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Triantafillidis J.K.,IASO General Hospital | Douvi G.,IASO General Hospital | Agrogiannis G.,National and Kapodistrian University of Athens | Patsouris E.,National and Kapodistrian University of Athens | Papalois A.E.,Experimental and Research Center
BioMed Research International | Year: 2014

Background. Experimental data suggest that oral iron (I.) supplementation can worsen colitis in animals. Aim. To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M.) and Prednisolone (P.) on the severity of TNBS colitis following orally administered I. Methods and Materials. 156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor-α (t-TNF-α) and tissue malondialdehyde (t-MDA) were estimated in all animal groups. Results. Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet) resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF-α levels (17.67±4.92 versus 14.58±5.71, P=0.102), although it significantly reduced the t-MDA levels (5.79±1.55 versus 3.67±1.39, P=0.000). Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet) did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF-α (16.57 ± 5.61 versus 14.65±3.88, P=0.296). However, M. significantly reduced the t-MDA levels (5.99±1.37 versus 4.04±1.41, P=0.000). Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF-α levels (17.67±4.92 versus 12.64±3.97, P=0.003) and the t-MDA levels (5.79±1.54 versus 3.47±1.21, P=0.001). Administration of P on TNBS colitis after high I. supplementation resulted in a significant improvement of the overall histological score and three individual histological parameters and significantly reduced the levels of t-TNF-α (16.6±5.6 versus 11.85±1.3, P=0.001). Conclusion. I. can induce colonic inflammation and aggravate TNBS colitis. M. and P. can significantly improve the inflammatory process in the colonic mucosa in TNBS colitis aggravated by orally administered I. P. has a stable anti-TNF-α effect. These findings suggest that the harmful. © 2014 John K. Triantafillidis et al.


Gazouli M.,National and Kapodistrian University of Athens | Bouziotis P.,Institute of Nuclear and Radiological science | Lyberopoulou A.,National and Kapodistrian University of Athens | Ikonomopoulos J.,Agricultural University of Athens | And 3 more authors.
In Vivo | Year: 2014

Background/Aim: The basic role of vascular endothelial growth factor (VEGF) in cancer is underscored by the approval of bevacizumab for first-line treatment of cancer patients. Recent anticancer therapeutics based on active tumor targeting by conjugating tumor-specific antibodies has become of great interest in oncology. Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers able to deliver specific molecule payloads in a selective manner to improve the efficacy and safety of cancer imaging and therapy. We herein aimed to determine the targeting ability of bevacizumab-conjugated quantum dots (QDs) in vitro and in vivo. Materials and Methods: We used QDs labeled with bevacizumab, in various in vitro experiments using cell lines derived from colorectal cancer (CRC) and breast cancer (BC). For a competition study of QD-bevacizumab complex and bevacizumab, the cells were pre-treated with bevacizumab (100 nmol/L) for 24 h before exposure to the QD-bevacizumab complex. The breast cancer cells (MDA-MB-231) were injected to 9 nude mice to make the xenograft tumor model. The QD-bevacizumab complex was injected into the tumor model and fluorescence measurements were performed at 1, 12, and 24 h post-injection. Results: Immunocytochemical data confirmed strong and specific binding of the QD-bevacizumab complex to the cell lines.The cells pre-treated with an excess of bevacizumab showed absence of QD binding. The in vivo fluorescence image disclosed that there was an increased signal of tumor after the injection of QDs. Ex vivo analysis showed 3.1±0.8%, 28.6±5.4% and 30.8±4.2% injected dose/g accumulated in the tumors at 1, 12 and 24 h respectively. Tumor uptake was significantly decreased in the animals pretreated with excess of bevacizumab (p=0.001). Conclusion: In conclusion, we could successfully detect the VEGF-expressing tumors using QDs-bevacizumab nanoprobes in vitro and in vivo, opening new perspectives for VEGF-targeted non-invasive imaging in clinical practice.


Tsiampa V.A.,National and Kapodistrian University of Athens | Ignatiadis I.,KAT Hospital | Papalois A.,Experimental and Research Center | Givissis P.,Aristotle University of Thessaloniki | And 3 more authors.
Journal of Plastic Surgery and Hand Surgery | Year: 2012

Improved tendon-to-tendon suturing techniques allow for consistent and immediate activation of transferred muscle after surgery. A pre-requisite for early training after tendon transfer surgery is sufficient mechanical integrity of the tendon-to-tendon attachment. This in vitro study compared the mechanisms and magnitudes of load-to-failure response of two different repair techniques (side-to-side running, n = 7) and weave sutures (n = 8) in sheep front foot tendons. Tensile tests were performed by placing pre-conditioned tendons in a testing machine and stretching at a constant speed to failure. The length of the tendons overlap was the same (50 mm) for both repair techniques. The results of the load to failure tests showed that the side-to-side repairs were significantly stronger than the weave repairs. The failure mechanisms were also different. While the side-to-side attachment failed by longitudinal separation of tendon material of the donor tendon but with the fibres locked to the running sutures attached to the recipient tendon, the weave repairs failed by knot slipping or by suture pullout from the tendon substance. It is concluded that use of the side-to-side repair technique can provide early active training of new motors that not only prevent the formation of adhesions but also facilitate the voluntary recruitment of motors powering new functions before immobilisation-related swelling and stiffness restrain muscle contractions. © 2012 Informa Healthcare.


Athanasopoulos P.,University of Cambridge | Mastoraki A.,National and Kapodistrian University of Athens | Papalois A.,Experimental and Research Center | Nastos C.,National and Kapodistrian University of Athens | And 4 more authors.
Journal of Investigative Surgery | Year: 2016

Purpose/Aim: Hepatic ischemia/reperfusion (I/R) describes the paradox of additional tissue injury caused by reperfusion. The aim of this survey was to investigate the mRNA expression of genes exerting their inflammatory and regenerative reaction in a porcine model of I/R and extended hepatectomy.Material and methods: Twelve pigs were used, weighing 30-35 kg in average, which were allocated in two groups: the I/R group with eight pigs and the sham-operated (control) one with four pigs. The I/R group underwent portacaval anastomosis and Pringle maneuver followed by extended hepatectomy. The hepatoduodenal ligament was occluded for 150 min and the liver remnant was reperfused for 24 hours. Blood samples were steadily received throughout the surgical procedure, where hepatic biopsies were taken for pathological evaluation. Animals were sacrificed in 24 hours after the onset of reperfusion.Results: Between the two groups, statistically significant differences were noticed in serum values of AST, ALT, ALP, and total bilirubin in the early and late phase of reperfusion. The mRNA expression of iNOS, IL-1b, and TGF-a did not increase significantly in the I/R group. Conversely, the mRNA modification of IL-6, STAT-3, and E-selectin demonstrated significantly increased expression in I/R animals.Conclusions: In the present survey, a new I/R swine model was proposed and specific parameters were analyzed, revealing differences between the study groups. © 2015 Taylor & Francis Group, LLC.


PubMed | Agricultural University of Athens, Experimental and Research Center, Institute of Nuclear and Radiological science and National and Kapodistrian University of Athens
Type: Journal Article | Journal: In vivo (Athens, Greece) | Year: 2014

The basic role of vascular endothelial growth factor (VEGF) in cancer is underscored by the approval of bevacizumab for first-line treatment of cancer patients. Recent anticancer therapeutics based on active tumor targeting by conjugating tumor-specific antibodies has become of great interest in oncology. Current progress in nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers able to deliver specific molecule payloads in a selective manner to improve the efficacy and safety of cancer imaging and therapy. We herein aimed to determine the targeting ability of bevacizumab-conjugated quantum dots (QDs) in vitro and in vivo.We used QDs labeled with bevacizumab, in various in vitro experiments using cell lines derived from colorectal cancer (CRC) and breast cancer (BC). For a competition study of QD-bevacizumab complex and bevacizumab, the cells were pre-treated with bevacizumab (100 nmol/L) for 24 h before exposure to the QD-bevacizumab complex. The breast cancer cells (MDA-MB-231) were injected to 9 nude mice to make the xenograft tumor model. The QD-bevacizumab complex was injected into the tumor model and fluorescence measurements were performed at 1, 12, and 24 h post-injection.Immunocytochemical data confirmed strong and specific binding of the QD-bevacizumab complex to the cell lines. The cells pre-treated with an excess of bevacizumab showed absence of QD binding. The in vivo fluorescence image disclosed that there was an increased signal of tumor after the injection of QDs. Ex vivo analysis showed 3.1 0.8%, 28.6 5.4% and 30.8 4.2% injected dose/g accumulated in the tumors at 1, 12 and 24 h respectively. Tumor uptake was significantly decreased in the animals pretreated with excess of bevacizumab (p=0.001).In conclusion, we could successfully detect the VEGF-expressing tumors using QDs-bevacizumab nanoprobes in vitro and in vivo, opening new perspectives for VEGF-targeted non-invasive imaging in clinical practice.


Koniari I.,University of Patras | Mavrilas D.,University of Patras | Apostolakis E.,University of Ioannina | Papadimitriou E.,University of Patras | And 6 more authors.
Journal of Cardiovascular Pharmacology and Therapeutics | Year: 2016

Aims: This study aims to evaluate atherosclerosis, oxidative stress, and arterial stiffness attenuation by simvastatin and ivabradine in hyperlipidemic rabbits. Methods and Results: Forty rabbits were randomly divided into 4 groups: atherogenic diet (group C), atherogenic diet plus simvastatin (group S), atherogenic diet plus ivabradine (group I), and atherogenic diet plus simvastatin and ivabradine (group S + I). After 9 weeks, rabbits were euthanized and descending aortas excised for mechanical testing. Atherogenic diet induced the development of significant atherosclerotic lesions in group C animals but in none of groups S, I, and S + I. RAM-11 and HHF-35-positive cells were significantly reduced in groups S, I, and S + I compared with group C (P < .001). A significant neointimal hyperplasia and intima-media ratio reduction was demonstrated in groups S (P = .015 and P < .001), I (P = .021 and P < .001), and S + I (P = .019 and P < .001) compared with group C. Protein nitrotyrosine levels were significantly decreased in group S compared with group C (P = .009), and reactive oxygen species levels were decreased in group I compared with group C (P = .011). Aortic stiffness was significantly reduced in groups S, I, and S + I compared with group C (P = .003, P = .011, and P = .029). Conclusion: Simvastatin and ivabradine significantly inhibited intimal hyperplasia and oxidative stress contributing to aortic stiffness reduction in hyperlipidemic rabbits. © The Author(s) 2015.


Valerie A.,Phoniatrics and Applied Otorhinolaryngology Center | Vassiliki K.,IASO Maternity Hospital | Irini M.,IASO Maternity Hospital | Nikolaos P.,Experimental and Research Center | And 2 more authors.
Stem Cells International | Year: 2016

Background. The aim of the study was to assess the histological effects of autologous infusion of adipose-derived stem cells (ADSC) on a chronic vocal fold scar in a rabbit model as compared to an untreated scar as well as in injection of hyaluronic acid. Study Design. Animal experiment. Method. We used 74 New Zealand rabbits. Sixteen of them were used as control/normal group. We created a bilateral vocal fold wound in the remaining 58 rabbits. After 18 months we separated our population into three groups. The first group served as control/scarred group. The second one was injected with hyaluronic acid in the vocal folds, and the third received an autologous adipose-derived stem cell infusion in the scarred vocal folds (ADSC group). We measured the variation of thickness of the lamina propria of the vocal folds and analyzed histopathologic changes in each group after three months. Results. The thickness of the lamina propria was significantly reduced in the group that received the ADSC injection, as compared to the normal/scarred group. The collagen deposition, the hyaluronic acid, the elastin levels, and the organization of elastic fibers tend to return to normal after the injection of ADSC. Conclusions. Autologous injection of adipose-derived stem cells on a vocal fold chronic scar enhanced the healing of the vocal folds and the reduction of the scar tissue, even when compared to other treatments. © 2016 Angelou Valerie et al.


PubMed | Experimental and Research Center
Type: Journal Article | Journal: Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology | Year: 2010

To investigate whether AcSDKP can inhibit proliferation and collagen synthesis in cultured rat cardiac fibroblasts mediated by PDGF.Neonatal rat cardiac fibroblasts were isolated. The cell proliferation was observed by 3H-proline incorporation assay.On the culture of 0.4% FBS, PDGF stimulated cardiac fibroblasts proliferation and collagen synthesis with a dose-dependent manner at the concentrations from 1 ng/ml to 20 ng/ml, in which 10 ng/ml PDGF reached its peak. AcSDKP at the concentration from 10(-10) mol/L to 10(-8) mol/L could inhibit cardiac fibroblasts proliferation and collagen synthesis mediated by PDGF. 10(-9) mol/L AcSDKP attained its peak on inhibiting cardiac fibroblasts proliferation and collagen synthesis.AcSDKP can inhibit proliferation and collagen synthesis in cultured rat cardiac fibroblasts mediated by PDGF.

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