Oxygen-derived free radicals and hemolysis during open heart surgery

Reperfusion injury occurs during open-heart surgery after prolonged cardioplegic arrest. Cardiopulmonary bypass also is known to cause hemolysis. Since reperfusion of ischemic myocardium is associated with the generation of oxygen free radicals, and since free radicals can attack a protein molecule, it seems reasonable to assume that hemolysis might be the consequence of free radical attack on hemoglobin protein. The results of this study demonstrated that reperfusion following ischemic arrest caused an increase in free hemoglobin and free heme concentrations, simultaneously releasing free iron and generating hydroxyl radicals. In vitro studies using pure hemoglobin indicated that superoxide anion generated by the action of xanthine oxidase on xanthine could release iron from the heme ring and cause deoxygenation of oxyhemoglobin into ferrihemoglobin. This study further demonstrated that before the release of iron from the heme nucleus, oxyhemoglobin underwent deoxygenation to ferrihemoglobin. The released iron can catalyze the Fenton reaction, leading to the formation of cytotoxic hydroxyl radical (OH·). In fact, the formation of OH. in conjunction with hemolysis occurs during cardiac surgery, and when viewed in the light of the in vitro results, it seems likely that oxygen-derived free radicals may cause hemolysis during cardiopulmonary bypass and simultaneously release iron from the heme ring, which can catalyze the formation of OH·.     

Physical characteristics of bone composite materials

To study the effects of varying mineral content and various trace elements in bone composities on its electrical behavior and possible use in design of transducers, various physical, dielectric, piezoelectric, and electromechanical parameters have been measured. For electrical characterization of various such composites in the high-frequency region (1–108 MHz), variation of impedance (Z), phase angle (tan ), and relative output voltage with frequency has been examined. Furtherfore, the Curie temperature has been determined and the temperature variation of capacitance and loss factor (tan ) studied (24–225°C). Two types of bone composites were prepared and studied. First, powdered collagen and apatite obtained from full bone were mixed intimately in various proportions by weight to prepare eleven bone compositions. Second, such bone materials were made to contain 5–10% various doping foreign additives (A1Br₃, Na₂CO₃, SrCO₃, LiCO₃, Sb₂O₃, ZnO, Nb₂O₅, piezoelectric ceramic (PZT), and Pb(NO₃)₂. It has been observed that a bone composition of 50% collagen + 50% apatite has possible piezoelectric application and other compositions [85% collagen + 15% apatite, 90% collagen + 10% ZnO, and 90% bone + 10% Ba(OH)₂] have a sharp rise in capacitance near the Curie temperature. The Curie temperature is generally shifted towards higher values by additives. It is expected that such results will be relevant in characterizing bone behavior.     

Survival of ram testicular spermatozoa invitro: Effects of glucose,glucose metabolites,rete testis fluid-proteins,selected androgens and phospholipids

The effects of glucose, glucose metabolites, protein-enriched rete testis fluid (RTF), selected androgens and phospholipids on the survival of testicular spermatozoa $\text{in}$$\text{vitro}$ have been studied. The oxidative and glycolytic activity, motility and percentage of live cells were the criteria for assessing the viability of the spermatozoa washed free of the substances that had been added during storage. The addition of lithium lactate, sodium lactate and sodium pyruvate but not glucose was beneficial to the survival of testicular spermatozoa. Following 10 to 12 days storage at 4°C with added lactate or pyruvate testicular spermatozoa had a higher glycolytic activity than did control spermatozoa. The respiratory activity of stored testicular spermatozoa was maintained or depressed, depending on the density of spermatozoal suspension during storage. After 10 to 11 days storage in concentrated RTF or after exposure to selected androgens testicular spermatozoa utilized more glucose than after storage with lactate alone. However, this apparent response to androgens and RTF-proteins was the consequence of a higher survival rate of the spermatozoa rather than an increase in the metabolic activity of individual spermatozoa. These results indicate that metabolites of glucose may serve as substrates for spermatozoa in the epididymis while certain androgens and macromolecules occurring in reproductive tract fluids may play important roles in the survival of spermatozoa during their period of maturation in the epididymis.     

Age dependent alterations in phospholipid composition of a saprophytic and a pathogenic strain of Nocardia

Nocardia polychromogenes (saprophytic) and Nocardia asteroides (pathogenic) showed characteristic patterns in changes of cellular lipids during growth. Total lipids and total phospholipids decreased with the age of the culture in the saprophytic strain, whereas in the pathogenic strain total lipids increased throughout the culture period and the total phospholipids decreased in the late stationary phase. The decrease in total phospholipids in saprophytic strain was reflected in the individual phosphatides. In the pathogenic strain, the phosphatidylinositomannoside content doubled in early stationary phase. Differences were observed in fatty acid composition of phosphatides at various stages of growth, but the ratio of saturated to unsaturated fatty acids remained unaltered.     

Revisiting the Role of Conductivity and Polarity of Host Materials for Long‐Life Lithium–Sulfur Battery

Despite their high theoretical energy density and low cost, lithium–sulfur batteries (LSBs) suffer from poor cycle life and low energy efficiency owing to the polysulfides shuttle and the electronic insulating nature of sulfur. Conductivity and polarity are two critical parameters for the search of optimal sulfur host materials. However, their role in immobilizing polysulfides and enhancing redox kinetics for long‐life LSBs are not fully understood. This work has conducted an evaluation on the role of polarity over conductivity by using a polar but nonconductive platelet ordered mesoporous silica (pOMS) and its replica platelet ordered mesoporous carbon (pOMC), which is conductive but nonpolar. It is found that the polar pOMS/S cathode with a sulfur mass fraction of 80 wt% demonstrates outstanding long‐term cycle stability for 2000 cycles even at a high current density of 2C. Furthermore, the pOMS/S cathode with a high sulfur loading of 6.5 mg cm^?2 illustrates high areal and volumetric capacities with high capacity retention. Complementary physical and electrochemical probes clearly show that surface polarity and structure are more dominant factors for sulfur utilization efficiency and long‐life, while the conductivity can be compensated by the conductive agent involved as a required electrode material during electrode preparation. The present findings shed new light on the design principles of sulfur hosts towards long‐life and highly efficient LSBs.     

HY5-COP1: the central module of light signaling pathway

Journal of Plant Biochemistry and Biotechnology - Light acts catalytically to initiate a cascade of events to eventually regulate different aspects of plant development. The cascade of light signal...     

A detailed model and Monte Carlo simulation for predicting DIP genome length distribution in baculovirus infection of insect cells

Baculoviruses have enormous potential for use as biopesticides to control insect pest populations without the adverse environmental effects posed by the widespread use of chemical pesticides. However, continuous baculovirus production is susceptible to DNA mutation and the subsequent production of defective interfering particles (DIPs). The amount of DIPs produced and their genome length distribution are of great interest not only for baculoviruses but for many other DNA and RNA viruses. In this study, we elucidate this aspect of virus replication using baculovirus as an example system and both experimental and modeling studies. The existing mathematical models for the virus replication process consider DIPs as a lumped quantity and do not consider the genome length distribution of the DIPs. In this study, a detailed population balance model for the cell‐virus culture is presented, which predicts the genome length distribution of the DIP population along with their relative proportion. The model is simulated using the kinetic Monte Carlo algorithm, and the results agree well with the experimental results. Using this model, a practical strategy to maintain the DIP fraction to near to its maximum and minimum limits has been demonstrated.     

Cholesterol Diet Withdrawal Leads to an Initial Plaque Instability and Subsequent Regression of Accelerated Iliac Artery Atherosclerosis in Rabbits

Effect of long term cholesterol diet withdrawal on accelerated atherosclerosis in iliac artery of New Zealand White (NZW) rabbits has not been explored so far. Atherosclerosis was thus induced in rabbits by a combination of balloon injury and atherogenic diet (AD) (1% cholesterol and 6% peanut oil) feeding for 8 weeks (baseline) followed by chow diet (CD) feeding for 4, 8, 16, 32, 50 and 64 weeks. The plaque characterization was done using histology, real time RT-PCR and vasoreactivity studies. Significant elevation in plasma lipids with AD feeding was normalized following 16 weeks of CD feeding. However, baseline comparison showed advanced plaque features even after 8 weeks of CD period with significant elevation in intima/media thickness ratio and plaque area later showing reduction at 50 and 64 weeks CD periods. Lesion lipid accumulation and CD68 positivity was maintained till 16 weeks of CD feeding which significantly reduced from 32 to 64 weeks CD periods. Baseline comparison showed significant increase in ground substance, MMP-9 and significant decrease in α-actin and collagen content at 8 weeks CD period indicating features of unstable plaque. These features regressed up to 64 weeks of CD. Partial restoration of functional vasoconstriction and vasorelaxation was seen after 64 weeks of CD feeding. mRNA expression of MCP-1, VCAM-1, collagen type I and III, MMP-9, TIMP-1, IFN-γ, TNF-α, IL-10 and eNOS supported the above findings. The study thus reveals insights into initial plaque instability and subsequent regression on AD withdrawal in this model. These results are suggestive of an appropriate window for drug intervention for plaque stability/regression and restenosis as well as improves understanding of plaque regression phenomenon in this model.     

Hydroxyquinoline-derived compounds and analoguing of selective Mcl-1 inhibitors using a functional biomarker

Anti-apoptotic Bcl-2 family proteins are important oncology therapeutic targets. To date, BH3 mimetics that abrogate anti-apoptotic activity have largely been directed at Bcl-2 and/or Bcl-xL. One observed mechanism of resistance to these inhibitors is increased Mcl-1 levels in cells exposed to such therapeutics. For this reason, and because Mcl-1 is important in the onset of lymphoid, myeloid, and other cancers, it has become a target of great interest. However, small molecule inhibitors displaying potency and selectivity for Mcl-1 are lacking. Identifying such compounds has been challenging due to difficulties in translating the target selectivity observed at the biochemical level to the cellular level. Herein we report the results of an HTS strategy coupled with directed hit optimization. Compounds identified have selective Mcl-1 inhibitory activity with greater than 100-fold reduced affinity for Bcl-xL. The selectivity of these compounds at the cellular level was validated using BH3 profiling, a novel personalized diagnostic approach. This assay provides an important functional biomarker that allows for the characterization of cells based upon their dependencies on various anti-apoptotic Bcl-2 proteins. We demonstrate that cells dependent on Mcl-1 or Bcl-2/Bcl-xL for survival are commensurately responsive to compounds that genuinely target those proteins. The identification of compound 9 with uniquely validated and selective Mcl-1 inhibitory activity provides a valuable tool to those studying the intrinsic apoptosis pathway and highlights an important approach in the development of a first-in-class cancer therapeutic.