scholarly journals Enhancing esophageal repair with bioactive bilayer mesh containing FGF

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ozkan Cesur ◽  
Tugba Endogan Tanir ◽  
Pinar Celepli ◽  
Fatma Ozarslan ◽  
Sema Hucumenoglu ◽  
...  

AbstractWe aimed to prepare a bioactive and biodegradable bilayer mesh formed by fibroblast growth factor (FGF) loaded gelatin film layer, and poly ε-caprolactone (PCL) film layer, and to investigate its treatment efficacy on esophageal anastomosis. It is envisaged that the bioactive mesh in in vivo model would improve tissue healing in rats. The full thickness semicircular defects of 0.5 × 0.5 cm2 were created in anterior walls of abdominal esophagus. The control group had abdominal esophagus isolated with distal esophageal blunt dissection, and sham group had primary anastomosis. In the test groups, the defects were covered with bilayer polymeric meshes containing FGF (5 μg/2 cm2), or not. All rats were sacrificed for histopathology investigation after 7 or 28 days of operation. The groups are coded as FGF(−)-7th day, FGF(+)-7th day, and FGF(+)-28th day, based on their content and operation day. Highest burst pressures were obtained for FGF(+)-7th day, and FGF(+)-28th day groups (p < 0.005) and decreased inflammation grades were observed. Submucosal and muscular collagen deposition scores were markedly increased in these groups compared to sham and FGF(−)-7th day groups having no FGF (p = 0.002, p = 0.001, respectively). It was proved that FGF loaded bioactive bilayer mesh provided effective repair, reinforcement and tissue healing of esophageal defects.

2021 ◽  
Author(s):  
Ozkan Cesur ◽  
Tugba Endogan Tanir ◽  
Pinar Celepli ◽  
Fatma Ozarslan ◽  
Sema Hucumenoglu ◽  
...  

Abstract We aimed to prepare a bioactive and biodegradable bilayer mesh formed by fibroblast growth factor (FGF) loaded gelatin film layer, and poly ε-caprolactone (PCL) film layer, and to investigate its treatment efficacy on esophageal anastomosis. It is envisaged that the bioactive mesh in in vivo model would improve tissue regeneration in rats. The full thickness semicircular defects of 0.5x0.5 cm2 were created in anterior walls of abdominal esophagus. The control group had abdominal esophagus isolated with distal esophageal blunt dissection, and sham group had primer anastomosis. In the test groups, the defects were covered with bilayer polymeric meshes containing FGF (5µg/2 cm²), or not. All rats were sacrificed for histopathology investigation after 7 or 28 days of operation. The groups are coded as FGF(-)-7th d, FGF(+)-7th d, and FGF(+)-28th d, based on their content and operation day. Highest burst pressures were obtained for FGF(+)-7th d, and FGF(+)-28th d groups (p < 0.005) and decreased inflammation grades were observed. Submucosal and muscular collagen deposition scores were markedly increased in these groups compared to sham and FGF(-)-7th d groups having no FGF (p = 0.002, p = 0.001, respectively). It was proved that FGF loaded bioactive bilayer mesh provided effective repair, reinforcement and tissue regeneration of esophageal defects.


2021 ◽  
Vol 36 (1) ◽  
pp. 45-59
Author(s):  
Olfa Rebai ◽  
Sami Fattouch ◽  
Mohamed Amri

Glyphosate, the active substance in RoundupR, is the most widely used pesticide in the world and may be present as a residue in derived foods and drinking water. Previous reports have confirmed that extracts from leaves of Morus alba exert many pharmacological activities. However, renoprotective effects of M. alba extract and its underling molecular mechanism is still unknown. Wistar rats (180-200 g) were used in this study (n=5-6). A control group received 0.2 ml normal saline intraperitoneally (i.p) once daily for two weeks. Control animals received standard diet. Treated groups received either polyphenolic extract (100 mg/kg,i.p) or glyphosate (100 mg/kg, i.p), or co-administration (extract ?g ml?1 kg b.w. and glyphosate 100 mg kg?1 b.w, i.p), daily until the 15thday of treatment. Lactate deshydrogenase LDH, serum concentrations of blood urea, creatinine and nitric oxide were measured using standard coloromertic methods. Renal oxidative stress, evidenced by increased malondialdehyde (MDA) and protein carbonyl levels and decline in superoxide dismutase (SOD) activity, was significantly alleviated by mulberry leaves extract (MLE) administration. MLE also appears to be able to modulate altered biochemical parametres by maintaining free iron and Ca2 + homeostasis, and regulate the endogenous antioxidant enzymes system. It seems that concurrent use of the aqueous acetonic fraction of M. alba, rich in chlorogenic acid and its isomeres, can protect kidneys from glyphosate-induced nephrotoxicity. Overall, MLE may possess protective activity against glyphosate-induced toxicity, which may be attributed to chlorogenic acid and its isomers, the most abundant phenolic acids present in its extracts. Mulberry leaves are a source of phenolic compounds and can be a good start towards discovering a new chemical compound which may lead to a new drug. A mulberry extract supplement could serve as a candidate for developing a safe, and promising nutraceutical product for the management of nephrotoxicity.


2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Hend Maarof Tag ◽  
Ahlem Bargougui ◽  
Sara Gamal Alshayyal ◽  
Amany Kamal ◽  
Hekmat M. Tantawy ◽  
...  

Punica granatum (POM) and Silybum marianum (MT) receiving attention as potential potent anti-oxidant and anti-mutant agents. In this context, the present study was designed to highlight their effects either in vitro as well as in vivo model of induced Hepatocellular carcinoma (HCC). Human hepatoma (HepG2 cells) were treated with MT and POM to explore their antitumor activity then in vivo were carried out on thirty-six male albino rats divided into six groups (n=6). Two weeks after induction of HCC, rats were co-treated with either MT or POM ethanolic extract (500 mg/kg, orally) daily for 8 weeks. The results displayed marked reduction in the viability of HepG2 cells with IC50 equal to 48.4 and 8.6 μg/mL of POM and MT treatment respectively. Considering, in vivo experiment HCC group displayed significant elevation liver function indices (p<0.05). It also elicited depletion of liver reduced glutathione (GSH), and increased content of liver malondialdehyde (MDA) compared to control group. HCC was proved after a significantly elevated alpha-fetoprotein (AFP) level (p<0.05). All of these measurements were diminished significantly after POM and MT treatments, except the GSH level that was increased significantly. Supplementation of pomegranate and milk thistle extracts had a protective effect against chemically induced HCC. 


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1720-1720
Author(s):  
Julia Schüler ◽  
Dagmar Wider ◽  
Dietmar Pfeifer ◽  
Martin Wagner ◽  
Heinz-Herbert Fiebig ◽  
...  

Abstract For a better understanding of myeloma disease and biology, the establishment of reproducible in vivo models is pursued worldwide. We have established a cell linebased, disseminated myeloma model in NOD/SCID-IL2-receptor-gamma-chain−/− (IL2−/−) mice. In the current study, this model was validated in various treatment groups, using 1. bortezomib (0.7mg/kg/day (d); d0, d4, d11), 2. sorafenib (200mg/kg/d; d0–11), 3. dexamethasone (3mg/kg/d, d0–4 + 7–11), in comparison with 4. a control group. L363 cells were injected intratibialy (it) into IL2−/− mice and respective therapies were started 7 days after L363-it-injection (d0). Tumor growth was monitored with daily monitoring of MM symptoms, fluorescence-based in vivo imaging (FI) performed every 2. week and flow-cytometry (FACS; detection of human HLA−A, B, C + CD138) performed once weekly by sacrificing 2 mice per group and analyzing bone marrow (BM), spleen, peripheral blood (PB) and liver. Based on the FACS data, tumor inhibition was calculated as the median percentage of MM cells at respective compartments of the test- vs. control-group multiplied by 100 (optimal test/control (T/C) in %). Furthermore, hollow bones of the injected mice were retrieved when mice were sacrificed for FACS analyses, cells flushed out and MM cells purified by MACS microbeads. Total RNA was isolated from these cells and gene expression profiles will be analyzed using the HG-U133 Plus 2.0 array (Affymetrix) and the Expressionist software (Genedata AG, Basel). L363 engrafted reliably (take rate=100%) at the injection site and in distant organs, such as BM (100%), spleen (38%) and rarely liver (8%). Control mice developed MM symptoms, such as hind limb pareses, weight loss and osteolyses. L363 cells were detected by FACS and FI, not only at injection sites, but also in the BM, hollow bones and spleen. Primary tumor development was markedly reduced by sorafenib (optimal T/C of 23% on d14), as well as with dexamethasone and bortezomib, albeit to a much lesser extend (optimal T/C: 81% + 62% on d14, respectively). BM metastases were also significantly reduced by sorafenib with an optimal T/C value of 67% on d28. Dexamethasone and bortezomib, the latter possibly due to subclinical doses (determined after titration and toxicity experiments), had no relevant influence on BM metastases suppression (97% + 100% optimal T/C on d28, respectively). Thus, L363 engraftment into IL2−/− is a valuable in vivo model for MM which exhibits high reproducibility, take- and metastases-rates and closely mimics the clinical situation. Collection of whole-body FI data proved to be a time- and animal-saving analysis that allows to closely monitor MM growth. Further investigations will validate the very promising antitumor activity of sorafenib and evaluate the potentially synergistic effect of bortezomib and sorafenib. Amongst others, a detailed characterization of the antitumor activity of both compounds will be provided by the gene expression profile of L363 cells isolated from untreated as well as treated mice. The evaluation of new therapeutic approaches in comparison to standard agents was thus successfully conducted, suggesting that our model serves as a valuable tool in the development of new anticancer strategies.


1997 ◽  
Vol 86 (6) ◽  
pp. 998-1006 ◽  
Author(s):  
Paul D. Sawin ◽  
Vincent C. Traynelis ◽  
Gretchen Rich ◽  
Bruce A. Smith ◽  
Timothy J. Maves ◽  
...  

✓ The mechanism of action underlying chymopapain (Chymodiactin) chemonucleolysis remains obscure. Radiographic studies suggest that chymopapain does not alter disc fragment size acutely; nonetheless, patients often report symptom resolution within a few days, even hours, of treatment. The authors postulate that, in addition to its chemonucleolytic action, chymopapain may possess antiinflammatory properties. To test this hypothesis, the authors assessed the ability of chymopapain to modulate the activity of the proinflammatory enzyme phospholipase A2 (PLA2) and to ameliorate behavioral changes associated with inflammatory neuropathy in an in vivo model of sciatica. Thirty-nine male Fischer rats were randomly assigned to one of three treatment groups: 1) saline, 2) betamethasone, or 3) chymopapain. All of the rats underwent unilateral sciatic nerve ligation with loose chromic gut suture to induce inflammatory mononeuropathy. The animals were tested for thermal and mechanical hyperalgesia on Days 0 (preoperation), 7 (pretreatment), and 14 (prior to death). Three animals were killed on Day 0 to determine the baseline PLA2 activity within unmanipulated rat sciatic nerves. On Day 7, three animals from each group were killed to assess PLA2 activity prior to treatment. The remainder were given a single infusion of saline, betamethasone (0.3 mg/kg), or chymopapain (100 pKat U) around the inflamed nerve. On Day 14, the remaining animals were killed and their sciatic nerves were removed. The tissue was homogenized and the PLA2 activity was determined using [14C]arachidonate—labeled Escherichia coli phospholipid membrane as a substrate. Lipids were extracted and separated by thin-layer chromatography. All animals developed behavioral changes consistent with inflammatory mononeuropathy 24 to 72 hours postoperatively; these included gait disturbance, flexion deformity, and hyperalgesia of the involved hindlimb. The degree of mechanical and thermal hyperalgesia was comparable between groups at Day 7. By Day 14, the thermal hyperalgesia had resolved; the mechanical hyperalgesia was less evident in the betamethasone- and chymopapain-treated groups than in the saline-treated controls (p = 0.003; saline- vs. chymopapain-treated groups p = 0.004; saline- vs. betamethasone-treated groups p = 0.008). The mean PLA2 activity at baseline (Day 0) was 11.6 ± 4.9 nmol phospholipid hydrolyzed per minute per milligram of protein. The PLA2 activity at Day 7 was 74.4 ± 18.2 (ligated side) and 21.2 ± 11.7 (nonligated side). At Day 14, PLA2 activity was reduced in the chymopapain- (47.8 ± 12.3) and betamethasone- (39.7 ± 9.5) treated groups compared with the saline control group (62.3 ± 11.2), (saline- vs. chymopapain-treated groups p < 0.05; saline- vs. betamethasone-treated groups p < 0.01). The PLA2 activity in nonligated specimens was 18.6 ± 10.1. These data indicate that chymopapain exhibits antiinflammatory properties in vivo, reducing PLA2 activity and ameliorating mechanical hyperalgesia in this model of inflammatory sciatic neuropathy.


VASA ◽  
2015 ◽  
Vol 44 (4) ◽  
pp. 285-288 ◽  
Author(s):  
Ye Sun ◽  
Ping Mao ◽  
Jingwei Lu ◽  
Lan Li ◽  
Wanli Lu ◽  
...  

Abstract. Background: Ischemic preconditioning (IPC) has many beneficial effects on the cardiovascular system. However, whether localized lower extremity IPC could be protective against the thrombogenic activity generated by lower extremity ischemia is unclear. Material and methods: 41 male Sprague-Dawley rats were randomly assigned to either a IPC group or a sham group. The lower extremity blood inflow was previously treated with 4 cycles of 5 min ischemia followed by 5 min of reperfusion by clamping the abdominal aortic just before ligature of the left iliac vein(LIV) in the IPC group. Rats in the sham group had a 40-minute blank before left iliac vein ligation. The rats were euthanized at day 2 after ligation and the thrombosed LIV was carefully dissected out, while thrombi harvested from the LIV were measured with weight (g), length (mm) and weight/length (mg/mm). Influence of IPC on coagulation function was also tested. Results: 21 and 20 rats were randomly assigned to einter the IPC group or the control group. Left iliac vein thrombosis was successfully generated in all 41 rats. IPC significantly protects the rats from experimental lower extremity thrombosis. Compared to control group, generated thrombus in rats in the IPC group showed significantly lower weight (2.73 ± 0.16 mg vs 1.82 ± 0.13 mg, P < 0.001), length (2.99 ± 0.17 mm vs 2.44 ± 0.08 mm, P < 0.009) and density (0.95 ± 0.05 mg/mm vs 0.75 ± 0.05 mg/mm, P = 0.01). Influence on coagulation function by IPC itself was not significant (P > 0.05). Conclusions: Our study demonstrated that localized lower extremity IPC could reduce DVT formation in rats in an in vivo experimental thrombosis model.


2016 ◽  
Vol 696 ◽  
pp. 212-222
Author(s):  
Gabriel Maia Kammer ◽  
Suelen Cristina Sartoretto ◽  
Rodrigo Resende ◽  
Marcelo Uzeda ◽  
Jhonathan Raphael Nascimento ◽  
...  

Bone tissue is a composite material that has hydroxyapatite (HA) as its main inorganic phase component. The biological apatites have low crystallinity and contain cationic and anionic substitutions in their structure, which differ from the available synthetic ceramics. The purpose of this study is to evaluate the biocompatibility of nanostructured carbonated hydroxyapatite microspheres containing 5 wt% strontium (SrcHA) compared with the biocompatibility of carbonated hydroxyapatite (cHA), both synthesized at 37°C and non-sintered, used to control stoichiometric HA microspheres in subcutaneous tissue of mice. The biomaterials (BM) were characterized using X-ray Diffraction (XRD), Vibrational Spectroscopy in an Infrared Fourier Transform (VSIRFT) and Scanning Electron Microscopy (SEM). Forty five balb-C mice were randomly divided into four groups of 15 animals each: SrcHA, cHA, HA, and without material implantation (Sham group). All samples were histologically processed for descriptive evaluation of the biological effect. At each experimental period (1, 3 and 9 weeks), there was a higher biosorption of the tested biomaterials observed in contrast with the HA. The cHA group was the only group completely phagocytosed by macrophages and giant cells after 9 weeks. All biomaterials proved to be biocompatible, and the cHA and SrcHA 3% groups exhibited a faster bioabsorption in comparison with the control group. The doping of strontium did not cause a greater biological response after the 3 experimental periods.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Patricia Trindade ◽  
Elaine Soares ◽  
Elisa Monteiro ◽  
Nathalia Moura-Nunes ◽  
Danielly Costa ◽  
...  

Abstract Objectives Body adiposity is an important risk factor for the development of chronic non-communicable diseases. The aim of this study was to investigate the effects of açai seed extract (ASE) on adipogenesis. Methods We investigated the effects of ASE in a mouse model of high-fat diet (HFD)-induced obesity. We also evaluated the effects of ASE as a pre-treatment and treatment on 3T3-L1 adipocytes cell proliferation, cell differentiation and expression of proteins involved in lipid metabolism, such as PPARɣ, SREBP-1 and FAS, using westernbloting. Results In our work high-fat diet–fed mice treated with ASE (HFD-ASE) showed a lower adipose index (−32.63%, p < 0.001) than the high-fat diet–fed mice group (HFD) and the adipocytes from the HFD group were considerably enlarged (p < 0.001) compared to those in the control group (CG) and HFD-ASE group (+175% and +123%, respectively). We also evaluated the effects of ASE on the modulation of adipogenesis in 3T3-L1 cells. ASE exposure led to a decrease of 26.6 (P < 0.05) in proliferation and also inhibited preadipocyte differentiation through the decreasing expression (P < 0.05) of transcription factors and adipogenic proteins such as PPARɣ, SREBP-1 and FAS. Conclusions These results show that the ASE reduce adipogenesis and suppress lipid accumulation in in vivo model and in 3T3-L1 adipocytes and reinforce the potential ASE as a potential strategy to modulate adipogenesis. Funding Sources The financial support of Brazilian funding agencies: FAPERJ, E-26/202.829/2015 and E-26/010.002632/2014; Conselho Nacional de Desenvolvimento Científico e Tecnológico, 472711/2013-0; and Coordenação de Aperfeiçoamento de Pesssoal de Nível Superior-Brazil (CAPES) – Finance code 001. Supporting Tables, Images and/or Graphs


Author(s):  
Siddhi Raveendran ◽  
A. V. Tilak ◽  
Shraddha Yadav ◽  
Sayan Das ◽  
Vishwadeep Madrewar ◽  
...  

Background: The International Association for Study of pain, has defined pain as actual or potential tissue damage or described in terms of such damage. But the burden of unwanted side effects with current regimens are high. To explore the potential of Ayurveda drugs, this study is done by using Origanum vulgare.Methods: In vivo model used-Hot plate method. Origanum vulgare (84 mg/kg p.o) was administered in mice. The analgesic activity was studied by recording the reaction time after administration of the drug at frequent intervals up to 3 hrs. The results were analysed by ANOVA and Tukey’s test. P value <0.05 was considered as significant. Pentazocine showed statistically prolongation in the reaction time after 30 min as compared to Origanum vulgare.Results: In hot plate method, pentazocine showed statistically significant increase in the reaction time after 30 min of administration as compared to control group. However, Origanum vulgare in a dose of 84 mg/kg showed significantly increase in the reaction time after 30 min of administration as compared to control group. On comparing pentazocine and Origanum vulgare, pentazocine showed highly significant increase in the reaction time after 30 min as compared to Origanum vulgare at 84 mg/kg dose.Conclusions: From the present study, it was concluded that extract of Origanum vulgare exerted analgesic activity in both the models. However, it was less potent than pentazocine. Thus, Origanum vulgare can be used in mild to moderate painful conditions.


2018 ◽  
Vol 22 ◽  
pp. 287-292
Author(s):  
L. L. Matsevych ◽  
A. Ye. Papuga ◽  
T. P. Ruban ◽  
T. V. Beregova ◽  
L. L. Lukash

Aim. The aim was to estimate the influence of cell suspension quality on the therapeutic efficiency of cell-containing dermal coverages in animal model in vivo. Methods. We carried out the application of gel wound coverages with different quality of cellular compound on the third degree burns of ICR line mice. In the negative control group animals were treated with fresh medium-containing gel, and in positive control – by gel containing high quality cell suspension. Photo fixation of burn wound status was carried out once a day. The results were estimated by ANOVA approach. Results. There was a statistically significant difference of burn wounds development and healing between positive control and both experimental groups. The decreasing of alive cell fraction in prepared gel within 5 hours has been shown as well. Conclusions. It has been shown the dependence of wound healing properties of coatings containing cells on the cell compound quality, in particular, from the viability and integrity of cells. These results are important for developing of clinical protocols using such cell‑containing dermal equivalents. Keywords: burn wound, dermal equivalent, stem cells, skin substitute, tissue engineering.


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