scholarly journals Efficacy of a Novel Medical Adhesive for Sealing Lung Parenchyma: An in vitro Study in Rabbit Lungs

2021 ◽  
pp. 1-7
Author(s):  
Sebastian Kalverkamp ◽  
Anna Mantas ◽  
Jan Spillner ◽  
Flutura Hima ◽  
Stephanie Sarah Kanzler ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Lung Parenchyma ◽  
The Novel ◽  
Air Leak ◽  
In Vivo Models ◽  
Suture Group ◽  
Surgical Sutures ◽  
Medical Adhesive

<b><i>Introduction:</i></b> During thoracic resection procedures, complete hemostasis and aerostasis are priorities. A persistent alveolar air leak is associated with increased morbidity and mortality rates. This study aimed to evaluate whether the novel medical adhesive VIVO (Adhesys Medical GmbH Aachen, Germany) is a reliable alternative sealing technique to routine surgical procedures. <b><i>Methods:</i></b> We conducted an in vitro animal study by analyzing 21 lungs of New Zealand (<i>n</i> = 19) and Chinchilla Bastard (<i>n</i> = 2) rabbits (age, 11–18 weeks; weight, 2,400–3,600 g). Three groups, each comprising 7 animals, were evaluated. VIVO (VIVO-group) was compared with standard surgical lung parenchymal lesion closure with a polypropylene suture (Suture-group) and TachoSil® (TachoSil-group). We adopted a stable, pressure-controlled ventilation protocol. After explantation, a surgical incision 0.5-cm deep and 1.5-cm wide was made in the lungs using a customized template. Air leak was measured quantitatively (mL/min) using a respirator and visualized qualitatively by 2 observers who made independent judgments. Next, the leak was closed using VIVO, suture, or TachoSil® as specified by the manufacturer. Subsequently, positive end-expiratory pressure (PEEP) and inspiratory pressure were gradually increased until a maximum of 15 and 30 mbar were attained, respectively. <b><i>Results:</i></b> At PEEPs of 8, 10, and 15 mbar, VIVO achieved complete sealing of the profound parenchymal defect in all (<i>n</i> = 7) lungs. After closure of the incision, we observed an air leak variation of 127 ± 114 mL/min (Suture-group), 31 ± 49 mL/min (VIVO-group), and 114 ± 134 mL/min (TachoSil-group). VIVO showed a significantly lower air leak than surgical sutures (<i>p</i> = 0.031) and TachoSil® (<i>p</i> = 0.046). <b><i>Conclusion:</i></b> VIVO offers sufficient closure of the lung parenchymal lesions. The novel adhesive enabled significantly better sealing with lower persistent air leakage than TachoSil® or surgical sutures. Further investigation using in vivo models is strongly encouraged to confirm our findings.

5009 ORAL Significant antitumour activity of the novel epothilone ZK-EPO against in vitro and in vivo models of ovarian cancer

2007 ◽  
Vol 5 (4) ◽  
pp. 313-314 ◽  
Author(s):  
S. Hammer ◽  
N. Arnold ◽  
F. Hilpert ◽  
K. Bräutigam ◽  
A. Sommer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Antitumour Activity ◽  
The Novel ◽  
In Vivo Models

scholarly journals Minimal modification in the factor VIII B-domain sequence ameliorates the murine hemophilia A phenotype

Blood ◽  
2013 ◽  
Vol 121 (21) ◽  
pp. 4396-4403 ◽  
Author(s):  
Joshua I. Siner ◽  
Nicholas P. Iacobelli ◽  
Denise E. Sabatino ◽  
Lacramiora Ivanciu ◽  
Shangzhen Zhou ◽  
...  
Keyword(s):  
Hemophilia A ◽  
The Novel ◽  
In Vivo Models ◽  
Domain Sequence ◽  
Key Points ◽  
Minimal Modification ◽  
Therapy Strategies ◽  
Enhanced Stability

Key Points The novel FVIII variant (FVIII-RH) has enhanced stability and procoagulant activity in both in vitro and in vivo models. FVIII-RH is efficacious and safe; thus, it is an attractive molecule for protein replacement and as a transgene in gene-therapy strategies.

The Multi-Kinase Inhibitor TG02 targets CD34+CD38-CD123+ AML Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1823-1823
Author(s):  
Monica Pallis ◽  
Francis Burrows ◽  
Nigel H. Russell
Keyword(s):  
Kinase Inhibitor ◽  
In Vitro Toxicity ◽  
The Novel ◽  
In Vivo Models ◽  
Erk Activation ◽  
Akt Phosphorylation ◽  
Flt3 Inhibitor ◽  
Flt3 Inhibitors

Abstract Abstract 1823 In clinical trials, FLT3 inhibitors are reported to kill circulating AML blasts, but the bone marrow is protected. We have previously reported that niche-like conditions (fibronectin and a cytokine cocktail) significantly reduced the in vitro toxicity of the FLT3 inhibitor AG1296 to AML cells. Moreover, the toxicity of AG1296 to the chemoresistant leukaemic CD34+CD38-CD123+ subset was completely abolished under niche-like conditions. The novel multi-kinase inhibitor TG02 has selectivity against cell cycle and transcriptional CDKs and JAK2 as well as FLT3. TG02 has efficacy in in vivo models and induces apoptosis in primary AML cells. We have now evaluated its in vitro toxicity under niche-like conditions in bulk AML cells and in the CD34+CD38-CD123+ subset. In a cohort of six FLT3-ITD and five FLT3-wildtype samples, 100nM TG02 induced decreases of 30% in bulk cells and 32% in CD34+CD38-CD123+ cells, whereas AG1296 (5μM) induced a median 21% decrease in bulk cells under niche-like conditions but a 0% decrease in CD34+CD38-CD123+ cells. Lestaurtinib, sorafenib and sunitinib were used as comparators (all at 100 nM) and induced, respectively, 13%, 4% and 13% decrease in bulk cells and 10%, 0% and 8% decrease in CD34+CD38-CD123+ cells. FLT3 wildtype as well as ITD samples were targeted. In order to establish the molecular pathways involved in niche-mediated chemoresistance and its reversal, we treated primary AML samples with TG02 or AG1296 for 3 hours in the presence and absence of niche proteins; we measured activating phosphorylations of STAT3 (tyr705), STAT5 (tyr694), ERK1/2 (thr202/tyr404) and AKT(ser473). Basal levels of activating phosphorylations were generally higher in the bulk cells than the CD34+CD38-CD123+ cells, possibly reflecting the increased quiescence of the latter subset. STAT3, STAT5 and ERK1/2 phosphorylation were reduced by TG02 to a slightly greater degree than by AG1296 in bulk cells. However, in CD34+CD38-CD123+ cells this contrast was enhanced, such that AG1296 was ineffective, whereas TG02 was at least as effective as in bulk cells. Niche-like conditions induced an increase in phosphorylation of STAT5, but not of the other proteins tested. TG02 reduced this to basal levels in both bulk cells and CD34+CD38-CD123+ cells. AG1296 partially blocked niche-induced STAT5 phosphorylation in bulk cells, but not in CD34+CD38-CD123+ cells. It had no effect on ERK signalling. AKT phosphorylation was not informative. In conclusion, TGO2 is more cytotoxic than comparatively selective FLT3 inhibitors towards CD34+CD38-CD123+ AML cells as well as bulk cells under niche conditions and the toxicity is associated with downregulation of STAT3, STAT5 and ERK activation. Disclosures: Pallis: Tragara Pharmaceuticals: Research Funding. Burrows:Tragara Pharmaceuticals: Employment.

scholarly journals Feasibility of a Three-Dimensional Porous Uncalcined and Unsintered Hydroxyapatite/poly-d/l-lactide Composite as a Regenerative Biomaterial in Maxillofacial Surgery

Materials ◽  
2018 ◽  
Vol 11 (10) ◽  
pp. 2047 ◽  
Author(s):  
Yunpeng Bai ◽  
Takahiro Kanno ◽  
Hiroto Tatsumi ◽  
Kenichi Miyamoto ◽  
Jingjing Sha ◽  
...  
Keyword(s):  
Maxillofacial Surgery ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
In Vitro Study ◽  
Marker Genes ◽  
The Novel ◽  
Beta Tricalcium Phosphate ◽  
Related Transcription Factor

This study evaluated the feasibility of a novel three-dimensional (3D) porous composite of uncalcined and unsintered hydroxyapatite (u-HA) and poly-d/l-lactide (PDLLA) (3D-HA/PDLLA) for the bony regenerative biomaterial in maxillofacial surgery, focusing on cellular activities and osteoconductivity properties in vitro and in vivo. In the in vitro study, we assessed the proliferation and ingrowth of preosteoblastic cells (MC3T3-E1 cells) in 3D-HA/PDLLA biomaterials using 3D cell culture, and the results indicated enhanced bioactive proliferation. After osteogenic differentiation of those cells on 3D-HA/PDLLA, the osteogenesis marker genes runt-related transcription factor-2 (Runx2), and Sp7 (Osterix) were upregulated. For the in vivo study, we evaluated the utility of 3D-HA/PDLLA biomaterials compared to the conventional bone substitute of beta-tricalcium phosphate (β-TCP) in rats with critical mandibular bony defects. The implantation of 3D-HA/PDLLA biomaterials resulted in enhanced bone regeneration, by inducing high osteoconductivity as well as higher β-TCP levels. Our study thus showed that the novel composite, 3D-HA/PDLLA, is an excellent bioactive/bioresorbable biomaterial for use as a cellular scaffold, both in vitro and in vivo, and has utility in bone regenerative therapy, such as for patients with irregular maxillofacial bone defects.

scholarly journals Hemolysis of Human Erythrocytes by Argovit™ AgNPs from Healthy and Diabetic Donors: An In Vitro Study

Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 2792
Author(s):  
Roberto Luna-Vázquez-Gómez ◽  
María Evarista Arellano-García ◽  
Juan Carlos García-Ramos ◽  
Patricia Radilla-Chávez ◽  
David Sergio Salas-Vargas ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Relevant Information ◽  
Toxicity Tests ◽  
Metallic Silver ◽  
Experimental Conditions ◽  
Hemolysis Assay ◽  
In Vivo Models ◽  
Hemolytic Effect

The use of nanomaterials is becoming increasingly widespread, leading to substantial research focused on nanomedicine. Nevertheless, the lack of complete toxicity profiles limits nanomaterials’ uses, despite their remarkable diagnostic and therapeutic results on in vitro and in vivo models. Silver nanoparticles (AgNPs), particularly Argovit™, have shown microbicidal, virucidal, and antitumoral effects. Among the first-line toxicity tests is the hemolysis assay. Here, the hemolytic effect of Argovit™ AgNPs on erythrocytes from one healthy donor (HDE) and one diabetic donor (DDE) is evaluated by the hemolysis assay against AgNO3. The results showed that Argovit™, in concentrations ≤24 µg/mL of metallic silver, did not show a hemolytic effect on the HDE or DDE. On the contrary, AgNO3 at the same concentration of silver ions produces more than 10% hemolysis in both the erythrocyte types. In all the experimental conditions assessed, the DDE was shown to be more prone to hemolysis than the HDE elicited by Ag+ ions or AgNPs, but much more evident with Ag+ ions. The results show that Argovit™ is the least hemolytic compared with the other twenty-two AgNP formulations previously reported, probably due to the polymer mass used to stabilize the Argovit™ formulation. The results obtained provide relevant information that contributes to obtaining a comprehensive toxicological profile to design safe and effective AgNP formulations.

scholarly journals Mechanical strength and hydrostatic testing of VIVO adhesive in sutureless microsurgical anastomoses: an ex vivo study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marius Heitzer ◽  
Julia Brockhaus ◽  
Kristian Kniha ◽  
Felix Merkord ◽  
Florian Peters ◽  
...  
Keyword(s):  
Animal Studies ◽  
Ex Vivo ◽  
Coronary Vessels ◽  
In Vitro Study ◽  
The Novel ◽  
Ex Vivo Model ◽  
Interrupted Suture ◽  
Tensile Forces

AbstractConventional anastomoses with interrupted sutures are challenging and inevitably associated with trauma to the vessel walls. The goal of this study was to evaluate a novel alternative adhesive-based suture-free anastomosis technique that uses an intraluminal stent. Overall, 120 porcine coronary vessels were analyzed in an ex vivo model and were examined for their mechanical (n = 20 per cohort) and hydrostatic strength (n = 20 per cohort). Anastomoses were made using the novel VIVO adhesive with an additional intraluminal nitinol stent and was compared to interrupted suture anastomosis and to native vessels. Sutureless anastomoses withstood pressures 299 ± 4.47 [mmHg] comparable to native vessels. They were performed significantly faster 553.8 ± 82.44 [sec] (p ≤ 0.001) and withstood significantly higher pressures (p ≤ 0.001) than sutured anastomoses. We demonstrate that the adhesive-based anastomosis can also resist unphysiologically high longitudinal tensile forces with a mean of 1.33 [N]. Within the limitations of an in vitro study adhesive-based suture-free anastomosis technique has the biomechanical potential to offer a seamless alternative to sutured anastomosis because of its stability, and faster handling. In vivo animal studies are needed to validate outcomes and confirm safety.

scholarly journals Nanohydroxyapatite as a Biomaterial for Peripheral Nerve Regeneration after Mechanical Damage—In Vitro Study

2021 ◽  
Vol 22 (9) ◽  
pp. 4454
Author(s):  
Benita Wiatrak ◽  
Paulina Sobierajska ◽  
Marta Szandruk-Bender ◽  
Paulina Jawien ◽  
Maciej Janeczek ◽  
...  
Keyword(s):  
Average Length ◽  
Antioxidant Properties ◽  
In Vitro Study ◽  
Mitochondrial Activity ◽  
Neuronal Cultures ◽  
Free Oxygen Radicals ◽  
Primary Neuronal Cultures ◽  
In Vivo Models

Hydroxyapatite has been used in medicine for many years as a biomaterial or a cover for other biomaterials in orthopedics and dentistry. This study characterized the physicochemical properties (structure, particle size and morphology, surface properties) of Li+- and Li+/Eu3+-doped nanohydroxyapatite obtained using the wet chemistry method. The potential regenerative properties against neurite damage in cultures of neuron-like cells (SH-SY5Y and PC12 after differentiation) were also studied. The effect of nanohydroxyapatite (nHAp) on the induction of repair processes in cell cultures was assessed in tests of metabolic activity, the level of free oxygen radicals and nitric oxide, and the average length of neurites. The study showed that nanohydroxyapatite influences the increase in mitochondrial activity, which is correlated with the increase in the length of neurites. It has been shown that the doping of nanohydroxyapatite with Eu3+ ions enhances the antioxidant properties of the tested nanohydroxyapatite. These basic studies indicate its potential application in the treatment of neurite damage. These studies should be continued in primary neuronal cultures and then with in vivo models.

scholarly journals miR-199b-3p Promotes Radiation-induced Oral Mucositis via DDIT4-mediated mTOR Signal Pathway

2021 ◽  
Author(s):  
Jiantang Yang ◽  
Lili Fu ◽  
Yi Zeng ◽  
Chen Yuan
Keyword(s):  
Western Blot ◽  
Oral Mucositis ◽  
Ectopic Expression ◽  
Luciferase Assay ◽  
The Novel ◽  
In Vivo Models ◽  
Radiation Induced

Abstract Background: Radiation-induced oral mucositis (RIOM) is an adverse reaction in patients of head and neck cancer after radiotherapy. However, the key regulatory factors in the pathogenesis of RIOM remain largely unclear. In this article, we discover a novel role of DNA damage-inducible transcript 4 (DDIT4) in regulating RIOM pathogenesis.Methods: We established RIOM in vitro and in vivo models to mimic the biological processes of RIOM. The level of DDIT4 in RIOM was analyzed by real-time PCR and Western blot. Through the bioinformatics analysis and luciferase assay, the relationship between miR-199b-3p and DDIT4 was performed. The level of mTOR signaling were explored by Western blot. Besides, Clone Formation and EDU assay were performed to investigate the effects of miR-199b-3p/DDIT4 on cell proliferation. H&E and immunohistochemistry experiments examined the effects of miR-199b-3p/DDIT4 on RIOM in vivo. Results: We found that the level of DDIT4 was significantly reduced during the RIOM formation, and up-regulated of DDIT4 suppressed the progression of RIOM in vitro and in vivo. Besides, we found DDIT4 was a direct target of miR-199b-3p. Ectopic expression of miR-199b-3p repressed the level of DDIT4 and activated mTOR signal conduction to promote RIOM progress, whereas the silencing of miR-199b-3p promoted the DDIT4-mediated RIOM regulation both in vitro and in vivo. Conclusion: Collectively, our studies not only identified the novel functional role of DDIT4 in modulating pathogenic processes of RIOM but also provided new directions and ideas for the future treatment of radiotherapy oral mucositis.

Surgeon Ability to Appropriately Address the Calcified Cartilage Layer: An In Vitro Study of Arthroscopic and Open Techniques

2019 ◽  
Vol 47 (11) ◽  
pp. 2584-2588
Author(s):  
Adam B. Yanke ◽  
Andrew S. Lee ◽  
Vasili Karas ◽  
Geoffrey Abrams ◽  
Mark L. Riccio ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Cartilage Defects ◽  
Micro Computed Tomography ◽  
In Vivo Models ◽  
Cartilage Layer ◽  
Calcified Cartilage ◽  
Restoration Technique ◽  
Significant Difference

Background: Microfracture is a commonly utilized cartilage restoration technique for articular cartilage defects. While the removal of the calcified cartilage layer (CCL) has been shown to be critical with in vivo models, little is known with regard to surgeon reliability to adequately perform the technique. Purpose: To evaluate surgeon reliability in removing the CCL utilizing open and arthroscopic techniques. Study Design: Controlled laboratory study. Methods: Eleven cadaveric knees were utilized to create four 12-mm diameter defects in the anterior and posterior medial femoral condyles. Eleven fellowship-trained surgeons were asked to perform the following procedures: remove the CCL open, retain the CCL open, remove the CCL arthroscopically, and retain the CCL arthroscopically. Samples underwent histologic staining and analysis with 3-dimensional micro–computed tomography. The latter was used to calculate the percentage of the CCL that was removed or retained across the entire defect. Results: When surgeons were asked to retain the CCL arthroscopically, 48% ± 41% (mean ± SD) remained. When surgeons were asked to remove the CCL arthroscopically, 24% ± 35% remained. There was no statistical difference between these groups ( P > .05). When the CCL was retained during open preparation, 60% ± 39% remained. During attempts to remove the CCL in an open manner, 19% ± 28% remained. There was a significant difference in the amount of CCL remaining between the open removal and open retaining groups ( P = .03). There were no significant differences in the percentage of CCL remaining between the open and arthroscopic preservation groups and between the open and arthroscopic removal groups. Conclusion/Clinical Relevance: This study highlights the significant variability in surgeon ability to reliably retain or remove the CCL. However, there appears to be improved ability of surgeons to more reliably remove or retain the CCL in an open fashion as compared with the arthroscopic approach.

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