Browsing by Subject "rat"

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Open Access
Antiangiogenic response after 70% hepatectomy and its relationship with hepatic regeneration and angiogenesis in rats
(2010) Dogrul, A.B.; Colakoglu, T.; Kosemehmetoglu, K.; Birben, E.; Yaman, E.; Gedikoglu G.; Abbasoglu O.
Background: The aim of this study was to evaluate the antiangiogenic response and its relation to regeneration and angiogenesis after 70% hepatectomy in a rat model. Methods: Sixty-four Wistar albino rats were included in the study. Animals were allocated into 8 groups (n = 8). After a 70% hepatectomy, liver regeneration, angiogenesis, and antiangiogenic response were evaluated in the remnant liver on days 0, 1, 2, 3, 5, 7, 10, and 14. Regeneration and angiogenesis were determined with immunoreactivity to proliferating cell nuclear antigen and vascular endothelial growth factor. Antiangiogenic response was evaluated by detecting collagen 18 m RNA with reverse transcriptase polymerase chain reaction. Results: We showed that liver regeneration peaked at day 1, whereas angiogenesis in the periportal and perisinusoidal areas reached their peak values on days 3 and 7, respectively. Both regeneration and angiogenic activity around perisinusoidal hepatocytes returned to basal activity on the day 10. Antiangiogenic response first appeared on day 5, reached a peak on day 10, and returned to basal values on day 14. Conclusion: Collagen18 mRNA expression is present in the normal liver during the regenerative process. We suggest that the stimulus that causes the cessation of regeneration process may come from hepatocytes, and collagen 18 produced by hepatocytes may modulate this event by inhibiting the angiogenesis. © 2010 Mosby, Inc. All rights reserved.
Open Access
Application of a customized pathway-focused microarray for gene expression profiling of cellular homeostasis upon exposure to nicotine in PC12 cells
(2004) Konu Ö.; Xu X.; Ma J.Z.; Kane J.; Wang J.; Shi, S.J.; Li, M.D.
Maintenance of cellular homeostasis is integral to appropriate regulation of cellular signaling and cell growth and division. In this study, we report the development and quality assessment of a pathway-focused microarray comprising genes involved in cellular homeostasis. Since nicotine is known to have highly modulatory effects on the intracellular calcium homeostasis, we therefore tested the applicability of the homeostatic pathway-focused microarray on the gene expression in PC-12 cells treated with 1 mM nicotine for 48 h relative to the untreated control cells. We first provided a detailed description of the focused array with respect to its gene and pathway content and then assessed the array quality using a robust regression procedure that allows for the exclusion of unreliable measurements while decreasing the number of false positives. As a result, the mean correlation coefficient between duplicate measurements of the arrays used in this study (control vs. nicotine treatment, three samples each) has increased from 0.974±0.017 to 0.995±0.002. Furthermore, we found that nicotine affected various structural and signaling components of the AKT/PKB signaling pathway and protein synthesis and degradation processes in PC-12 cells. Since modulation of intracellular calcium concentrations ([Ca2+]i) and phosphatidylinositol signaling are important in various biological processes such as neurotransmitter release and tissue pathogenesis including tumor formation, we expect that the homeostatic pathway-focused microarray potentially can be used for the identification of unique gene expression profiles in comparative studies of drugs of abuse and diverse environmental stimuli, such as starvation and oxidative stress. © 2003 Elsevier B.V. All rights reserved.
Open Access
Chitosan scaffolds with BMP-6 loaded alginate microspheres for periodontal tissue engineering
(2012) Soran, Z.; Aydin, R.S.T.; Gumusderelioglu, M.
The aim of this study is to develop an effective growth factor releasing scaffold-microsphere system for promoting periodontal tissue engineering. Bone morphogenetic protein-6 (BMP-6)-loaded alginate microspheres in narrow size distribution were produced by optimising electrospraying conditions. The addition of these microspheres to chitosan gels produced a novel scaffold in which not only the pore sizes and interconnectivity were preserved, but also a controlled release vehicle was generated. Loading capacity was adjusted as 50ng or 100ng BMP-6 for each scaffold and the controlled release behaviour of BMP-6 from chitosan scaffolds was observed during seven days. Cell culture studies were carried out with rat mesenchymal stem cells derived from bone marrow in three groups; chitosan scaffolds, chitosan scaffolds containing BMP-6-loaded alginate microspheres and chitosan scaffolds with free BMP-6 in culture medium. Results showed that controlled delivery of BMP-6 from alginate microspheres has a significant effect on osteogenic differentiation. © 2012 Informa UK Ltd All rights reserved.
Open Access
Development of a thulium (Tm:YAP) laser system for brain tissue ablation
(2011) Bilici, T.; Mutlu, S.; Kalaycioglu H.; Kurt, A.; Sennaroglu, A.; Gulsoy, M.
In this study, a thulium (Tm:YAP) laser system was developed for brain surgery applications. As the Tm:YAP laser is a continuous-wave laser delivered via silica fibers, it would have great potential for stereotaxic neurosurgery with highest local absorption in the IR region. The laser system developed in this study allowed the user to set the power level, exposure time, and modulation parameters (pulse width and on-off cycles). The Tm:YAP laser beam (200-600 mW, 69-208 W/cm 2) was delivered from a distance of 2 mm to cortical and subcortical regions of ex-vivo Wistar rat brain tissue samples via a 200-μm-core optical fiber. The system performance, dosimetry study, and ablation characteristics of the Tm:YAP laser were tested at different power levels by maximizing the therapeutic effects and minimizing unwanted thermal side-effects. The coagulation and ablation diameters were measured under microscope. The maximum ablation efficiency (100 × ablation diameter/coagulation diameter) was obtained when the Tm:YAP laser system was operated at 200 mW for 10 s. At this laser dose, the ablation efficiency was found to be 71.4% and 58.7% for cortical and subcortical regions, respectively. The fiber-coupled Tm:YAP laser system in hence proposed for the delivery of photothermal therapies in medical applications. © 2011 Springer-Verlag London Ltd.
Open Access
Effect of double growth factor release on cartilage tissue engineering
(2013) Ertan, A.B.; Yilgor P.; Bayyurt, B.; Çalikoǧlu, A.C.; Kaspar Ç.; Kök F.N.; Kose G.T.; Hasirci V.
The effects of double release of insulin-like growth factor I (IGF-I) and growth factor β1 (TGF-β1) from nanoparticles on the growth of bone marrow mesenchymal stem cells and their differentiation into cartilage cells were studied on PLGA scaffolds. The release was achieved by using nanoparticles of poly(lactic acid-co-glycolic acid) (PLGA) and poly(N-isopropylacrylamide) (PNIPAM) carrying IGF-I and TGF-β1, respectively. On tissue culture polystyrene (TCPS), TGF-β1 released from PNIPAM nanoparticles was found to have a significant effect on proliferation, while IGF-I encouraged differentiation, as shown by collagen type II deposition. The study was then conducted on macroporous (pore size 200-400μm) PLGA scaffolds. It was observed that the combination of IGF-I and TGF-β1 yielded better results in terms of collagen type II and aggrecan expression than GF-free and single GF-containing applications. It thus appears that gradual release of a combination of growth factors from nanoparticles could make a significant contribution to the quality of the engineered cartilage tissue. © 2011 John Wiley & Sons, Ltd.
Open Access
Identification of novel neutralizing single-chain antibodies against vascular endothelial growth factor receptor 2
(2011) Erdag, B.; Koray Balcioglu, B.; Ozdemir Bahadir, A.; Serhatli, M.; Kacar O.; Bahar, A.; Seker, U.O.S.; Akgun, E.; Ozkan, A.; Kilic, T.; Tamerler, C.; Baysal, K.
Human vascular endothelial growth factor (VEGF) and its receptor (VEGFR-2/kinase domain receptor [KDR]) play a crucial role in angiogenesis, which makes the VEGFR-2 signaling pathway a major target for therapeutic applications. In this study, a single-chain antibody phage display library was constructed from spleen cells of mice immunized with recombinant human soluble extracellular VEGFR-2/KDR consisting of all seven extracellular domains (sKDR D1-7) to obtain antibodies that block VEGF binding to VEGFR-2. Two specific single-chain antibodies (KDR1.3 and KDR2.6) that recognized human VEGFR-2 were selected; diversity analysis of the clones was performed by BstNI fingerprinting and nucleotide sequencing. The single-chain variable fragments (scFvs) were expressed in soluble form and specificity of interactions between affinity purified scFvs and VEGFR-2 was confirmed by ELISA. Binding of the recombinant antibodies for VEGFR-2 receptors was investigated by surface plasmon resonance spectroscopy. In vitro cell culture assays showed that KDR1.3 and KDR2.6 scFvs significantly suppressed the mitogenic response of human umbilical vein endothelial cells to recombinant human VEGF 165 in a dose-dependent manner, and reduced VEGF-dependent cell proliferation by 60% and 40%, respectively. In vivo analysis of these recombinant antibodies in a rat cornea angiogenesis model revealed that both antibodies suppressed the development of new corneal vessels (p < 0.05). Overall, in vitro and in vivo results disclose strong interactions of KDR1.3 and KDR2.6 scFvs with VEGFR-2. These findings indicate that KDR1.3 and KDR2.6 scFvs are promising antiangiogenic therapeutic agents. © 2011 International Union of Biochemistry and Molecular Biology, Inc.
Open Access
Resveratrol affects histone 3 lysine 27 methylation of vessels and blood biomarkers in DOCA salt-induced hypertension
(Kluwer Academic Publishers, 2015) Han, S.; Uludag, M.O.; Usanmaz, S.E.; Ayaloglu-Butun F.; Akcali, K.C.; Demirel-Yilmaz, E.
Hypertension is a risk factor for the cardiovascular diseases. Although, several drugs are used to treat hypertension, the success of the antihypertensive therapy is limited. Resveratrol decreases blood pressure in animal models of hypertension. This study researched the mechanisms behind the effects of resveratrol on hypertension. Hypertension was induced by using the deoxycorticosterone acetate (DOCA)-induced (15 mg/kg twice per week, subcutaneously) salt-sensitive hypertension model of Wistar rats. Hypertension caused a decrease in endothelium-dependent relaxations of the isolated thoracic aorta. Resveratrol treatment (50 mg/l in drinking water) prevented DOCA salt-induced hypertension, but did not improve endothelial dysfunction. Plasma nitric oxide (NO), asymmetric dimethylarginine (ADMA), total antioxidant capacity (TAC) and hydrogen sulfide (H2S) levels were not changed by DOCA salt application. However, treatment of resveratrol significantly decreased ADMA and increased TAC and H2S levels. NO level in circulation was not significantly changed by resveratrol. DOCA salt application and resveratrol treatment also caused an alteration in the epigenetic modification of vessels. Staining pattern of histone 3 lysine 27 methylation (H3K27me3) in the aorta and renal artery sections was changed. These results show that preventive effect of resveratrol on DOCA salt-induced hypertension might due to its action on the production of some blood biomarkers and the epigenetic modification of vessels that would focus upon new aspect of hypertension prevention and treatment. © 2014, Springer Science+Business Media Dordrecht.