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The experimental evidence from the last decade made telomerase a prominent member of a family of moonlighting proteins performing different functions at various cellular loci. However, the study of extratelomeric functions of the catalytic subunit of mammalian telomerase (TERT) is often complicated by the fact that it is sometimes difficult to distinguish them from its role(s) at the chromosomal ends. Here, we present an experimental model for studying the extranuclear function(s) of mammalian telomerase in the yeast Saccharomyces cerevisiae. We demonstrate that the catalytic subunit of mammalian telomerase protects the yeast cells against oxidative stress and affects the stability of the mitochondrial genome. The advantage of using S. cerevisiae to study of mammalian telomerase is that (1) mammalian TERT does not interfere with its yeast counterpart in the maintenance of telomeres, (2) yeast telomerase is not localized in mitochondria and (3) it does not seem to be involved in the protection of cells against oxidative stress and stabilization of mtDNA. Thus, yeast cells can be used as a 'test tube' for reconstitution of mammalian TERT extranuclear function(s).

Some experts believe lapses in protocols for the cleaning and disinfection or sterilization of endoscopes occur more frequently than may be reported in the media. If so, this may increase the potential risk for endoscope cross-contamination. The ECRI Institute, Plymouth Meeting, Pa., called attention to this issue recently by ranking the potential for cross-contamination of endoscopes the No. 1 technology hazard in its third annual report on the subject. But by establishing and executing proper protocols for endoscope reprocessing, hospitals can better manage this risk.

Varying the counter-ion is a highly supportive practice in tackling the problem of poor water-solubility of metal complexes of pharmaceutical importance. As a matter of fact, the relevant structural modification may alter the metabolic pathways and possibly the mode of action of a drug. To prove that this does not take place for one of the lead anticancer metal-based developmental compounds, indazolium trans-[RuCl(4)(1H-indazole)(2)] (KP1019), its reactivity toward human serum proteins was assessed under simulated physiological conditions and compared to that of a much more soluble analogue, sodium trans-[RuCl(4)(1H-indazole)(2)] (KP1339). For such kinetic assaying, capillary electrophoresis (CE) interfaced online with inductively coupled plasma mass spectrometry (ICP-MS) to specifically monitor changes in the metal speciation following the formation of ruthenium-protein adducts was applied. The rate constants of interaction with albumin and transferrin were determined at pharmacologically fitting drug-to-protein ratios as on average 0.0319+/-0.0021 min(-1) and 0.0931+/-0.0019 min(-1) (KP1019) and 0.0316+/-0.0018 min(-1) and 0.0935+/-0.0053 min(-1) (KP1339), respectively. The results of this brief study showed that changing from organic to inorganic counter-ion at the stage of formulation could commonly be recommended for improving ruthenium-based drug solubility and bioavailability.

Background: The aim of the study is to prospectively determine the incidence of inflow stenoses in dysfunctional hemodialysis access arteriovenous fistulae (AVFs) and grafts (AVGs)., Methods: Contrast-enhanced magnetic resonance angiography (CE-MRA) was performed of 66 dysfunctional AVFs and 35 AVGs in 56 men and 45 women (mean age, 62 years; age range, 31 to 86 years). Complete inflow (from the subclavian artery), shunt region, and complete outflow (including subclavian vein) were shown at CE-MRA. In addition to standard digital subtraction angiography (DSA) of the shunt region and outflow, DSA of the complete inflow was obtained through access catheterization of all cases in which CE-MRA showed an inflow stenosis. Vascular stenosis is defined as greater than 50% decrease in luminal diameter compared with an uninvolved vascular segment located adjacent to the stenosis. Endovascular intervention of stenoses was performed in connection with DSA., Results: CE-MRA showed 19 arterial stenoses in 14 patients (14%). DSA confirmed 18 of these lesions in 13 patients and showed no additional inflow lesions. Of the 13 patients, 7 patients had arterial stenoses only and 6 patients had accompanying stenoses in the shunt region and/or outflow. Referral criteria for the 13 patients to undergo access evaluation had been decreased flow rates (9 patients), steal symptoms (2 patients), and insufficient access maturation (2 patients). Access flow of the 9 patients with a low-flow access improved from 477 +/- 74 mL/min to 825 +/- 199 mL/min after angioplasty. One patient with steal symptoms became symptom free after angioplasty. Endovascular intervention in 3 patients proved to be unsuccessful., Conclusion: Inflow stenoses are not uncommon in dysfunctional hemodialysis access shunts. We suggest that radiological evaluation comprise assessment of the complete arterial inflow.

The objectives of the present report were to examine the ability of 18 strains of Escherichia coli O157:H7 to grow in EC broth at 42.4, 43.5, 44.5, and 45.5 degrees C, and to document the incidence of phenotypic variants present in low numbers that are capable of growth at 45.5 degrees C in EC broth. Among the 18 strains of E. coli O157:H7 studied, only 3 were capable of producing turbid growth with gas formation in EC broth at 45.5 degrees C with 1 x 10(2) initial CFU/ml. Higher initial densities of CFU resulted in turbid growth and gas formation in EC broth at 45.5 degrees C with all strains. The presence of bile salts #3 in EC broth was found to be inhibitory at 45.5 degrees C. All 18 strains were found to be capable of growth at 45.5 degrees C in nonselective media. The ability of at least one sensitive strain to grow in EC broth at 45.5 degrees C was found to be dependent on the initial number of CFU/ml. Prior growth of cells of a sensitive strain in EC broth at 45.5 degrees C from a cell density of 2.0 x 10(7) to 8.0 x 10(7) CFU/ml followed by removal of cells and reinoculation at a cell density of 2.0 x 10(6) CFU/ml resulted in growth at 45.5 degrees C that did not occur without such conditioning of the inhibitory medium. These results indicate that the ability of most strains of E. coli O157:H7 to grow in EC broth at 45.5 degrees C is dependent on the initial density of CFU and that at low densities of CFU the ability to initiate growth is dependent on either low numbers of phenotypic variants tolerant to the presence of bile salts #3 in EC broth at 45.5 degrees C or to conditioning of the medium with prior elevated numbers of cells.