Maintaining PGC-1α expression following pressure overload-induced cardiac hypertrophy preserves angiogenesis but not contractile or mitochondrial function.

During pathological hypertrophy, peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) is repressed in concert with reduced mitochondrial oxidative capacity and fatty acid oxidation (FAO). We therefore sought to determine if maintaining or increasing PGC-1α levels in the context of pressure overload hypertrophy (POH) would preserve mitochondrial function and prevent contractile dysfunction. Pathological cardiac hypertrophy was induced using 4 wk of transverse aortic constriction (TAC) in mice overexpressing the human PGC-1α genomic locus via a bacterial artificial chromosome (TG) and nontransgenic controls (Cont). PGC-1α levels were increased by 40% in TG mice and were sustained following TAC. Although TAC-induced repression of FAO genes and oxidative phosphorylation (oxphos) genes was prevented in TG mice, mitochondrial function and ATP synthesis were equivalently impaired in Cont and TG mice after TAC. Contractile function was also equally impaired in Cont and TG mice following TAC, as demonstrated by decreased +dP/dt and ejection fraction and increased left ventricular developed pressure and end diastolic pressure. Conversely, capillary density was preserved, in concert with increased VEGF expression, while apoptosis and fibrosis were reduced in TG relative to Cont mice after TAC. Hence, sustaining physiological levels of PGC-1α expression following POH, while preserving myocardial vascularity, does not prevent mitochondrial and contractile dysfunction.

Ultrastructural effects of diabetes in the right atrium cardiomyocytes of elderly Wistar rats.

The present study aimed to evaluate the effects of diabetes on quantitative parameters of right atrial cardiomyocytes of elderly rats. Wistar rats (14 months of age) were divided into two groups: streptozotocin-diabetic rats (DG) and control rats (CG). The groups were sacrificed at 16 months. Ultrafine sections of the right atrium were analyzed by electron microscopy. In elderly diabetic animals, histograms of the frequency distribution of natriuretic peptides according to their size showed increased number of small and medium peptides in relation to large peptides, which increased its numerical density leading to a decrease in the mean diameter of both natriuretic peptides. However, elderly diabetic animals remained normotensive. No significant difference was observed between the groups for the volume density of mitochondria, endoplasmic reticulum, and Golgi apparatus. In conclusion, elderly diabetic rats showed increased functional activity of atrial cardiomyocytes with greater production of natriuretic peptides in association with a quantitative maintenance of cytoplasmic components.

Assimilation and transport of organic bound tritium in an irrigated pine forest.

The speciation of radioactive tritium (T) in a naturally-established subtropical loblolly pine forest that has been irrigated with highly-contaminated pond water for the last 20 years is reported. This irrigation project was created to limit the underground transport of a tritium-rich plume which also contains low levels of toxic organics, metals and radionuclides such as carbon-14 (14C) from a nearby low-level waste burial ground. The levels of tritiated water (HTO) in the wood cores were not influenced by recent irrigation activities. However, the tritium levels in the last 20 years of tree growth were more than 3-fold higher than that of tritium in the older growth. This was due to recent irrigation with organic-bound tritium (OBT)-rich water and subsequent accumulation of high levels tritium as OBT relative to tissue HTO. High levels of pond irrigation water OBT resulted from biogenic processes that converted HTO to OBT. Data for 14C that were acquired for some of the forest materials indicated that the processes controlling the movement and accumulation of 14C in this system are somewhat different than that of tritium. Spectroscopic characterization of tree core tissue of <20 years in age found no explanation for the unusually wide dark growth rings. It was concluded that the trees were over-irrigated based on results from other published studies with wood from severely-flooded areas. Although HTO is indeed toxic to biota, OBT represents a relatively greater hazard to biota because it can be bioaccumulated and retained for long periods of time in living tissues.

Influence of chromium-enriched yeast on blood glucose and insulin variables, blood lipids, and markers of oxidative stress in subjects with type 2 diabetes mellitus.

The aim of this study was to determine the effect of chromium (Cr)- enriched yeast on blood glucose and insulin variables, blood lipids, and blood markers of oxidative stress in persons with type 2 diabetes mellitus (median duration: 3.0 yr). Thirty-six subjects (9 men, 27 women; mean age: 61.3 yr; mean body mass index: 34.33 kg/m2) were supplemented with 400 microg Cr/d as Cr-enriched yeast (n = 19) or placebo (n = 17) for 12 wk in a randomized, double-blind study. The most interesting results were obtained by comparison of the change in the placebo group to the change in the Cr group. The Cr group showed a significantly greater increase in serum Cr compared to the placebo group (p < 0.05). Supplementation with Cr-enriched yeast was associated with a significant decrease in fasting serum glucose compared to placebo (p < 0.01). Blood markers of oxidative stress glutathione peroxidase activity and levels of reduced glutathione were essentially unchanged in the Cr group after 12 wk, but decreased significantly in the placebo group (p < 0.05, p < 0.01, respectively). Serum HbA1c and glycated protein (fructosamine) were essentially unchanged in the Cr group, whereas HbA1c tended to increase in the placebo group (from 6.94% to 7.11%). Fasting serum insulin decreased in both groups, with a greater tendency in the Cr group (-16.5% vs -9.5%). These data suggest that supplementation of well-controlled type 2 diabetics with Cr-enriched yeast is safe and can result in improvements in blood glucose variables and oxidative stress.

Infectivity of a Scottish isolate of Piscirickettsia salmonis for Atlantic salmon Salmo salar and immune response of salmon to this agent.

A Scottish isolate of Piscirickettsia salmonis (SCO-95A), previously shown by intraperitoneal injection to have a lethal dose (LD50) of < 2 x 10(3) infectious rickettsial units, was tested for virulence by bath challenge, surface application to the skin, or dorsal median sinus injection. Atlantic salmon Salmo salar post-smolts were used in all experiments, and exposure to 1 x 10(5) tissue culture infective doses (TCID) of P. salmonis ml(-1) for 1 h in a bath challenge resulted in only 1 mortality, 18 d later, in 10 exposed fish. Application of 2.5 x 10(6) TCID of P. salmonis SCO-95A to paper discs on the skin failed to induce any mortalities within 42 d. Intraperitoneally, fish were administered vaccines containing 10(9) heat-inactivated (100 degrees C, 30 min) or 10(9) formalin-inactivated P. salmonis SCO-95A in adjuvant, with a control group receiving phosphate-buffered saline (PBS) in adjuvant. After an induction period of over 6 mo fish were challenged by injection of P. salmonis into the dorsal median sinus. Mortalities in the control group reached 81.8% and the heat-inactivated and formalin-inactivated vaccines gave significant protection from P. salmonis, with relative percentage survivals of 70.7 and 49.6%, respectively. The nature of the protective antigen is unknown, but could be lipopolysaccharide or a heat-stable outer membrane protein. Fish that survived a dorsal median sinus challenge of P. salmonis or were cohabitants showed a strong immune response to P. salmonis.

Serum coenzyme Q10 concentrations in healthy men supplemented with 30 mg or 100 mg coenzyme Q10 for two months in a randomised controlled study.

Serum coenzyme Q10 (Q10) concentrations were evaluated in healthy male volunteers supplemented with 30 mg or 100 mg Q10 or placebo as a single daily dose for two months in a randomised, double-blind, placebo-controlled study. Median baseline serum Q10 concentration in 99 men was 1.26 mg/l (10%, 90% fractiles: 0.82, 1.83). Baseline serum Q10 concentration did not depend on age, while borderline significant positive associations were found for body weight and smoking 1-10 cigarettes/d. Supplementation with 30 mg or 100 mg Q10 resulted in median increases in serum Q10 concentration of 0.55 mg/l and 1.36 mg/l, respectively, compared with a median decrease of 0.23 mg/l with placebo. The changes in the Q10 groups were significantly different from that in the placebo group, and the increase in the 100 mg Q10 group was significantly greater than that in the 30 mg Q10 group. The change in serum Q10 concentration in the Q10 groups did not depend on baseline serum Q10 concentration, age, or body weight.

Plutonium oxidation and subsequent reduction by Mn(IV) minerals in Yucca Mountain tuff.

Plutonium oxidation state distribution on Yucca Mountain tuff and synthetic pyrolusite (beta-MnO2) suspensions was measured using synchrotron X-ray micro-spectroscopy and microimaging techniques as well as ultrafiltration/solventextraction techniques. Plutonium sorbed to the tuff was preferentially associated with manganese oxides. For both Yucca Mountain tuff and synthetic pyrolusite, Pu(IV) or Pu(V) was initially oxidized to more mobile Pu(V/VI), but over time, the less mobile Pu(IV) became the predominant oxidation state of the sorbed Pu. The observed stability of Pu(IV) on oxidizing surfaces (e.g., pyrolusite), is proposed to be due to the formation of a stable hydrolyzed Pu(IV) surface species. These findings have important implications in estimating the risk associated with the geological burial of radiological waste in areas containing Mn-bearing minerals, such as at the Yucca Mountain or the Hanford Sites, because plutonium will be predominantly in a much less mobile oxidation state (i.e., Pu(IV)) than previously suggested (i.e., Pu(V/VI).

Localization and speciation of chromium in subterranean clover using XRF, XANES, and EPR spectroscopy.

Optimization of phytoremediation and assessment of potential health hazards from metals in the environment requires an understanding of absorption, localization, and transport of the target metal by plants. The objectives of this study were to localize Cr and determine the oxidation state and possible complexation mode of Cr in intact plant tissue by means of XANES, synchrotron XRF microprobe spectroscopy, and EPR spectroscopy. Subterranean clover (Trifolium brachycalycinum) was grown hydroponically with Cr(VI) (0.04-2.0 mmol L(-1)) and compared with plants grown without Cr and with inorganic Cr(III) and various Cr(III)-organic sources. The uptake, translocation, and form of Cr in the plant were dependent on the form and concentration of supplied Cr. Chromium was found predominately in the +3 oxidation state, regardless of the Cr source supplied to the plant, though at high Cr(VI) treatment concentrations, Cr(VI) and Cr(V) were also observed. At low Cr(VI) concentrations, the plant effectively reduced the toxic Cr(VI) to less toxic Cr(III), which was observed both as a Cr(III) hydroxide phase at the roots and as a Cr(III)-organic complex in the roots and shoots. At low Cr(VI) treatment concentrations, Cr in the leaves was observed predominately around the leaf margins, while at higher concentrations Cr was accumulated at leaf veins.