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71.
72.
Wisniewska JM Rödl CB Kahnt AS Buscató E Ulrich S Tanrikulu Y Achenbach J Rörsch F Grösch S Schneider G Cinatl J Proschak E Steinhilber D Hofmann B 《Biochemical pharmacology》2012,83(2):228-240
5-Lipoxygenase (5-LO) is a crucial enzyme of the arachidonic acid (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) which are involved in inflammatory diseases and allergic reactions. The pathophysiological effects of LTs are considered to be prevented by 5-LO inhibitors. In this study we present cyclohexyl-[6-methyl-2-(4-morpholin-4-yl-phenyl)-imidazo[1,2-a]pyridin-3-yl]-amine (EP6), a novel imidazo[1,2-a]pyridine based compound and its characterization in several in vitro assays. EP6 suppresses 5-LO activity in intact polymorphonuclear leukocytes with an IC(50) value of 0.16μM and exhibits full inhibitory potency in cell free assays (IC(50) value of 0.05μM for purified 5-LO). The efficacy of EP6 was not affected by the redox tone or the concentration of exogenous AA, characteristic drawbacks known for the class of nonredox-type 5-LO inhibitors. Furthermore, EP6 suppressed 5-LO activity independently of the cell stimulus or the activation pathway of 5-LO contrary to what is known for some nonredox-type inhibitors. Using molecular modeling and site-directed mutagenesis studies, we were able to derive a feasible binding region within the C2-like domain of 5-LO that can serve as a new starting point for optimization and development of new 5-LO inhibitors targeting this site. EP6 has promising effects on cell viability of tumor cells without mutagenic activity. Hence the drug may possess potential for intervention with inflammatory and allergic diseases and certain types of cancer including leukemia. 相似文献
73.
Schiedel FM Pip S Wacker S Pöpping J Tretow H Leidinger B Rödl R 《The Journal of bone and joint surgery. British volume》2011,93(6):788-792
We report the results of intramedullary leg lengthening conducted between 2002 and 2009 using the Intramedullary Skeletal Kinetic Distractor in 69 unilateral lengthenings involving 58 femora and 11 tibiae. We identified difficulties that occurred during the treatment and assessed whether they were specifically due to the implant or independent of it. Paley's classification for evaluating problems, obstacles and complications with external fixators was adopted, and implant-specific difficulties were continuously noted. There were seven failures requiring premature removal of the device, in four due to nail breakage and three for other reasons, and five unsuccessful outcomes after completion of the lengthening. In all, 116 difficulties were noted in 45 patients, with only 24 having problem-free courses. In addition to the difficulties arising from the use of external fixators, there were almost the same number again of implant-specific difficulties. Nevertheless, successful femoral lengthening was achieved in 52 of the 58 patients (90%). However, successful tibial lengthening was only achieved in five of 11 patients (45%). 相似文献
74.
Evidence for a clade composed of molluscs with serially repeated structures: monoplacophorans are related to chitons 总被引:1,自引:0,他引:1
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Giribet G Okusu A Lindgren AR Huff SW Schrödl M Nishiguchi MK 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(20):7723-7728
Monoplacophorans are among the rarest members of the phylum Mollusca. Previously only known from fossils since the Cambrian, the first living monoplacophoran was discovered during the famous second Galathea deep-sea expedition. The anatomy of these molluscs shocked the zoological community for presenting serially repeated gills, nephridia, and eight sets of dorsoventral pedal retractor muscles. Seriality of organs in supposedly independent molluscan lineages, i.e., in chitons and the deep-sea living fossil monoplacophorans, was assumed to be a relic of ancestral molluscan segmentation and was commonly accepted to support a direct relationship with annelids. We were able to obtain one specimen of a monoplacophoran Antarctic deep-sea species for molecular study. The first molecular data on monoplacophorans, analyzed together with the largest data set of molluscs ever assembled, clearly illustrate that monoplacophorans and chitons form a clade. This "Serialia" concept may revolutionize molluscan systematics and may have important implications for metazoan evolution as it allows for new interpretations for primitive segmentation in molluscs. 相似文献
75.
Oystein Bakkevig Siri Steine Kari von Hafenbrädl Even Lærum 《Scandinavian journal of primary health care》2013,31(4):247-251
Objective - To evaluate whether measurement of albumin creatinine ratio (ACR) on a spot urine specimen can replace a timed overnight collection of urine albumin excretion rate (UAER) in patients with diabetes in primary care. Design - Patients with diabetes attending Rønvik Health Centre were asked to bring a timed overnight collection of urine for measurement of UAER. They were also asked to void a urine specimen for measurement of albumin creatinine ratio. Setting - Primary health care. Subjects - One-hundred-and-six persons with diabetes (47 women, 59 men) aged 13 to 78 years. Results - The sensitivity and specificity of ACR with cut-off values of 2.5 mg/mmol for men and 3.5 mg/mmol for women compared to UAER with cut-off value of 20 mg/24 h was 90%. Conclusions - Spot urine ACR analysed on a DCA 2000 can replace a timed (overnight) collection of urine and measurement of UAER when diabetic patients are reviewed in general practice. This simplifies procedures for the patient as a timed urine collection is no longer necessary. Another advantage is that the results are available after 7 min. 相似文献
76.
This paper examines regional changes in the prevalence of overweight (BMI ≥ 25 kg/m2) and obesity (BMI ≥ 30 kg/m2) among Austrian adults (aged ≥ 20 years) during a 35-year period, taking into account the social inequality with regard to obesity. Self-reported data from five cross-sectional nationally representative surveys (n = 178,818) conducted between 1973 and 2007 were analysed. The prevalence of overweight was higher in men than women (2007: 46.3 vs. 31.2 %;p < 0.001) and similar in all Austrian regions. There was a clear east-west gradient for obesity among both sexes, with the highest rates in Eastern Austria (in 2007, women: 18.1 %, men: 16.1 %;p < 0.001) and the lowest in Western Austria (in 2007, women: 12.6 %, men: 11.7 %;p < 0.001). Logistic regression analyses have shown a general decrease of overweight per year among women (OR = 0.991, 95 % CI 0.990-0.993) and men (OR = 0.999, 95 % CI 0.998-1.000), while the obesity prevalence has risen during the study period in every region (women: OR = 1.003, 95 % CI 1.001-1.005; men: OR = 1.011, 95 % CI 1.009-1.013), with the highest increase among women in Central Austria and men in Western Austria. Social inequalities for obesity showed a tendency to increase in the Western and Eastern region. Our results showed a significant regional difference for obesity prevalence during the entire study period. Obesity is a frequent health problem among Austrian adults residing in the Eastern region. 相似文献
77.
78.
Hernandez-Richter TM Wichmann MW Schrödl W Angele MK Heinritzi K Schildberg FW 《Clinical and experimental medicine》2001,1(1):35-41
Objective. Infection of prosthetic material is a major complication of vascular surgery. Therapy for it includes implantation of antimicrobial
prostheses bonded with different antimicrobial agents. These agents may, however, induce an acute phase reaction following
implantation in the host, thus compromising follow-up of the infection. It is not known whether the antimicrobial agent triclosan
induces a significant acute phase reaction when bonded to vascular prostheses. Methods. To study this, 34 adult swine weighing 20–30 kg were allotted randomly to the following groups: (1) controls with untreated
prostheses, (2) control group with triclosan-bonded prostheses, (3) therapy group with untreated prostheses, local infection
with Staphylococcus aureus, surgical revision, and exchange with new, untreated prostheses, and (4) therapy group with untreated prostheses, local infection
with S. aureus, surgical revision, and exchange with triclosan-bonded prostheses. Serum C-reactive protein (CRP) and haptoglobin values
were determined during the 28-day period after surgery. The study was performed at the Institute for Surgical Research of
the Ludwig Maximilian University School of Medicine in Munich. Results. Normal ranges of serum CRP and haptoglobin values were 10.7±1.4 μg/ml and 2.5±0.3 mg/ml, respectively. Following implantation
of untreated and triclosan-bonded vascular prostheses, significantly elevated serum CRP and haptoglobin values were observed.
No significant differences between results with triclosan-bonded and untreated prostheses were observed in control or treatment
groups. No correlation was found between acute phase reaction and the absence or presence of infection. Conclusions. Triclosan is the only antimicrobial agent that bonds to vascular prosthetic material without the need of a sealant. Our data
indicate that vascular prosthesis implantation, whether untreated and triclosan-bonded, results in a sigificant acute phase
reaction. No differences between antimicrobial and untreated prostheses were observed, independently of the absence or presence
of infection. The antimicrobial agent itself did not induce a severe acute phase response and may, therefore, be used in patients
at risk of infection.
Received: 16 August 2000 / Accepted: 17 November 2000 相似文献
79.
B. Urlesberger G. Zobel D. Dacar S. Rödl U. Trafojer A. Trantina J. Knez 《Intensive care medicine》1999,25(5):496-502
OBJECTIVE: To investigate the effect of the combination of kinetic therapy (KT) with partial liquid ventilation (PLV) on gas exchange, lung mechanics and hemodynamics in acute lung injury (ALI). DESIGN: Prospective, randomized, controlled pilot study. SETTING: University research laboratory. SUBJECTS: Eleven piglets weighing 8.3+/-0.9 kg. INTERVENTION: ALI was induced by the infusion of oleic acid (0.08 ml/kg) and repeated lung lavages with 0.9% NaCl (20 ml kg(-1)). Thereafter the animals were randomly assigned either for PLV or a combination of PLV with KT (PLV/KT). The dose of perfluorocarbon administered was 30 ml/kg, evaporative losses were substituted with 5 ml/kg per h. MEASUREMENTS AND MAIN RESULTS: Airway pressures, tidal volumes, dynamic compliance (Cdyn), expiratory airway resistance and arterial blood gases were measured. Hemodynamic monitoring included right atrial, mean pulmonary artery, pulmonary capillary wedge and mean systemic arterial pressures, and continuous flow recording of the pulmonary artery. In both groups the induction of ALI significantly reduced PaO2/FIO2 Cdyn and cardiac output, and significantly increased pulmonary artery pressure. After the initiation of PLV there was a significant increase of PaO2/FIO2, and Cdyn, and a significant decrease of pulmonary artery pressure in both groups. Except the PaCO2, which showed significantly lower values in the PLV/KT group, no variables showed any differences between the two groups. CONCLUSION: The additional use of KT did not show beneficial effects on oxygenation and lung mechanics during PLV. However, at constant minute ventilation PaCO2 levels were significantly lower during PLV/KT, indicating some positive influence on the ventilation/perfusion distribution within the lung. Extreme body positions during PLV/KT did not show any significant hemodynamic side effects. 相似文献
80.
R Marincsák BI Tóth G Czifra I Márton P Rédl I Tar L Tóth L Kovács T Bíró 《Oral diseases》2009,15(5):328-335
Objectives: Recent reports have unambiguously identified the presence and the growth-modulatory role of transient receptor potential vanilloid-1 (TRPV1), a central integrator of pain sensation, on numerous non-neuronal cell types and, of great importance, in certain malignancies. In this study, we have investigated the molecular expression of TRPV1 in the human tongue and its high-incidence malignant (squamous cell carcinoma, SCC) and premalignant (leukoplakia) conditions.
Methods: Immunohistochemistry, Western blotting and quantitative 'real-time' Q-PCR were performed to define the expression of TRPV1.
Results: A weak and sparse TRPV1-specific immunoreactivity was identified in the basal layers of the healthy human tongue epithelium. By contrast, we observed a dramatically elevated TRPV1-immunoreactivity in all layers of the epithelium both in precancerous and malignant samples. Furthermore, statistical analysis revealed that the marked overexpression of TRPV1 found in all grades of SCC showed no correlation with the degree of malignancy of the tumours. Finally, the molecular expression of TRPV1 was also identified in an SCC-derived cell line and was shown to be increased in parallel with the accelerated growth of the cells.
Conclusion: Collectively, our findings identify TRPV1 as a novel, promising target molecule in the supportive treatment and diagnosis of human tongue SCC. 相似文献
Methods: Immunohistochemistry, Western blotting and quantitative 'real-time' Q-PCR were performed to define the expression of TRPV1.
Results: A weak and sparse TRPV1-specific immunoreactivity was identified in the basal layers of the healthy human tongue epithelium. By contrast, we observed a dramatically elevated TRPV1-immunoreactivity in all layers of the epithelium both in precancerous and malignant samples. Furthermore, statistical analysis revealed that the marked overexpression of TRPV1 found in all grades of SCC showed no correlation with the degree of malignancy of the tumours. Finally, the molecular expression of TRPV1 was also identified in an SCC-derived cell line and was shown to be increased in parallel with the accelerated growth of the cells.
Conclusion: Collectively, our findings identify TRPV1 as a novel, promising target molecule in the supportive treatment and diagnosis of human tongue SCC. 相似文献