Medical Center Wuppertal

Wuppertal, Germany

Medical Center Wuppertal

Wuppertal, Germany
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Postberg J.,Witten/Herdecke University | Postberg J.,Medical Center Wuppertal | Tsytlonok M.,Witten/Herdecke University | Sparvoli D.,Witten/Herdecke University | And 2 more authors.
Gene | Year: 2012

It is well established that G-quadruplex DNA structures form at ciliate telomeres and their formation throughout the cell-cycle by telomere-end-binding proteins (TEBPs) has been analyzed. During replication telomeric G-quadruplex structure has to be resolved to allow telomere replication by telomerase. It was shown that both phosphorylation of TEBPβ and binding of telomerase are prerequisites for this process, but probably not sufficient to unfold G-quadruplex structure in timely manner to allow replication to proceed. Here we describe a RecQ-like helicase required for unfolding of G-quadruplex structures in vivo. This helicase is highly reminiscent of human RecQ protein-like 4 helicase as well as other RecQ-like helicase found in various eukaryotes and E. coli. In situ analyses combined with specific silencing of either the telomerase or the helicase by RNAi and co-immunoprecipitation experiments demonstrate that this helicase is associated with telomerase during replication and becomes recruited to telomeres by this enzyme. In vitro assays showed that a nuclear extract prepared from cells in S-phase containing both the telomerase as well as the helicase resolves telomeric G-quadruplex structure. This finding can be incorporated into a mechanistic model about the replication of telomeric G-quadruplex structures during the cell cycle. © 2012 Elsevier B.V.

Burgazl K.M.,Justus Liebig University | Burgazl K.M.,Medical Center Wuppertal | Bilgin M.,Justus Liebig University | Kavukcu E.,Medical Center Wuppertal | And 5 more authors.
Journal of the Turkish German Gynecology Association | Year: 2011

Deep vein thrombosis (DVT) is a common condition in which the approach to its diagnosis has evolved over the years. Currently, an algorithm strategy combining pre-test probability, D-Dimer testing and compression ultrasound imaging allows for safe and convenient investigation of suspected lower-extremity thrombosis. Patients with low pre-test probability and a negative D-Dimer test result can have proximal DVT excluded without the need for diagnostic imaging. The mainstay of treatment of DVT is anticoagulation therapy, whereas interventions such as thrombolysis and placement of inferior vena cava filters are reserved for special situations. The use of low-molecular-weight heparin (LMW) allows for outpatient management of most patients with DVT. The duration of anticoagulation therapy depends on whether the primary event was idiopathic or secondary to a transient risk factor. More research is required to optimally define the factors that predict an increased risk of recurrent DVT to determine which patients can benefit from extended anticoagulant therapy. DVT is also a serious problem in the antenatal and postpartum period of pregnancy. Thromboembolic complications are the leading cause of both maternal and fetal morbidity and mortality. The incidence of venous thromboembolism during normal pregnancy is six-fold higher than in the general female population of childbearing age. The treatment of DVT during pregnancy deserves special mention, since oral anticoagulation therapy is generally avoided during pregnancy because of the teratogenic effects in the first trimester and the risk of fetal intracranial bleeding in the third trimester. LMW heparin is the treatment of choice for DVT during pregnancy. If acute DVT occurs near term, interrupting anticoagulation therapy may be hazardous because of the risk of pulmonary embolism. In this situation, placement of a retrievable inferior vena cava filter must be considered. However, there is no consensus as to what the appropriate dose should be and whether anti-Xa levels need to be monitored. © 2011 by the Turkish-German Gynecological Education and Research Foundation.

Willems R.,Medical Center Wuppertal | Krych L.,Copenhagen University | Rybicki V.,Medical Center Wuppertal | Jiang P.,Copenhagen University | And 6 more authors.
Epigenomics | Year: 2015

Aim: To analyze how enteral food introduction affects intestinal gene regulation and chromatin structure in preterm pigs. Materials and methods: Preterm pigs were fed parenteral nutrition plus/minus slowly increasing volumes of enteral nutrition. Intestinal gene-expression and chromatin structure were analyzed 5 days after birth. Results: Enteral feeding led to differential upregulation of inflammatory and pattern recognition receptor genes, including IL8 (median: 5.8, 95% CI: 3.9-7.8 for formula; median: 2.2, 95% CI: 1.3-3.3 for colostrum) and TLR4 (median: 3.7, 95% CI: 2.6-4.8 for formula; no significant differences for colostrum) with corresponding decondensed chromatin configurations. On histology this correlated with mild mucosal lesions, particularly in formula-fed pigs. In CaCo-2 cells, histone hyperacetylation led to a marked increase in TLR4 mRNA and increased IL8 expression upon stimulation with lipopolysaccharide (median: 7.0; interquartile range: 5.63-8.85) compared with naive cells (median 4.2; interquartile range: 2.45-6.33; p = 0.03). Conclusion: Enteral feeding, particular with formula, induces subclinical inflammation in the premature intestine and more open chromatin structure in key inflammatory genes. This may increase the susceptibility for necrotizing enterocolitis. © 2015 Future Medicine Ltd.

Burgazi K.M.,Justus Liebig University | Chasan R.,Justus Liebig University | Kavukcu E.,Medical Center Wuppertal | Neuhof C.,Justus Liebig University | And 3 more authors.
Balkan Medical Journal | Year: 2012

Transcatheter Aortic Valve Implantation [TAVI] is widespread worldwide as an alternative therapy procedure to the patients suffering from severe aortic valve stenosis. However, we shouldn't forget that the conventional surgical aortic valve replacement is still the gold standard therapy for severe aortic valve stenosis. For the patients who cannot be treated conventionally because of high risk comorbid diseases and older age, TAVI is an effective alternative therapy method. The indications should be limited, concerning the high mortality rate, 10% within 30 days of intervention. Long term efficacy data are still inadequate. Although the indications are restricted to older patients with a STS score >10 or log-Euro Score >20, age is not a definite indication for this treatment. The patients should be assessed by a heart team including a non-interventional cardiologist, interventional cardiologist, cardiac anesthesiologist and cardiac surgeon according to their general status, frailty and STS-Euro score. In other words, assessment and treatment of the patient by a heart team is the main factor besides the limited power of the scoring systems. The treatment should be applied to the patients with an aortic annulus diameter between 18-27 mm and a life expectancy of at least over 1 year. The currently ongoing investigations are focused on parameters like safety, efficiency and long term reliability of TAVI. The scientific and technical developments lead to new definitions and parameters regarding the treatment indications of severe aortic valve stenosis. In this review, we present the actual data about TAVI and also our own experiences. © Trakya University Faculty of Medicine.

Burgazli K.M.,Justus Liebig University | Akdere H.,Medical Center Wuppertal | Bilgin M.,Bezmialem Foundation University | Kavukcu E.,Medical Center Wuppertal | And 2 more authors.
Journal of the Turkish German Gynecology Association | Year: 2012

Pregnancy, due to its adaptive physiological changes, is a risk factor for deep vein thrombosis. Incidence of thromboembolic complications during pregnancy ranges from 0.76 to 1.72 per 1000 births. We present in this case report a pregnant woman with iliofemoral-popliteal deep vein thrombosis diagnosed at the 35 th week of her pregnancy, who was treated with vena cava blockage and thrombectomy followed by cesarean section. Unfortunately, a rethrombosis developed in the patient after three days. We determined that the a-v fistula was blocked and not working. We found additionally that the deep vein thrombosis was closing the iliac vein completely on the left side and the blockage descending down through the inferior vena cava inlet with MRI. The patient underwent insertion of a retrievable vena cava filter, two stent implantation to the venous narrowings and surgical iliofemoral venous thrombectomy with concomitant re-creation of a temporary femoral arterio-venous fistula. Anticoagulation therapy with enoxaparine was started after the operation. The patient was discharged with warfarin under control of the INR value, and also with additional compression therapy (compression stockings) from the clinic. Without jeopardizing the mother and the baby, planning a combined surgical procedure, with a multidisciplinary approach is the best way to eliminate the risks of serious complications such as pulmonary embolism and mortality. © 2012 by the Turkish-German Gynecological Education and Research Foundation.

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