bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood CoQ10 levels and safety profile after singe‐dose or chronic administration of PureSorb‐Q™40: Animal and human studies
Authors: Nukui Kazuki , Yamagishi Toshihiko , Miyawaki Hiromi , Kettawan Aikkarach , Okamoto Tadashi , Belardinelli Romualdo , Tiano Luca , Littarru Gian Paulo , Sato Kiyoshi
Published: April 2009

Coenzyme Q10 (CoQ10) is known to be highly hydrophobic and, as such, insoluble in water: this leads to serious inconvenience when trying to incorporate it in food products. Its absorption is also known to be very limited. PureSorb‐Q™ 40 (P40) (Water‐soluble type CoQ10 powder, CoQ10 content 40 w/w %) was developed in order to improve its use with food products and to enhance its absorption. In the present study the absorption of this novel formulation was compared to a conventional lipid soluble CoQ10 by administering both products to rats and humans. Acute, single‐administration studies in rats showed that P40 has a higher absorption, compared to lipid soluble CoQ10, both in prandial and fasting states. Similarly, single administration in humans revealed a higher absorption level for P40, taken in the fasting state or together with meals. In the rat study, no adverse effects were observed with P40 at doses up to 2,000 mg/kg in both sexes. In a double‐blind, placebo controlled, comparative study conducted on 46 healthy volunteers and randomly divided into two groups, in the group receiving 900 mg of CoQ10 per day, for 4 consecutive weeks, the average level at two weeks was 8.79±3.34 μg/mL, similar to the corresponding level after 4 weeks (8.33±4.04 μg/mL). After 2 weeks of washout, serum CoQ10 level decreased to 1.30±0.49 μg/mL. P40 intake did not cause any significant changes in symptoms and clinical laboratory tests as assessed by physical, hematological, blood biochemical or urinalysis. Clinical examinations also did not reveal any abnormalities. The above blood (serum) CoQ10 level at 2 weeks after start of intake was compared with other reported values. The same dose of CoQ10 (900mg/day), when administered by softgel capsules yielded a plasma CoQ10 concentration of 3.6 μg/mL, while P40 levels were 8.79±3.34 μg/mL. These levels are remarkably high for instance when compared to the corresponding levels obtained, in patients affected by Parkinson's disease, with CoQ10 doses up to 2,400mg/day. A clinical study was conducted using doses of 300 mg/day and 600 mg/day, in patients affected by cardiovascular disease. Also in this case there was linearity in the response with the levels obtained by administering P40 at a dose of 100 and 900 mg/day.
Supplementation with CoQ10 lowers age‐related (ar) NOX levels in healthy subjects
Authors: Morré Dorothy M. , Morré D. James , Rehmus Wingfield , Kern Dale
Published: April 2009

Our work has identified an aging‐related ECTO‐NOX activity (arNOX), a hydroquinone oxidase which is cell surface located and generates superoxide. This activity increases with increasing age beginning > 30 y. Because of its cell surface location and ability to generate superoxide, the arNOX proteins may serve to propagate an aging cascade both to adjacent cells and to oxidize circulating lipoproteins as significant factors determining atherogenic risk. The generation of superoxide by arNOX proteins is inhibited by Coenzyme Q10 as one basis for an anti‐aging benefit of CoQ10 supplementation in human subjects.

In a preliminary pilot study, 25 female subjects between 45 and 55 y of age were recruited at Stanford University from the Palo Alto, CA area. Informed consent was obtained. Ten of the subjects received Coenzyme Q10 supplementation of 180 (3 × 60 mg) per day for 28 days. Serum, saliva and perspiration levels of arNOX were determined at 7, 14 and 28 days of CoQ10 supplementation and compared to the initial baseline value. Activity correlated with subject age up to a maximum between age 50 and 55 years of age for saliva and perspiration as well and then declined. With all three sources, the arNOX activity extrapolated to zero at about age 30. Response to Coenzyme Q10 also increased with age being least between ages 45 and 50 and greatest between ages 60 and 65. With all three biofluids, arNOX activity was reduced between 25 and 30% by a 3 × 60 mg daily dose Coenzyme Q10 supplementation. Inhibition was the result of Coenzyme Q10 presence.
Aging skin is functionally anaerobic: Importance of coenzyme Q10 for anti aging skin care
Authors: Prahl S. , Kueper T. , Biernoth T. , Wöhrmann Y. , Münster A. , Fürstenau M. , Schmidt M. , Schulze C. , Wittern K.‐P. , Wenck H. , Muhr G.‐M. , Blatt T.
Published: April 2009

The functional loss of mitochondria represents an inherent part in modern theories trying to explain the cutaneous aging process. The present study shows significant age‐dependent differences in mitochondrial function of keratinocytes isolated from skin biopsies of young and old donors. Our data let us postulate that energy metabolism shifts to a predominantly nonmitochondrial pathway and is therefore functionally anaerobic with advancing age. CoQ10 positively influences the age‐affected cellular metabolism and enables to combat signs of aging starting at the cellular level. As a consequence topical application of CoQ10 is beneficial for human skin as it rapidly improves mitochondrial function in skin in vivo.
Oxidative stress status in liver mitochondria and lymphocyte DNA damage of atherosclerotic rabbits supplemented with water soluble coenzyme Q10
Authors: Ramirez‐Tortosa M. Carmen , Granados Sergio , Ramirez‐Tortosa Cesar L. , Ochoa Julio J. , Camacho Pedro , García‐Valdós Luz , Battino Maurizio , Quiles Jose L.
Published: April 2009

The effects of the administration of water soluble coenzyme Q10 (25 mg/kg per day) over 30 days, after 50 days feeding on a high‐fat diet (3% lard + 1.3% cholesterol), were investigated in the plasma and liver mitochondria of rabbits. Results showed that this atherogenic diet enhanced lipid levels both in plasma and liver mitochondria, reduced plasma and mitochondrial concentrations of retinol and coenzyme Q10, led to higher DNA damage in peripheral blood lymphocytes and reactive oxygen species concentration in liver mitochondria. The treatment of animals with coenzyme Q10 reduced (to the healthy group levels) lipid concentration in liver mitochondria with no effect on plasma lipids, increased mitochondrial levels of α‐tocopherol, restored mitochondrial coenzyme Q10 and improved α‐tocopherol levels in plasma. Moreover, coenzyme Q10 supplementation reduced mitochondrial reactive oxygen species levels and decreased DNA damage in peripheral blood lymphocytes. The findings suggest that antioxidant therapy with coenzyme Q10 may be used in the treatment of liver pathologies associated to the intake of high‐fat, atherogenic, diets.
Ultrastructure of ulvan: A polysaccharide from green seaweeds
Authors: Robic Audrey , Gaillard Cédric , Sassi Jean‐François , Lerat Yannick , Lahaye Marc
Published: April 2009

Ultrastructural analysis of the gel forming green seaweed sulfated polysaccharide ulvan revealed a spherical‐based morphology (10–18 nm diameter) more or less aggregated in aqueous solution. At pH 13 in TBAOH (tetrabutyl ammonium hydroxyde) or NaOH, ulvan formed an open gel‐like structure or a continuous film by fusion or coalescence of bead‐like structures, while in acidic pH conditions, ulvan appeared as dispersed beads. Low concentrations of sodium chloride, copper or boric acid induced the formation of aggregates. These results highlight the hydrophobic and aggregative behavior of ulvan that are discussed in regard to the peculiar gel formation and the low intrinsic viscosity of the polysaccharide in aqueous solution. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 652–664, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Adhesion of pancreatic beta cells to biopolymer films
Authors: Williams S. Janette , Wang Qun , MacGregor Ronal R. , Siahaan Teruna J. , Stehno‐Bittel Lisa , Berkland Cory
Published: April 2009

Dramatic reversal of Type 1 diabetes in patients receiving pancreatic islet transplants continues to prompt vigorous research concerning the basic mechanisms underlying patient turnaround. At the most fundamental level, transplanted islets must maintain viability and function in vitro and in vivo and should be protected from host immune rejection. Our previous reports showed enhancement of islet viability and insulin secretion per tissue mass for small islets (<125 μm) as compared with large islets (>125 μm), thus, demonstrating the effect of enhancing the mass transport of islets (i.e. increasing tissue surface area to volume ratio). Here, we report the facile dispersion of rat islets into individual cells that are layered onto the surface of a biopolymer film towards the ultimate goal of improving mass transport in islet tissue. The tightly packed structure of intact islets was disrupted by incubating in calcium‐free media resulting in fragmented islets, which were further dispersed into individual or small groups of cells by using a low concentration of papain. The dispersed cells were screened for adhesion to a range of biopolymers and the nature of cell adhesion was characterized for selected groups by quantifying adherent cells, measuring the surface area coverage of the cells, and immunolabeling cells for adhesion proteins interacting with selected biopolymers. Finally, beta cells in suspension were centrifuged to form controlled numbers of cell layers on films for future work determining the mass transport limitations in the adhered tissue constructs. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 676–685, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Physicochemical studies on the biopolymer inulin: A critical evaluation of its self‐aggregation, aggregate‐morphology, interaction with water, and thermal stability
Authors: Dan Abhijit , Ghosh Soumen , Moulik Satya P.
Published: April 2009

Physicochemical properties viz., aggregation, molar mass, shape, and size of chicory inulin in solution were determined by fluorimetry, DLS, SLS, TEM, and viscometry methods. The thermal stability of the biopolymer was examined by TGA, DTA, and DSC measurements. The water vapor adsorption of desiccated inulin was also studied by the isopiestic method, and the data were analyzed in the light of the BET equation. On the basis of the obstruction to ion conductance by the inulin aggregates in solution and analysis of the data, the extent of hydration of inulin in solution was estimated. The result was coupled with the intrinsic viscosity, [η], of inulin to ascertain the shape of the biopolymer aggregates in aqueous solution. The critical aggregation concentration (cac) of inulin in aqueous as well as in salt solution was assessed by fluorimetry. The weight average molar mass, $ \overline M_{\rm w}$, of inulin monomer and its aggregate was found to be 4468 and 1.03 × 106 g/mol, respectively, in aqueous solution. This aggregated mass was 2.4 × 106 g/mol in 0.5M NH4SCN solution. The [η] values of the soft supramolecular aggregates in solution (without and with salt) were small and comparable with globular proteins evidencing spherical geometry of the biopolymer aggregates as supported by the TEM results. In DMSO, rod‐like aggregates of inulin was found by the TEM study. The [η] of the biopolymer in the DMSO medium was therefore, higher than that in the aqueous medium. Unlike aqueous medium, the aggregation in DMSO was not associated with a cac. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 687–699, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
The role of the octadecanoid pathway in the production of terpenoid indole alkaloids in Catharanthus roseus hairy roots under normal and UV‐B stress conditions
Authors: Peebles Christie A.M. , Shanks Jacqueline V. , San Ka‐Yiu
Published: April 2009

The octadecanoid pathway is responsible for producing jasmonic acid an important signaling molecule in plants, which controls the production of a variety of secondary metabolites. Previously the exogenous addition of jasmonic acid to Catharanthus roseus hairy roots caused an increase in terpenoid indole alkaloid (TIA) accumulation. The role of the endogenous production of jasmonic acid by the octadecanoid pathway in the production of TIAs in C. roseus hairy roots is examined. Feeding of octadecanoid pathway inhibitors suggests that the octadecanoid pathway does not actively control TIA production under normal growth conditions or during the UV‐B stress response in C. roseus hairy roots. Biotechnol. Bioeng. 2009;103: 1248–1254. © 2009 Wiley Periodicals, Inc.
Virus filtration of high‐concentration monoclonal antibody solutions
Authors: Marques Bruno F. , Roush David J. , Göklen Kent E.
Published: April 2009

The ability to process high‐concentration monoclonal antibody solutions (> 10 g/L) through small‐pore membranes typically used for virus removal can improve current antibody purification processes by eliminating the need for feed stream dilution, and by reducing filter area, cycle‐time, and costs. In this work, we present the screening of virus filters of varying configurations and materials of construction using MAb solutions with a concentration range of 4–20 g/L. For our MAbs of interest—two different humanized IgG1s—flux decay was not observed up to a filter loading of 200 L/m2 with a regenerated cellulose hollow fiber virus removal filter. In contrast, PVDF and PES flat sheet disc membranes were plugged by solutions of these same MAbs with concentrations >4 g/L well before 50 L/m2. These results were obtained with purified feed streams containing <2% aggregates, as measured by size exclusion chromatography, where the majority of the aggregate likely was composed of dimers. Differences in filtration flux performance between the two MAbs under similar operating conditions indicate the sensitivity of the system to small differences in protein structure, presumably due to the impact of these differences on nonspecific interactions between the protein and the membrane; these differences cannot be anticipated based on protein pI alone. Virus clearance data with two model viruses (XMuLV and MMV) confirm the ability of hollow fiber membranes with 19 ± 2 nm pore size to achieve at least 3–4 LRV, independent of MAb concentration, over the range examined. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Teaching chemical reaction engineering using EMSO simulator
Authors: Rodrigues Rodolfo , Soares Rafael P. , Secchi Argimiro R.
Published: April 2009

Nowadays, the use of computational tools in classroom is quite habitual and important by making the learning process more constructive and dynamic. The objective of this work is to introduce a support didactic material for use in computational classes of Chemical Reaction Engineering. The development of the work is based on a direct implementation of examples of the well‐known Fogler's textbook “Elements of Chemical Reaction Engineering” in an equation‐based dynamic simulator: EMSO. The problems were implemented in a way to preserve the structure of the problem as described in the textbook. The results are illustrated by graph plots generated in the simulator, allowing comparisons with the results presented in the textbook and detailed analyses for effects of variables in the problem. The problems are easily modified, allowing the student to analyze several possibilities, changing equations and values of variables, for example, and observing the results. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 607–618, 2010; View this article online at wileyonlinelibrary.com; DOI 10.1002/cae.20255
Tarennanosides A–H, Eight New Lignan Glucosides from Tarenna attenuata and Their Protective Effect on H2O2‐Induced Impairment in PC12 Cells
Authors: Yang Xian‐Wen , He Hong‐Ping , Du Zhi‐Zhi , Liu Hai‐Yang , Di Ying‐Tong , Ma Yan‐Lin , Wang Fang , Lin Hua , Zuo Yi‐Qing , Li Ling , Hao Xiao‐Jiang
Published: April 2009

magnified image

Eight new lignan glucosides, tarennanosides A–H (1–8, resp.), were isolated from the whole plant of Tarenna attenuata, together with three known compounds, fernandoside, (−)‐lyoniresinol, and (−)‐isolariciresinol. The planar structures of new compounds were elucidated mainly by analysis of physical and spectroscopic data, and the absolute configurations were determined by acid hydrolysis as well as CD spectroscopy. Compounds 1 and 2 exhibited potent antioxidant activities against H2O2‐induced impairment in PC12 cells. Preliminary mechanism study by the 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) method showed that these two compounds could act as radical scavengers.
Two Unusual Naphthalene‐Containing Compounds from a Freshwater Fungus YMF 1.01029
Authors: Dong Jin‐Yan , Song Hong‐Chuan , Li Jian‐Hua , Wang Chun‐Ren , Sun Rong , Tang Yu‐Shu , Shen Kai‐Ze , Wang Le , Wang Li‐Mei , Zhou Yong‐Ping , Li Lei , Zhang Ke‐Qin
Published: April 2009

magnified image

Two novel naphthalene‐containing compounds, colelomycerones A and B (1 and 2, resp.), and three known metabolites, including preussomerin D (3), (2RS,2′SR,3′E,3SR,4E,8E)‐1‐O‐(β‐D‐glucopyranosyl)‐3‐hydroxy‐2‐[(2‐hydroxyoctadec‐3‐enoyl)amino]‐9‐methyloctadeca‐4,8‐diene (4), and 3β‐hydroxy‐5α,8α‐epidioxyergosta‐6,22‐diene (5), were isolated from the culture broth of an unidentified freshwater water fungus YMF 1.01029. This fungus was collected from a decaying branch of an unidentified tree near Lake Fuxian in Yunnan Province, China. The structures of these five compounds were determined on the basis of their spectroscopic and mass‐spectrometric data. Colelomycerones A and B (1 and 2, resp.) represent unprecendented examples of naphthalene‐1,2‐diones with novel cyclic acetals. Compounds 1–3 showed noticeable antifungal and antibacterial activities.
Proton Speciation and Microspeciation of Serotonin and 5‐Hydroxytryptophan
Authors: Mazák Károly , Dóczy Veronika , Kökösi József , Noszál Béla
Published: April 2009

magnified image

Protonation equilibria of the neurotransmitter serotonin and its precursor 5‐hydroxytryptophan (5‐HTP) are characterized at the macroscopic and microscopic levels. 1H‐NMR–pH and UV–pH titrations were carried out to determine the macroconstants. Microconstants were obtained by appropriate combination of interactivity parameters and model compounds, allowing the calculation of all the twelve microconstants, the eight microspecies concentrations, and three site‐interactivity parameters of 5‐HTP, for which no microconstants have been reported earlier. NMR–pH Profiles, macro‐ and microscopic protonation schemes, and species‐specific distribution diagrams are presented. The physicochemical data obtained can help to understand the steric and electronic features governing the selectivity of binding and to design new therapeutic agents.
Seasonal Variations in Bioactive Marker Contents in Australian‐Grown Salvia miltiorrhiza Roots
Authors: Sheng Shu Jun , Pang Edwin C. K. , Xue Charlie Chang Li , Li Chun Guang
Published: April 2009

magnified image

Seasonal variations in contents of bioactive markers in Australian‐grown Salvia miltiorrhiza roots were investigated in a two‐year field trial. Cryptotanshinone, tanshinone I, tanshinone IIA, and salvianolic acid B were quantitatively determined by reversed‐phase (RP) HPLC. Similar accumulation patterns were observed for the three tanshinones throughout the trial period, although roots harvested in the first year was found to contain relatively higher contents of these compounds. In contrast, the content of salvianolic acid B was peaked at 250 days after planting in the first year, and subsequently maintained at a plateau level in the second‐year period. Linear correlations between the contents of individual tanshinones were observed, but not between those of tanshinones and salvianolic acid B. The findings suggest that tanshinones and salvianolic acid B have different accumulation patterns in Australian‐grown Salvia miltiorrhiza roots, which should be critically considered for optimum harvesting of the roots for pharmaceutical applications.
Quantitative Structure–Activity Relationship (QSAR) Modeling of Human Blood : Air Partitioning with Proper Statistical Methods and Validation
Authors: Basak Subhash C. , Mills Denise , Hawkins Douglas M. , Kraker Jessica J.
Published: April 2009

magnified image

Blood : air partition coefficient (BApc) is important in assessing toxicokinetics of chemicals. Since very few experimental data are available, quantitative structure–activity relationship (QSAR) models based on calculated molecular descriptors can be useful in estimating BApc. Since all descriptors used in the analysis are computed strictly from structure, they can be applied to any chemical, real or hypothetical. In this article, we report models for BApcestimation using four methods, including stepwise ordinary least‐squares regression, which is commonly used in QSAR studies but often results in an inflated ‘naïve’q2, over‐representing the predictive ability of the model. The models developed using proper statistical techniques hadq2values of 0.825 and 0.841, and may be used to reliably predict BApcvalues for new compounds that are structurally similar to those upon which the models are based. The models developed using improper techniques had associatedq2values, as computed using naïve methods, of 0.920 and 0.934, severely overstating their actual quality.
Anti‐Androgenic Activity of Fatty Acids
Authors: Liu Jie , Shimizu Kuniyoshi , Kondo Ryuichiro
Published: April 2009

In this study, we show that 5α‐reductase derived from rat fresh liver was inhibited by certain aliphatic free fatty acids. The influences of chain length, unsaturation, oxidation, and esterification on the potency to inhibit 5α‐reductase activity were studied. Among the fatty acids we tested, inhibitory saturated fatty acids had C12–C16 chains, and the presence of a CC bond enhanced the inhibitory activity. Esterification and hydroxy compounds were totally inactive. Finally, we tested the prostate cancer cell proliferation effect of free fatty acids. In keeping with the results of the 5α‐reductase assay, saturated fatty acids with a C12 chain (lauric acid) and unsaturated fatty acids (oleic acid and α‐linolenic acid) showed a proliferation inhibitory effect on lymph‐node carcinoma of the prostate (LNCaP) cells. At the same time, the testosterone‐induced prostate‐specific antigen (PSA) mRNA expression was down‐regulated. These results suggested that fatty acids with 5α‐reductase inhibitory activity block the conversion of testosterone to 5α‐dihydrotestosterone (DHT) and then inhibit the proliferation of prostate cancer cells.
Synthesis of (−)‐Epicatechin 3‐(3‐O‐Methylgallate) and (+)‐Catechin 3‐(3‐O‐Methylgallate), and Their Anti‐Inflammatory Activity
Authors: Iijima Takashi , Mohri Yoshihiro , Hattori Yasunao , Kashima Atsushi , Kamo Tsunashi , Hirota Mitsuru , Kiyota Hiromasa , Makabe Hidefumi
Published: April 2009

magnified image

A concise synthesis of (−)‐epicatechin 3‐(3‐O‐methylgallate) (1; ECG3″Me), which is a minor constituent of tea, and (+)‐catechin 3‐(3‐O‐methylgallate) (2; CG3″Me) via condensation of equimolar amount of catechin and gallate derivatives has been achieved. The anti‐inflammatory effect of the synthetic compounds on 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced inflammation of mouse ears was examined. Compounds 1 and 2 suppressed the TPA‐induced inflammation of mouse ears by 50 and 43%, respectively, at a dose of 200 μg. Their activities are stronger than those of indomethacin and glycyrrhetinic acid, the normally used anti‐inflammatory agents.
Structure–Activity Relationship Studies on the Mosquito Toxicity and Biting Deterrency of Callicarpenal Derivatives
Authors: Cantrell Charles L. , Klun Jerome A. , Pridgeon Julia , Becnel James , Green Solomon , Fronczek Frank R.
Published: April 2009

magnified image

Callicarpenal (=13,14,15,16‐tetranorclerod‐3‐en‐12‐al=[(1S,2R,4aR,8aR)‐1,2,3,4,4a,7,8,8a‐octahydro‐1,2,4a,5‐tetramethylnaphthalen‐1‐yl]acetaldehyde; 1) has previously demonstrated significant mosquito bite‐deterring activity against Aedes aegypti and Anopheles stephensi in addition to repellent activity against host‐seeking nymphs of the blacklegged tick, Ixodes scapularis. In the present study, structural modifications were performed on callicarpenal (1) in an effort to understand the functional groups necessary for maintaining and/or increasing its activity and to possibly lead to more effective insect control agents. All modifications in this study targeted the C(12) aldehyde or the C(3) alkene functionalities or combinations thereof. Mosquito biting deterrency appeared to be influenced most by C(3) alkene modification as evidenced by catalytic hydrogenation that resulted in a compound having significantly less effectiveness than 1 at a test amount of 25 nmol/cm2. Oxidation and/or reduction of the C(12) aldehyde did not diminish mosquito biting deterrency, but, at the same time, none of the modifications were more effective than 1 in deterring mosquito biting. Toxicities of synthesized compounds towards Ae. aegypti ranged from an LD50 value of 2.36 to 40.11 μg per mosquito. Similarly, LD95 values ranged from a low of 5.59 to a high of 104.9 μg.
Enzymatic Glycosylation of Triazole‐Linked GlcNAc/Glc–Peptides: Synthesis, Stability and Anti‐HIV Activity of Triazole‐Linked HIV‐1 gp41 Glycopeptide C34 Analogues
Authors: Huang Wei , Groothuys Stan , Heredia Alonso , Kuijpers Brian H. M. , Rutjes Floris P. J. T. , van Delft Floris L. , Wang Lai‐Xi
Published: April 2009

Long‐lasting sweet proteins: The chemoenzymatic synthesis of a triazole (T)‐linked glycosylated C34 fragment from HIV‐1 gp41 is described. The glycopeptide shows high solubility, excellent fusion inhibition, and as shown in the graph, promising protease resistance.

magnified image

Endoglycosidase‐catalyzed transglycosylation of triazole‐linked glucose (Glc) and N‐acetylglucosamine (GlcNAc)‐containing dipeptides and polypeptides was achieved by using synthetic sugar oxazoline as the donor substrate. It was found that both N‐ and C‐linked Glc/GlcNAc‐containing triazole derivatives were effective substrates for endo‐β‐N‐acetylglucosaminidase from Arthrobacter (Endo‐A) for transglycosylation; this demonstrates a broad acceptor substrate specificity for Endo‐A. This chemoenzymatic method was successfully used for the synthesis of a novel triazole‐linked C34 glycopeptide derived from the HIV‐1 envelope glycoprotein, gp41. We found that the synthetic C34 glycopeptide possesses potent anti‐HIV activity with an IC50 of 21 nM. The triazole‐linked C34 glycopeptide demonstrated a much enhanced stability against protease‐ and glycoamidase‐catalyzed digestion; this shows the protective effects of glycosylation and the stability of the triazole linkage. These favorable properties suggest that the triazole‐linked C34 glycopeptide might be valuable for further development as an anti‐HIV drug candidate.
Optimization of an Electrochemical DNA Assay by Using a 48‐Electrode Array and Redox Amplification Studies by Means of Scanning Electrochemical Microscopy
Authors: Neugebauer Sebastian , Zimdars Andreas , Liepold Petra , Gębala Magdalena , Schuhmann Wolfgang , Hartwich Gerhard
Published: April 2009

Sensible DNA: An electrochemical DNA assay based on specific Salmonella spp. capture probes and enzyme labeling with alkaline phosphatase was optimized by using a 48‐electrode microarray and scanning electrochemical microscopy (SECM). SECM was further used to evaluate potential amplification strategies due to redox cycling.

magnified image

Due to insufficient detection limits and selectivity, electrochemical DNA sensors are not yet used as everyday tools in diagnostics. Here, we present an electrochemical DNA assay that is based on specific Salmonella spp. capture probes. Our optimization strategies and the specific features of related electrochemical DNA sensor arrays, which are comprised of a chip with 48 gold electrodes, are also described. A ssDNA monolayer is formed by chemisorption of the thiol‐modified capture strand on the different gold electrodes of the array after spotting with a needle spotter. The assay parameters were optimized for the use of minimum amounts of sample and reagents and short assay times. Scanning electrochemical microscopy (SECM) has been used to visualize the local activity of an enzyme label used for amplified hybridization detection at high lateral resolution. The potential of SECM to further amplify the sensor signal by means of redox cycling is demonstrated by using single‐stranded DNA capture probe modified gold microelectrodes as SECM tips. The detection limit of the proposed DNA sensor is shown to be in the femtomolar range without redox cycling amplification.
Critical review of indications for renal artery stenting: Do randomized trials give the answer?
Authors: Schwarzwälder Uwe , Zeller Thomas
Published: April 2009

Significant renal artery stenosis (RAS) is a well accepted cause of deterioration of arterial hypertension and of renal insufficiency. Just recently, more interest has been focused on the impact of RAS on structural heart disease and patient survival. Technical improvements of diagnostic and interventional endovascular tools have lead to a more widespread use of endoluminal renal artery revascularization and extension of the indications for this type of therapy during the past 2 decades. Since the first renal artery angioplasties performed by Felix Mahler and Andreas Grüntzig, numerous single centre studies have reported the beneficial effect of percutaneous transluminal renal angioplasty, and since the early 1990's stenting of renal artery stenosis caused either by atherosclerosis or fibromuscular dysplasia. However, none of the so far published or presented randomized controlled trials (RCT) could prove a beneficial outcome of RAS revascularization compared with medical management. As a result of these negative trials including the recently presented ASTRAL trial, referrals to endovascular renal artery revascularization went down and moreover, reimbursement of these procedures became a matter of debate. This article summarizes the background and the limitations of the so far published and still ongoing controlled trials. Moreover, we discuss why well‐designed registries might give important insight on the impact of endovascular revascularization of hemodynamically relevant atherosclerotic RAS. © 2009 Wiley‐Liss, Inc.
Preliminary experiences using the MGuard stent platform in saphenous vein graft lesions
Authors: Vaknin‐Assa Hana , Assali Abid , Kornowski Ran
Published: April 2009

The MGuard stent has been designed as a plaque trapping device to treat athero‐thrombotic lesions in saphenous vein grafts and native coronary lesions. It was utilized in seven coronary bypass patients to treat eight vein grafts. The average graft age was 15 years. Procedural success was 100% without any intraprocedural, in‐hospital, and/or 30‐day major adverse cardiac events (e.g. death, myocardial infarction, and need for repeat graft revascularization). No patient experienced distal embolization and/or procedure‐related CK enzymatic rise. This strategy seems to be a promising approach in percutaneous vascular management of vein graft lesions. © 2009 Wiley‐Liss, Inc.
Dobutamine Infusion for Unmasking Long QT Syndrome and Torsades de Pointes
Authors: Quan Fang , Peng Gao , Kangan Cheng , Dayi Hu , Cuilan Li , Richard Conti C.
Published: April 2009

Prolonged QT interval is usually seen on routine electrocardiogram (ECG), but in some patients it may only be seen immediately before the evolution of torsades de pointes (Tdp). To unmask the potential risk of Tdp in a patient with normal or borderline prolongation of QTc interval and recurrent syncope, dobutamine was given intravenously at a rate of 20 µg/kg/min. Strikingly, QTc prolongation was induced along with syncope after dobutamine infusion. Torsades de pointes occurred 5 d later when the patient received an implantable cardioverter defibrillator (ICD). Genetic testing revealed a mutation of the KNCQ1‐gene encoding serine instead of glycine. The patient was treated with 75 mg of metoprolol twice daily, and at 12 mo follow‐up he had no syncope or chest tightness. The ICD revealed no ventricular tachyarrhythmias or therapy delivered. Copyright © 2009 Wiley Periodicals, Inc.
Comparison of Ischemic Side Effects of Levosimendan and Dobutamine with Integrated Backscatter Analysis
Authors: Duygu Hamza , Nalbantgil Sanem , Zoghi Mehdi , Ozerkan Filiz , Yildiz Ahmet , Akilli Azem , Akin Mustafa
Published: April 2009

Background

Levosimendan improves cardiac contractility without increasing oxygen consumption. However, its effects on ischemia were not supported with the utilization of a noninvasive parameter of myocardial characterization.

Hypothesis

The changes observed in integrated backscatter (IBS) may be reflective of change in myocardial ischemia. In this study, the effect of levosimendan on ischemia detected by IBS was evaluated in patients with ischemic heart failure (HF).

Methods

Patients who had LVEF < 40% and NYHA III–IV symptoms of HF were included in this study. Patients were randomized to levosimendan (n = 21), or to dobutamine (n = 25) groups. The cyclic variation of integrated backscatter (CVIBS) was determined as the difference between the maximal and minimal values in a cardiac cycle, average of three consecutive beats. CVIBS was taken from the mid‐anteroseptal, mid‐inferior, and mid‐posterolateral areas of the parasternal short axis images before the drug administration and at the end of the 24‐hour infusion period.

Results

Baseline characteristics and concomitant medications were similar in both groups. A significant reduction in CVIBS was detected in anteroseptal (7.6 ± 1.4 dB versus 5.9 ± 0.8 dB,p= 0.01), inferior wall (7.4 ± 0.8 dB versus 6.7 ± 1.5 dB,p= 0.03), and posterolateral wall (9.0 ± 1.2 dB versus 8.2 ± 0.6 dB,p= 0.04) after dobutamine administration, while no significant changes were observed in the levosimendan group in all walls.

Conclusions

Unlike dobutamine, levosimendan may not induce myocardial ischemia as shown by CVIBS at commonly used dosages in the setting of decompensated HF without active ischemia. Copyright © 2009 Wiley Periodicals, Inc.
Risk of Stroke and Thrombus Formation From Delay Incontinence of a PLAATO‐Device in Friedreich Ataxia
Authors: Stöllberger Claudia , Finsterer Josef , Avanzini Marion , Mölzer Günther , Weidinger Franz
Published: April 2009

We present the case of a 76‐year‐old female with suspected Friedreich ataxia, in whom leakage and thrombosis of a percutaneously implanted left atrial appendage occluder (PLAATO) was observed 2 years after implantation. Because of late developing leakages and thrombi, regular transesophageal echocardiographic examinations should be carried out in patients with occluded left atrial appendagaes. In view of these complications and the potential important hemodynamic role of the left atrial appendage, the benefit of its occlusion is questionable, and the indications of PLAATO should be strongly reconsidered. Copyright © 2009 Wiley Periodicals, Inc.
Markers of Thrombosis and Hemostasis in Acute Coronary Syndromes: Relationship to Increased Heart Rate and Reduced Heart‐Rate Variability
Authors: Hamaad Ali , Sosin Michael D. , Blann Andrew D. , Lip Gregory Y. H. , MacFadyen Robert J.
Published: April 2009

Background

Acute coronary syndromes (ACS) are characterized by abnormal heart‐rate variability (HRV) and biomarkers of endothelial damage and thrombosis.

Hypothesis

We hypothesized an association between these factors in patients with ACS.

Methods

We studied 99 patients with ACS measuring HRV and plasma markers of endothelial damage/dysfunction (von Willebrand factor, vWF) and thrombosis/hemostasis (soluble P‐selectin (s‐Psel); CD40‐ligand (CD40‐L); D‐dimer). HRV and plasma indices were compared to age‐ and gender‐matched controls. Measures were repeated at 4 months in a subset. vWF, s‐Psel and D‐Dimer levels were raised compared to control.

Results

HRV indices were reduced (mean RR, SDNN, SDNNi, RMSSD, Triangular index, LF and HF). There were weak correlations between mean RR and s‐Psel (R = − 0.234, p = 0.023) and D‐dimer (R = − 0.219, p = 0.041). At 4‐month follow‐up, significant correlations were between mean RR and CD40L (R = − 0.414, p = 0.008) and D‐dimer (R = − 0.363, p = 0.012). On multivariate logistic regression analysis statin use (p = 0.046) was the only independent predictor of acute s‐Psel levels. Age (p = 0.004) and mean RR interval (p = 0.01) were independent predictors of D‐dimer levels at follow‐up.

Conclusions

Abnormal HRV is associated with markers of hemostasis and thrombosis in ACS, and present both in the acute and rehabilitation phases. Copyright © 2009 Wiley Periodicals, Inc.
Interatrial Block: Correlation with P‐Terminal Force
Authors: Spodick David H. , Ariyarajah Vignendra , Goldberg Robert
Published: April 2009

Background and Hypothesis

Interatrial block (IAB: P‐duration > 100 ms) is poorly recognized in hospital populations. In addition to reduced left atrial function and left atrial enlargement it predicts atrial fibrillation and other arrthymias. P‐terminal force (Ptf): ± biphasic P in lead V1 ≥ area of 1 small square on the electrocardiogram (ECG) grid also indicates left atrial abnormality, particularly left atrial enlargement. These 2 should be related. We determined the intercorrelation.

Methods and Results

Two blinded observers evaluated 500 consecutive patients' ECGs for both Ptf and IAB utilizing all 12 leads for IAB and V1 for Ptf. Measurement differences were resolved in a consensus conference. Among 482 usable ECGs, IAB and Ptf were strongly and significantly correlated (χ2 = 68.041; P≤.001).

Conclusion

IAB and Ptf are significantly and strongly correlated and one should be expected in the majority of cases when the other is recognized. Copyright © 2009 Wiley Periodicals, Inc.
The Importance of Gamma‐Glutamyltransferase Activity in Patients with Coronary Artery Disease
Authors: Demircan Sabri , Yazici Mustafa , Durna Kenan , Kilicaslan Fethi , Demir Serdar , Pinar Mesut , Gulel Okan
Published: April 2009

Background

In this study, we sought to investigate the relation of gamma‐glutamyltransferase (GGT) levels with the significance of coronary artery disease (CAD), clinical presentation, left ventricular (LV) function, and inflammatory activity.

Methods

A total of 235 patients (mean age: 60.1 ± 10.5 years, 166 [70%] males) who had coronary angiography were included in the study. Patients who had CAD constituted the study group (Group 1, n=189) and patients who had insignificant coronary disease or normal coronary activity constituted the control group (Group 2, n=46).

Results

GGT levels were higher in Group 1 than Group 2 (38.7 ± 30.9 U/L versus 27.5 ± 17.5 U/L, p =0.025). Left ventricular ejection fraction (LVEF) was lower in Group 1 than Group 2 (52.6% ± 11.7% versus 58.8% ± 11.3%, p < 0.002). GGT activity (40.2 ± 32.5 U/L versus 29.1 ± 18.3 U/L, p < 0.002) and c‐reactive protein (CRP) levels (33.9 ± 43.6 mg/dl versus 17.8 ± 29.8 mg/dl, p < 0.002) were higher, LVEF (52.6% ± 12.1% versus 56.5% ± 11.0%, p =0.021) was lower in patients with acute coronary syndrome compared with stable CAD group. In regression analysis, CRP levels (p < 0.0001, odds ratio [OR]=3.77, 95% confidence interval [CI] 0.10 < OR < 0.32), LVEF (p =0.016, OR=− 2.44, 95% CI − 0.95 < OR < − 0.10) and LV end‐diastolic pressure (p =0.015, OR=4.31, 95% CI − 1.19 < OR < − 0.13) were independent predictors of GGT activity.

Conclusions

The increased GGT activity is related to LV function, clinical stability, and inflammatory activity rather than the severity of CAD. Measurement of GGT activity may be useful in predicting cardiovascular risk. Copyright © 2009 Wiley Periodicals, Inc.
Cutting Balloon Angioplasty and Stent Implantation for Aorto‐ostial Lesions: Clinical Outcome and 1‐year Follow‐up
Authors: Nassar Hisham , Gotsman Israel , Gerganski Penko , Moseri Morris , Lotan Chaim , Gotsman Mervyn
Published: April 2009

Background

Percutaneous interventions for aorto‐ostial narrowing of native coronary arteries are challenging because of early elastic recoil after the procedure and the high restenosis rate. Cutting balloon angioplasty may reduce this complication.

Hypothesis

The purpose of the study was to evaluate the clinical outcomes of cutting balloon angioplasty and stent implantation for aorto‐ostial lesions with a 1‐year clinical follow‐up.

Methods

All patients with aorto‐ostial lesions in our laboratory underwent cutting balloon angioplasty and were followed for approximately 1 year.

Results

Forty‐eight patients underwent balloon angioplasty; 36 of whom had lesions in the ostial right coronary artery, and 12 of whom had lesions in the left main coronary artery (LMCA). Thirty‐five patients (73%) had a stent implanted. Procedural success was achieved in all patients. The in‐hospital rate of major adverse cardiac events (MACEs) was 2.1% because of the death of 1 patient following urgent bypass surgery. Mean clinical follow‐up was 11.6 ± 7 month. Twelve patients (27%) required repeat coronary angiography, and restenosis was found in 7 patients (16%). Six patients (13.6%) had MACEs.

Conclusions

Cutting balloon angioplasty in combination with bare metal stent (BMS) implantation has a good clinical outcome. This technique should be compared with implantation of drug‐eluting stents (DESs) in a controlled study. Copyright © 2009 Wiley Periodicals, Inc.
Infective Endocarditis of Unusual Location Following Surgical Correction of a Complex Congenital Heart Disease
Authors: Viana‐Tejedor Ana , Sánchez‐Recalde Angel , Oliver José , Maté Isabel , Sobrino José , Bret M. , López de Sá y Areses Esteban , Lopez Sendon Jose
Published: April 2009

A 40‐year‐old woman from Ecuador diagnosed with a complex congenital heart disease was admitted complaining of fever chills, night sweats, and productive cough 6 months after surgical correction of the anomalies. An echocardiography showed vegetations located on the interatrial pericardium patch. To the best of our knowledge, this is the first reported case of postoperative infective endocarditis on this location. Copyright © 2009 Wiley Periodicals, Inc.
Stem Cells Improve Left Ventricular Function in Acute Myocardial Infarction
Authors: Singh Sarabjeet , Arora Rohit , Handa Kamna , Khraisat Ahmad , Nagajothi Nagapradeep , Molnar Janos , Khosla Sandeep
Published: April 2009

Background

Animal studies have suggested dramatic improvement in cardiac function after acute myocardial infarction (AMI) through regeneration of the myocardium or neovascularization by transfer of cells derived from bone marrow (BMC) generated clinical studies. Recently published small sized studies have yielded mixed results, leaving the question unanswered.

Hypothesis

We analyzed data from these studies in a meta‐analysis to investigate if intracoronary stem cell therapy was effective in improving cardiac function.

Methods

A total of 7 randomized controlled trials meeting the inclusion criteria were identified by a systematic literature search. Primary endpoint was change in global left ventricular ejection fraction (LVEF) baseline to follow‐up (ranging between 3 to 6 months). The meta‐analysis consisted of 516 patients (BMC group, 256; control group, 260). A 2‐sided α error of less than .05 was considered to be statistically significant (P<.05).

Results

There were no significant differences in patient characteristics between the BMC treatment and control groups at baseline. Compared to the control group, patients in the BMC treatment group had significantly greater increase in LVEF from baseline to follow‐up (mean difference: 6.108%; SE: 1.753%; 95% confidence interval [CI]: 2.672%− 9.543%; P<.001).

Conclusions

The present meta‐analysis suggests that intracoronary bone marrow stem cell infusion may be effective in improving left ventricular systolic function in patients after acute myocardial infarction. Copyright © 2009 Wiley Periodicals, Inc.
Ignition Delay for Atmospheric Pressure Microplasmas
Authors: Porteanu H. E. , Kühn S. , Gesche R.
Published: April 2009

The ignition process in microplasmas is characterized by time resolved microwave reflection coefficient measurements, using a specially equipped vector network analyzer. We measured the time between the switching on of the microwave power and the onset of the plasma state in air at atmospheric pressures. The delay time decreases from approx. 3 ms to 60 μ s by increasing the microwave power from values just above the ignition threshold to higher values. A simple model shows the role of the free electrons in air and of the electrodes in the ignition process (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Energy Evaluation of Mono‐Energetic Electron Beam Produced by Ellipsoid Cavity Model in the Bubble Regime
Authors: Sadighi‐Bonabi R. , Rahmatallahpor S. , Navid H. , Lotfi E. , Zobdeh P. , Reiazie Z. , Bostandoust M. , Mohamadian M.
Published: April 2009

The electron acceleration in the bubble regime is considered during the laser‐plasma interaction. The PIC and experimental results show that the obtained ellipsoid cavity model is more consistent than the spherical model. We prove the fields inside the cavity depend linearly on the coordinates and the spherical cavity is a special case of the ellipsoid model. The quasi mono‐energetic electrons output beam tracing the laser plasma can be more appropriately described with this model (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Mean Motion in Stochastic Plasmas With a Space‐Dependent Diffusion Coefficient
Authors: Wittkowski R. , Schelin A. B. , Spatschek K. H.
Published: April 2009

Radial transport in the tokamap, which has been proposed as a simple model for the motion in a stochastic plasma, is investigated. A theory for previous numerical findings is presented. The new results are stimulated by the fact that the radial diffusion coefficient is space‐dependent. The space‐dependence of the transport coefficient has several interesting effects which have not been elucidated so far. Among the new findings are the analytical predictions for the scaling of the mean radial displacement with time and the relation between the Fokker‐Planck diffusion coefficient and the running diffusion coef.cient from the mean square displacement. The applicability to other systems is also discussed (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Estimates of the Radial Electric Field in Tokamak‐Like Plasmas
Authors: Ou J.
Published: April 2009

The radial electric field is studied in tokamak‐like plasmas using a simple one dimensional model. The simulation results show that in the core plasma region, the radial electric field generally follows the toroidal velocity term, whereas at the edge, the pressure gradient term is more significant. Simultaneously, the effect of the poloidal velocity term on the radial electric field is associated with the poloidal rotation velocity near the separatrix. In addition, the ambipolar radial electric field in the non‐ambipolar state is also discussed in this paper (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)