bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of the met receptor tyrosine kinase signaling enhances the chemosensitivity of glioma cell lines to CDDP through activation of p38 MAPK pathway
Authors: Lou Xiuqin , Zhou Qibing , Yin Ying , Zhou Cheng , Shen Yan
Published: May 2009

The Met receptor tyrosine kinase is known to be overexpressed in many solid tumors and plays a crucial role in tumor invasive growth and metastasis. In this study, we showed that hepatocyte growth factor-induced Met activation as well as Met-dependent downstream signaling of AKT and p44/42 mitogen-activated protein kinase (MAPK) could be efficiently blocked by TAT-coupled carboxyl-terminal tail peptide of Met receptor (TCTP), and inactivation of Met signaling significantly enhanced the sensitivity of T98G and U251 glioma cells to cis-diaminedichloroplatinum (CDDP, cisplatin). However, neither phosphoinositide 3-kinase/AKT inhibitor LY294002 nor p44/42 MAPK inhibitor PD98059 alone or combined could imitate the effect of TCTP on chemosensitivity enhancement of T98G cells to CDDP, indicating that Met-dependent inactivation of AKT and p44/42 MAPK signaling was not the main cause for the increased chemosensitivity to CDDP. Further studies revealed that TCTP significantly activated p38 MAPK in T98G and U251 cell lines. Activation of p38 MAPK by sorbitol pretreatment resembled the sensitization effects, whereas inhibition of p38 MAPK activation by its inhibitor SB202190 counteracted the sensitization effects induced by TCTP. Therefore, p38 MAPK activation was one of the major causes for the increased chemosensitivity to CDDP induced by Met inactivation. Taken together, the study indicated that Met receptor played an important role in regulating cell response to chemotherapy and suggested that inhibition of Met signaling could be used in combination with other chemotherapeutic regimens in treatment of tumor patients. [Mol Cancer Ther 2009;8(5):1126–36]
Effects of cytokine-induced macrophages on the response of tumor cells to banoxantrone (AQ4N)
Authors: Mehibel Manal , Singh Simendra , Chinje Edwin C. , Cowen Rachel L. , Stratford Ian J.
Published: May 2009

Tumor-associated macrophages (TAMs) are found in many solid tumors and have often been shown to accumulate in the hypoxic regions surrounding areas of necrosis. TAMs are the major site of expression of nitric oxide synthase (NOS), a heme-containing homodimeric enzyme consisting of oxygenase and reductase domains. The latter has a high degree of sequence homology to cytochrome P450 reductase and a functional consequence of this is the ability of NOS, under hypoxic conditions, to activate the bioreductive drugs tirapazamine and RSU1069. Banoxantrone (AQ4N) is a bioreductive prodrug activated in hypoxia by an oxygen-dependent two-electron reductive process to yield the topoisomerase II inhibitor AQ4. A feature of this process is that the final product could potentially show bystander cell killing. Thus, in this study, we investigated the ability of inducible NOS (iNOS)-expressing TAMs to activate AQ4N and elicit toxicity in cocultured human tumor cells. Murine macrophages were induced to overexpress iNOS by treatment with a combination of cytokines, mixed with HT1080 and HCT116 human tumor cells, and the toxicity of AQ4N was determined under aerobic or hypoxic conditions. The aerobic toxicity of AQ4N toward tumor cells was not affected through coculturing with macrophages. However, under hypoxic conditions, the induction of iNOS activity in the macrophages was associated with an increase in AQ4N metabolism and a substantial increase in tumor cell toxicity, which was dependent on the proportion of macrophages in the culture. This study is the first demonstration of TAM-mediated prodrug activation to result in bystander killing of human tumor cells.[Mol Cancer Ther 2009;8(5):1261–9]
Targeting both HIF-1 and HIF-2 in human colon cancer cells improves tumor response to sunitinib treatment
Authors: Burkitt Kyunghee , Chun Sang Y. , Dang Duyen T. , Dang Long H.
Published: May 2009

Sunitinib is an oral small-molecule multitargeted receptor tyrosine kinase inhibitor that has recently been shown to have clinical benefit as a single agent in renal cell cancer and gastrointestinal stromal tumors, leading to its Food and Drug Administration approval for treatment of these cancers. However, the benefit is short-lived; and for the majority of cancers, sunitinib single-agent clinical activity is low. Therefore, combination strategies with sunitinib are currently in clinical development. The hypoxia-inducible transcription factors, HIF-1 and HIF-2, induce gene programs important for cancer cell growth and angiogenesis. We hypothesized that inhibiting HIF-1 and HIF-2 would further improve tumor response to sunitinib therapy. To test this hypothesis, HIF-1α and HIF-2α genes were disrupted in colon cancer cells. We found that disruption of HIF-1α, HIF-2α, or both HIF-1α and HIF-2α genes led to improved tumor response to sunitinib. For xenografts in which both HIF-1α and HIF-2α genes were disrupted, there was prolonged complete remission with sunitinib treatment in 50% of mice. This enhanced response was mediated by two potential mechanisms. First, tumor angiogenesis and perfusion were almost completely inhibited by sunitinib when both HIF-1α and HIF-2α genes were disrupted. The enhanced inhibitory effect on tumor angiogenesis was mediated by the inhibition of multiple proangiogenic factors, including vascular endothelial growth factor and angiopoietin-like protein 4, and the induction of the antiangiogenic factor, thrombospondin 1. Second, disruption of HIF-1α, HIF-2α, or both HIF-1α and HIF-2α genes directly inhibited tumor cell proliferation. These preclinical findings have clinical implications and suggest novel clinical trials. [Mol Cancer Ther 2009;8(5):OF1–9]
Soluble c-Met receptors inhibit phosphorylation of c-Met and growth of hepatocyte growth factor: c-Met–dependent tumors in animal models
Authors: Coxon Angela , Rex Karen , Meyer Susanne , Sun Jianling , Sun Jilin , Chen Qing , Radinsky Robert , Kendall Richard , Burgess Teresa L.
Published: May 2009

c-Met is a receptor tyrosine kinase frequently overexpressed or amplified in many types of human cancers. Hepatocyte growth factor (HGF, also known as scatter factor) is the only known ligand for c-Met. In this study, soluble human and murine c-Met receptor-Fc fusion proteins were generated and were shown to bind to human and murine HGF as measured by fluorescence-activated cell sorting and surface plasmon resonance (Biacore) assays. Also, both human and murine c-Met-Fc showed activity in functional cell assays, inhibiting HGF-induced c-Met phosphorylation in PC3 and 4T1 cells, respectively, and inhibiting HGF-driven cellular invasion in a dose-dependent manner. Pharmacokinetic analysis showed that both reagents were suitable for in vivo testing. Systemic administration of human c-Met-Fc significantly inhibited tumor growth in the human HGF-dependent U-87 MG xenograft model at daily doses of 30 or 100 μg (P < 0.0001). Similarly, murine c-Met-Fc, at 100 μg daily, significantly inhibited tumor growth in the murine HGF–dependent CT-26 syngeneic tumor model (P < 0.002). Human and murine c-Met-Fc seemed to be well-tolerated in animals. In conclusion, both mouse and human versions of c-Met-Fc effectively block HGF-induced activation of c-Met and inhibit growth of tumor xenografts, providing further evidence that c-Met is an important target for oncology therapeutics.[Mol Cancer Ther 2009;8(5):1119–25]
NM23-H2 may play an indirect role in transcriptional activation of c-myc gene expression but does not cleave the nuclease hypersensitive element III1
Authors: Dexheimer Thomas S. , Carey Steven S. , Zuohe Song , Gokhale Vijay M. , Hu Xiaohui , Murata Lauren B. , Maes Estelle M. , Weichsel Andrzej , Sun Daekyu , Meuillet Emmanuelle J. , Montfort William R. , Hurley Laurence H.
Published: May 2009

The formation of G-quadruplex structures within the nuclease hypersensitive element (NHE) III1 region of the c-myc promoter and the ability of these structures to repress c-myc transcription have been well established. However, just how these extremely stable DNA secondary structures are transformed to activate c-myc transcription is still unknown. NM23-H2/nucleoside diphosphate kinase B has been recognized as an activator of c-myc transcription via interactions with the NHE III1 region of the c-myc gene promoter. Through the use of RNA interference, we confirmed the transcriptional regulatory role of NM23-H2. In addition, we find that further purification of NM23-H2 results in loss of the previously identified DNA strand cleavage activity, but retention of its DNA binding activity. NM23-H2 binds to both single-stranded guanine- and cytosine-rich strands of the c-myc NHE III1 and, to a lesser extent, to a random single-stranded DNA template. However, it does not bind to or cleave the NHE III1 in duplex form. Significantly, potassium ions and compounds that stabilize the G-quadruplex and i-motif structures have an inhibitory effect on NM23-H2 DNA-binding activity. Mutation of Arg88 to Ala88 (R88A) reduced both DNA and nucleotide binding but had minimal effect on the NM23-H2 crystal structure. On the basis of these data and molecular modeling studies, we have proposed a stepwise trapping-out of the NHE III1 region in a single-stranded form, thus allowing single-stranded transcription factors to bind and activate c-myc transcription. Furthermore, this model provides a rationale for how the stabilization of the G-quadruplex or i-motif structures formed within the c-myc gene promoter region can inhibit NM23-H2 from activating c-myc gene expression. [Mol Cancer Ther 2009;8(5):1363–77]
Inhibition of CREB Function in Mouse Epidermis Reduces Papilloma Formation
Authors: Rozenberg Julian , Rishi Vikas , Orosz Andras , Moitra Jaideep , Glick Adam , Vinson Charles
Published: May 2009

We used a double transgenic tetracycline system to conditionally express A-CREB, a dominant negative protein that prevents the DNA binding and function of cAMP-responsive element binding protein (CREB) family members, in mouse basal epidermis using the keratin 5 promoter. There was no phenotype in the adult. However, following a 7,12-dimethylbenz(a)anthracene (DMBA)/phorbol-12-myristate-13-acetate two-stage skin carcinogenesis experiment, A-CREB–expressing epidermis develop 5-fold fewer papillomas than wild-type controls. However, A-CREB expression one month after DMBA treatment does not prevent papilloma formation, suggesting that CREB functions at an early stage of papilloma formation. Oncogenic H-Ras genes with A→T mutations in codon 61 were found in wild-type skin but not in A-CREB–expressing skin 2 days after DMBA treatment, suggesting that A-CREB either prevents DMBA mutagenesis or kills oncogenic H-Ras cells. In primary keratinocyte cultures, A-CREB expression induced apoptosis of v-RasHa–infected cells and suppressed the expression of cell cycle proteins cyclin B1 and cyclin D1. These results suggest that inhibiting CREB function is a valuable cancer prevention strategy.(Mol Cancer Res 2009;7(5):654–64)
High-Resolution Genomic Copy Number Profiling of Glioblastoma Multiforme by Single Nucleotide Polymorphism DNA Microarray
Authors: Yin Dong , Ogawa Seishi , Kawamata Norihiko , Tunici Patrizia , Finocchiaro Gaetano , Eoli Marica , Ruckert Christian , Huynh Thien , Liu Gentao , Kato Motohiro , Sanada Masashi , Jauch Anna , Dugas Martin , Black Keith L. , Koeffler H. Phillip
Published: May 2009

Glioblastoma multiforme (GBM) is an extremely malignant brain tumor. To identify new genomic alterations in GBM, genomic DNA of tumor tissue/explants from 55 individuals and 6 GBM cell lines were examined using single nucleotide polymorphism DNA microarray (SNP-Chip). Further gene expression analysis relied on an additional 56 GBM samples. SNP-Chip results were validated using several techniques, including quantitative PCR (Q-PCR), nucleotide sequencing, and a combination of Q-PCR and detection of microsatellite markers for loss of heterozygosity with normal copy number [acquired uniparental disomy (AUPD)]. Whole genomic DNA copy number in each GBM sample was profiled by SNP-Chip. Several signaling pathways were frequently abnormal. Either the p16(INK4A)/p15(INK4B)-CDK4/6-pRb or p14(ARF)-MDM2/4-p53 pathways were abnormal in 89% (49 of 55) of cases. Simultaneous abnormalities of both pathways occurred in 84% (46 of 55) samples. The phosphoinositide 3-kinase pathway was altered in 71% (39 of 55) GBMs either by deletion of PTEN or amplification of epidermal growth factor receptor and/or vascular endothelial growth factor receptor/platelet-derived growth factor receptor α. Deletion of chromosome 6q26-27 often occurred (16 of 55 samples). The minimum common deleted region included PARK2, PACRG, QKI, and PDE10A genes. Further reverse transcription Q-PCR studies showed that PARK2 expression was decreased in another collection of GBMs at a frequency of 61% (34 of 56) of samples. The 1p36.23 region was deleted in 35% (19 of 55) of samples. Notably, three samples had homozygous deletion encompassing this site. Also, a novel internal deletion of a putative tumor suppressor gene, LRP1B, was discovered causing an aberrant protein. AUPDs occurred in 58% (32 of 55) of the GBM samples and five of six GBM cell lines. A common AUPD was found at chromosome 17p13.3-12 (included p53 gene) in 13 of 61 samples and cell lines. Single-strand conformational polymorphism and nucleotide sequencing showed that 9 of 13 of these samples had homozygous p53 mutations, suggesting that mitotic recombination duplicated the abnormal p53 gene, probably providing a growth advantage to these cells. A significantly shortened survival time was found in patients with 13q14 (RB) deletion or 17p13.1 (p53) deletion/AUPD. Taken together, these results suggest that this technique is a rapid, robust, and inexpensive method to profile genome-wide abnormalities in GBM.(Mol Cancer Res 2009;7(5):665–77)
Nanoliposomal Short-Chain Ceramide Inhibits Agonist-Dependent Translocation of Neurotensin Receptor 1 to Structured Membrane Microdomains in Breast Cancer Cells
Authors: Heakal Yasser , Kester Mark
Published: May 2009

Neurotensin (NTS) receptor 1 (NTSR1) is a G protein–coupled receptor that has been recently identified as a mediator of tumorigenicity and metastasis. NTSR1, as well as its endogenous ligand, NTS, are coexpressed in several breast cancer cell lines and breast cancer tumor samples but not in normal breast tissue. We have previously published that ceramide mimetics could inhibit breast cancer growth in vitro and in vivo. Thus, understanding the biochemical and biophysical regulation of NTSR1 by ceramide can help further define NTSR1 as a novel target in breast cancer. Our results show that nanoliposomal formulations of ceramide inhibit NTSR1-mediated MDA-MB-231 breast cancer progression (mitogenesis, migration, and matrix metalloproteinase-9 activity). In addition, liposomal ceramide inhibited NTSR1-mediated, but not phorbol 12-myristate 13-acetate–mediated, activation of the mitogen-activated protein kinase pathway. Mechanistically, nanoliposomal short-chain ceramide reduces NTSR1 interaction with Gαq/11 subunits within structured membrane microdomains, consistent with diminished NTS-induced translocation of NTSR1 into membrane microdomains. Collectively, our findings suggest that exogenous short-chain ceramide has the potential to be used as an adjuvant therapy to inhibit NTS-dependent breast cancer progression. (Mol Cancer Res 2009;7(5):724–34)
Antithrombotic Agents in the Prevention of Ischemic Stroke
Authors: Bousser Marie-Germaine
Published: May 2009

The role of antithrombotic drugs in the prevention of cerebral infarction is well established: antiplatelet drugs, at present mostly aspirin, clopidogrel, and aspirin + extended-release dipyridamole, decrease the relative risk of cerebral infarction, myocardial infarction and vascular death by 25% in patients with a cerebral ischemic event due to large- or small-artery disease of the brain. In primary prevention, aspirin decreases stroke risk by 19% in women but not in men. In patients with nonvalvular atrial fibrillation (NVAF), aspirin decreases the risk of ischemic stroke by 20%. Oral anticoagulants, at present only vitamin K antagonists, decrease the risk of cerebral infarction in NVAF by 65–70% compared with placebo and by 40% compared with aspirin. Oral anticoagulants are as effective as aspirin in arterial diseases of the brain, but induce more hemorrhages and are less convenient. Studies are ongoing with new antiplatelet drugs and new anticoagulants which might modify the present state of the art. Studies are also needed to evaluate the benefit/risk ratio of the combination of anticoagulants and antiplatelet drugs in aged subjects with both NVAF and arterial diseases of the brain.
TP Receptor Antagonism: A New Concept in Atherothrombosis and Stroke Prevention
Authors: Chamorro Angel
Published: May 2009

Conventional antiplatelet agents such as aspirin, ticlopidine, and clopidogrel are currently used in the prevention of cardiovascular and cerebrovascular events. However, side effects such as bleeding complications and gastrointestinal disorders and, in some patients, resistance have made the development of new agents desirable. Recently, thromboxane receptors (thromboxane and prostaglandin endoperoxide PGG2-PGH2 receptors) called TP receptors have received increasing attention. These receptors are membrane-bound G-coupled receptors found not only on platelets but also on macrophages, monocytes, vascular endothelial cells, and smooth muscle cells. Antagonists of TP receptors have advantages over aspirin as they not only block the effect of thromboxane A2 on platelets, but also inhibit other ligands such as prostaglandin endoperoxides and isoprostanes. Given the distribution of TP receptors in platelets, in circulating inflammatory cells, in the vascular wall and in atherosclerotic plaques, they also inhibit the effects of thromboxane A2 over TP receptors on vascular cells or in the plaque. Terutroban (Triplion® or S18886), a new oral specific TP receptor antagonist, has, aside from being an antithrombotic agent, important vascular properties. It improves endothelial function and has an antiatherosclerotic effect. The potential therapeutic applications of terutroban in the prevention of atherothrombosis, particularly in the cerebrovascular and cardiovascular fields including stroke and coronary artery disease, are based on a number of convincing experimental animal and clinical studies. A large trial is currently comparing the efficacy and safety of terutroban versus aspirin in secondary prevention of cardiovascular events in patients who have suffered a stroke or transient ischemic attack (PERFORM Study).
Hemodynamic Instability after Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension Correlates with Cytokine Network Hyperstimulation
Authors: Lindner J. , Maruna P. , Kunstyr J. , Jansa P. , Gürlich R. , Kubzova K. , Zakharchenko M. , Linhart A.
Published: May 2009

Background: Pulmonary endarterectomy (PEA) is an effective treatment for chronic thromboembolic pulmonary hypertension (CTEPH). The present study tested the hypothesis that inflammation, as determined by circulating cytokine levels, may contribute to the difficulty in controlling arterial blood pressure after PEA. Materials and Methods:  Thirty-six patients with CTEPH (22 males and 14 females) underwent PEA using cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest. Plasma concentrations of tumor necrosis factor α, interleukin (IL)-1β, IL-6 and IL-8 were measured repeatedly in arterial blood samples. Results: A significant correlation between norepinephrine support and IL-6 plasma concentrations was shown at the separation from CPB (k = 0.742) and 12 h after it (k = 0.801) as well as between norepinephrine support and IL-8 concentrations 12 h after the separation from CPB. Furthermore, a significant correlation was found between the cardiac index (CI) and both IL-6 and IL-8 at the separation from CPB. Conclusions: Hemodynamic instability after PEA has been associated with higher postoperative plasma concentrations of IL-6 and IL-8. The positive relation between inflammatory cytokines and CI, or cytokines and vasopressor support, is in accordance with the hypothesis that cytokine activation may be among the neurohumoral factors responsible for cardiodepression and systemic vasoplegia in CTEPH patients undergoing PEA.
Factors Associated with Vascular Stiffness: Cross-Sectional Analysis from the Chronic Renal Insufficiency Standards Implementation Study
Authors: Eddington Helen , Sinha Smeeta , Li Elizabeth , Hegarty Janet , Ting Jeanette , Lane Beverley , Chrysochou Constantina , Foley Robert , O’Donoghue Donal , Kalra Philip A. , Middleton Rachel
Published: May 2009

Background: Vascular stiffness is associated with increased cardiovascular risk. This study aimed to identify factors associated with vascular stiffness in a cohort of chronic kidney disease (CKD) patients. Methods: The Chronic Renal Insufficiency Standards Implementation Study is a prospective epidemiological study of CKD patients not on dialysis, who are managed in a clinic setting. Phenotypic parameters were collected annually, and vascular stiffness was assessed using augmentation index (AI). Cross-sectional analysis was performed across quintiles of AI to evaluate factors associated with vascular stiffness. Results: Mean patient age was 66.1 ± 14.1 years and estimated glomerular filtration rate (eGFR) was 31.2 ± 5.7 ml/min. Corrected calcium was 2.26 ± 0.2 SD mmol/l, phosphate 1.2 ± 0.4 SD mmol/l and intact parathyroid hormone 94 ± 96 SD pg/ml; 18.3% of patients had cardiovascular disease. Increased age and systolic blood pressure were associated with increased AI (all p < 0.001). No statistical association was present between AI and eGFR, intact parathyroid hormone, phosphate or protein excretion. Conclusion: This study identified blood pressure as a potentially modifiable risk factor associated with AI, whereas eGFR was not associated with increased AI in a population of CKD stage 3–5 patients. Further knowledge of factors which influence progression of vascular stiffness will be important in risk quantification and management.
Association of Single Nucleotide Polymorphisms in the Eosinophil Peroxidase Gene with Allergic Rhinitis in the Czech Population
Authors: Hrdlickova Barbara , Izakovicova-Holla Lydie
Published: May 2009

Background: Eosinophil peroxidase (EPO) gene codes a cationic protein released from the specific granules of activated eosinophils. Eosinophil granulocytes play a central role in the protection of organisms against parasites. They are also regarded as key effector cells in allergic inflammation. We attempted to determine the polymorphisms in the EPO gene typical for the Czech population and to analyze their associations with allergic rhinitis and its intermediary phenotypes. Methods: We sequenced all 12 exons of the EPO gene, and selected variants were subsequently analyzed by polymerase chain reaction and restriction fragment length polymorphism methods in a case-control study comprising a total of 613 subjects (319 controls and 294 patients with rhinitis). Results: In total, 5 polymorphisms (–1710T/C and –1710T/CTCC, 2649T/C, 3097A/G and 3979A/G) were found in the EPO gene. Polymorphisms 2649T/C and 3097A/G were in complete linkage disequilibrium (D′ = 1 for both groups), and both of them were in a strong disequilibrium with the 3979A/G variant (D′ = 0.801 for controls, D′ = 0.848 for rhinitics). Consequently, these 3 polymorphisms were studied in association with the allergic phenotype. In a single locus analysis, only 3979A/G single nucleotide polymorphism was marginally significantly associated with rhinitis (p = 0.030, pcorr > 0.05). This polymorphism also showed a marginal association with total serum IgE levels (loge IgE, mean ± SD: genotypes GG = 2.60 ± 1.20; GA = 2.47 ± 1.88; AA = 2.38 ± 1.49; p < 0.05). Furthermore, significant differences in haplotype frequencies between patients and healthy subjects were observed (p < 0.05). Conclusions: Our study supports the hypothesis that genetic variability in the EPO gene may contribute to the susceptibility to allergic rhinitis (or related phenotypes) in the Czech population.
When Is a Genetic Test Suitable for Prime Time? Predicting the Risk of Prostate Cancer as a Case-Example
Authors: Li-Wan-Po A. , Farndon P. , Cooley C. , Lithgow J.
Published: May 2009

Advances in genomics promise to deliver personalized medicine both for prevention and treatment of disease. Considerable effort is being directed towards translating observed associations between various genetic variants, such as single nucleotide polymorphisms (SNPs), and disease or drug response into clinically useful genetic tests. Unfortunately, because reported associations are usually weak or moderate, tests based on them are generally not accurate enough for use in routine clinical practice, and therefore, ensuring the appropriate use of genetic tests is important. In a recent report, a combination of 5 SNPs was claimed to improve the predictive value of the test for prostate cancer, compared with the individual SNPs. This led the authors to suggest that a 5-SNP-test could be used to predict the risk of prostate cancer. We evaluate the characteristics of the proposed test, comment on it, and summarize the views of others on its potential clinical utility. We hope that this may serve as a case-example for the evaluation of the many new genetic tests being suggested for adoption.
Vollständige parenterale Ernährung
Authors: Wretlind A.
Published: May 2009

Ausgedehnte experimentelle und klinische Untersuchungen haben ergeben, dass man eine vollständige intravenöse Ernährung mit Hilfe von Aminosäuregemischen, Glukose oder Fruktose, Fett-emulsionen, Elektrolyten und Vitaminen durchführen kann. Mit dieser Alternative zur oralen Nahrungsaufnahme ist es möglich, bei Patienten, bei denen eine orale Nahrungszufuhr unmöglich oder nicht angezeigt ist, einen guten Ernährungszustand zu erreichen und das Wachstum bei Kindern über längere Zeit zu gewährleisten. Durch die parenterale Ernährung ist es bei Kleinkindern und Säug-lingen einerseits möglich, postoperative Körpereiweiss- und Ge-wichtsverluste zu verhindern und andererseits die Neubildung von Körpereiweiss anzuregen und das Wachstum zu fördern. Manche Fragen, die mit der parenteralen Ernährung in Zusammen-hang stehen, müssen im Laufe ihrer weiteren Anwendung noch be-antwortet werden, wie z. B. Fragen der optimalen und maximalen Fettzufuhr, der optimalen Zusammensetzung von Aminosäuregemischen und des Energie-Nährstoffbedarfes. Unser heutiges Wissen über eine vollständige parenterale Ernährung ist jedoch so weit-reichend, um eine Mangelernährung, wie sie als Begleitsymptom bei den verschiedensten inneren und chirurgischen Erkrankungen auf-zutreten pflegt, ausschalten zu können.
Intravenöse Ernährung auf Intensivbehandlungsstationen
Authors: Schwander D. , Kohlschütter Brigitte
Published: May 2009

Es ist eine verbreitete Ansicht, daβ man nach schwerem Trauma eine katabole Reaktion des Organismus hinzunehmen habe. Dabei wird übersehen, daβ zu den auβergewöhnlichen Stoffwechselproble-men des Organismus oft noch diejenigen einer kalorischen Mangel-ernährung, nämlich der konventionellen intravenösen Therapie, hinzutreten. Aufgrund unserer Beobachtungen an schwer traumati-sierten oder septischen Patienten glauben wir, dem Hyperkata-bolismus rasch durch ein hohes und zweckmäβiges Kalorienangebot entgegenwirken zu müssen. Die aufgeführten Beispiele belegen, daβ hierdurch in desperaten Situationen ein entscheidender thera-peutischer Fortschritt möglich ist.
Die Verwertung von Kohlenhydraten in Streß-Situationen
Authors: Geser C.A.
Published: May 2009

Infolge der herabgesetzten Glukosetoleranz in Streβ-Situationen sind Glukoseinfusionen als einzige Kohlenhydratquelle ungeeignet, da sie die Glukosehomöostase schwer beeinträchtigen können. Als Glukoseaustauschstoffe stehen Fruktose, Sorbit und Xylit zur Ver-fügung. Sie haben den Vorteil, insulinunabhängig verwertet zu werden und die Glukosehomöostase nicht wesentlich zu beeinflussen. Dagegen führt ihre hochdosierte Verabreichung, besonders im Fall der Fruktose, zu unerwünschten Nebenerscheinungen wie Laktat-anstieg und Abfall von Standardbikarbonat und pH. Aufgrund theo-retischer Überlegungen und klinischer Erfahrungen ist eine Kombi-nation von Glukose, Fruktose und Xylit für die parenterale Kohlen-hydratzufuhr in Streβ-Situationen zu empfehlen.
Infusionslösungen – ein Hauptkostenfaktor für die Krankenhausapotheke
Authors: Abel E.-H.
Published: May 2009

Innerhalb des medizinischen Sachbedarfs eines Krankenhauses ste-hen die Ausgaben für Arzneimittel an erster Stelle. Einer der Haupt-kostenfaktoren sind die Ausgaben für Infusionslösungen. Die Bun-despflegesatzverordnung läβt eine Berechnung neben dem Pflege-satz nicht mehr zu. Die Krankenhäuser sind gehalten, diesen Haupt-ausgabefaktor der Apotheke zu überwachen und zu steuern. Im Rahmen des Selbstkostennachweises muβ jedes Krankenhaus die Höhe der Ausgaben aufgliedern.
Die postoperative Steigerung der Darmmotilität durch Infusionstherapie
Authors: Bastian H.P. , Kowohl K. , Flossdorf W.
Published: May 2009

Die primären Ursachen der funktionellen Darmmotilitätsstörungen werden aufgezählt. In der älteren Literatur beträgt die Letalítät durch Darmatonien bis zu 22,2%. Wir fanden in unserem Krankengut nach 1468 Eingriffen, wobei 1356 retroperitoneal und 112 transperitoneal durchgeführt wurden, in 1% eine Darmatonie. Nach der Art der Maβnahmen zur post-operativen Steigerung der Darmmotilität fand sich nach Bepanthen® und Prostigmin® in 5,8%, nach Ubretid® in 0,5% und nach Rheomacrodex® 10% mit Sorbit 20% in 0% eine Darmatonie. Ab-schlieβend wird ein Behandlungsplan zur Steigerung der postoperativen Darmmotilität aufgezeigt.
Grundlagen der parenteralen Ernährung des akuten Nierenversagens
Authors: Gofferje H.
Published: May 2009

Aus theoretischen Erwägungen und aufgrund klinischer Erfahrungen darf eine adequate Eiweiß- bzw. Aminosäurenzufuhr bei Patienten mit akutem Nierenversagen nicht länger als Kontraindikation angesehen werden. Wie verschiedene klinische Studien gezeigt haben, wird durch frühzeitige Zufuhr von Eiweiß bzw. Aminosäuren zusammen mit ausreichenden Mengen von Kalorienträgern eine beschleunigte Regeneration geschädigter Tubuluszellen und damit eine raschere Wiederaufnahme der Nierenfunktion ermöglicht. Bei parenteraler Ernährung empfiehlt sich, auf die Applikation nichtessentieller Aminosäuren weitgehend zu verzichten und lediglich essentielle Aminosäuren zusammen mit hochkonzentrierten Kohlenhydratkombinationslösungeneinzusetzen.
The Insulin:Glucagon Ratio and the Secretion of Growth Hormone after Intravenous Administration of Amino Acids and Carbohydrates in Healthy Subjects
Authors: Geser C.A. , Müller-Hess R. , Felber J.P.
Published: May 2009

In ten normal male subjects, the influence of amino acid and carbohydrate infusions on the plasma concentrations of glucose, free fatty acids, inorganic phosphate, insulin, glucagon, and growth hormone was studied. The molar insulin:glucagon ratio was calculated. Three different solutions were used: A mixture of 13 amino acids (50 g/l) = group I, solution (1) plus sorbitol (50 g/l) plus xylitol (50 g/l) = group II, and solution (1) plus glucose (100 g/l) = group III. According to Unger, the relative concentrations of insulin and glucagon control the hepatic glucose balance and the organism’s energy requirement. The insulin:glucagon ratio is inversely correlated with increased glucose production of the liver. A high ratio indicates glucose storage and increased protein synthesis, whereas a low one is a sign of increased gluconeogenesis from amino acids. Our data are in agreement with the clinical observation that, in parenteral nutrition, amino acids should be given together with carbohydrates to produce an anabolic effect. The insulin:glucagon ratio remained unchanged in group I and showed a rise from 6.4 to 14.8 in group II. In group III, a marked increase in the ratio was observed with a maximum of 46 after 60 minutes. Thus, in normal subjects, the combination of amino acids and glucose has a stronger effect on glucose storage and protein synthesis than the combination of amino acids and sorbitol and xylitol. The determination of the insulin:glucagon ratio can be useful for evaluating the anabolic effect of carbohydrate and amino acid solutions in parenteral nutrition.
Zur Verwertung von Fettemulsionen in der parenteralen Ernährung des Menschen
Authors: Eckart J.
Published: May 2009

1st die Indikation zur parenteralen Ernährung gegeben, dann sollten neben Glukose und Aminosäuren Zuckeraustauschstoffe und Fett-emulsionen verabfolgt werden, um Nebenwirkungen der parenteral hyperalimentation wie Hyperglykämie, hyperosmolares nichtketotisches Koma und osmotische Diurese zu vermeiden. SojabohnenöT emulsionen stellen nicht nur eine bedeutende Energiequelle dar, son-dern sind auβerdem geeignet, einen Mangel an essentiellen Fettsäuren im Rahmen einer längerdauernden parenteralen Ernährung zu korri-gieren. Die Utilisation parenteral verabfolgter Fettemulsionen konnte wie-derholt nachgewiesen werden. Um zu klären, wie schnell und in welcher Menge parenteral verabreichte Fettemulsionen von Patienten metabolisiert werden, wurden spontan atmenden Kranken postoperativ oder posttraumatisch C14-markierte Triglyzeride in Lipofundin® S 10% infundiert. Die C14O2-Aktivität in der Ausatemluft wurde mit Hilfe einer lonisationskammer gemessen, deren untere Nachweisgrenze bei 0,1 nCi/Liter Exspirationsluft lag. Die gewonnenen Ergebnisse zeigen, daβ parenteral verabfolgte Fettemulsionen zum Teil akut zu CO2 und Wasser oxydiert, zum Teil vom Organismus gespeichert oder auf andere Weise metabolisiert werden. Aus den Untersuchungen läβt sich folgern, daβ eine parenterale Verabfolgung von Fettemulsionen gerechtfertigt ist. Die Verabreichung von Fettemulsionen bei unterernährten Patienten in der parenteralen Langzeiternährung oder beim Vorliegen hyperkataboler Stoffwechselvorgänge erscheint jedoch besonders indiziert.
Zur parenteralen Verabreichung von Zuckeraustauschstoffen mit besonderer Berücksichtigung des Diabetes mellitus
Authors: Haslbeck M.
Published: May 2009

Die Kohlenhydrate Glukose, Fruktose, Sorbit und Xylit sind die wichtigsten Kalorienträger in der parenteralen Ernährung. Im Gegensatz zu Glukose werden die Zuckeraustauschstoffe zu über 80% in der Leber metabolisiert. Ihr Vorteil beruht auf der insulinunabhängigen Verwertung in der Leber. Die dort aus Zuckeraustauschstoffen zum groβen Teil gebildete Glukose wird verzögert an die Peripherie abgegeben. Inwieweit Insulin am weiteren Umsatz der neu synthetisierten Glukose beteiligt ist, ist noch nicht geklärt, da die charakteristischen Anzeichen für einen gesteigerten Glukoseumsatz (deutliche Änderung der Blutglukose- und Seruminsulinkonzentration) nach Verabreichung von Zuckeraustauschstoffen fehlen. Für eine anfängliche Beteiligung des Insulins am Metabolismus der Fruktose sprechen kurzfristige signifikante Änderungen der Blutglukose-und Seruminsulinkonzentrationen zu Beginn von Dauerinfusionen beim Menschen (0,5 bzw. 0,8 g/kg Körpergewicht/h). Im Gegensatz zur Glukoseapplikation fehlen nach Infusion von Fruktose, Xylit oder entsprechender Mischlösungen überschieβende Gegen-regulationen wie Hypoglykämie und Anstieg der Konzentration der freien Plasmafettsäuren bis zu 300% des Ausgangswertes. Dies zeigt einen weiteren grundsätzlichen Unterschied zwischen Glukose und Zuckeraustauschstoffen und spricht für deren weitgehend insulinunabhängige Verwertung. Für die Zuckeraustauschstoffe ist eine gesteigerte Harnsäuresynthese spezifisch. Glykogenbildung, Laktatämie und stickstoff-sparender Effekt sind Folge eines gesteigerten Kohlenhydratumsatzes. Die insulinunabhängige Verminderung der Ketogenese und der Abfall der freien Fettsäuren mit fehlendem Rebound-Effekt sind wünschenswerte metabolische Wirkungen. Indikationen für die Verwendung von Zuckeraustauschstoffen in der parenteralen Ernährung bilden der manifeste Diabetes und viele andere, zumeist schwere Erkrankungen (Streßsituationen), bei denen es infolge einer verminderten Glukosetoleranz bei Therapie mit Glukose und Insulin zu zusätzlichen Komplikationen kommen kann.
China and the Escalation of the Vietnam War: The First Years of the Johnson Administration
Authors: Lin Mao
Published: May 2009

This article reexamines how concerns about China contributed to the escalation of the Vietnam War during the first years of Lyndon Johnson's administration. Johnson escalated the war in Vietnam to protect America's global credibility as the leader and defender of the non-Communist world in the face of the threat posed by China's “wars of national liberation” strategy in Vietnam. U.S. officials evaluated this threat in the context of the broadening Sino-Soviet split. The concern in Washington was that if Hanoi, a regime openly supported by Beijing as a star in the “wars of national liberation,” were to take over South Vietnam, the Soviet Union might then be forced to discard the “peaceful coexistence” principle and the incipient détente with the West. The escalation in Vietnam was spurred largely by apprehension that a failure to contain China in Vietnam might prompt the Soviet Union to shift back to a hard line toward the West.
Images of the Adversary: NATO Assessments of the Soviet Union, 1953–1964
Authors: Hatzivassiliou Evanthis
Published: May 2009

The article presents the analysis of the study groups set up by the North Atlantic Treaty Organization (NATO) to assess the non-military aspects of Soviet power and potential during the era of Nikita Khrushchev. Following Stalin's death, the Western alliance tried to form a comprehensive view of the strengths and weaknesses of the USSR's economy and political system. This was part of NATO's effort to adjust to the realities of a long Cold War, the outcome of which would not be decided by military force alone. The NATO reports were largely successful in describing the long-term trends of the Soviet economy and the weaknesses of the Soviet system. However, they usually failed to anticipate specific, though significant and potentially dangerous, initiatives of the Soviet regime. On balance they were a crucial input for NATO ministers, and their importance in the shaping of Western policies needs to be evaluated carefully.
Television, Religious Objects and Secularism
Authors: Bahar Mehri
Published: May 2009

The major claim of this paper concerns the following question: 'Do the religious tools and symbols presented in the media lose their holiness at the time when they are being represented in the media?' To answer this question I propose that we should consider the media as a new creation of text for religion. Of course, we have to consider the capacities and meaning of media and religion when it arrives in the media. In other words, we should accept that the level of discourse and function of the media (whether religious or other types of media) in presenting a religious ceremony directed towards a series of spiritual values, and occasionally the values which are shown on the screens or through T.V. programmes are not the same as a religious ceremony performed outside the media area as, for example, in a mosque. Two main phenomena are important in each religious ceremony: sacred space and sacred time. It seems that in media these two are lost by the new atmosphere of the media. In this article we consider what is the religious media, and the traits and the nature of religious media. In order to discuss this concept, importance is put on three main concepts in the media. We try to say that media could present a new possibility and present religious experience for its audiences. Many of the ideas of Hoover and Eliade, even ones not mentioned in this study, are important for the study.
Policy of Religious Media in Iran: Interactive, Dynamic and Convergent System of Religious Communication
Authors: Bahonar Nasser
Published: May 2009

The presenting of religion has been indebted to traditional media for centuries. The presence of mass media, especially Radio and Television, in the twentieth century makes it possible to transfer messages to large groups of addressees. This important situation has caused groups and official religious organizations, from eighty years ago, to take great measures in this respect by using electronic media. During the pre-history of Islam and afterward, Iran has always been challenged with crises of the legitimating of communication. The penetration of the Islamic belief among people is caused by traditional Islamic communication, and the legitimacy of Islamic leaders also assigns a legitimacy for the modern media. Whereas governments in the history of Iran have never had a religious and politic legitimacy among people so the communications system of Iran has been abandoned from media convergence. The Islamic Republic of Iran is experiencing a convergence in traditional and modern communications for the first time. Lack of scientific research and a shortage of religious literature in broadcasting make for continual disorder in the process of policy-making for the planning of the religious medium. In this article the writer benefits from the result of two researches conducted in Iran, in the field of religious media, and analyses the content of religious programmes of television followed by the presentation of a theoretic view in making for a desired religious media policy in the Islamic Republic of Iran.
Media and Public Sphere in Iran
Authors: Dehghan Ali Reza
Published: May 2009

The Habermasian notion of the public sphere is an independent area free of government intervention. In the Iranian case, the ownership and management of radio and television is with the government. Therefore, no programme can harshly criticise basic government policies. There are news sections, news reports, political commentaries, and interviews with political experts, first, second, or third ranked politicians and government officials, or even interviews with the public in which administrative inefficiencies, commodity shortages and even people's complaints and grievances are discussed. However, television productions, whether political, economic or cultural, cannot be oppositional. To change national television from being (mostly) propagandistic in nature to more public sphere in orientation needs time and more economic and political changes. Unlike television, in Iran we do not categorize the function of newspapers as a monologtype or one-way communication. Reformist papers do present alternative political and economic views. Nonetheless, financial and political problems such as opposing expectations and demands from readers and the judiciary system, low readership figures, a limited advertising market, and the shortage of imported and domestically produced paper prevent them from functioning as an effective and influential part of the Iranian public sphere. Recently, however, there have been some changes in the broadcast policy of Iranian television in terms of more channels, more dialog-type content, and an apparently non-biased and neutral position regarding reformists and conservatives. To assess how this new policy may change national television from (mostly) a propaganda type to a public sphere type requires more time and reliable evidence still not available.
Liturgy and Justice
Authors: Burns Stephen
Published: May 2009

This article charts a number of pathways in exploring the relationship between liturgy and justice. Liturgy is presented as 'public service' that to a greater or lesser extent, in different church styles, embraces texts, the arts and a range of other symbolic and kinaesthetic media. Aspects of each of these are examined in order to highlight both ambiguities and promise in liturgical data's promotion of justice.
Bringing a Dispute Concerning ICSID Cases and the ICSID Convention Before the International Court of Justice
Authors: Vannieuwenhuyse Gauthier
Published: May 2009

The relationship between the ICSID and the ICJ was contemplated from the beginning of the drafting of the ICSID Convention. The ICSID Convention contains two mechanisms that regulate the legal framework of this relationship. First, a clause providing for the ICJ's jurisdiction in case of a dispute concerning the interpretation or application of the convention is included in Article 64 of the ICSID. This mechanism has never been used by any States. However, some controversial issues such as the scope of power of annulment committees or the denunciation of the ICSID Convention may have crucial consequences in the settlement of investment disputes. Thus, some States may have an interest in using this mechanism. Besides, the relationship between the ICSID and the ICJ may be analyzed with regard to the mechanism of diplomatic protection that can be exercised in the case of non-compliance with an ICSID award according to Article 27 of the ICSID Convention.
Ovarian Tissue Cryopreservation: Promises and Uncertainties
Authors: de Wert Guido , Olsthoorn-Heim Els
Published: May 2009

Cancer in children and young adults is increasingly being cured by operations, radiotherapy and/or chemotherapy. However, one of the serious side effects of these treatments is the risk of damage to fertility. Whereas the most important goal used to be survival, now increasing attention is being paid to the quality of life in the long term, thanks to the success of these treatments. Infertility affects the quality of life. In post-pubescent boys and men semen can be frozen for later use prior to treatment that harms the spermatogenesis. In girls and young women the solution for reduced fertility or infertility after ovary damaging treatment, may consist of the cryopreservation of ovarian tissue prior to this treatment. At a later stage a decision can be made to transplant this ovarian tissue into the patient or to follow an IVF procedure. There are important normative questions regarding this experimental treatment. The main question is, whether it may be introduced in health care as a regular treatment or should be subject to medical research first. In the Netherlands, a working party of both doctors and ethical, legal and psychological experts recommended to carry out proper research before introducing ovarian tissue cryopreservation in regular health care. This article is meant to elucidate this policy and, including some relevant updates, thus to contribute to the discussion on this question in other European countries.
The European Economic Area Agreement: A Case of Legal Pluralism
Authors: Harbo Tor-Inge
Published: May 2009

In the article the author discusses the European Economic Area (EEA) Agreement in light of theories of constitutional and legal pluralism. The author begins with a presentation of the EEA Agreement and compares it with the European Union (EU) legal order. It is pointed out that one of the differences between the two legal regimes is the fact that the EU law principle of direct effect is not applicable in EEA law. Since there is no provision in the EEA Agreement which hinders the establishment of direct effect in EEA law, the author seeks to find the deeper explanation for the rejection of the principle. This leads into an elaboration of the pragmatic concept of law. An important feature of this concept of law is the dominant role of the will of the legislator. This constitutional set-up is also reflected in the concept of sovereignty, which is one leading rational of the EEA Agreement. Being in the squeeze between the two rationalities of the EEA Agreement: sovereignty and homogeneity, the European Free Trade Association (EFTA) Court has been willing to take into consideration contextual particularities. This contextual or legal pluralistic approach is a result of an implicit and explicit judicial dialogue, which secures the legitimacy of the EFTA Court and the EEA Agreement.