Effects of maleimide-polyethylene glycol-modified human hemoglobin (MP4) on tissue necrosis in SKH1-hr hairless mice

<p>Abstract</p> <p>Objective</p> <p>Tissue hypoxia after blood loss, replantation and flap reperfusion remains a challenging task in surgery. Normovolemic hemodilution improves hemorheologic properties without increasing oxygen carrying capacity. Red blood cell transfusion is the current standard of treatment with its attendant risks. The aim of this study was to investigate the potential of the chemically modified hemoglobin, MP4, to reduce skin flap necrosis and its effect on selected blood markers and kidneys.</p> <p>Materials and methods</p> <p>Tissue ischemia was induced in the ear of hairless mice (n = 26). Hemodilution was performed by replacing one third of blood volume with the similar amount of MP4, dextran, or blood. The extent of non-perfused tissue was assessed by intravital fluorescent microscopy.</p> <p>Results</p> <p>Of all groups, MP4 showed the smallest area of no perfusion (in percentage of the ear ± SEM: 16.3% ± 2.4), the control group the largest (22.4% ± 3.5). Leukocytes showed a significant increase in the MP4 and dextran group (from 8.7 to 13.6 respectively 15.4*10⁹/l). On histology no changes of the kidneys could be observed.</p> <p>Conclusion</p> <p>MP4 causes an increase of leukocytes, improves the oxygen supply of the tissue and shows no evidence of renal impairment.</p

Optimization of an Alkylpolyglucoside-Based Dishwashing Detergent Formulation.

The aim of this work was to formulate and optimize the washing performance of an alkylpolyglucoside-based dishwashing detergent. The liquid detergent was formulated with five ingredients of commercial origin: anionic (linear sodium alkylbenzenesulfonate and sodium laurylethersulfate), nonionic (C12–C14 alkylpolyglucoside) and zwitterionic (a fatty acid amide derivative with a betaine structure) surfactants, and NaCl for viscosity control. In addition to the plate test, other properties were investigated including ‘‘cloud point’’, viscosity, and emulsion stability. Statistical analysis software was used to generate a central composite experimental design. Then, a second order design and analysis of experiments approach, known as the Response Surface Methodology, was set up to investigate the effects of the five components of the formulation on the studied properties in the region covering plausible component ranges. The method proved to be efficient for locating the domains of concentrations where the desired properties were met

Electromagnetic Form Factors of the SU(3) Octet Baryons in the semibosonized SU(3) Nambu-Jona-Lasinio Model

The electromagnetic form factors of the SU(3) octet baryons are investigated in the semibosonized SU(3) Nambu--Jona-Lasinio model (chiral quark-soliton model). The rotational $1/N_c$ and strange quark mass corrections in linear order are taken into account. The electromagnetic charge radii of the nucleon and magnetic moments are also evaluated. It turns out that the model is in a remarkable good agreement with the experimental data.Comment: RevTex is used. 37 pages. The final version to appear in Phys. Rev. D. 13 figures are include

Evaluation of Therapeutic Oligonucleotides for Familial Amyloid Polyneuropathy in Patient-Derived Hepatocyte-Like Cells

Familial amyloid polyneuropathy (FAP) is caused by mutations of the transthyretin (TTR) gene, predominantly expressed in the liver. Two compounds that knockdown TTR, comprising a small interfering RNA (siRNA; ALN-TTR-02) and an antisense oligonucleotide (ASO; IONIS-TTRRx), are currently being evaluated in clinical trials. Since primary hepatocytes from FAP patients are rarely available for molecular analysis and commercial tissue culture cells or animal models lack the patient-specific genetic background, this study uses primary cells derived from urine of FAP patients. Urine-derived cells were reprogrammed to induced pluripotent stem cells (iPSCs) with high efficiency. Hepatocyte-like cells (HLCs) showing typical hepatic marker expression were obtained from iPSCs of the FAP patients. TTR mRNA expression of FAP HLCs almost reached levels measured in human hepatocytes. To assess TTR knockdown, siTTR1 and TTR-ASO were introduced to HLCs. A significant downregulation (>80%) of TTR mRNA was induced in the HLCs by both oligonucleotides. TTR protein present in the cell culture supernatant of HLCs was similarly downregulated. Gene expression of other hepatic markers was not affected by the therapeutic oligonucleotides. Our data indicate that urine cells (UCs) after reprogramming and hepatic differentiation represent excellent primary human target cells to assess the efficacy and specificity of novel compounds

A Top Quark Soliton and its Anomalous Chromomagnetic Moment

We show that under the assumption of dynamical symmetry breaking of electro weak interactions by a top quark condensate, motivated by the Top Mode Standard Model, the top quark in this effective theory can be considered then as chiral color soliton (qualiton). This is realized in an effective four-fermion interaction with chiral $SU(3)_c$ as well as $SU(2)_L\otimes U_Y(1)$ symmetry. In the pure top sector the qualiton consists of a top valence quark and a Dirac sea of top and anti-top quark coupled to a color octet of Goldstone pions. The mass spectra, isoscalar quadratic radii and the anomalous chromomagnetic moment due to a non-trivial color form factor are calculated with zero and finite current top masses and effects at the Hadron Colliders are discussed. The anomalous chromomagnetic moment turns out to have a value consistent with the top production rates of the D0- and CDF-measurements.Comment: LaTeX, using RevTeX.sty and aps.sty, without figures, 16 pages, to be published in Physical Review D. Full postscript version and figures available on request or via ftp://hadron.tp2.ruhr-uni-bochum.de/preprint.tp2/1995/08-95.tar.g

Cardiovascular development: towards biomedical applicability: Regulation of cardiomyocyte differentiation of embryonic stem cells by extracellular signalling

Investigating the signalling pathways that regulate heart development is essential if stem cells are to become an effective source of cardiomyocytes that can be used for studying cardiac physiology and pharmacology and eventually developing cell-based therapies for heart repair. Here, we briefly describe current understanding of heart development in vertebrates and review the signalling pathways thought to be involved in cardiomyogenesis in multiple species. We discuss how this might be applied to stem cells currently thought to have cardiomyogenic potential by considering the factors relevant for each differentiation step from the undifferentiated cell to nascent mesoderm, cardiac progenitors and finally a fully determined cardiomyocyte. We focus particularly on how this is being applied to human embryonic stem cells and provide recent examples from both our own work and that of others

A strategy to discover new organizers identifies a putative heart organizer

Organizers are regions of the embryo that can both induce new fates and impart pattern on other regions. So far, surprisingly few organizers have been discovered, considering the number of patterned tissue types generated during development. This may be because their discovery has relied on transplantation and ablation experiments. Here we describe a new approach, using chick embryos, to discover organizers based on a common gene expression signature, and use it to uncover the anterior intestinal portal (AIP) endoderm as a putative heart organizer. We show that the AIP can induce cardiac identity from non-cardiac mesoderm and that it can pattern this by specifying ventricular and suppressing atrial regional identity. We also uncover some of the signals responsible. The method holds promise as a tool to discover other novel organizers acting during development