HIV protease inhibitors have become the foundation for combination antiretroviral chemotherapy, have reduced the mortality and morbidity of advanced HIV disease, and are now widely used. Peripheral ...lipodystrophy has been reported among patients receiving protease inhibitors, and hypertriglyceridemia has been reported with ritonavir. Gemfibrozil appeared to reduce serum triglyceride levels effectively in adult male HIV-1-positive patients with protease inhibitor-associated hypertriglyceridemia. This represents a preliminary, uncontrolled observation that should be confirmed with prospective, randomized trials.
In addition to its search for extrasolar planets, the NASA Kepler mission provides exquisite data on stellar oscillations. We report the detections of oscillations in 500 solar-type stars in the ...Kepler field of view, an ensemble that is large enough to allow statistical studies of intrinsic stellar properties (such as mass, radius, and age) and to test theories of stellar evolution. We find that the distribution of observed masses of these stars shows intriguing differences to predictions from models of synthetic stellar populations in the Galaxy.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The negative ion electrostatic accelerator for the neutral beam injector of the International Thermonuclear Experimental Reactor (ITER) is designed to deliver a negative deuterium current of 40 A at ...1 MeV. Inside the accelerator there are several types of interactions that may create secondary particles. The dominating process originates from the single and double stripping of the accelerated negative ion by collision with the residual molecular deuterium gas (≃29% losses). The resulting secondary particles (positive ions, neutrals, and electrons) are accelerated and deflected by the electric and magnetic fields inside the accelerator and may induce more secondaries after a likely impact with the accelerator grids. This chain of reactions is responsible for a non-negligible heat load on the grids and must be understood in detail. In this paper, we will provide a comprehensive summary of the physics involved in the process of secondary emission in a typical ITER-like negative ion electrostatic accelerator together with a precise description of the numerical method and approximations involved. As an example, the multiaperture-multigrid accelerator concept will be discussed.
Full text
Available for:
CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM, UPUK
Beam experiments and calculations aimed at characterising and suppressing the negative deuterium ion beam halo have been performed at IRFM, CEA-Cadarache. Using a “classic” plasma grid, we ...established that no halo (<2%) is present during volume operation (no caesium present in the ion source) at low accelerator pressure (<0.01
Pa). Around 8% beam halo is measured in caesiated operation, at perveance match.
We hypothesized that significant halo originates from negative ions being formed on the metal parts of the plasma grid (as could happen when neutral atoms from the source hit the plasma grid covered with caesium). Based on this hypothesis we tested a new design for the plasma grid, aimed at substantially reducing the halo. The test was successful and the halo was reduced from 8% to 3%.
The single beamlet profiles show an asymmetry that is caused by the presence of the electron suppression magnets in the accelerator.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A helicon-based plasma source is under development and exploration at CEA-IRFM to produce an efficient and dense magnetized plasma column. The final objective of this development is the extraction ...and acceleration of a blade-like negative ion beam in view of future neutral beam injector systems for fusion reactors. The extraction of a negative ion beam from a magnetized plasma column requires a specific topology of the magnetic confinement, which significantly impacts the plasma parameters and wave propagation along the column. The magnetic confinement under investigation is based on water-cooled internal coils implemented under vacuum along the source (column) axis; these coils are supplied with a high DC current (∼1000 A), providing the axial magnetic field (B// ∼ 10 mT). Different diagnostics developed in academic laboratories, such as 3D B-dot probes, optical emission spectroscopy and Langmuir probes, have been used for plasma characterization. The paper reports the experimental results obtained under different operating conditions of this particular magnetic confinement.
OBJECTIVE:
To review the impact that factors such as HIV infection, antiretrovirals, and other commonly used drug therapies have on glucose metabolism in HIV-infected patients.
DATA SOURCES:
...Pertinent literature was identified via a MEDLINE search from 1980 to April 2000 and through secondary sources (abstracts presented at recent scientific meetings, manufacturers' package inserts). The key words used were antiretroviral therapy, HIV infection, insulin resistance, and metabolic abnormalities. All information deemed relevant to evaluate the impact that HIV infection and drug therapy have on glucose metabolism in HIV-infected patients was included.
DATA SYNTHESIS:
The viral burden and stress that are present in HIV-infected patients elicit a complex hormonal and immunologic response that may alter various biochemical pathways, including glucose metabolism. Although rare before the era of potent antiretroviral therapy, insulin resistance has now been described as an important component of the lipodystrophy syndrome. The complex and multifactorial nature of glucose metabolism dysregulation makes management of hyperglycemia or diabetes mellitus challenging in HIV-infected patients. In such a context, a set of recommendations was developed to guide practitioners in assessing, treating, and monitoring hyperglycemia or diabetes mellitus in HIV-infected patients.
CONCLUSIONS:
Alterations of glucose metabolism observed in HIV-infected patients are more frequent since the introduction of potent antiretroviral therapy. Although the etiology of such abnormalities remains unknown, protease inhibitors and, to a lesser extent, nucleoside reverse transcriptase inhibitors are believed to participate in their pathogenic mechanisms. Because of similarities to the pathogenesis of diabetes mellitus, management of antiretroviral-induced hyperglycemia could follow that the recommendations of the American Diabetes Association, with special considerations for monitoring patients with HIV infection. Future studies of altered glucose metabolism in HIV-infected patients should focus on understanding the precise mechanism or causes of this complication so that preventive and therapeutic guidelines can be further evaluated.
Full text
Available for:
NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
We examined the differentiation potential of an adult liver stem cell line (WB F344) in a cardiac microenvironment,
ex vivo
. WB F344 cells were established from a single cloned nonparenchymal ...epithelial cell isolated from a normal male adult rat liver. Genetically modified, WB F344 cells that express β-galactosidase and green fluorescent protein or only β-galactosidase were co-cultured with dissociated rat or mouse neonatal cardiac cells. After 4 to 14 days, WB F344-derived cardiomyocytes expressed cardiac-specific proteins and exhibited myofibrils, sarcomeres, and a nascent sarcoplasmic reticulum. Further, rhythmically beating WB F344-derived cardiomyocytes displayed calcium transients. Fluorescent recovery after photobleaching demonstrated that WB F344-derived cardiomyocytes were coupled with adjacent neonatal cardiomyocytes and other WB F344-derived cardiomyocytes. Fluorescence
in situ
hybridization experiments suggested that fusion between WB F344 cells and neonatal mouse cardiomyocytes did not take place. Collectively, these results support the conclusion that these adult-derived liver stem cells respond to signals generated in a cardiac microenvironment
ex vivo
acquiring a cardiomyocyte phenotype and function. The identification
ex vivo
of microenvironmental signals that appear to cross germ layer and species specificities should prove valuable in understanding the molecular basis of adult stem cell differentiation and phenotypic plasticity.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
4-Monochlorobiphenyl (PCB3) is found in small amounts in commercial PCB mixtures, indoor and outdoor air, and in food. In contrast to highly chlorinated congeners that are more resistant to metabolic ...attack, PCB3 is more readily converted by xenobiotic-metabolizing enzymes to monohydroxy-PCBs and further to dihydroxy-metabolites, which can be oxidized to quinones. Our recent studies demonstrated the initiating action of PCB3 in the livers of male rats. Therefore we hypothesized that PCB3 and/or its metabolite(s) are mutagenic in rat livers in vivo. To investigate the mutagenicity and the types of mutations generated by PCB3, male Fischer 344 BigBlue® rats, transgenic for the lacI gene, were injected intraperitoneally with PCB3 (600 μmol/kg), 4-hydroxy-PCB3 (4-HO-PCB3, 400 μmol/kg), 3-methylcholanthrene (3-MC, 300 μmol/kg, positive control) and corn oil (negative control) once per week, for 4 weeks. Animals were killed 17 days after the last injection and the mutant frequency of the liver lacI gene determined. 3-MC induced a 4-fold increase of the mutant frequency of the lacI gene in the liver. The mutant frequency in PCB3-treated animals was also significantly elevated. In contrast, 4-HO-PCB3 induced a non-significant doubling of the mutant frequency. The mutation spectrum of solvent control mutants was characterized by transitions, whereas in 3-MC-animals, transversion and frameshift mutations predominated. The PCB3-induced mutation spectrum was similar to that of the 3-MC-induced mutants. In contrast, the mutation spectrum of the 4-HO-PCB3 group hardly differed from that of the control animals. This study demonstrates for the first time the mutagenicity of a PCB in vivo.
PDF
