Administration Extreme Environment Mission Operations (NEEMO) underwater habitat is a useful analogue for spaceflight. However, the increased air pressure in the habitat exposes crewmembers to higher oxygen pressures, which increases their risk for oxidative damage to DNA, proteins, and lipids. Studies from a previous NEEMO mission suggested that DNA oxidation occurs at an increased level, similar to that in smokers and astronauts returning from space.

Energy metabolism in brain cells: effects of elevated ammonia concentrations.

Both neurons and astrocytes have high rates of glucose utilization and oxidative metabolism. Fully 20% of glucose consumption is used for astrocytic production of glutamate and glutamine, which during intense glutamatergic activity leads to an increase in glutamate content, but at steady state is compensated for by an equally intense oxidation of glutamate. The amounts of ammonia used for glutamine synthesis and liberated during glutamine hydrolysis are large, compared to the additional demand for glutamine synthesis in hyperammonemic animals and patients with hepatic encephalopathy.

Nutritional status is altered in the self-neglecting elderly.

Elder self-neglect is the most common form of elder mistreatment. Individuals who cannot provide basic needs for themselves may develop social, functional, and physical deficits. The systematic characterization of self-neglecting individuals is the goal of the Consortium for Research in Elder Self-Neglect of Texas project.

Survival and cell death in cells constitutively unable to synthesize glutathione.

We examined the role of GSH in survival and cell death using GCS-2 cells that are deficient in glutamate cysteine ligase (gamma-glutamyl cysteine synthetase, gammaGCS), an enzyme essential for GSH synthesis. Cells maintained in 2.5 mM GSH have GSH levels that are approximately 2% of wild type and grow indefinitely; however, they express both pro- and anti-apoptotic Bcl-2 family members and have detectable levels of cytoplasmic cytochrome C.

Ammonia effects on pyruvate/lactate production in astrocytes--interaction with glutamate.

Ammonia exerts a multitude of metabolic and non-metabolic effects on brain tissue. In the present communication we have investigated its effect on lactate production rates, pyruvate production rates and pyruvate/lactate ratios in mouse cerebrocortical astrocytes and neurons in primary cultures. No effects were found in neurons.

Malignant vasovagal syndrome?

We present the management of a patient with nasopharyngeal carcinoma with a history of recurrent syncopal attacks diagnosed as malignant vasovagal syndrome. We discuss clinical presentation as well as the resolution of disease symptoms. The importance of metastatic nasopharyngeal malignancy in relation to syncope is discussed.

Formation and urinary excretion of arsenic triglutathione and methylarsenic diglutathione.

Taking advantage of mice deficient in gamma-glutamyl transpeptidase that are unable to metabolize glutathione (GSH), we have identified two previously unrecognized urinary metabolites of arsenite: arsenic triglutathione and methylarsenic diglutathione. Following administration of sodium arsenite to these mice, approximately 60-70% of urinary arsenic is present as one of these GSH conjugates. We did not detect the dimethyl derivative, dimethyl arsenic GSH; however, dimethyl arsenic (DMAV) represented approximately 30% of urinary arsenic.

Oxygen-induced pulmonary injury in gamma-glutamyl transpeptidase-deficient mice.

We used mice with a targeted disruption in g-glutamyl transpeptidase (GGT-deficient mice) to study the role of glutathione (GSH) in protection against oxygen-induced lung injury. These mice had reduced levels of lung GSH and restricted ability to synthesize GSH because of low levels of cysteine. When GGT-deficient mice were exposed to 80% oxygen, they developed diffuse pulmonary injury and died within eight days.

Accumulation of DNA damage in the organs of mice deficient in gamma-glutamyltranspeptidase.

We have used a differential alkaline single cell gel electrophoresis assay of DNA ("omet assay" at pH 13 and 12.3) to evaluate DNA damage as a function of age in mice with an inherited defect in gluthathione (GSH) metabolism. The mice are homozygous null for gamma-glutamyltranspeptidase (GGT), the enzyme responsible for initiating the catabolism of GSH, and paradoxically have reduced levels of GSH and cysteine in many organs.

Reproductive defects in gamma-glutamyl transpeptidase-deficient mice.

Mice deficient in gamma-glutamyl transpeptidase (GGT) are growth retarded as a result of cysteine deficiency secondary to excessive glutathione excretion in urine and display coat color defects and cataracts. Although GGT is widely expressed throughout the mouse reproductive axis, little is known about its role in reproduction. Here, we present an analysis of the reproductive phenotypes of GGT-deficient mice.

Altered gene expression in the liver of gamma-glutamyl transpeptidase-deficient mice.

We used mice deficient in gamma-glutamyl transpeptidase (GGT) to analyze the effects of GGT deficiency and altered thiol levels on gene expression in liver. GGT-deficient mice have markedly reduced levels of glutathione (GSH), cysteine, methionine, and cysteinylglycine in liver. Steady-state RNA levels of the catalytic subunit of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme in GSH synthesis, are elevated 4-fold in these mice, while those for glutathione synthetase (GSH syn) are elevated 2-fold.

The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required for biliary excretion of arsenic.

Worldwide, millions of people are exposed to arsenic in drinking water that exceeds the World Health Organization standard of 10 microg/liter by as much as 50-300-fold, yet little is known about the molecular basis for arsenic excretion. Here we show that transport of arsenic into bile depends on the MRP2/cMOAT transporter and that glutathione is obligatory for such transport. Using reversed phase liquid chromatography/mass spectrometry, we demonstrate that two arsenic-glutathione complexes not previously identified in vivo, arsenic triglutathione and methylarsenic diglutathione, account for most of the arsenic in the bile.

Neuronal-astrocytic and cytosolic-mitochondrial metabolite trafficking during brain activation, hyperammonemia and energy deprivation.

A novel concept is described, according to which both neurons and astrocytes are capable of metabolizing glucose all the way to CO(2) and water, but in addition interact metabolically in a process generating glutamate from glucose, and subsequently, metabolizing excess glutamate to CO(2) and water Hertz, L., Dringen, R., Schousboe, A.

Glutathione synthesis is essential for mouse development but not for cell growth in culture.

Glutathione (GSH) is a major source of reducing equivalents in mammalian cells. To examine the role of GSH synthesis in development and cell growth, we generated mice deficient in GSH by a targeted disruption of the heavy subunit of gamma-glutamylcysteine synthetase (gammaGCS-HS(tm1)), an essential enzyme in GSH synthesis. Embryos homozygous for gammaGCS-HS(tm1) fail to gastrulate, do not form mesoderm, develop distal apoptosis, and die before day 8.

Stimulation of Na+,K+-ATPase activity, increase in potassium uptake, and enhanced production of ouabain-like compounds in ammonia-treated mouse astrocytes.

Active potassium (K+) uptake and Na+,K+-ATPase activity were measured in primary cultures of mouse astrocytes. Both parameters were virtually unaffected by acute ammonia treatment but increased after chronic exposure to pathophysiologically relevant concentrations of ammonia (0.3 or 3 mM) for 1-4 days.

Response from lieberman and colleagues.

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165

Cyclosiloxanes produce fatal liver and lung damage in mice.

To examine the toxicity of cyclosiloxanes (CSs), the predominant low molecular weight cyclic silicones found in breast implants, we injected female CD-1 mice intraperitoneally with different doses of distillate (3.5-35 g/kg body weight) containing cyclosiloxane D3 (hexamethylcyclotrisiloxane; CS-D3), cyclosiloxane D4 (octamethylcyclotetrasiloxane; CS-D4), cyclosiloxane D5 (decamethylcyclopentasiloxane; CS-D5), and cyclosiloxane D6 (dodecamethylcyclohexasiloxane; CS-D6). The distillate was found to be lethal and all the mice injected with 35 g/kg died within 5-8 days.