Objectives: The algorism for physiological control has been controversial in the patients supported with continuous flow LVAD, in which supplied blood flow is regulated by the pressure gradient ...between aortic and left ventricular pressure when operated at constant rotation speed. Little has known relating physiological control algorism, such as achieving physiological circadlan rhythm. Motor current was evaluated in terms of the existence of circadlan variation in dilated cardiomyopathy patients supported with centrifugal-continuous flow LVAD. Methods: The motor speed (rpm) and electric current (micro ampere) data were collected every 10 minutes after device implantation and were divided in every 30-day data and calculated by Least Spectrum method. Results: Patients were 37.3 plus or minus 14.8 years old, weighed 63.8 plus or minus 15.1 kg at the time of operation. As of March 1, 2011, mean support duration was 1299.8 days (968 - 2124 days). Of the 6 patients, 3 received heart transplantation (at 1164, 1115 and 988 days of support) and 3 were still supported by LVAS with the mean support duration of 1517 plus or minus 535 days. The circadian variation of motor current was observed in all patients during almost entire course of LVAD support The calculated periods of the circadian variation was 24.00 plus or minus 1.00 hours. The amplitude of the circadlan variation was 11.48 plus or minus 4.50 mu A. The circadlan variation of the motor current was tended to be relatively low during night time whereas that was tended to be relatively high during day time. There were significant night- and day-time variations (p<0.01). Conclusions: Circadian rhythm of motor current could be observed in fixed rotation speed centrifugal-continuous flow LVAD support. The cause and effect of this variation are still unclear although it is speculated to be correlated to physiological changes of some hemodynamic-related parameters of patients.
Both experimental and clinical evidence suggest that pulse pressure is not required from a blood pump. End-organ function is well maintained with nonpulsatile systems, though pulse pressure may ...accelerate recovery from cardiogenic shock. Form follows function, so the effects of reduced pulse pressure on the arterial wall are not surprising. The ability to alter aortic wall morphology by reducing pulse pressure may have important implications for the future treatment of arterial pathology. Both centrifugal and axial-flow pumps can be miniaturized and are silent. Their reliability and user-friendly status may soon allow implantation at an earlier stage of cardiac deterioration. Doubts about the feasibility of long-term pulseless circulation are disappearing.
Heteroduplex joints are general intermediates of homologous genetic recombination in DNA genomes. A heteroduplex joint is formed between a single-stranded region (or tail), derived from a cleaved ...parental double-stranded DNA, and homologous regions in another parental double-stranded DNA, in a reaction mediated by the RecA/Rad51-family of proteins. In this reaction, a RecA/Rad51-family protein first forms a filamentous complex with the single-stranded DNA, and then interacts with the double-stranded DNA in a search for homology. Studies of the three-dimensional structures of single-stranded DNA bound either to Escherichia coli RecA or Saccharomyces cerevisiae Rad51 have revealed a novel extended DNA structure. This structure contains a hydrophobic interaction between the 2′ methylene moiety of each deoxyribose and the aromatic ring of the following base, which allows bases to rotate horizontally through the interconversion of sugar puckers. This base rotation explains the mechanism of the homology search and base-pair switch between double-stranded and single-stranded DNA during the formation of heteroduplex joints. The pivotal role of the 2′ methylene-base interaction in the heteroduplex joint formation is supported by comparing the recombination of RNA genomes with that of DNA genomes. Some simple organisms with DNA genomes induce homologous recombination when they encounter conditions that are unfavorable for their survival. The extended DNA structure confers a dynamic property on the otherwise chemically and genetically stable double-stranded DNA, enabling gene segment rearrangements without disturbing the coding frame (i.e., protein-segment shuffling). These properties may give an extensive evolutionary advantage to DNA.
Evolving blood pump technology has produced user-friendly continuous-flow left ventricular assist devices, but uncertainty exists about the safety of chronic nonpulsatile circulation. Recent ...experimental and clinical evidence suggest that pulse pressure is not required from a blood pump. End-organ function is well maintained with nonpulsatile systems, although pulse pressure may accelerate recovery from cardiogenic shock. Form follows function, so the effects of reduced pulse pressure on the arterial wall are not surprising. The ability to alter aortic wall morphology by reducing pulse pressure may have important implications for the future treatment of arterial pathology. Both centrifugal and axial-flow pumps can be miniaturized and are reliable and silent. Doubts about the feasibility of long-term circulation with reduced pulse pressure are disappearing.
Acceleration of the polyol pathway under hyperglycemia is among the mechanisms implicated in the pathogenesis of diabetic complications. Although aldose reductase (AR), the rate-limiting enzyme in ...this pathway, is a target for pharmacological intervention of diabetic complications, the clinical efficacy of AR inhibitors has not been consistently proved. Because nitric oxide (NO) plays important roles in vascular hemodynamics and inflammatory responses that are affected under diabetic conditions, the interaction of NO with AR was investigated with rat aortic smooth muscle cells. Spontaneous NO donors, S-nitroso-N-acetylpenicillamine (SNAP) and 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamin e, elicited a dose-dependent increase in AR mRNA to a maximum of 7-fold in 12 h. The activity of AR was elevated after 10 h of SNAP treatment. These effects of NO donors were suppressed by the addition of 2-(trimethylammoniophenyl)-4,4,5, 5-tetramethylimidazoline-1-oxy 3-oxide, a scavenger of NO. Induction of AR mRNA by SNAP was completely abolished by actinomycin D or cycloheximide, but unaffected by guanylate cyclase inhibitors or genistein, a tyrosine kinase inhibitor. Pretreatment of the cells with N-acetyl-L-cysteine significantly suppressed the SNAP-induced up-regulation of AR mRNA. Under normal glucose conditions, inclusion of the AR inhibitor ponalrestat augmented the cytotoxic effect of SNAP on the cells. The level of AR mRNA also was elevated in a murine macrophage cell line RAW 264.7 stimulated with lipopolysaccharide and interferon-gamma. Inhibition of NO synthesis completely abolished the increase in AR mRNA in the stimulated cells. The up-regulation of AR by NO in the vascular lesions may modulate NO-induced cell death and the ensuing vascular remodeling during inflammatory responses.
Escherichia coli RecA is a representative of proteins from the RecA family, which promote homologous pairing and strand exchange between double-stranded DNA and single-stranded DNA. These reactions ...are essential for homologous genetic recombination in various organisms. From NMR studies, we previously reported a novel deoxyribose-base stacking interaction between adjacent residues on the extended single-stranded DNA bound to RecA protein. In this study, we found that the same DNA structure was induced by the binding to Saccharomyces cerevisiae Rad51 protein, indicating that the unique DNA structure induced by the binding to RecA-homologs was conserved from prokaryotes to eukaryotes. On the basis of this structure, we have formulated the structure of duplex DNA within filaments formed by RecA protein and its homologs. Two types of molecular structures are presented. One is the duplex structure that has the N-type sugar pucker. Its helical pitch is ≈ 95 angstrom (18.6 bp/turn), corresponding to that of an active, or ATP-form of the RecA filament. The other is one that has the S-type sugar pucker. Its helical pitch is ≈ 64 angstrom (12.5 bp/turn), corresponding to that of an inactive, or ADP-form of the RecA filament. During this modeling, we found that the interconversion of sugar puckers between the N-type and the S-type rotates bases horizontally, while maintaining the deoxyribose-base stacking interaction. We propose that this base rotation enables base pair switching between double-stranded DNA and single-stranded DNA to take place, facilitating homologous pairing and strand exchange. A possible mechanism for strand exchange involving DNA rotation also is discussed.
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