scholarly journals The Addition of High Doses of Hyaluronic Acid to a Biphasic Bone Substitute Decreases the Proinflammatory Tissue Response

2019 ◽  
Vol 20 (8) ◽  
pp. 1969 ◽  
Author(s):  
Dominik Sieger ◽  
Tadas Korzinskas ◽  
Ole Jung ◽  
Sanja Stojanovic ◽  
Sabine Wenisch ◽  
...  

Biphasic bone substitutes (BBS) are currently well-established biomaterials. Through their constant development, even natural components like hyaluronic acid (HY) have been added to improve both their handling and also their regenerative properties. However, little knowledge exists regarding the consequences of the addition of HY to their biocompatibility and the inflammatory tissue reactions. Thus, the present study was conducted, aiming to analyze the influence of two different amounts of high molecular weight HY (HMWHY), combined with a BBS, on in vitro biocompatibility and in vivo tissue reaction. Established in vitro procedures, using L929 cells, were used for cytocompatibility analyses under the test conditions of DIN EN:ISO 10993-5. For the in vivo part of the study, calvarial defects were created in 20 Wistar rats and subsequently filled with BBS, and BBS combined with two different HMWHY amounts, i.e., BBS + HY(L) and BBS + HY(H). As controls, empty defects were used. Established histological, immunohistochemical, and histomorphometrical methods were applied to analyze the tissue reactions to the three different materials, including the induction of pro- and anti-inflammatory macrophages and multinucleated giant cells (BMGCs). The in vitro results showed that none of the materials or compositions caused biological damage to the L929 cells and can be considered to be non-toxic. The in vivo results showed that only the addition of high doses of HY to a biphasic bone substitute significantly decreases the occurrence of pro-inflammatory macrophages (* p < 0.05), comparable to the numbers found in the control group, while no significant differences within the three study groups for M2-macrophages nor BMGCs were detected. In conclusion, the addition of different amounts of HMWHY does not seem to affect the inflammation response to BBS, while improving the material handling properties.

2021 ◽  
pp. 63-67
Author(s):  
I.I. Khusnitdinov ◽  

Purpose. Еxperimental substantiation of the effectiveness of biocompatible biodegradable hydrogels based on hyaluronic acid and chitosan succinate as a carrier of ranibizumab in antiglaucoma operations. Material and methods. Hydrogel drainage (HD) was obtained immediately before surgery. A solution of ranibizumab (0.23 ml) was mixed with a solution of hyaluronic acid dialdehyde (0.5 ml), then a solution of chitosan succinate (0.5 ml) was added. Experimental studies were performed in 12 (12 eyes) healthy rabbits. The first group consisted of 6 eyes – 0.187 ml of ranibizumab per 1 ml of gel. In the control group, HD was used intraoperatively without the addition of ranibizumab (6 eyes). Morphological studies were performed on 7th, 21st, and 42nd days. Results. In experimental studies in vitro and in vivo, it was proved that ranibizumab, administered as a part of 0.1 ml of hydrogel drainage in the antiglaucoma surgery area is released within 3 weeks and suppresses vascularization, scarring of the operating area, and preserves the intrascleral cavity. The optimal concentration of ranibizumab was selected-0.02 ml in 0.1 ml of gel. Conclusion. The safety and effectiveness of the use of hydrogel drainage with ranibizumab based on hyaluronic acid dialdehyde and chitosan succinate in anti-glaucoma operations has been proven. Key words: experimental research, hydrogel drainage, ranibizumab, glaucoma surgery.


2019 ◽  
Vol 8 (9) ◽  
pp. 1486 ◽  
Author(s):  
Barbara De Angelis ◽  
Margarida Fernandes Lopes Morais D’Autilio ◽  
Fabrizio Orlandi ◽  
Giampiero Pepe ◽  
Simone Garcovich ◽  
...  

Chronic ulcers are characterized by loss of substance without a normal tendency towards spontaneous healing. The Wound Bed Preparation Guideline advises that after diagnosis, the expert should correct the biological state of the ulcer micro-environment based on TIME principles (Tissue, Infection, Moisture balance, Epidermal). There are many ways to treat such ulcers, for example through use of advanced dressings, negative pressure, surgical toilets, dermal substitutes, autologous skin grafting, and free or local flaps. In vitro and in vivo pre-clinical models hold widely acknowledged potential yet complex limitations. Tissue bioengineering could be an ideal approach to foster innovative strategies in wound healing. Our observational study reports on an in vitro and in vivo evaluation of a bio-functionalized scaffold composed of platelet-rich plasma (PRP) and hyaluronic acid (HA) used in 182 patients affected by chronic ulcers (diabetic and vascular), comparing the results with a control group of 182 patients treated with traditional dressings (HA alone). After 30 days the patients who had undergone the combined treatment (PRP + HA), showed 96.8% ± 1.5% re-epithelialization, as compared to 78.4% ± 4.4% in the control group (HA only). Within 80 days, they had 98.4% ± 1.3% re-epithelialization as compared to 87.8% ± 4.1% in the control group (HA only; p < 0.05). No local recurrence was observed during the follow-up period. PRP + HA treatment showed stronger regenerative potential in terms of epidermal proliferation and dermal renewal compared with HA alone.


2006 ◽  
Vol 309-311 ◽  
pp. 607-610
Author(s):  
Sander C.G. Leeuwenburgh ◽  
Joop G.C. Wolke ◽  
M.C. Siebers ◽  
J. Schoonman ◽  
John A. Jansen

The dissolution and precipitation behavior of various porous, ESD-derived calcium phosphate coatings was investigated a) in vitro after soaking in Simulated Body Fluid (SBF) for several time periods (2, 4, 8, and 12 weeks), and b) in vivo after subcutaneous implantation in the back of goats for identical time periods. At the end of these studies, the physicochemical properties of the coated substrates were characterized by means of Scanning Electron Microscopy (SEM), XRay Diffraction (XRD), Fourier-Transform InfraRed spectroscopy (FTIR) and Energy Dispersive Spectroscopy (EDS). Moreover, part of the implants was prepared for light microscopical evaluation of the tissue response. In vitro, a highly bioactive behavior was observed for all ESD-coatings, characterized by the deposition of a thick and homogeneous carbonate hydroxyapatite precipitation layer on top of the porous coatings. Regarding the in vivo study, no adverse tissue reactions (toxic effects/inflammatory cells) were observed using light microscopy, and all coatings became surrounded by a thin, dense fibrous tissue capsule after implantation. The ESD-coatings degraded gradually at a dissolution rate depending on the specific chemical phase, thereby enabling synthesis of CaP coatings with a tailored degradation rate.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Hugo Vigerelli ◽  
Juliana Mozer Sciani ◽  
Maria Andrea Camarano Eula ◽  
Luciana Almeida Sato ◽  
Marta M. Antoniazzi ◽  
...  

Bufotenine is an alkaloid derived from serotonin, structurally similar to LSD and psilocin. This molecule is able to inhibit the rabies virus infection in in vitro and in vivo models, increasing the survival rate of infected animals. Being a very promising molecule for an incurable disease and because of the fact that there is no consensus regarding its neurological effects, this study aimed to evaluate chronic treatment of bufotenine on behavior, pathophysiology, and pharmacokinetics of mice. Animals were daily treated for 21 consecutive days with 0.63, 1.05, and 2.1 mg/animal/day bufotenine and evaluated by open field test and physiological parameters during all the experiment. After this period, organs were collected for histopathological and biodistribution analysis. Animals treated with bufotenine had mild behavioral alterations compared to the control group, being dose-response relationship. On the other hand, animals showed normal physiological functions and no histological alterations in the organs. With high doses, an inflammatory reaction was observed in the site of injection, but with no cellular damage. The alkaloid could be found in the heart and kidney with all doses and in the lungs and brain with higher doses. These results show that the effective dose, 0.63 mg/day, is safe to be administered in mice, since it did not cause significant effects on the animals’ physiology and on the CNS. Higher doses were well tolerated, causing only mild behavioral effects. Thus, bufotenine might be a drug prototype for rabies treatment, an incurable disease.


Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1183
Author(s):  
Álvaro Zubizarreta-Macho ◽  
Cristina Rico-Romano ◽  
María Jesús Fernández-Aceñero ◽  
Jesús Mena-Álvarez ◽  
Belén Cabal ◽  
...  

Current endodontic procedures continue to be unsuccessful for completely removing pathogens present inside the root canal system, which can lead to recurrent infections. In this study, we aimed to assess the antimicrobial capacity and tissue response of two inorganic bactericidal additives incorporated into a paste root canal sealer on contaminated root dentin in vivo. An experimental study was performed in 30 teeth of five Beagle dogs. After inducing microbiological contamination, root canal systems were treated by randomly incorporating one of two antimicrobial additives into a commercial epoxy-amine resin sealer (AH Plus), i.e., G3T glass-ceramic (n = 10) and ZnO-enriched glass (n = 10); 10 samples were randomized as a control group. After having sacrificed the animals, microbiological, radiological, and histological analyses were performed, which were complemented with an in vitro bactericidal test and characterization by field emission scanning electron microscopy. The tested groups demonstrated a non-significant microbiological reduction in the postmortem periapical index values between the control group and the bactericidal glass-ceramic group (p = 0.885), and between the control group and the ZnO-enriched glass group (p = 0.169). The histological results showed low values of inflammatory infiltrate, and a healing pattern characterized by fibrosis in 44.4% of the G3T glass-ceramic and 60.0% of ZnO-enriched glass. Bactericidal glassy additives incorporated in this root canal sealer are safe and effective in bacterial reduction.


1990 ◽  
Vol 29 (03) ◽  
pp. 120-124
Author(s):  
R. P. Baum ◽  
E. Rohrbach ◽  
G. Hör ◽  
B. Kornhuber ◽  
E. Busse

The effect of triiodothyronine (T3) on the differentiation of cultured neuroblastoma (NB) cells was studied after 9 days of treatment with a dose of 10-4 M/106 cells per day. Using phase contrast microscopy, 30-50% of NB cells showed formation of neurites as a morphological sign of cellular differentiation. The initial rise of the mitosis rate was followed by a plateau. Changes in cyclic nucleotide content, in the triphosphates and in the activity of the enzyme ornithine decarboxylase (ODC) were assessed in 2 human and 2 murine cell lines to serve as biochemical parameters of the cell differentiation induced by T3. Whereas the cAMP level increased significantly (3 to 7 fold compared with its initial value), the cGMP value dropped to 30 to 50% of that of the control group. ATP and GTP increased about 200%, the ODC showed a decrease of about 50%. The present studies show a biphasic effect of T3 on neuroblastoma cells: the initial rise of mitotic activity is followed by increased cell differentiation starting from day 4 of the treatment.


1979 ◽  
Vol 41 (03) ◽  
pp. 465-474 ◽  
Author(s):  
Marcia R Stelzer ◽  
Thomas S Burns ◽  
Robert N Saunders

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.


2020 ◽  
Author(s):  
K. Zerrouki ◽  
N. Djebli ◽  
L. Gadouche ◽  
I. Erdogan Orhan ◽  
F. SezerSenol Deniz ◽  
...  

Nowadays, because of the industrialization, a lot of contaminant were available ; the consequences of this availability are apparition of diseases including neurodegeneration. Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. This study is based on the effect of the Boswellic resin, which is from a medicinal plant and known for its antioxidant effects on nerve cell damage. The objective of this work was to evaluate the in vitro and in vivo effects of the Boswellic resin on anticholinesterase activity and Alzheimer’s disease (AD) induced by D-galactose and aluminum tetrachloride in Swiss mice. Chemical composition of the resin essential oil was identified by the CG-MS analysis. The antioxidant activity was also assessed by the DMPD and metal chelation methods. In order to understand the mechanism of memory improvement, the acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, inhibitory assays were performed. In vivo part of the study was achieved on Swiss mice divided into four groups: control, AD model, treated AD, and treated control group. The identification of chemical composition by CG-MS reach the 89.67% of the total extract compounds presented some very important molecules (p-Cymene, n-Octyl acetate, α-Pinene…). The present study proves that Boswellic resin improves memory and learning in treated Alzheimer’s group, modulates the oxidative stress and be involved in the protective effect against amyloid deposition and neurodegeneration, and stimulates the immune system in mice’s brain.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jennifer K. Dowling ◽  
Remsha Afzal ◽  
Linden J. Gearing ◽  
Mariana P. Cervantes-Silva ◽  
Stephanie Annett ◽  
...  

AbstractMitochondria are important regulators of macrophage polarisation. Here, we show that arginase-2 (Arg2) is a microRNA-155 (miR-155) and interleukin-10 (IL-10) regulated protein localized at the mitochondria in inflammatory macrophages, and is critical for IL-10-induced modulation of mitochondrial dynamics and oxidative respiration. Mechanistically, the catalytic activity and presence of Arg2 at the mitochondria is crucial for oxidative phosphorylation. We further show that Arg2 mediates this process by increasing the activity of complex II (succinate dehydrogenase). Moreover, Arg2 is essential for IL-10-mediated downregulation of the inflammatory mediators succinate, hypoxia inducible factor 1α (HIF-1α) and IL-1β in vitro. Accordingly, HIF-1α and IL-1β are highly expressed in an LPS-induced in vivo model of acute inflammation using Arg2−/− mice. These findings shed light on a new arm of IL-10-mediated metabolic regulation, working to resolve the inflammatory status of the cell.


Author(s):  
Joon M. Jung ◽  
Hae K. Yoon ◽  
Chang J. Jung ◽  
Soo Y. Jo ◽  
Sang G. Hwang ◽  
...  

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing–related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant ( P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.


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