In vivo performance of decellularized tracheal grafts in the reconstruction of long length tracheal defects: Experimental study

2021 ◽  
pp. 039139882110259
Author(s):  
Jaime Villalba-Caloca ◽  
Avelina Sotres-Vega ◽  
David M Giraldo-Gómez ◽  
Miguel O Gaxiola-Gaxiola ◽  
Maria C Piña-Barba ◽  
...  

Background: The repair of long-segment tracheal lesions remains an important challenge. Nowdays no predictable and dependable substitute has been found. Decellularized tracheal scaffolds have shown to be a promising graft for tracheal transplantation, since it is non-immunogenic. Objective: Evaluate in vivo decellularized tracheal allografts performance to replace long tracheal segment. Methods: Forty-five swines underwent surgery as follows: Fifteen trachea donors and 30 receptors of decellularized trachea allografts. The receptors were randomly divided in five groups ( n = 6). In groups I and II, donor trachea segment was decellularized by 15 cycles with sodium deoxycholate and deoxyribonuclease, in group II, the allograft was reinforced with external surgical steel wire. Groups, III, IV, and V decellularization was reduced to seven cycles, supplemented with cryopreservation in group IV and with glutaraldehyde in group V. A 10 rings segment was excised from the receptor swine and the decellularized trachea graft was implanted to re-establish trachea continuity. Results: Both decellularization cycles caused decreased stiffness. All trachea receptors underwent euthanasia before the third post-implant week due to severe dyspnea and trachea graft stenosis, necrosis, edema, inflammation, hemorrhage, and granulation tissue formation in anastomotic sites. Histologically all showed total loss of epithelium, separation of collagen fibers, and alterations in staining. Conclusions: Both decellularization techniques severely damaged the structure of the trachea and the extracellular matrix of the cartilage, resulting in a no functional graft, in spite of the use of surgical wire, cryopreservation or glutaraldehyde treatment. An important drawback was the formation of fibrotic stenosis in both anastomosis.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Okutucu ◽  
C Sabanoglu ◽  
A Saglam Ayhan ◽  
E Tulumen ◽  
H Aksoy ◽  
...  

Abstract Background Calcific aortic valve disease (CAVD) is the most common valvular heart disease. Bisphosphonates are stable analogs of pyrophosphates and commonly prescribed in the treatment of osteoporosis. The effects of bisphosphonate treatment on CAVD are not clearly known and there are inconsistent results. Similarly, the effect of calcium supplementation on CAVD remains controversial. Purpose The aim of this study was to assess the effects of bisphosphonate therapy on the normal aortic valve and vitamin D induced in vivo rabbit aortic stenosis (AS) model. Methods The impact of calcium supplementation on the rabbit AS model was also evaluated. A total of 30 New Zealand white rabbits were divided into five equal groups: no treatment (Group I); 25,000 IU/day vitamin D3 (cholecalciferol) (Group II, rabbit AS model); 25,000 IU/day cholecalciferol plus 2500 mg/day calcium carbonate (Group III); 20 μg/kg/week intravenous alendronate (Group IV) and 25,000 IU/day cholecalciferol plus 2500 mg/day calcium carbonate plus 20μg/kg/week alendronate (Group V). Echocardiography was performed at baseline and after 12 weeks of treatment. The left ventricular mass index (LVMI), aortic valve area (AVA), transvalvular velocities and gradients were recorded. Radiologic and histopathologic examination was performed at the end of the 12th week. Control animals displayed no abnormalities of the aortic valve. Results There was no echocardiographic change in Group IV. In Groups II, III and V, there was a significant decrease in AVA and increases in transvalvular velocities and gradients. However, these stenotic changes were significantly prominent in Group V (p=0.001 for all, via repeated measures ANOVA). Moreover, LVMI was only increased in Group V (p<0.05). Calcification of aortic valvar complex was detected in 14 (46.7%) cases by radiologic imaging and 10 (33.3%) cases by histopathologic examination. Most frequent calcification was found in Group V (5 for each method, 83.3%). Agatston, volume and equivalent mass scores of calcific foci in Group V were significantly higher than other groups (p<0.05 for all). There was no significant difference between groups regarding with presence of osteoclasts in calcific foci. Conclusion Calcium supplementation has no effect on the in vivo rabbit AS model. Alendronate treatment aggravates the stenosis and increases the calcification in the rabbit AS model. Alendronate treatment has no effect on the normal valve in which there was no osteogenesis and osteoclastogenesis. Based on these findings, in patients with CAVD, alendronate treatment should be given with regular echocardiographic follow-up or may not be preferred. Central figure Funding Acknowledgement Type of funding source: None


2004 ◽  
Vol 12 (2) ◽  
pp. A14-A14 ◽  
Author(s):  
D‐L. Gu ◽  
I. Atencio ◽  
D. Looper ◽  
D.W. Kang ◽  
D. Maneval ◽  
...  

1990 ◽  
Vol 110 (2) ◽  
pp. 437-448 ◽  
Author(s):  
R A Nixon ◽  
I Fischer ◽  
S E Lewis

Microtubule-associated proteins (MAPs) in neurons establish functional associations with microtubules, sometimes at considerable distances from their site of synthesis. In this study we identified MAP 1A in mouse retinal ganglion cells and characterized for the first time its in vivo dynamics in relation to axonally transported tubulin. A soluble 340-kD polypeptide was strongly radiolabeled in ganglion cells after intravitreal injection of [35S]methionine or [3H]proline. This polypeptide was identified as MAP 1A on the basis of its co-migration on SDS gels with MAP 1A from brain microtubules; its co-assembly with microtubules in the presence of taxol or during cycles of assembly-disassembly; and its cross-reaction with well-characterized antibodies against MAP 1A in immunoblotting and immunoprecipitation assays. Glial cells of the optic nerve synthesized considerably less MAP 1A than neurons. The axoplasmic transport of MAP 1A differed from that of tubulin. Using two separate methods, we observed that MAP 1A advanced along optic axons at a rate of 1.0-1.2 mm/d, a rate typical of the Group IV (SCb) phase of transport, while tubulin moved 0.1-0.2 mm/d, a group V (SCa) transport rate. At least 13% of the newly synthesized MAP 1A entering optic axons was incorporated uniformly along axons into stationary axonal structures. The half-residence time of stationary MAP 1A in axons (55-60 d) was 4.6 times longer than that of MAP 1A moving in Group IV, indicating that at least 44% of the total MAP 1A in axons is stationary. These results demonstrate that cytoskeletal proteins that become functionally associated with each other in axons may be delivered to these sites at different transport rates. Stable associations between axonal constituents moving at different velocities could develop when these elements leave the transport vector and incorporate into the stationary cytoskeleton.


FEBS Letters ◽  
2001 ◽  
Vol 509 (1) ◽  
pp. 95-100 ◽  
Author(s):  
Mitsuo Toyoda ◽  
Hisashi Takayama ◽  
Norio Horiguchi ◽  
Toshiyuki Otsuka ◽  
Toshio Fukusato ◽  
...  

2001 ◽  
Vol 44 (3) ◽  
pp. 97-100 ◽  
Author(s):  
Cem Koçkar ◽  
Mustafa Öztürk ◽  
Nüket Bavbek

In this study, in vivo effectiveness of ascorbic acid (AA), beta carotene (BC) and allicin in HP eradication were evaluated. 210 patients who are HP positive in biopsy were involved in this study. The patients randomised to seven treatment groups (each group consisting of 30 patients). The first group was given standard eradication treatment (lansaprasol 30 mg bid, clarithromycin 500 mg bid, amoxicillin 1 g bid for 14 days). Second group received AA 1000 mg/day in addition to the standard treatment. Third group received only AA 1000 mg/day for 14 days. Fourth group was treated with standard regiment plus 120 mg/day BC. Fifth group was given only BC 120 mg/day for 14 days. Sixth group was given standard regiment and allicin 4200 μg/day. Seventh group received only Allicin 1200 μg/day for 14 days. The eradication was achieved in 20 (66.6 %) in group I, 15 (50 %) in group II, 3 (10 %) in group III, 15 (50 %) in group IV, 0 (0 %) in group V, 27 (90 %) in group VI and 7 (23.3 %) in group VII. Allicin seemed to be potentially effective agent for HP eradication but ascorbic acid, beta caroten was found to be ineffective.


Author(s):  
A. I. Shah ◽  
D. M. Patel ◽  
N. P. Sarvaiya ◽  
S. P. Madhira

This study was undertaken on 36 freshly calved cows randomly divided into 6 equal groups under field conditions. Cows of group-VI that shed placenta within 8-12 hours postpartum naturally served as healthy control. The cows with retained fetal membranes (RFM, n = 18) for more than 12 hrs were managed either by manual removal of placenta without antibiotics (group-I), parenteral antibiotic (Ceftiofur 1 g i/m) for three consecutive days (group-II) or a combination of both (group-III). In group-IV and group-V, cows were administered with Inj. Oxytocin @ 50 IU i/m and Inj. Dinoprost tromethamine (PGF2α) @ 25 mg i/m, respectively, immediately after parturition and time of placental shedding was recorded. The overall prevalence of Brucellosis by RBPT was found to be 5.55 % amongst these 36 animals. The placental expulsion in groups following medicinal treatment was found to be 50 (3/6) % in Ceftiofur alone by 3 days (group-II), and 66.67 (4/6) % in Oxytocin (group-IV) and 100 (6/6) % in PGF2α inj. (group-V) groups within 12 hrs. The time of uterine involution in groups I to VI was found to be 42.00 ± 1.94, 39.50 ± 0.99, 40.67 ± 1.39, 38.33 ± 1.55, 37.50 ± 1.02 and 37.33 ± 1.76 days, respectively, while the interval for the appearance of first postpartum estrus was 54.83 ± 2.06, 51.00 ± 1.05, 52.17 ± 1.96, 50.17 ± 2.03, 48.67 ± 1.90 and 49.17 ± 1.55 days, respectively, which did not vary statistically. The mean serum progesterone profile obtained on day 0 and day 21 postpartum was statistically non-significant between groups. However, it was significantly (p less than 0.05) lower on day 0 as compared to day 21 in group-I, II and VI. The levels on day 0 coincided with the time of blood sampling after calving. The high level of serum P4 on day 0 in group-IV and V could be due to sampling immediately after calving. The serum calcium and phosphorus levels were significantly(p less than 0.05) lower on day 0 than on day 21, but not the magnesium. The group effect was however non-significant for any of three minerals. It was observed that manual removal of RFM without parenteral antibiotics, resulted in puerperal metritis, cervicitis, pyometra which ultimately resulted into delayed uterine involution, delayed first postpartum estrus and thus, reduced the postpartum reproductive efficiency. It was inferred that the PGF2α and Oxytocin injections could be used as a treatment of choice for prevention of RFMs in cattle.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1731
Author(s):  
Yu Maw Htwe ◽  
Huashan Wang ◽  
Patrick Belvitch ◽  
Lucille Meliton ◽  
Mounica Bandela ◽  
...  

Lung endothelial dysfunction is a key feature of acute lung injury (ALI) and clinical acute respiratory distress syndrome (ARDS). Previous studies have identified the lipid-generating enzyme, group V phospholipase A2 (gVPLA2), as a mediator of lung endothelial barrier disruption and inflammation. The current study aimed to determine the role of gVPLA2 in mediating lung endothelial responses to methicillin-resistant Staphylococcus aureus (MRSA, USA300 strain), a major cause of ALI/ARDS. In vitro studies assessed the effects of gVPLA2 inhibition on lung endothelial cell (EC) permeability after exposure to heat-killed (HK) MRSA. In vivo studies assessed the effects of intratracheal live or HK-MRSA on multiple indices of ALI in wild-type (WT) and gVPLA2-deficient (KO) mice. In vitro, HK-MRSA increased gVPLA2 expression and permeability in human lung EC. Inhibition of gVPLA2 with either the PLA2 inhibitor, LY311727, or with a specific monoclonal antibody, attenuated the barrier disruption caused by HK-MRSA. LY311727 also reduced HK-MRSA-induced permeability in mouse lung EC isolated from WT but not gVPLA2-KO mice. In vivo, live MRSA caused significantly less ALI in gVPLA2 KO mice compared to WT, findings confirmed by intravital microscopy assessment in HK-MRSA-treated mice. After targeted delivery of gVPLA2 plasmid to lung endothelium using ACE antibody-conjugated liposomes, MRSA-induced ALI was significantly increased in gVPLA2-KO mice, indicating that lung endothelial expression of gVPLA2 is critical in vivo. In summary, these results demonstrate an important role for gVPLA2 in mediating MRSA-induced lung EC permeability and ALI. Thus, gVPLA2 may represent a novel therapeutic target in ALI/ARDS caused by bacterial infection.


2021 ◽  
Vol 10 (13) ◽  
pp. 2951
Author(s):  
Maria Baldovin ◽  
Diego Cazzador ◽  
Claudia Zanotti ◽  
Giuliana Frasson ◽  
Athanasios Saratziotis ◽  
...  

Bilateral choanal atresia (CA) is a rare congenital malformation frequently associated with other anomalies. CHARGE association is closely linked to bilateral CA. The aim of this study was to describe the outcomes of the endoscopic repair in bilateral CA, and to assess the role of postoperative nasal stenting in two cohorts of CHARGE-associated and non-syndromic CA. Thirty-nine children were retrospectively analyzed (16 patients had CHARGE-associated CA). The rate of postoperative neochoanal restenosis was 31.3% in the CHARGE population, and 47.8% in the non-syndromic CA cohort. Data on postoperative synechiae and granulation tissue formation, need for endonasal toilette and dilation procedures, and number of procedures per patient were presented. Stent positioning led to a higher number of postoperative dilation procedures per patient in the non-syndromic cohort (p = 0.018), and to a higher rate of restenosis both in the CHARGE-associated, and non-syndromic CA populations. Children with CHARGE-associated and non-syndromic bilateral CA benefitted from endonasal endoscopic CA correction. The postoperative application of an endonasal stent should be carefully evaluated.


Vascular ◽  
2021 ◽  
pp. 170853812199985
Author(s):  
Yuanyuan Guo ◽  
Fan Zhu ◽  
Xiong Zhang ◽  
Guangmin Wu ◽  
Pinting Fu ◽  
...  

Objectives Vein graft adaptation (VGA) is a process that vein as a vascular graft conduits in arterial reconstructive surgery; VGA can lead to postoperative vein graft stenosis (VGS) and complications after coronary artery bypass graft and other peripheral artery bypass surgeries. VGA is characterized by vein graft loss the venous features without exhibiting arterial features; furthermore, the activation of ERK inhibited the maintenance of venous properties of the vein graft. We hypothesized that ERK inhibition can affect vein VGS through regulating the expression of EphB4. Methods Rat vein transplantation model was established using wild-type and EphB4+/− Sprague-Dawley rats. Hematoxylin-eosin, Masson, Verhoeff, actin staining, and immunohistochemistry were applied to observe the structure of the vein grafts. Vascular smooth muscle cells (VSMCs) were isolated from the vein and vein grafts. Western blotting was used to determine the expression of p-ERK1/2 and EphB4, and immunofluorescence was applied to detect the expression and location of EphB4. Cell wound scratch assay and CCK8 assay were used to determine the migration and proliferation of VSMCs. Real-time polymerase chain reaction was used to determine the mRNA expression of EphB4. Results Western blotting in vein sample and vein graft sample detected p-ERK1/2 and ERK1/2 expression in both EphB4+/+ and EphB4+/− rats. The expression of p-ERK was increased in vein graft compared to vein. Immunofluorescence in VSMCs form EphB4+/+ and EphB4+/− rats detected EphB4 expression in both cells, and the expression of EphB4 was increased in VSMCs form EphB4+/+ rats. SCH772984 reduces the proliferation and migration of VSMCs. Inhibition of ERK suppressed the increase of vein graft wall thickness, and the expression of collagen fibers, elastic fibers, and α-actin was decreased. Vein graft from EphB4+/− rats reduces the expression of EphB4, and SCH772984 suppressed the decrease of EphB4 in vivo. Vein graft from EphB4+/− rats increased the expression of EphB4, and SCH772984 suppressed the increase of EphB4 in vivo. Conclusions The inhibition of ERK1/2 suppressed the process of VGS by decreasing the proliferation of VSMCs. The ERK-inhibitor SCH772984 suppressed the level of VGS by extending the time of EphB4 expression during the process of VGA, thus maintaining the venousization of vein graft. The mechanism may be that the inhibitor SCH772984 suppresses the level of VGS by extending the time of EphB4 expression during the process of VGA. Therefore, our research provides a new target of VGS treatment by inhibiting the expression of ERK1/2 through the process of VGA.


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