bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of an enrichment process for circulating tumor cells from the blood of head and neck cancer patients through depletion of normal cells
Authors: Yang Liying , Lang James C. , Balasubramanian Priya , Jatana Kris R. , Schuller David , Agrawal Amit , Zborowski Maciej , Chalmers Jeffrey J.
Published: July 2008

The optimization of a purely negative depletion, enrichment process for circulating tumor cells (CTCs) in the peripheral blood of head and neck cancer patients is presented. The enrichment process uses a red cell lysis step followed by immunomagnetic labeling, and subsequent depletion, of CD45 positive cells. A number of relevant variables are quantified, or attempted to be quantified, which control the performance of the enrichment process. Six different immunomagnetic labeling combinations were evaluated as well as the significant difference in performance with respect to the blood source: buffy coats purchased from the Red Cross, fresh, peripheral blood from normal donors, and fresh peripheral blood from human cancer patients. After optimization, the process is able to reduce the number of normal blood cells in a cancer patient's blood from 4.05 × 109 to 8.04 × 103 cells/mL and still recover, on average, 2.32 CTC per mL of blood. For all of the cancer patient blood samples tested in which CTC were detected (20 out of 26 patients) the average recovery of CTCs was 21.7 per mL of blood, with a range of 282 to 0.53 CTC. Since the initial number of CTC in a patient's blood is unknown, and most probably varies from patient to patient, the recovery of the CTC is unknown. However, spiking studies of a cancer cell line into normal blood, and subsequent enrichment using the optimized protocol indicated an average recovery of approximately 83%. Unlike a majority of other published studies, this study focused on quantifying as many factors as possible to facilitate both the optimization of the process as well as provide information for current and future performance comparisons. The authors are not aware any other reported study which has achieved the performance reported here (a 5.66 log10) in a purely negative enrichment mode of operation. Such a mode of operation of an enrichment process provides significant flexibility in that it has no bias with respect to what attributes define a CTC; thereby allowing the researcher or clinician to use any maker they choose to define whether the final, enrich product contains CTCs or other cell type relevant to the specific question (i.e., does the CTC have predominately epithelial or mesenchymal characteristics?). Biotechnol. Bioeng. 2009;102: 521–534. © 2008 Wiley Periodicals, Inc.
Development of a rapid and sensitive liquid chromatography/tandem mass spectrometry method for the determination of 1,2‐[bis(1,2‐benzisoselenazolone‐3(2H)‐ketone)]‐ethane (BBSKE), a novel anti‐cancer agent in rat plasma
Authors: Zhou Hai‐Yan , Dou Gui‐Fang , Meng Zhi‐Yun , Lou Ya‐Qing , Zhang Guo‐Liang
Published: July 2008

A rapid and sensitive liquid chromatography/electrospray ionization tandem mass spectrometric (LC/ESI‐MS/MS) method has been developed to determine 1, 2‐[bis(1,2‐benzisoselenazolone‐3(2H)‐ketone)]‐ethane (BBSKE), a novel antineoplastic agent, in rat plasma. The analytes were separated on a C18 column with a mobile phase of methanol–water (75:25, v/v) and detected using a triple‐quadrupole mass spectrometer in positive mode with the selective reaction monitoring. The characteristic ion dissociation transitions were m/z 603.0 → 448.9 for derivatized BBSKE and m/z 631.0 → 476.8 for derivatized internal standard. The assay was linear over a range of 1–1000 ng/mL with a lower limit of quantification of 1 ng/mL. Intra‐ and inter‐day precisions were less than 9.6 and 5.0%, respectively, and the accuracy ranged from −5.2 to 4.0%. The validated method was successfully applied to the characterization of pharmacokinetic profile of BBSKE after oral administration in rats. Copyright © 2008 John Wiley & Sons, Ltd.
Simultaneous determination of quinolone antibacterials in bovine milk by liquid chromatography–mass spectrometry
Authors: Zafra‐Gómez Alberto , Garballo Antonio , Ballesteros Oscar , Navalón Alberto , García‐Ayuso Luís E.
Published: July 2008

A new liquid chromatography–mass spectrometry (LC–MS) method has been developed and validated for the simultaneous determination of eight quinolone antibacterials for veterinary use in processed bovine milk samples. The quinolones studied included marbofloxacin, ciprofloxacin, danofloxacin, enrofloxacin, sarafloxacin, difloxacin, oxolinic acid and flumequine. Also, a new sample‐treatment procedure was used for extraction and preconcentration of these compounds. It involved defatting by centrifugation, protein precipitation by adding a mixture of glacial acetic acid–acetonitrile and removing acetonitrile with dichloromethane; finally, the acidified aqueous layer was evaporated to dryness in a speed vac system, resuspended in the mobile phase and filtered prior to LC injection. The mobile phase was composed of a formic acid aqueous solution 0.1% (v/v) and acetonitrile, with an initial composition of water–acetonitrile 95: 5 (v/v) and using linear gradient elution. Norfloxacin was used as internal standard. The limits of quantification found (2–7 ng g−1) were in all cases lower than the maximum residue limits tolerated by the European Union for these compounds in milk. Copyright © 2008 John Wiley & Sons, Ltd.
Determination and pharmacokinetic study of tussilagone in rat plasma by RP‐HPLC method
Authors: Liu Yu‐Feng , Yang Xiu‐Wei , Lu Wei , Xin Xiu‐Lan
Published: July 2008

A simple and rapid high‐performance liquid chromatographic method was used to study the pharmacokinetics of tussilagone, one of the main bioactive constituents in the flower buds ofTussilago farfaraL. of traditional Chinese medicines, in rat plasma. Plasma was deproteinized by ethyl acetate for sample clean‐up. The drugs were separated on a Dikma Diamonsil™ C18column (4.6 × 250 mm, 5.0 µm), and detected by UV absorption at 220 nm. Methanol–water (75:25, v/v) was used as the mobile phase. It was applied to the pharmacokinetic study of tussilagone in rats after a dose of 5 mg/kg by intravenous administration and a dose of 200 mg/kg by intragastrical administration. A biphasic phenomenon with a rapid distribution followed by a slower elimination phase was observed from the plasma concentration–time curve by intravenous administration, while the plasma concentration–time curve of tussilagone conformed to a one‐compartment model by intragastrical administration. The absolute bioavailability of tussilagone is about 1.31%. Copyright © 2008 John Wiley & Sons, Ltd.
LC‐MS/MS method for the determination of cynandione A in rat plasma and tissues
Authors: Zhang Yaping , Shan Lei , Xu Wen , Yang Ming , Zhang Weidong , Li Haiyun
Published: July 2008

A rapid and sensitive method using liquid chromatography–tandem mass spectroscopy (LC‐MS/MS) was developed and validated for the quantitative determination of cynandione A in rat plasma and tissues. The plasma samples were pretreated by liquid–liquid extraction with ethyl acetate after the internal standard (honokiol) had been spiked. The tissue samples were homogenized with physiological saline and treated further like the plasma samples. The separation was performed using a Zorbax SB‐C18 column (3.5 µm, 2.1 × 100 mm) and a C18 guard column (5 µm, 4.0 × 2.0 mm) with an isocratic mobile phase consisting of methanol–0.1% formic acid (78:22, v/v) at a flow rate of 0.2 mL/min. The Agilent G6410A triple quadrupole LC/MS system was operated under the multiple‐reaction monitoring mode using the electrospray ionization technique in negative mode. The nominal retention times for cynandione A and honokiol were 1.41 and 2.63 min, respectively. The method was validated within the concentration range 0.2–1000 ng/mL in plasma and homogenized tissue for cynandione A, and the calibration curves were linear with correlation coefficients >0.992. The lower limit of quantification of cynandione A was 0.2 ng/mL. The intra‐day and inter‐day precision and accuracy of the assay in plasma were less than 14.4%, while the intra‐day and inter‐day precision and accuracy of the assay in tissue homogenate were less than 14.2%. This method proved to be suitable for study of pharmacokinetics and tissue distribution of cynandione A in rat. Copyright © 2008 John Wiley & Sons, Ltd.
Determination of dehydrodiisoeugenol in rat tissues using HPLC method
Authors: Li Fei , Yang Xiu‐wei
Published: July 2008

Dehydrodiisoeugenol (DDIE) is a bioactive neolignan from the seeds of Myristica fragrans Houtt., which exhibits good anti‐inflammatory activity. A rapid and simple high‐performance liquid chromatographic (HPLC) method has been developed for the determination of DDIE in rat tissues after intravenous administration. The tissue samples were processed by liquid–liquid extraction. The analyses were successfully carried out on a Diamonsil™ ODS C18 column (250 × 4.6 mm i.d., 5 µm) equipped with a C18 guard column (8 × 4.6 mm i.d., 5 µm). The mobile phase was the system of methanol–water (4:1, v/v). The UV detection was set at 270 nm. The calibration curves were linear from 0.4 to 200.0 µg/g with the correlation coefficients (r2) greater than 0.998. The intra‐ and inter‐day precisions in quality control samples were less than 10% and the accuracies were in the range 85.4–110.3%. The average recoveries from all the tissues were between 84.4 and 106.0%. This assay method has been successfully used to study the tissues distribution of DDIE in rats after intravenous administration. The result suggests that DDIE is distributed to rat tissues rapidly with possibly greater initial concentrations in liver and brain than in other tissues. Copyright © 2008 John Wiley & Sons, Ltd.
High‐throughput LC‐MS/MS assay for 6‐methoxy‐2‐naphthylacetic acid, an active metabolite of nabumetone in human plasma and its application to bioequivalence study
Authors: Patel Bhavin N. , Sharma Naveen , Sanyal Mallika , Prasad Arpana , Shrivastav Pranav S.
Published: July 2008

A simple, precise and accurate assay for the determination of 6‐methoxy‐2‐naphthylacetic acid (6‐MNA), an active metabolite of nabumetone in human plasma, was developed and validated using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). The analyte (6‐MNA) and propranolol (internal standard, IS) were extracted from 200 µL aliquot of human plasma via solid‐phase extraction employing HLB Oasis cartridges and separated on a Discovery® HS C18 (50 × 4.6 mm, 5 µm) column. Detection of analyte and IS was done by tandem mass spectrometry with a turbo ion spray interface operating in positive ion and multiple reaction monitoring acquisition mode. The total chromatographic runtime was 3.0 min with retention time for 6‐MNA and IS at 1.97 and 1.26 min, respectively. The method was validated over a dynamic linear range of 0.20–60.00 µg/mL for 6‐MNA with mean correlation coefficient r ≥ 0.9986. The intra‐batch and inter‐batch precision (%CV) across five validation runs (lower limit of quantiation, low‐, medium‐ and high‐quality controls and upper limit of quantitation) was less than 7.5%. The accuracy determined at these levels was within −5.8 to +0.2% in terms of percentage bias. The method was successfully applied for a bioequivalence study of 750 mg nabumetone tablet formulation in 12 healthy Indian male subjects under fasted condition. Copyright © 2008 John Wiley & Sons, Ltd.
Application of RP‐TLC technique for the determination of dissociation constants of 1‐substituted pyrrolidin‐2‐one derivatives
Authors: Kulig Katarzyna , Rybicka Karolina , Malawska Barbara
Published: July 2008

The procedures for measuring dissociation constants (pKa) of twenty 1‐substituted pyrrolidin‐2‐one derivatives are described. The dissociation constants of the compounds tested were determined using potentiometric titration, reversed‐phase thin‐layer chromatography (RP‐TLC) and calculated using Pallas and Marvin programs. It was found that the RP‐TLC method of determination of pKa could be considered as a feasible alternative to potentiometric titration. The Marvin program is a better tool for preliminary estimation of dissociation constant than the Pallas one. Copyright © 2008 John Wiley & Sons, Ltd.
Structural elucidation of in vitro metabolites of emodin by liquid chromatography–tandem mass spectrometry
Authors: Song Rui , Xu Fengguo , Zhang Zunjian , Liu Ying , Dong Haijuan , Tian Yuan
Published: July 2008

Liquid chromatography–electrospray ionization tandem mass spectrometry (LC‐ESI‐MS/MS) was employed to investigate the in vitro metabolism of emodin. Emodin was incubated with rat liver microsomes in the presence of a NADPH‐generating system, followed by extraction with ethyl acetate. After separation on a reversed‐phase C18 analytical column with a linear gradient elution of methanol and 0.1% formic acid in water, negative electrospray ionization tandem mass spectrometry experiments were performed. As a result, the parent drug and its six metabolites were detected from rat liver microsomal incubations. The identification of the metabolites and elucidation of their structure were performed by comparing the changes in molecular masses (ΔM), retention times and MS2 spectral patterns of metabolites with those of parent drug. Besides three mono‐hydroxylated metabolites (ω‐hydroxyemodin, 2‐hydroxyemodin, 4‐hydroxyemodin), three other metabolites were identified, which were emodic acid, 3‐carbomethoxy‐6‐methoxy‐1,8‐dihydroxyanthraquinone and physcion, respectively. Copyright © 2008 John Wiley & Sons, Ltd.
Improved HPLC method for doxorubicin quantification in rat plasma to study the pharmacokinetics of micelle‐encapsulated and liposome‐encapsulated doxorubicin formulations
Authors: Wei Guangli , Xiao Shuhua , Si Duanyun , Liu Changxiao
Published: July 2008

An improved simple, rapid and accurate HPLC method for quantification of doxorubicin derived from micelle‐encapsulated or liposome‐encapsulated doxorubicin formulation in rat plasma was described. The mobile phase consisting of a mixture of methanol–water [containing 0.1% formic acid anhydrous and 0.1% ammonia solution (25%), pH 3.0], 60:40, was delivered at a flow rate of 1.0 mL/min. Sample preparation for micelle‐ or liposome‐encapsulated doxorubicin in rat plasma were achieved directly by protein precipitation with acetonitrile. Doxorubicin and daunorubicin (internal standard, IS) were separated on a C18 reversed‐phase HPLC column and quantified by a fluoresence detection with an excitation wavelength of 475 nm and an emission wavelength of 580 nm. The linearity was obtained over the range of 5.0–1000.0 ng/mL and 1.0–200.0 µg/mL for doxorubicin and the lower limit of quantitation was 5.0 ng/mL. For each level of quality control samples, inter‐ and intra‐assay precision was less than 9.6 and 5.1% (relative standard deviation), respectively, and percentage error was within ±2.6%. The extraction recoveries of doxorubicin in the range of 10 ng/mL to 100 µg/mL in rat plasma were between 94.1 and 105.6%. This method was successfully applied to the pharmacokinetic study of doxorubicin formulations after i.v. administration to rats. Copyright © 2008 John Wiley & Sons, Ltd.
Development of a pretreatment method for amyloid β‐protein analysis based on the effect of acetic acid on the dissolution of plasma polypeptides
Authors: Goda Ryoya , Masumoto Hiroshi , Okazaki Osamu , Sudo Kenichi
Published: July 2008

During the evaluation of a pretreatment method for the simultaneous quantification of four amyloid β‐protein fragments in transgenic mice plasma by a new gradient system, we have found that acetic acid has potency to completely dissolve plasma polypeptides in the presence of an organic solvent. Based on this observation, we designed a simple pretreatment method using an ultrafiltration membrane. An analysis of the filtrate obtained by this method suggests the possibility that acetic acid inhibits the interaction between amyloid β‐protein fragments and plasma polypeptides, which leads to a higher recovery of the amyloid β‐protein fragments from mouse plasma. In addition, higher dilution of mouse plasma using a dilution solution produced higher recovery as well. The highest recovery of amyloid β‐protein 1–38, 1–40, 1–42 and 1–43 fragments was 101.7, 94.9, 96.2 and 84.8%, respectively. Furthermore, calibration curves with the lower limit of quantification of 0.65 nm were successfully constructed with good accuracy using the developed method. Consequently, a pretreatment method using an ultrafiltration membrane is a powerful tool to determine the amyloid β‐protein fragments in transgenic mice plasma containing an abundance of plasma polypeptides such as albumin. Copyright © 2008 John Wiley & Sons, Ltd.
Simultaneous quantification of acylated and desacylated ghrelin in biological fluids
Authors: Aydin Suleyman , Karatas Fikret , Geckil Hikmet
Published: July 2008

This study reports simultaneous quantification of both acylated and desacylated forms of ghrelin in biological samples, utilizing a reverse‐phase high‐performance liquid chromatography (HPLC) system. The HPLC assay was also compared with RIA assays in use. Biological samples (serum, saliva, urine, milk) known for the presence of ghrelin were collected from a total of eight post‐partum women and eight male volunteers. Analysis of ghrelin with HPLC was also validated for linearity, precision, detection limit and accuracy. An elution time of 6 min was observed for pure (commercial) desacylated human ghrelin and for the same form of the hormone from all body fluids studied. The elution time for acylated pure human ghrelin and that in body fluids, however, was around 16 min. The mean recovery rate was over 90% for both forms with no significant interference. The lowest detectable levels for acylated and desacylated ghrelin with the method used here were 11 (±2) and 14 (±3) pg mL−1, respectively. Given its simplicity, accuracy, time and cost‐effectiveness, the HPLC method described here for determination of two forms of ghrelin (active and inactive) might prove useful for certain diagnostic purposes. Copyright © 2008 John Wiley & Sons, Ltd.
LC/MS/MS for identification of in vivo and in vitro metabolites of jatrorrhizine
Authors: Zhang Yi , Wu Wenhua , Han Fengmei , Chen Yong
Published: July 2008

The in vivo and in vitro metabolism of jatrorrhizine has been investigated using a specific and sensitive LC/MS/MS method. In vivo samples including rat feces, urine and plasma collected separately after dosing healthy rats with jatrorrhizine (34 mg/kg) orally, along with in vitro samples prepared by incubating jatrorrhizine with rat intestinal flora and liver microsome, respectively, were purified using a C18 solid‐phase extraction cartridge. The purified samples were then separated with a reversed‐phase C18 column with methanol–formic acid aqueous solution (70:30, v/v, pH3.5) as mobile phase and detected by on‐line MS/MS. The structural elucidation of the metabolites was performed by comparing their molecular weights and product ions with those of the parent drug. As a result, seven new metabolites were found in rat urine, 13 metabolites were detected in rat feces, 11 metabolites were detected in rat plasma, 17 metabolites were identified in intestinal flora incubation solution and nine metabolites were detected in liver microsome incubation solution. The main biotransformation reactions of jatrorrhizine were the hydroxylation reaction, the methylation reaction, the demethylation reaction and the dehydrogenation reaction of parent drug and its relative metabolites. All the results were reported for the first time, except for some of the metabolites in rat urine. Copyright © 2008 John Wiley & Sons, Ltd.
Aib Residues in Peptaibiotics and Synthetic Sequences: Analysis of Nonhelical Conformations
Authors: Aravinda Subrayashastry , Shamala Narayanaswamy , Balaram Padmanabhan
Published: July 2008

The α‐aminoisobutyric (Aib) residue has generally been considered to be a strongly helicogenic residue as evidenced by its ability to promote helical folding in synthetic and natural sequences. Crystal structures of several peptide natural products, peptaibols, have revealed predominantly helical conformations, despite the presence of multiple helix‐breaking Pro or Hyp residues. Survey of synthetic Aib‐containing peptides shows a preponderance of 310‐, α‐, and mixed 310/α‐helical structures. This review highlights the examples of Aib residues observed in nonhelical conformations, which fall ‘primarily’ into the polyproline II (PII) and fully extended regions of conformational space. The achiral Aib residue can adopt both left (αL)‐ and right (αR)‐handed helical conformations. In sequences containing chiral amino acids, helix termination can occur by means of chiral reversal at an Aib residue, resulting in formation of a Schellman motif. Examples of Aib residues in unusual conformations are illustrated by surveying a database of Aib‐containing crystal structures.
Conformational Effects on the Electron‐Transfer Efficiency in Peptide Foldamers Based on α,α‐Disubstituted Glycyl Residues
Authors: Gatto Emanuela , Porchetta Alessandro , Stella Lorenzo , Guryanov Ivan , Formaggio Fernando , Toniolo Claudio , Kaptein Bernard , Broxterman Quirinus B. , Venanzi Mariano
Published: July 2008

Peptide foldamers based on α,α‐disubstituted glycyl residues were synthesized and chemically characterized to investigate the effects of the electric field generated by a 310‐helix on the rate of intramolecular photoinduced electron‐transfer reactions. To this end, two new octapeptides having identical sequences were suitably side‐chain functionalized with the same electron‐transfer donor–acceptor pair, but inverting the position of the pair along the main chain. The electron‐transfer rate constants, measured by time‐resolved spectroscopy techniques (nanosecond transient absorption and time‐resolved fluorescence), indicated that, in the case of the 310‐helix, the electrostatic effect is significant, but smaller than that obtained for α‐helical peptides. This finding can be likely ascribed to the distortion of the H‐bond network with respect to the helical axis taking place in the former secondary structure. Overall, these results could have implications on electron‐transfer phenomena in model and biomembranes facilitated by peptaibiotics.
Two New Bromotyrosine Derivatives from the Marine Sponge Pseudoceratina sp.
Authors: Ma Ke , Yang Yi , Deng Zhiwei , de Voogd Nicole J. , Proksch Peter , Lin Wenhan
Published: July 2008

Two new bromotyrosine alkaloids, purealidins T and U (1 and 2, resp.), along with five known bromotyrosines 3–7, were isolated from marine sponge Pseudoceratina sp. Their structures were elucidated on the basis of extensive spectroscopic data (CD, IR, 1D‐ and 2D‐NMR, and MS) analysis.
Leaf Essential Oil Composition of Three Species of Myrcianthes from Monteverde, Costa Rica
Authors: Cole Ramona A. , Haber William A. , Lawton Robert O. , Setzer William N.
Published: July 2008

To examine the chemical diversity of essential oils from Myrcianthes species (Myrtaceae) as well as potential chemotaxonomic relationships between them, the leaf essential oils of M. fragrans (Sw.) McVaugh, M. rhopaloides (Kunth) McVaugh, and an undescribed species, Myrcianthes ‘black fruit’, from Monteverde, Costa Rica, were isolated by hydrodistillation and analyzed by GC/MS. The most abundant components of the essential oil of M. fragrans were 1,3,5‐trimethoxybenzene (15.7%), (Z)‐hex‐3‐en‐1‐ol (10.0%), α‐cadinol (10.4%), eudesma‐4(15),7‐dien‐1β‐ol (9.0%), caryophyllene oxide (7.8%), and spathulenol (7.5%). The leaf oils of two different samples of Myrcianthes rhopaloides were quantitatively different with one sample composed mostly of linalool (17.7%), α‐cadinol (14.4%), spathulenol (11.1%), τ‐cadinol (9.6%), and 1‐epicubenol (6.9%), and the other was made up largely of (E)‐hex‐2‐enal (46.1%), 1,8‐cineole (12.5%), linalool (9.1%), α‐cadinol (6.7%), and α‐terpineol (4.4%). The major components in the leaf essential oil of Myrcianthes ‘black fruit’ were 1,8‐cineole (38.3%), α‐terpineol (21.2%), heptan‐2‐ol (15.5%), terpinen‐4‐ol (4.2%), and β‐pinene (3.8%). The leaf oil compositions of Myrcianthes in this study are very different from leaf oils from other members of Myrcianthes reported in the literature. A cluster analysis reveals large chemical variation not only between members of the genus, but also between samples of the same species.
A New Indole Alkaloid and Anti‐Inflammatory Constituents from Strychnos cathayensis
Authors: Chen Jih‐Jung , Luo Yu‐Ting , Hwang Tsong‐Long , Sung Ping‐Jyun , Wang Tai‐Chi , Chen Ih‐Sheng
Published: July 2008

A new indole alkaloid, 11,12‐dimethoxyhenningsamine (1), was isolated from the roots of Strychnos cathayensis, together with 19 known compounds. The structure of this new compound was determined through spectroscopic and mass‐spectrometric analyses. Among the isolated compounds, 11‐methoxyhenningsamine (3) and aesculetin dimethyl ether (4) exhibited potent inhibition (IC50<5.5 μg/ml) on superoxide‐anion generation and elastase release by human neutrophils in response to fMet‐Leu‐Phe/cytochalasin B.
Natural Inhibitors of DNA Topoisomerase I with Cytotoxicities
Authors: Han Hong‐Jin , Tan Ning‐Hua , Zeng Guang‐Zhi , Fan Jun‐Ting , Huang Huo‐Qiang , Ji Chang‐Jiu , Jia Rui‐Rui , Zhao Qin‐Shi , Zhang Ying‐Jun , Hao Xiao‐Jiang , Wang Li‐Qin
Published: July 2008

DNA Topoisomerase I can cause DNA breaks and play a key role during cell proliferation and differentiation. It is an important target for anticancer agents. While screening for anticancer compounds, seven natural compounds, 1–7, showed potent cytotoxicities against a panel of ten cancer cell lines. Moreover, an inhibition assay demonstrated that they are also DNA topoisomerase I inhibitors, in which inhibitors 1–5 are new ones.
Two New Triterpene Saponins from the Anti‐Inflammatory Saponin Fraction of Ilex pubescens Root
Authors: Wang Jing‐Rong , Zhou Hua , Jiang Zhi‐Hong , Liu Liang
Published: July 2008

The saponin fraction from the ethanolic extracts of the root of Ilex pubescens Hook. et Arn. (Ilexaceae) was found to exhibit potent anti‐inflammatory effects on carrageenan‐induced paw edema in rats. Two novel triterpene saponins, pubescenosides C and D (1 and 2, resp.), together with five known saponins were isolated from this saponin fraction. The structures of 1 and 2 were elucidated as (20β)‐3‐O‐[β‐D‐glucopyranosyl‐(1→2)‐β‐D‐xylopyranosyl]ursa‐12,18‐dien‐28‐oic acid 28‐O‐β‐D‐glucopyranosyl ester, and (20β)‐3‐O‐[α‐L‐rhamnopyranosyl‐(1→2)‐β‐D‐glucopyranosyl‐(1→2)‐β‐D‐xylopyranosyl]ursa‐ 12,18‐dien‐28‐oic acid 28‐O‐β‐D‐glucopyranosyl ester, respectively, on the basis of chemical and spectroscopic data. Five known saponins isolated from the saponin fraction were identified as ilexsaponin B1, B2, B3, A1, and chikusetsusaponin IVa (3–7, resp.).
A New Dihydroagarofuranoid Sesquiterpene and Antituberculosis Constituents from the Root of Microtropis japonica
Authors: Chou Tsung‐Hsien , Chen Ih‐Sheng , Peng Chien‐Fang , Sung Ping‐Jyun , Chen Jih‐Jung
Published: July 2008

A new dihydroagarofuran‐based sesquiterpene, 15‐acetoxyorbiculin A (1), was isolated from the root of Microtropis japonica, together with 13 known compounds. Their structures were determined through in‐depth spectroscopic and mass‐spectrometric analyses. Among the isolated compounds, celahin C (6) and salasol A (7) exhibited potent in vitro antituberculosis activity, both with an MIC value of 15.0 μg/ml against Mycobacterium tuberculosis H37Rv.
Biochemistry of PUFA Double Bond Isomerases Producing Conjugated Linoleic Acid
Authors: Liavonchanka Alena , Feussner Ivo
Published: July 2008

The biotransformation of linoleic acid (LA) into conjugated linoleic acid (CLA) by microorganisms is a potentially useful industrial process. In most cases, however, the identities of proteins involved and the details of enzymatic activity regulation are far from clear. Here we summarize available data on the reaction mechanisms of CLA‐producing enzymes characterized until now, from Butyrivibrio fibrisolvens, Lactobacillus acidophilus, Ptilota filicina, and Propionibacterium acnes. A general feature of enzymatic LA isomerization is the protein‐assisted abstraction of an aliphatic hydrogen atom from position C‐11, while the role of flavin as cofactor for the double bond activation in CLA‐producing enzymes is also discussed with regard to the recently published three‐dimensional structure of an isomerase from P. acnes. Combined data from structural studies, isotopic labeling experiments, and sequence comparison suggest that at least two different prototypical active site geometries occur among polyunsaturated fatty acid (PUFA) double bond isomerases.
SAR by Oxime‐Containing Peptide Libraries: Application to Tsg101 Ligand Optimization
Authors: Liu Fa , Stephen Andrew G. , Waheed Abdul A. , Aman M. Javad , Freed Eric O. , Fisher Robert J. , Burke Terrence R.
Published: July 2008

HIV‐1 viral assembly requires a direct interaction between a Pro‐Thr‐Ala‐Pro (“PTAP”) motif in the viral protein Gag‐p6 and the cellular endosomal sorting factor Tsg101. In an effort to develop competitive inhibitors of this interaction, an SAR study was conducted based on the application of post solid‐phase oxime formation involving the sequential insertion of aminooxy‐containing residues within a nonamer parent peptide followed by reaction with libraries of aldehydes. Approximately 15–20‐fold enhancement in binding affinity was achieved by this approach.
An evidence‐based approach to the use of rotational and directional coronary atherectomy in the era of drug‐eluting stents: When does it make sense?
Authors: Tran Trung , Brown Michael , Lasala John
Published: July 2008

Advances in percutaneous interventions have profoundly changed the way we manage patients with coronary and peripheral arterial disease. Though the use of stents, particularly drug‐eluting stents, is the preferred method for revascularization because of ease of use and lower restenosis rates, there are many short comings. Ostial and bifurcation lesions as well as heavily calcified and tortuous arteries remain problematic. Mechanical debulking with rotational and direct coronary atherectomy may be beneficial in these situations. In this review, we present the general concepts of mechanical debulking and attempt to summarize the available data on its use in the setting of drug‐eluting stents. In addition, we will discuss its special role in the management of peripheral arterial disease. © 2008 Wiley‐Liss, Inc.
Radiation‐induced peripheral artery disease
Authors: Jurado Javier A. , Bashir Riyaz , Burket Mark W.
Published: July 2008

Radiation therapy is a cause of cardiovascular morbidity and mortality. This is due to the significant degree of atherosclerosis seen in the vessels in the vicinity of the area being irradiated. Radiation‐induced peripheral arterial disease is increasingly being recognized as large populations of cancer patients survive longer, yet it is a problem that is often under reported. Although it has most commonly been associated with carotid artery disease, all vascular beds are prone to this form of injury. The injury is accelerated by usual risk factors for atherosclerosis. Developing a healthy lifestyle, dietary prudence and the aggressive treatment of hypertension, diabetes mellitus, and dyslipidemia should all be encouraged in this patient population. When revascularization strategies are warranted, the percutaneous approach may be superior to open surgery as technical difficulties may arise in the fibrotic, scarred tissue. Stenting with distal embolic protection devices should be considered as the treatment of choice for patients with radiation‐induced carotid artery disease. Several reports also suggest good results with balloon angioplasty with or without stenting in the case of radiation‐induced renal, iliac, and femoral artery disease. Lifelong antiplatelet therapy may be appropriate. © 2008 Wiley‐Liss, Inc.
Impact of intravascular ultrasound for the treatment of calcified infrarenal aortic stenosis: A case report study
Authors: Hara Masahiko , Nishino Masami
Published: July 2008

We report two cases of heavily calcified infrarenal aortic stenosis that were successfully treated by Intravascular ultrasound‐ (IVUS)‐guided stenting. Two middle‐aged women visited our hospital due to intermittent claudication. Diagnostic arteriography revealed possible infrarenal aortic stenosis even though the findings were equivocal. IVUS demonstrated heavily calcified atherosclerotic lesions and allowed the accurate assessment of the types and extents of the lesions to be treated in both cases. The patients successfully underwent stent implantation according to the findings of IVUS. IVUS significantly contributed to the interventional successes. © 2008 Wiley‐Liss, Inc.
High‐frequency vibration for the recanalization of guidewire refractory chronic total coronary occlusions
Authors: Tiroch Klaus , Cannon Louis , Reisman Mark , Caputo Ronald , Caulfield Todd , Heuser Richard , Braden Greg , Low Reginald , Stone Gregg , Almonacid Alexandra , Popma Jeffrey J.
Published: July 2008

Background: Recanalization of coronary chronic total occlusions (CTOs) remains a clinical challenge, particularly when standard guidewire attempts fail. Objectives: We sought to determine the safety and efficacy of a novel method that used high‐frequency (20 kHz) vibration to fragment occlusive fibrous tissue and facilitate guidewire crossing into the distal vessel. Methods: A total of 125 patients with CTO, who failed at attempts of conventional guidewire recanalization after more than 5 min of fluoroscopy time, were enrolled in the study. The primary efficacy endpoint was the advancement of the CROSSER™ catheter through the occlusion and attainment of coronary guidewire positioning in the distal coronary lumen. The primary safety endpoint was the occurrence of death, myocardial infarction, clinical perforation, or target vessel revascularization within the first 30 days. Results: The average fluoroscopy time while delivering the CROSSER catheter was 12.4 min. CROSSER‐assisted guidewire recanalization was achieved in 76 (60.8%) procedures and a final diameter stenosis <50% was obtained in 68 (54.4%) of cases. Major adverse events occurred in 11 (8.8%) patients, lower than the predefined objective performance criteria. Angina frequency and quality of life were improved in patients with successful guidewire recanalization. Conclusions: We conclude that high‐frequency vibration using the CROSSER catheter is a safe and effective therapy for patients with CTO, which are refractory to standard guidewire recanalization. © 2008 Wiley‐Liss, Inc.
Sirolimus‐eluting stents versus bare‐metal stents in patients with in‐stent restenosis: Results of a pooled analysis of two randomized studies
Authors: Alfonso Fernando , Pérez‐Vizcayno Maria‐José , Hernandez Rosana , Fernandez Cristina , Escaned Javier , Bañuelos Camino , Bethencourt Armando , López‐Mínguez Jose R , Angel Juan , Cequier Angel , Sabaté Manel , Morís Cesar , Zueco Javier , Seabra‐Gomes Ricardo
Published: July 2008

Background:

Treatment of patients with in‐stent restenosis (ISR) remains a challenge. We sought to compare results of sirolimus‐eluting stents (SES) with those of bare‐metal stents (BMS) in patients with ISR.

Methods:

The results obtained in the stent arm of two randomized studies were analyzed. The RIBS I study (450 patients with ISR) allocated 224 patients to BMS; the RIBS II study (150 patients with ISR) allocated 76 patients to SES. Complete 1‐year follow‐up was obtained in all 300 patients treated with stents.

Results:

Although inclusion/exclusion criteria were identical in the two studies, when compared with patients in the BMS group, patients in the SES arm had more adverse baseline characteristics, more diffuse lesions, and smaller vessels. However, late angiographic findings including in‐segment recurrent restenosis rate (11 vs. 38%, P < 0.001), minimal lumen diameter (2.52 vs. 1.63 mm, P < 0.001), and late loss (0.13 vs. 1.04 mm, P < 0.001) were significantly better after SES. The 1‐year event‐free survival was also significantly improved in the SES group (88 vs. 78%, P < 0.05), as the result of a lower requirement for repeated revascularizations (10.5 vs. 19.6%, P < 0.05). Prespecified subgroup analyses were consistent with the main outcome measures. After adjusting for (a) imbalances in baseline characteristics (restenosis OR 0.11 [95% confidence interval (CI) 0.03–0.36]; adverse events hazard ratios (HR) 0.33 [95% CI 0.13–0.84]) and (b) the propensity score (restenosis OR 0.08 [95% CI 0.03–0.28]; adverse events HR 0.24 [95% CI 0.09–0.66]), results of the SES group were superior to those obtained in the BMS group.

Conclusions:

When compared with BMS, SES improved the long‐term clinicaland angiographic outcome of patients with ISR. © 2008 Wiley‐Liss, Inc.
Subintimal tracking and re‐entry technique with contrast guidanc: A safer approach
Authors: Carlino Mauro , Godino Cosmo , Latib Azeem , Moses Jeffrey W. , Colombo Antonio
Published: July 2008

Objectives: To assess the procedural and clinical outcomes from a modified subintimal tracking and re‐entry (STAR) procedure performed using contrast guidance. Background: Previous data showed that recanalizing a chronic total occlusion (CTO) with the STAR technique was possible. However, this technique was considered difficult and therefore has only been adopted by a limited number of experienced operators. Methods: Patients (n = 68) with a CTO of a native coronary artery treated by a single operator with this technique were included. Results: The right coronary artery was involved in 79.4%, the morphology was blunt in 77.9%, and CTO length was longer than 20 mm in 67.6%. Angiographic success rate was 80.9% with a 70.6% rate of complete recanalization. Stent implantation was performed in 82.3% of cases, with drug‐eluting stents (DES) implanted in the majority (92.7%). Procedural complications occurred in 10.3% of cases. There were no episodes of myocardial infarction during follow‐up, with 1 case (1.5%) of cardiac death. There were no cases of definite or probable stent thrombosis, and there was 1 (1.5%) possible stent thrombosis. The overall rate of in‐segment binary restenosis was 44.7%, and target lesion revascularization (TLR) was performed in 25% of lesions. The rate of TLR in lesions treated with DES was 29.4% and in those treated with bare‐metal stents was 50%. Conclusion: The contrast‐guided STAR technique appears to be feasible and relatively safe. However, this procedure is limited by a high rate of restenosis even with DES, and a second procedure may be necessary to obtain a definitive result. © 2008 Wiley‐Liss, Inc.
Transcatheter closure of patent ductus arteriosus and aorto‐pulmonary vessels using non‐ferromagnetic Inconel MReye embolization coils
Authors: Grifka Ronald G. , Fenrich Arnold L. , Tapio Jason B.
Published: July 2008

Objectives. We report the use of non‐ferromagnetic embolization coils for transcatheter PDA closure. Background. Transcatheter patent ductus arteriosus (PDA) closure has been performed for 40 years. A number of devices have been used with varying degrees of success. Gianturco embolization coils have been used frequently since 1992 with excellent results. These coils are a stainless steel alloy, and create an artifact when subsequent MRI imaging is performed. Methods. Eight patients underwent right and left heart catheterization and transcatheter PDA closure. Angiography displayed a PDA with left to right shunting. The minimum PDA diameter was measured. An Inconel MReye coil was implanted using standard retrograde technique. A postimplant angiogram was performed. Evaluations were performed the following morning and after 2 months. Results. The median age was 5.5 years, median weight was 24 kg. The PDA minimum diameter was 1.7 mm (range 1.4–2.4 mm), with a median Qp:Qs=1.33:1. In all patients, the PDA was completely immediately closed using one Inconel coil. Two patients also had a small aorto‐pulmonary collateral vessel that was occluded using a separate Inconel coil. All patients had follow‐up evaluation the following day; the PDA remained completely occluded and there was no obstruction of the pulmonary artery branches or descending aorta. Seven patients had subsequent follow‐up and echocardiograms; the PDA remained completely occluded. There were no complications. Conclusion. The Inconel MReye coil is safe and effective for coil occlusion of small PDA and aorto‐pulmonary vessels. Additional studies are needed to define the maximum vessel diameter for Inconel coil occlusion. © 2008 Wiley‐Liss, Inc.
Interventional therapy for neonates with critical congenital heart disease
Authors: Kutty Shelby , Zahn Evan M.
Published: July 2008

Transcatheter interventional therapies for children continue to evolve at a remarkable rate. Perhaps no where are these procedures more important than in the critically ill newborn. In this core curriculum review article several of the most commonly performed interventions performed in critically ill newborns are discussed with regards to technique and outcomes. © 2008 Wiley‐Liss, Inc.
Endovascular repair of popliteal artery aneurysms with anaconda limbs: Technique and early results
Authors: Cinà C.S. , Moore R. , Maggisano R. , Kucey D. , Dueck A. , Rapanos T.
Published: July 2008

Objectives: The objective is to report the feasibility and technique of treating popliteal artery aneurysms (PAA) with a stent made of nitinol rings externally supported by thin polyester (Anaconda limbs). Background: PAA are the most common peripheral aneurysms. The main limitations of stents used in these settings are: short lengths, longitudinal and horizontal compliance mismatch; graft failure from angulation and movement at the joint level; and dislodgment. Methods: This is a prospective multicenter cohort study of consecutive symptomatic and asymptomatic PAA treated in tertiary vascular centers. Outcomes included patency of the stent and postoperative time‐to‐independent‐ambulation and to‐climb‐a‐flight‐of‐stairs. Results: Fourteen PAA were treated in 12 men, age 72 ± 3 years. The median ASA classification was 2.5. The length of artery covered was 147 ± 41 mm. The PAA diameter was 31 ± 5 mm, 6 were symptomatic. One stent was used in 6 aneurysms, two in 7, and three in 1. The average stent diameter was 10 ± 1 mm. The length of the proximal neck was 24 ± 6 mm with a diameter of 9.8 ± 1.9, and length of the distal neck 23 ± 3 mm with a diameter of 8.7 ± 1.2 mm. In 6 aneurysms, the stent crossed the knee joint. There was no mortality, and one stent occluded (primary patency 93% at 6 ± 3 months). The median hospital stay was 1.7 days, time to independent ambulation was 3 hr and the time to climbing a flight of stairs was 1 day. Conclusions: The use of Anaconda limbs for endovascular repair of PAA is feasible and safe. © 2008 Wiley‐Liss, Inc.
High incidence of recurrent in stent thrombosis after successful treatment of a first in stent thrombosis
Authors: Lemesle Gilles , Sudre Arnaud , Modine Thomas , Delhaye Cédric , Rosey Guillaume , Gourlay Terry , Bauters Christophe , Lablanche Jean‐Marc
Published: July 2008

Objectives: We attempted to investigate incidence and predictors of recurrent in stent thrombosis (IST) after successful treatment of a first IST. Background: The occurrence of recurrent IST after successful treatment of a first IST may be a decisive factor for patient clinical outcome. However, incidence and predictors of recurrent IST are currently poorly described in the literature. Methods: Between 2003 and 2005, 2,190 patients underwent a percutaneous coronary intervention in our center. During a median follow‐up of 19.4 months, 49 patients (2.24%) presented a first definite IST. Patients presenting with a first IST were followed during an additional median period of 40 months. Their baseline characteristics were listed and cardiovascular events especially recurrent IST as defined by the Academic Research Consortium definition were systematically indexed. Results: Altogether 39 (80%) patients were successfully treated with an effective reperfusion after percutaneous coronary intervention. Fourteen (36%) patients presented a recurrent IST and three presented multiple recurrent IST. The median occurrence time of recurrent IST was 5 days, range between 1 and 11 days. Multivariate analysis identified history of neoplasia (HR = 11.53, 95% CI 2.32–57.37, P = 0.003), residual diameter stenosis (HR = 1.15, 95% CI 1.02–1.29, P = 0.02), and residual dissection after treatment (HR = 8.78, 95% CI 1.85–41.62, P = 0.006), as independent predictors of recurrent IST. Conclusion: Recurrent IST is a frequent and early event after successful treatment of a first IST. Our results suggest that mechanical factors like residual dissection and residual diameter stenosis should be carefully tracked down. In addition, patients with multiple recurrent IST and the early time course of recurrent IST also suggest a potential role of inadequate antiplatelet therapy. © 2008 Wiley‐Liss, Inc.
Multicenter international registry of unprotected left main coronary artery percutaneous coronary intervention with drug‐eluting stents in patients with myocardial infarction
Authors: Lee Michael S. , Sillano Dario , Latib Azeem , Chieffo Alaide , Biondi Zoccai Giuseppe , Bhatia Ravi , Sheiban Imad , Colombo Antonio , Tobis Jonathan
Published: July 2008

Background: Patients who present with myocardial infarction (MI) and unprotected left main coronary artery (ULMCA) disease represent an extremely high‐risk subset of patients. ULMCA percutaneous coronary intervention (PCI) with drug‐eluting stents (DES) in MI patients has not been extensively studied. Methods: In this retrospective multicenter international registry, we evaluated the clinical outcomes of 62 consecutive patients with MI who underwent ULMCA PCI with DES (23 ST‐elevation MI [STEMI] and 39 non‐ST‐elevation MI [NSTEMI]) from 2002 to 2006. Results: The mean age was 70 ± 12 years. Cardiogenic shock was present in 24%. The mean EuroSCORE was 10 ± 8. Angiographic success was achieved in all patients. Overall in‐hospital major adverse cardiac event (MACE) rate was 10%, mortality was 8%, all due to cardiac deaths from cardiogenic shock, and one patient suffered a periprocedural MI. At 586 ± 431 days, 18 patients (29%) experienced MACE, 12 patients (19%) died (the mortality rate was 47% in patients with cardiogenic shock), and target vessel revascularization was performed in four patients, all of whom had distal bifurcation involvement (two patients underwent repeat PCI and two patients underwent bypass surgery). There was no additional MI. Two patients had probable stent thrombosis and one had possible stent thrombosis. Diabetes [hazard ratio (HR) 4.22, 95% confidence interval (CI) (1.07–17.36), P = 0.04), left ventricular ejection fraction [HR 0.94, 95% CI (0.90–0.98), P = 0.005), and intubation [HR 7.00, 95% CI (1.62–30.21), P = 0.009) were significantly associated with increased mortality. Conclusions: Patients with MI and ULMCA disease represent a very high‐risk subgroup of patients who are critically ill. PCI with DES appears to be technically feasible, associated with acceptable long‐term outcomes, and a reasonable alternative to surgical revascularization for MI patients with ULMCA disease. Randomized trials are needed to determine the ideal revascularization strategy for these patients. © 2008 Wiley‐Liss, Inc.
ChemInform Abstract: Cation Substitution Effects in the System Sr2‐xBaxBi3 (0 ≤ x 1.3): Structural Distortions Induced by Chemical Pressure.
Authors: Kim Sung‐Jin , Ponou Simeon , Faessler Thomas F.
Published: July 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Er17Ru6Te3: A Highly Condensed Metal‐Rich Ternary Telluride.
Authors: Mehta Akash , Corbett John D.
Published: July 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.