bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenovirus binding to cultured synoviocytes triggers signaling through MAPK pathways and induces expression of cyclooxygenase‐2
Authors: Crofford Leslie J. , McDonagh Kevin T. , Guo Sutang , Mehta Hemal , Bian Huimin , Petruzelli Lilli M. , Roessler Blake J.
Published: March 2005

Background

Recombinant adenovirus can be administered in vivo to achieve transduction of a number of cell types including human synoviocytes. Immunogenicity of adenoviruses has limited their utility as vectors for gene delivery; however, specific mechanisms underlying the acute inflammatory response to adenovirus are not well understood. Activation of a number of signal transduction pathways occurs rapidly upon adenovirus binding to cell‐surface receptors. We investigated stimulated expression of mitogen‐activated protein kinases (MAPKs), cyclooxygenase‐2 (COX‐2) and prostaglandin E2 (PGE2) in human primary synovial fibroblasts to adenovirus expressing the E. coli β‐galactosidase gene.

Methods

Cultured rheumatoid synoviocytes were exposed to transduction‐competent Ad/RSVlacZ recombinant adenovirus or transduction‐incompetent (psoralen/UV‐irradiated) Ad/RSVlacZ. The effects on COX‐2 expression, PGE2 levels and MAPK signaling in synoviocytes were assessed using a combination of reverse‐transcription polymerase chain reaction amplification and immunoblotting.

Results

Adenovirus treatment of synoviocytes increased levels of COX‐2 mRNA and protein as well as PGE2. Psoralen‐treated transcriptionally inactive adenovirus was equivalent to untreated adenovirus for early COX‐2 induction suggesting that viral genes were not required. Adenovirus treatment stimulated phosphorylation of ERK‐1/‐2, p38 MAPK, and JNK. Inhibition of the ERK and p38 MAPK pathways inhibited COX‐2 expression and PGE2 production.

Conclusions

Taken together, these data demonstrate that a MAPK‐dependent increase in COX‐2 results in local prostaglandin production. These findings have clinical implications for use of adenovirus as vectors for in vivo gene delivery. Copyright © 2004 John Wiley & Sons, Ltd.
Use of a murine secreted alkaline phosphatase as a non‐immunogenic reporter gene in mice
Authors: Mælandsmo Gunhild M. , Joel Ross P. , Pavliv Marta , Meulenbroek Robert A. , Evelegh Carole , Muruve Daniel A. , Graham Frank. L. , Parks Robin J.
Published: March 2005

Background

The development of any vector system as a gene delivery system requires its optimization in vitro and in vivo. Preliminary studies frequently involve the use of a reporter gene, which allows for the rapid and simple assay of vector function through monitoring expression levels of the reporter gene. However, evaluation of vector efficacy can be compromised by immune responses directed against immunogenic reporter proteins.

Methods

We have cloned a murine secreted alkaline phosphatase (mSEAP), and explored its use as a reporter gene in the context of an early region 1 (E1)‐deleted adenovirus (Ad) vector. Studies involved characterization of gene expression in vitro and in vivo, and immunological responses after gene delivery to mice.

Results

In tissue culture, we show that mSEAP is easily measured quantitatively using a sensitive, commercially available chemiluminescent assay, or visualized directly using histological staining. The level of transgene expression from AdmSEAP was similar to that observed for an Ad vector encoding the human placental secreted alkaline phosphatase (hSEAP). After intravenous administration in mice, AdmSEAP continued to express at high levels for the duration of the experiment (1 month), whereas expression from AdhSEAP declined to background levels over the course of the experiment. Although cytotoxic T‐lymphocytes were not detected against either the murine or human SEAP proteins in mice, antibodies were readily detected against the human protein. No antibodies were detected to mSEAP.

Conclusions

Taken together, these data illustrate that mSEAP is a sensitive, non‐immunogenic reporter gene for preclinical mouse studies. Copyright © 2004 John Wiley & Sons, Ltd.
Solid tissues can be manipulated ex vivo and used as vehicles for gene therapy
Authors: Hasson E. , Slovatizky Y. , Shimoni Y. , Falk H. , Panet A. , Mitrani E.
Published: March 2005

Background

Organ fragments can be cultured for weeks in vitro if they are prepared of microscopic thickness and if the basic organ structure is preserved. Such organ fragments, which we termed micro‐organs (MOs), express in culture endogenous tissue‐specific gene products. We have exploited this methodology to engineer MOs ex vivo by gene transfer.

Methods

MOs prepared from spleen, lung, colon and skin were infected using: herpes simplex type‐1, adeno virus, vaccinia virus and murine leukemia virus (MuLV), carrying the reporter gene β‐galactosidase.

Results

All four viral vectors infected MOs in culture, with adeno infection giving significantly higher values. After optimization, high levels of expression (>15% positive cells), comparable to those obtained with the adeno construct, were also obtained using the MuLV construct both in vitro and after implantation into syngeneic hosts. After implantation, the engineered tissue was found to remain localized, become vascularized, and to express the transduced gene for several months.

Conclusions

The system can be used to study interactions between viruses and tissues both ex vivo and in vivo. Furthermore, the approach proposes a novel platform for ex vivo gene therapy. Such engineered structures could be used as autologous biological pumps for continuous secretion in vivo of gene products of clinical importance. Copyright © 2005 John Wiley & Sons, Ltd.
Variability in starch physicochemical and functional properties of yam (Dioscorea sp) cultivated in Ivory Coast N'Guessan Georges Amani Alain Buléon Alphonse Kamenan Paul Colonna Journal of the Science of Food and Agriculture 84(15):2085–2096 (2004)
Authors: Georges Amani N'Guessan , Buléon Alain , Kamenan Alphonse , Colonna Paul
Published: March 2005

The original article to which this Erratum refers was published in Journal of the Science of Food and Agriculture 84(15):2085–2096 (2004)
Rural and agri‐tourism as a tool for reorganising rural areas in old and new member states — a comparison study of Ireland and Poland
Authors: Hegarty Cecilia , Przezborska Lucyna
Published: March 2005

Both assessment of the physical, economic and social impacts of enlargement and monitoring the implementation of policy directives are vital to future European Union operation. This paper investigates tourism development within relatively underdeveloped regions within Ireland and Poland, and it suggests implications for tourism operations. Comparison is made between product and service offerings in both regions. Strong similarities exist between the profiles of operators, operator motivations differ, and business diversification depends on regional resources and dependency on tourism markets. The level of diversification ultimately determines rural tourism development. The value of using Ireland as a reference model for Polish development and critical issues for tourism advisors and policy makers are discussed. Copyright © 2005 John Wiley & Sons, Ltd.
International tourism as bricolage: an analysis of central Europe on the brink of European Union membership
Authors: Baláž Vladimír , Williams Allan M.
Published: March 2005

This paper examines the trajectory of international tourism and its economic role in the Czech Republic, Hungary, Poland and Slovakia during the post‐1989 transition, leading to their European Union (EU) accession in 2004. Although there are relatively simple, and broadly comparable, trends in all four countries in visitor and tourism flows, this is based on chaotic conceptualisation of international mobility. This apparent bricolage is explored further by considering the role of international tourism in the formal and informal economies. In general, there has been as much change as continuity in the transition period, and this provides the dominant frame of reference for understanding the likely impacts of EU membership. Copyright © 2005 John Wiley & Sons, Ltd.
Tourism in Brussels, capital of the ‘New Europe’
Authors: Jansen‐Verbeke Myriam , Vandenbroucke Sylvia , Tielen Sofie
Published: March 2005

This paper considers the potentials and pitfalls of European Union enlargement for tourism development in Brussels, and it explores the role of eurocrats in mediating Brussels as a destination. As a result of enlargement, Brussels may consolidate and eventually strengthen its position as a destination for business tourism. Eurocrats may be a major consumer group but as champions their role is tempered by a discrepancy between visitation and appreciation of the city's offer. By inspecting eurocrats' views in a framework of current marketing attempts and the politics of promotion, the paper attempts to make recommendations on how to take advantage of new opportunities accession may bring. Copyright © 2005 John Wiley & Sons, Ltd.
Kaliningrad — the last piece in the Baltic jigsaw?
Authors: Worthington Barry , Sedakat Pat
Published: March 2005

This paper explores tourism development in the Kaliningrad Oblast associated with European Union (EU) enlargement. Although politically part of the Russian Federation, Kaliningrad now exists as an exclave, distant from the Russian border and surrounded by EU territory. Situated in discourse on cross‐border tourism, this paper argues for a more active analysis of the geopolitics of tourism. Kaliningrad's future is intricately linked with the possible re‐establishment of a former tourism region along the southeastern Baltic coast which crosses several state borders. The potential for this to be achieved, however, is a function of the resolution of the strategic interests of neighbouring states and the EU. Copyright © 2005 John Wiley & Sons, Lid.
Neovascularization in prefabricated flaps using a tissue expander and an implanted arteriovenous pedicle
Authors: The Hoang Nguyen , Kloeppel Marcus , Staudenmaier Rainer , Schweinbeck Sabine , Biemer Edgar
Published: March 2005

Creating prefabricated flaps using tissue expanders in combination with the implantation of maximal blood flow vascular pedicles into suitable tissue areas represents a new tendency in the reconstruction of large skin defects. In 42 Chinchilla Bastard female rabbits weighing 3,700–4,600 g, skeletonized arteriovenous pedicles with maximal blood flow, dissected from the femoral and saphena magna bundles, were implanted underneath abdominal fasciocutaneous flaps. Oval tissue expanders of 250 ml were placed and fixed on the abdominal wall to expand these prefabricated flaps. The evaluation parameters were macroscopic observation, blood analysis, selective microangiography, histology, and scintigraphy. The study results showed that neovascularization in expanded prefabricated flaps was established from newly formed vessels generated from the implanted pedicles and their vascular connections with the originally available vasculature in the flap. After 20 days of prefabrication, the entirety of the expanded prefabricated flaps was perfused by blood flow supplied from newly implanted arteriovenous pedicles. The study indicated that an expanded prefabricated flap can be successfully created by the simultaneous implantation of a maximal blood flow pedicle in combination with flap expansion. © 2005 Wiley‐Liss, Inc. Microsurgery 25:1–7, 2005.
Proposed new method for angiographically quantifying neovascularization in prefabricated flaps
Authors: Hoang Nguyen T. , Kloeppel Marc , Werner Jürgen , Staudenmaier Rainer , Biemer Edgar
Published: March 2005

Prefabricated flaps have many potential applications in plastic and reconstructive surgery. Despite numerous experimental investigations and clinical applications, a standard quantification procedure for analyzing neovascularization in prefabricated flaps has not yet been established in the literature. In this study, we developed a new method for quantifying neovascularization, using a standard integral line plate including 25 evenly spaced lines corresponding to a 15‐cm flap length, which was subsequently analyzed under a 2× magnification loupe. Vessel quantity was determined by counting the total number of times that vessels perfused by Micropaque intersected the integral lines over the entire surface of the flap. This new method was used for quantifying neovascularization in 156 prefabricated flaps, and we concluded that this technique is very simple and useful, allowing precise determination of the amount of neovascularization in prefabricated flaps on angiograms. Based on this principle, the quantification of neovascularization in any size of prefabricated flap can be easily performed using suitably modified integral line plates corresponding to the various flap dimensions. © 2005 Wiley‐Liss, Inc. Microsurgery 25:00–00 2005.
Heterotopic cardiac xenotransplantation in rodents: Report of a refined technique in a hamster‐to‐rat model
Authors: Dedja Arben , Dall'olmo Luigi , Cadrobbi Roberto , Baldan Nicola , Fante Fabio , Calabrese Fiorella , Rigotti Paolo , Ferraresso Mariano , Delriviere Luc , Cozzi Emanuele , Ancona Ermanno
Published: March 2005

Hamster‐to‐rat heterotopic cardiac xenotransplantation is widely used as an experimental model to study xenograft rejection, accommodation, and tolerance, as well as in studies aimed at developing immunosuppressive strategies in xenotransplantation. Despite its widespread application, no detailed description of a surgical technique for this model has been provided in the literature. Indeed, all publications so far on the use of this species combination refer to the rat allotransplantation technique. Hence the present paper provides a detailed, up‐to‐date description of the surgical method adopted at our center for the hamster‐to‐rat heterotopic cardiac xenotransplantation model. Considerable effort went into developing a reliable, reproducible experimental model in rodents, and the description given here is enriched with “tips” that we learned in the process. The discussion of the technique also addresses several significant related issues, e.g., the anesthesia and organ preservation solution used (aspects that, in our experience, are crucial to a good surgical outcome). © 2005 Wiley–Liss, Inc. Microsurgery 25:1–8, 2005.
Use of varioscope in free microvascular tissue transplants
Authors: Spyriounis Petros K.
Published: March 2005

Since July 2002, the author has performed 12 consecutive free flaps using a new device, the Varioscope AF3, in order to evaluate its efficacy. The Varioscope is a world‐patent novelty by Life Optics (Vienna, Austria) that combines the philosophy of microscopes and loupes. Specific advantages such as reduced cost, freedom of movement, portability, and a magnification range between 3.6–7,2× are some of the reasons that convinced the author to use the Varioscope initially. The overall success rate is similar to that obtained with a microscope or high‐power loupes. The results show that the Varioscope AF3 could be safely employed in the majority of free‐tissue transfers as sole means of magnification. However, for digital replantations or vessels with a diameter of less than 1 mm, a microscope might be necessary. © 2005 Wiley‐Liss, Inc. Microsurgery 25:00–00 2005.
Salvage operations of free tissue transfer following internal jugular venous thrombosis: A review of 4 cases
Authors: Miyasaka Muneo , Ichikawa Kota , Nishimura Masaki , Yamazaki Akihisa , Taira Hiroyuki , Imagawa Kotaro , Tanino Ryuzaburo
Published: March 2005

The internal jugular vein (IJV) is used as the optimal recipient for free‐tissue transfer in reconstruction following modified radical neck dissection. Some reports documented rare cases of flap compromise following IJV thrombosis, but large sample studies are few. We present cases of emergent exploration and an analysis of factors to improve salvage rates of compromise due to IJV thrombosis. From a survey of 756 patients, four developed congestion due to IJV thrombosis and returned to the operating room. A restrospective analysis was made from the case records.This represents a rate of 0.5% for the entire series. Three flaps survived,and one failed. Detection of compromise ranged from 7–25 h postoperatively. All four IJVs recovered to provide adequate drainage after thrombectomy.While flap compromise following IJV thrombosis is rare, careful observation and early exploration are crucial for salvage, as in other microvascular venous crises. © 2005 Wiley‐Liss, Inc. Microsurgery 25:00–00 2005.
Gracilis muscle flap for aesthetic reconstruction in the head and neck region
Authors: Huemer Georg M. , Bauer Thomas , Wechselberger Gottfried , Schoeller Thomas
Published: March 2005

Microsurgical tissue transfer has constantly improved the therapeutic options for reconstruction in the head and neck region, but the ideal flap has yet to be found. The purpose of this study is to discuss the aesthetic potential of the free gracilis muscle flap in difficult head and neck reconstruction. We report our experience with the free gracilis muscle flap in seven patients who underwent reconstruction in the head and neck region for a variety of indications. In all seven patients, the transplanted muscle flaps healed well, with no flap loss. Postoperative complications consisted of skin‐graft loss in one patient requiring a second split‐thickness skin graft. Donor‐site morbidity was minimal in all patients. For difficult reconstruction in the head and neck region, the free gracilis muscle flap offers a number of advantages, including reliable vascular anatomy, relatively great plasticity, and a concealed donor area. Thus this type of flap offers a valuable option whenever an aesthetically pleasing result is sought. © 2005 Wiley‐Liss, Inc. Microsurgery 25:00–00, 2005.
Model of murine interpositional vein grafting
Authors: Cooley Brian C.
Published: March 2005

A new murine model is presented for interpositional vein grafting into an artery. In ICR (outbred) mice, the femoral vein or a branch of the jugular vein was harvested and placed into a femoral artery defect, using standard microvascular techniques to achieve end‐to‐end anastomoses with 11‐0 nylon suture. The technique requires a high level of microsurgical experience and competence. Success rates (vessel patency) were higher with moderate systemic heparinization (200 units/kg body weight, single i.v. bolus). Vein grafts were successfully transplanted between syngenic C57Bl/6J mice, with patency demonstrated from 1 day to 3 months postoperatively. The model is applicable to studies of vein graft stenosis using murine transgenic/knockout models. © 2005 Wiley‐Liss, Inc. Microsurgery 25:00–00 2005.
Onset and course of chronic inflammatory demyelinating polyneuropathy
Authors: Mygland Å. , Monstad P. , Vedeler C.
Published: March 2005

Chronic inflammatory demyelinating polyneuropathy (CIDP) is clinically heterogeneous. Our purpose was to determine whether initial progression time, clinical features, and distribution of nerve conduction slowing at presentation correlate with clinical course and prognosis. We examined how findings at presentation related to clinical course during an average follow‐up time of 4.0 (range 1.0–9.0) years in 44 patients with CIDP. We calculated terminal latency index (TLI), a measure of differential slowing in distal relative to more proximal nerve segments. Patients with acute or subacute onset (progression over less than 8 weeks) had a higher remission rate (P = 0.012) than patients with chronic onset (progression over more than 8 weeks). Patients with proximal weakness had a higher remission rate than patients with the distal phenotype (P < 0.001). All 5 patients with a relapsing course had subacute onset. They had lower TLIs, suggesting a more distal pattern of demyelination, than patients with a monophasic or chronic course. In conclusion, subacute onset and presence of proximal weakness are good prognostic signs that correlate with a high rate of recovery to normal in CIDP. Distal accentuation of conduction slowing at presentation correlates with subacute onset and a relapsing course. Muscle Nerve, 2005
Mathematical model that predicts isometric muscle forces for individuals with spinal cord injuries
Authors: Ding Jun , Lee Samuel C. K. , Johnston Therese E. , Wexler Anthony S. , Scott Wayne B. , Binder‐Macleod Stuart A.
Published: March 2005

The ideal functional electrical stimulation (FES) system requires a mathematical model to provide feedforward control of the stimulation parameters such that they are optimal for different individuals across a range of physiological conditions, muscles, and tasks. Recently we tested and validated such a model using able‐bodied subjects. The purpose of this study was to determine whether this model applied to persons with spinal cord injuries (SCI). To this end, the isometric force responses of the paralyzed quadriceps femoris muscles of 14 adolescents and young adults were tested. For each subject, the force responses to two six‐pulse stimulation trains were used to identify the parameter values of the model and then the model was used to predict the force responses to three train patterns across a range of frequencies in both a nonfatigued and fatigued condition. The intraclass correlation coefficients (ICCs) between the experimental and predicted force–time integrals and peak forces were above 0.90 for 12 of the 13 stimulation trains tested in the nonfatigued condition and all 13 trains tested in the fatigued condition. The success of our model with SCI subjects leads us to believe that our model may be useful for designing optimal stimulation parameters for standing and ambulation in patients who use FES. Muscle Nerve, 2005
Phototherapy for enhancing peripheral nerve repair: A review of the literature
Authors: Gigo‐Benato Davilene , Geuna Stefano , Rochkind Shimon
Published: March 2005

Posttraumatic nerve repair continues to be a major challenge of restorative medicine. Although enormous progress has been made in surgical techniques over the past three decades, functional recovery after a severe lesion of a major nerve trunk is often incomplete and sometimes unsatisfactory. It is thus particularly important to investigate clinical protocols to enhance nerve regeneration after surgical nerve repair. The present article reviews literature on one possible rehabilitation approach for enhancing nerve recovery, namely phototherapy. The number of experimental studies that have reported on the promoting action of phototherapy on peripheral nerve regeneration, together with the few known side effects related to the use of this type of physical therapy, make it possible to suggest that the time for broader clinical trials has come. Muscle Nerve, 2005
Rippling muscle disease may be caused by “silent” action potentials in the tubular system of skeletal muscle fibers
Authors: Lamb Graham D.
Published: March 2005

Rippling muscle disease (RMD) is a generally benign, myotonic‐like myopathy associated with rapid rolling contractions and percussion‐induced contractions. These contractions are electrically silent in electromyographic recordings, which is taken as evidence that action potentials are not involved in the phenomena. The pathophysiological mechanisms underlying the symptoms have not been elucidated. Many cases of RMD are caused by mutations in caveolin‐3, and aberrations in the tubular system are commonly observed. Here, recent data are discussed showing that action potentials can travel over substantial distances entirely within the transverse and longitudinal tubular systems of a muscle fiber and that stretch can induce such action potentials. Action potentials travelling in the tubular system in most circustances probably cannot excite the sarcolemma and hence would not be dected. It is suggested that the distinctive contractions in RMD may be due to stretch‐induced generation of action potentials within the tubular system. Muscle Nerve, 2005
Die Biologie der Taxane: Arzneimittel aus der Natur
Authors: Leistner Eckhard
Published: March 2005

Paclitaxel ist eine Verbindung, die innerhalb der Vertreter der Gattung Taxus verbreitet ist. Erstaunlicherweise kommt die Verbindung nicht nur in Höheren Pflanzen, sondern in sehr geringer Menge in einer ganzen Reihe von in vitro kultivierbaren Pilzen und sogar in Bakterien vor. In der Vergangenheit hat eine Untersuchung der Biosynthese des Paclitaxels gute Fortschritte gemacht, so dass die Möglichkeit besteht, die Herstellung des Paclitaxels in pflanzlichen Zellkulturen durch “Metabolic Pathway Engineering” zu optimieren. Eine mikrobielle Produktion des Paclitaxels scheint ebenfalls möglich, wenn molekularbiologische Verfahren zur Optimierung eingesetzt werden.
Wirkmechanismus der Taxane: Angriff auf die mitotische Spindel
Authors: Bartsch Volker
Published: March 2005

Die zytotoxische und proliferationshemmende Wirkung der Taxane beruht auf ihrer Intervention am Spindelapparat der sich teilenden Zellen. Die Mitosespindel besteht aus den Mikrotubuli, die bei der Zellteilung an den Chromosomen ansetzen, sich dann verkürzen und auf diese Weise die Schwesterchromatiden auf die beiden Tochterzellen verteilen. Die Taxane mit ihren Hauptrepräsentanten Paclitaxel und Docetaxel docken an die Mikrotubuli an und stabilisieren sie so weit, dass sie ihre Aufgabe bei der Zellteilung nicht mehr ordnungsgemäß wahrnehmen können. Die Krebszellen sterben daraufhin ab, wobei apoptotische Mechanismen eine zentrale Rolle spielen. Inzwischen kennt man zahlreiche weitere Naturstoffe und deren Derivate, die ähnlich wie die Taxane die Mikrotubuli stabilisieren; ihr klinischer Stellenwert lässt sich derzeit aber noch nicht abschließend beurteilen.
Neue Mikrotubuli‐Stabilisatoren: Jenseits von Paclitaxel und Docetaxel
Authors: Baumann Knut
Published: March 2005

Die im Handel befindlichen Taxane sind oral nicht bioverfügbar. Auf Grund der Hydrophobie der Moleküle bereitet die Formulierung der Arzneiformen Schwierigkeiten. Die verwendeten Hilfsstoffe werden für unerwünschte Arzneimittelwirkungen verantwortlich gemacht. Außerdem wird angenommen, dass u.a. durch Expression des ATP‐abhängigen Effluxtransporters P‐Glykoprotein (MDR1‐Gen) in den Tumorzellen eine Resistenz gegenüber der Taxantherapie entwickelt wird, was zu Rückfällen bei den Patienten führt. Taxane der zweiten Generation und die neue Substanzklasse der Epothilone, die hier vorgestellt wurden, zeigen die genannten Nachteile in der präklinischen Testung größtenteils nicht mehr. Die klinische Prüfung muss nun zeigen, ob die Erwartungen erfüllt werden können.
Entwicklung neuer Taxan‐Formulierungen: Herausforderung an die Galenik
Authors: Haas Heinrich
Published: March 2005

Taxane und insbesondere Paclitaxel gehören zu den am intensivsten untersuchten Zytostatika bei der Entwicklung pharmazeutischer Formulierungen. Derzeit befinden sich verschiedene neue Produkte in der Phase klinischer Prüfung. In Anbetracht der breiten Basis an Untersuchungen, die für Paclitaxel vorliegt, ist die Anzahl der realisierten oder in Entwicklung befindlichen Produkte allerdings erstaunlich gering. Eine der Ursachen liegt in den ungünstigen Löslichkeitseigenschaften, da Paclitaxel nicht nur in Wasser, sondern auch in vielen der verwendeten Solubilisierungsvehikel nicht ausreichend gut löslich ist. Eine umfassende physikalisch‐chemische Charakterisierung und das daraus resultierende Verständnis grundlegender molekularer Zusammenhänge könnten eine Grundlage für die zielgerichtete Entwicklung neuer optimierter Formulierungen darstellen.
Pharmakokinetik und Interaktionspotenzial der Taxane: Paclitaxel und Docetaxel sicher anwenden
Authors: Simons Sven , Jaehde Ulrich
Published: March 2005

Paclitaxel und Docetaxel sind hoch wirksame Zytostatika, deren Pharmakokinetik durch eine hohe Proteinbindung, ausgeprägten hepatischen Metabolismus und eine nur geringe renale Exkretion charakterisiert ist. Trotz dieser Gemeinsamkeit gibt es einen wesentlichen Unterschied: Während Docetaxel eine lineare Pharmakokinetik aufweist, steigen bei Paclitaxel die Plasmakonzentrationen mit zunehmender Dosis überproportional an. Heute geht man davon aus, dass die Nichtlinearität nicht durch Sättigungsphänomene bei Verteilung und Elimination, sondern im Wesentlichen durch Einschluss in Cremophor‐EL‐Mizellen nach Gabe höherer Dosen zu erklären ist. Das Interaktionspotenzial beider Substanzen ist unterschiedlich. Beim Paclitaxel steht der Einfluss auf die Pharmakokinetik und Toxizität von Anthrazyklinen im Vordergrund und hat zu der Empfehlung geführt, Doxorubicin und Epirubicin mindestens 24 Stunden vor Paclitaxel zu applizieren. Beim Docetaxel ist der Einfluss von Induktoren bzw. Inhibitoren von Enzymen der CYP3A‐Subfamilie zu beachten. Durch die Entwicklung neuer Formulierungen wird die Pharmakokinetik dieser Stoffklasse sicher auch in Zukunft intensiv untersucht und zu einem besseren Verständnis der zugrunde liegenden Mechanismen führen.
Kosten‐Nutzen‐Aspekte der Taxan‐Therapie: Pharmakoökonomische Studien im Überblick
Authors: Dietrich Eva Susanne
Published: March 2005

In der Krebstherapie gibt es unterschiedliche Behandlungsstrategien weltweit und daraus resultierend unterschiedliche Erfahrungswerte. Bevor die Schlussfolgerung einer pharmakoökonomischen Studie zu Taxanen adaptiert werden kann, muss der Apotheker daher die Vergleichbarkeit des Studien‐ und des eigenen Settings vor allem hinsichtlich Studienpatientenselektion, Gesundheitssystem, Behandlung und Kosten pro Ressourceneinheit prüfen. Obwohl die Methoden pharmakoökonomischer Analysen international weitgehend konsentiert sind, finden sich doch erhebliche Abweichungen in der Vorgehensweise von Studie zu Studie. Diese Problematik ist auch aus dem Bereich klinischer Studien bekannt, jedoch bei pharmakoökonomischen Analysen noch stärker ausgeprägt, da zusätzliche Ergebnis‐bestimmende Faktoren in den Evaluationen eine Rolle spielen. Eine Folge all dieser Aspekte ist eine Vielfalt von Studienergebnissen, die selbst bei ähnlichen Settings erheblich voneinander abweichen können.

Dennoch können pharmakoökonomische Studien gute Hinweise auf zu berücksichtigende Kostenaspekte geben und es lassen sich auch einige allgemeingültige Erkenntnisse ableiten. So ist beim nicht‐kleinzelligen Bronchialkarzinom die Kombinationstherapie allgemein kosteneffektiver als die Monotherapie, eine dreistündige Infusion kosteneffektiver als eine 24‐Stunden‐Infusion, Regime ohne G‐CSF kosteneffektiver als Regime mit G‐CSF, Kombinationen mit Cisplatin kosteneffektiver als solche mit Carboplatin, und die Kosten pro zusätzlicher Outcome‐Einheit liegen sehr hoch. Beim fortgeschrittenen Ovarialkarzinom ist eine Taxan‐Therapie mit erheblichen zusätzlichen Kosten pro Outcome‐Einheit verbunden. Diese können jedoch durch den Einsatz einer Monotherapie in Zukunft eventuell reduziert werden. Die Indikation Mammakarzinom wurde in den vorliegenden Studien nur in der Sekundärtherapie untersucht. Dabei zeigte sich eine starke Abhängigkeit des Ergebnisses vom Preis des gewählten Therapieregimes, sofern Taxane miteinander verglichen wurden. Beim Vergleich mit anderen Arzneimitteln ergaben sich wiederum erhebliche zusätzliche Kosten.
Arzneistoff freisetzende Koronarstents: Ungewöhnliche Anwendung von Paclitaxel
Authors: Brüggmann Jörg , Kleber Franz‐Xaver
Published: March 2005

Paclitaxel freisetzende Koronarstents sind eine innovative Angioplastie‐Methode, bei der das Restenose‐Risiko gegenüber der bisher üblichen Ballon‐Dilatation deutlich reduziert ist. Die ersten Studienergebnisse sehen positiv aus. Es fehlen allerdings noch Langzeitstudien, die belegen, dass diese Intervention zu einem längeren Überleben führt.
Applikation taxanhaltiger Arzneimittel: Beachtenswerte Besonderheiten
Authors: Barth Jürgen
Published: March 2005

Die Taxane sind technologisch‐pharmazeutisch anspruchsvolle Verbindungen und wertvolle Wirkstoffe in der antitumoralen Therapie (“backbones of anticancer therapy”). Bei der Applikation von Taxol® ist zu beachten, dass PVC‐freie Infusionsbestecke verwendet werden. Zudem ist eine In‐Line‐Filtration notwendig. Substanz‐ und/oder formulierungsbedingt besteht vom Grundsatz her das Risiko anaphylaktischer Reaktionen. Publizierte Daten und klinische Erfahrungen zeigen, dass eine Chemotherapie mit einem Taxan ambulant/tagesstationär sicher durchführbar ist. Allerdings bedürfen die Patienten trotz Prämedikation vor allem während der ersten (drei) Infusionen besonderer Beobachtung.
Aggressivität von Krebserkrankungen vorhersagbar
Authors: Dingermann Theo , Zündorf Ilse
Published: March 2005

Das Protein RAB25 bei Brust‐ und Eierstockkrebs entscheidet darüber, ob Patientinnen eine gute Heilungs‐ bzw. Überlebenschance haben und könnte eine interessante neue Zielstruktur für Tumortherapeutika sein.
Artemisinin und Nachfolger
Authors: Holzgrabe Ulrike
Published: March 2005

Die Extrakte aus Quinghao (Artemisia annua) wurden über 1500 Jahre in der chinesischen Medizin zur Bekämpfung von Fieber eingesetzt, bevor man feststellte, dass der Inhaltsstoff Artemisinin, der durch einen trizyklische Endoperoxid‐Struktur gekennzeichnet ist, ein potentes Antimalaria‐Mittel ist.
Paclitaxel zur Alzheimer‐Behandlung
Authors: Holzgrabe Ulrike
Published: March 2005

Paclitaxel und andere Mikrotubuli‐Stabilisatoren könnten zukünftig auch bei Morbus Alzheimer Verwendung finden.
Preparation and characterization of proton‐exchange hybrid membranes
Authors: Linares Amelia , Acosta José Luis
Published: March 2005

Two types of composite were prepared, based on a thermoplastic polymer, polyvinylidene fluoride (PVDF), and an elastomer, ethylene‐propylene‐diene terpolymer (EPDM), respectively. We obtained both series by addition of an inorganic proton‐conducting antimonic acid derivative (HSb) and polystyrene crosslinked with a small percentage of divinylbenzene (PS‐co‐DVB). From these composites, membranes were obtained and subjected to a heterogeneous‐phase sulfonation reaction with chlorosulfonic acid. All experimental materials were characterized from a morphological and electrical point of view, by means of techniques such as differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), non‐isothermal crystallization and complex impedance analysis. Copyright © 2005 Society of Chemical Industry
Ambient‐temperature copper‐catalyzed atom transfer radical polymerization of methacrylates in ethylene glycol solvents
Authors: Kimani Solomon M. , Moratti Stephen C.
Published: March 2005

The use of ethylene glycol solvents in the room‐temperature atom transfer radical polymerization (ATRP) of various hydrophobic and hydrophilic methacrylates is demonstrated. Unlike many of the very polar solvents described in the literature for room‐temperature ATRP, these solvents have good solvency for a wide range of polymers and monomers and are cheap and relatively nontoxic. Ethylene glycols with one hydroxyl and one methoxy group, such as tri(ethylene glycol) monomethyl ether (TEGMME), provide optimal results. The polymerization of methyl methacrylate in TEGMME with CuBr/N,N,N′N′,N″‐pentamethyldiethylenetriamine as the catalyst requires the addition of CuCl2 at the beginning of the reaction to produce well‐controlled polymerizations. This leads to polymers with predictable molecular weights and relatively narrow polydispersities. Polymerization in solvents that are fully methoxy‐capped terminate prematurely because of catalyst precipitation. The electrochemical behavior of copper complexes in selected solvents is examined to determine why these solvents provide good rates at room temperature. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1588–1598, 2005
Effect of alkylaluminum on ethylene polymerization catalyzed by 2,6‐bis(imino)pyridyl complexes of Fe(II)
Authors: Wang Qi , Li Lidong , Fan Zhiqiang
Published: March 2005

In the presence of tetraethylaluminoxane (TEAO), iron complexes were used to catalyze ethylene polymerizations with extremely high activities and generally produced polyethylene with a bimodal molecular weight distribution (MWD). This bimodal MWD of polyethylene was mainly derived from residual triethylaluminum in TEAO and was produced through a mechanism of chain transfer to aluminum. Ethylaluminoxane and tetraisobutylaluminoxane also were used to polymerize ethylene with high activities in the presence of iron complexes, and only polyethylene with a unimodal MWD was produced. The ratio of the rate constant of chain transfer to aluminum (ktrA) to the rate constant of chain propagation (kp) was determined to be 0.12 for {[ArNC(Me)]2C5H3N}FeCl2 when Ar was 2,6‐diisopropylphenyl (1) and 2.48 for {[ArNC(Me)]2C5H3N}FeCl2 when Ar was 2,6‐dimethylphenyl (2); these values are far larger than those for metallocene‐based catalysts. This explains why an iron complex usually produces polyethylene with a broader MWD than metallocene‐based catalysts. Additionally, it can be concluded from the great difference between 1 and 2 with respect to ktrA/kp that an iron complex with less congested aryl substituents is subjected to chain transfer to aluminum. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1599–1606, 2005
Donor–acceptor‐based poly(toluidine‐co‐chloroaniline)s: Synthesis and characterization
Authors: Savitha P. , Sathyanarayana D. N.
Published: March 2005

A series of poly(o‐/m‐toluidine‐co‐o‐/m‐chloroaniline) copolymers of different compositions were synthesized by an emulsion method with ammonium persulfate as the oxidant. The conductivity of the copolymers was two to five orders of magnitude higher than that of the homopolymers poly(o‐toluidine) and poly(m‐chloroaniline). Among the copolymers, the copolymer of o‐toluidine and m‐chloroaniline exhibited a maximum conductivity of 0.14 S cm−1. The conductivity of these copolymers was also higher than that of poly(aniline‐co‐chloroaniline). The properties of the copolymers were greatly influenced by the positions of the substituents and the concentrations of the individual monomers in the feed. All the copolymers were completely soluble in polar solvents such as dimethyl sulfoxide and showed higher heat stability as the chloroaniline concentration increased. These effects could be interpreted in terms of extensive hydrogen bonding and interchain linking and, therefore, higher electron delocalization in these copolymers due to the presence of electron‐rich toluidine rings adjacent to electron‐deficient chloroaniline. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1579–1587, 2005
Self‐assembly of oligo(p‐phenylenevinylene)‐block‐poly(ethylene oxide) in polar media and solubilization of an oligo(p‐phenylenevinylene) homooligomer inside the assembly
Authors: Mori Takeshi , Watanabe Takushi , Minagawa Keiji , Tanaka Masami
Published: March 2005

Rod–coil amphiphilic diblock copolymers, consisting of oligo(p‐phenylenevinylene) (OPV) as a rod and hydrophobic block and poly(ethylene oxide) (PEO) as a coil and hydrophilic block, were synthesized by a convergent method. The aggregation behavior of the block copolymers in a selective solvent (tetrahydrofuran/H2O) was probed with the absorption and emission of the OPV block. With increasing H2O concentration, the absorption maximum was blueshifted, the emission from the molecularly dissolved OPV decreased, and that from the aggregated OPV increased. This indicated that the OPV blocks formed H‐type aggregates in which the OPV blocks aligned in a parallel orientation with one another. The transmission electron microscopy observation revealed that the block copolymers with PEO weight fractions of 41 and 62 wt % formed cylindrical aggregates with a diameter of 6–8 nm and a length of several hundreds nanometers, whereas the block copolymer with 79 wt % PEO formed distorted spherical aggregates with an average diameter of 13 nm. Furthermore, the solubilization of an OPV homooligomer with the block copolymer was studied. When the total polymer concentration was less than 0.1 wt %, the block copolymer solubilized OPV with a 50 mol % concentration. The structure of the aggregates was a cylinder with a relatively large diameter distribution. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1569–1578, 2005
Unusual inorganic phase formation in ultraviolet‐curable organic–inorganic hybrid films
Authors: Zong Zhengang , Soucek Mark D. , Xue Chenchen
Published: March 2005

Inorganic–organic hybrid materials were prepared with a cycloaliphatic epoxide adduct of linseed oil with tetraethylorthosilicate (TEOS) oligomers via a cationic UV‐curing process. The TEOS oligomers were prepared in the presence of water and ethanol with hydrochloric acid as a catalyst. The TEOS oligomers were characterized with 1H and 29Si NMR and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. Hybrid films were cured, and the dynamic mechanical and thermal properties of the hybrid films were evaluated as a function of the TEOS oligomer content. The morphology of the hybrid films was examined with atomic force microscopy, transmission electron microscopy, and small‐angle light scattering. The microscopy and dynamic mechanical data indicated that the hybrid films were heterogeneous materials with various inorganic particle sizes dispersed within the organic matrix. In addition, 29Si solid‐state NMR spectroscopy was used to investigate the coupling between the silicate region and organic regions. A schematic model is proposed to address structural features of hybrid materials. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1607–1623, 2005
Diffusion, elasticity, and shear flow in self‐assembled block copolymers: A molecular dynamics study
Authors: Fraser Blair , Denniston Colin , Müser Martin H.
Published: March 2005

Self‐assembled ordered structures composed of block copolymers are simulated by molecular dynamics under stress‐free conditions and under shear. We address several methodological points. The system must be allowed to adjust its size to accommodate natural periods of self‐assembled structures. In addition, these structures need to be capable of rotating freely under shear. An examination of the diffusion of polymer molecules in the lamellar phase reveals subdiffusion along translationally invariant directions between the ballistic and diffusive regime. The diffused distancedincreases with timetasd∝t1/3. We also examine the possibility of mapping structures such as cylindrical phases onto particle–field types of models. Using measurements of the wavevector‐dependent dynamic matrix, we show that this cannot be done with only two‐body potentials. We then examine the molecular origin of shear alignment of lamellar phases. Lamellae oriented parallel to the shear direction become unstable at high shear rates when the major axis of the tensor of gyration of individual polymers forms an average angle of 45° with the lamellae. This instability can be understood in analogy to similar transitions in liquid crystals. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 970–982, 2005
The psychological impact of mammographic screening on women with a family history of breast cancer—a systematic review
Authors: Watson Eila K. , Henderson Bethan J. , Brett Joanne , Bankhead Clare , Austoker Joan
Published: March 2005

This systematic review aims to assess the psychological impact of mammographic screening on women with a family history of breast cancer. Women with a family history, and hence increased risk, of breast cancer are known to experience higher levels of anxiety about cancer. They are also often offered screening from an earlier age. The psychological consequences of screening are therefore of particular importance for this group of women. A comprehensive search of 4 electronic databases was conducted from 1982 to 2003, combining sets of terms relating to (1) breast screening or mammography (breast screen*; mammogra*), (2) psychological impact (adverse effects; anxi*; distress; nervous; psych*, psychological consequences; stress; worry) and (3) family history. Reference lists from relevant papers were examined for additional papers. The review identified seven papers from four countries. Overall, the findings indicate that, similar to women in the general population, most women with a family history do not appear to experience high levels of anxiety associated with mammographic screening. Although women who are recalled for further tests do experience increased anxiety the levels appear to be no greater than for women without a family history. We conclude that further research on this topic is required—this should include studies designed specifically to consider both the negative and positive impact of mammographic screening on women with a family history, using validated measures of anxiety and worry in combination with qualitative research. Copyright © 2005 John Wiley & Sons, Ltd.
Differences in quality of life between non‐Hodgkin's lymphoma survivors meeting and not meeting public health exercise guidelines
Authors: Vallance Jeffrey K.H. , Courneya Kerry S. , Jones Lee W. , Reiman Tony
Published: March 2005

The primary purpose of this study was to examine differences in quality of life (QoL) between non‐Hodgkin's lymphoma (NHL) survivors meeting and not meeting public health exercise guidelines. A secondary purpose was to examine exercise behavior changes across three distinct cancer‐related time periods (i.e. prediagnosis, on treatment and off treatment). Using a retrospective survey design, 438 NHL survivors residing in Alberta, Canada completed a mailed questionnaire that assessed self‐reported exercise prediagnosis, on treatment and off treatment, and current QoL. Descriptive analyses indicated that 33.8, 6.5 and 23.7% of NHL survivors met public health exercise guidelines during prediagnosis, on treatment, and off treatment time periods, respectively. Multivariate analyses of variance indicated that NHL survivors meeting public health exercise guidelines during postdiagnosis time periods had higher current QoL scores than NHL survivors not meeting guidelines. QoL difference scores between the two groups met proposed standards for clinically important differences. Multivariate analyses also indicated significant differences in exercise behavior across the three cancer‐related time periods (all p's<0.01). These analyses were unchanged after statistically controlling for important medical and demographic variables. The results of this study provide evidence that NHL survivors meeting public health exercise guidelines on and off treatment reported higher current QoL than those survivors not meeting guidelines. These findings corroborate research examining exercise behavior in other cancer survivor groups and provide preliminary data to support a randomized controlled trial on exercise and QoL in this population. Copyright © 2005 John Wiley & Sons, Ltd.
A qualitative study of work and work return in cancer survivors
Authors: Main Deborah S. , Nowels Carolyn T. , Cavender Tia A. , Etschmaier Martine , Steiner John F.
Published: March 2005

Few studies have examined the impact of cancer on the survivor's quality of work life. The purpose of this qualitative study is to describe the work experiences among a diverse group of cancer survivors and to explore factors influencing decisions about work after cancer diagnosis and treatment. We interviewed 28 participants with a broad range of socioeconomic backgrounds and primary cancer sites. Qualitative results indicate that after learning about their cancer diagnosis, participants had diverse and complex patterns of work return and work change, and experienced a variety of factors that influenced post‐cancer decisions. Experiences at work after cancer also varied in relation to how others responded, changes in productivity, effects of cancer and treatment on work, and feelings about work. Most respondents received little guidance from their physicians about work, and many participants described their cancer as impacting their priority of work relative to other aspects of their lives. Our findings reinforce the complexity of measuring employment outcomes and the range of adaptations made to improve the quality of work life. Additional research is needed to identify prognostic factors that can guide clinical or workplace efforts to restore cancer survivors to their desired level of work function and economic productivity. Copyright © 2005 John Wiley & Sons, Ltd.