scholarly journals Anti-fibrotic effects of the antihistamine ketotifen in a rabbit model of arthrofibrosis

2020 ◽  
Vol 9 (6) ◽  
pp. 302-310
Author(s):  
Meagan E Tibbo ◽  
Afton K Limberg ◽  
Christopher G Salib ◽  
Travis W Turner ◽  
Alex R McLaury ◽  
...  

Aims Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310.

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ourania I. Koukou ◽  
Lampros D. Pappas ◽  
Pelagia Chloropoulou ◽  
Maria A. Kouroupi ◽  
Konstantinos I. Koukos ◽  
...  

Background. Strontium ranelate (StR) is an antiosteoporotic agent previously utilized for the enhancement of fracture union. We investigated the effects of StR on fracture healing using a rabbit model. Methods. Forty adult female rabbits were included in the study and were divided in 2 equal groups, according to StR treatment or untreated controls. All animals were subjected to osteotomy of the ulna, while the contralateral ulna remained intact and served as a control for the biomechanical assessment of fracture healing. Animals in the study group received 600 mg/kg/day of StR orally. All animals received ordinary food. At 2 and 4 weeks, all animals were euthanatized and the osteotomy sites were evaluated for healing through radiological, biomechanical, and histopathological studies. Results. The treatment group presented statistically significant higher callus diameter, total callus area, percentage of fibrous tissue ( p < 0.001 ), vessels/mm2, number of total vessels, and lower osteoclast number/mm2 ( p < 0.05 ) than the control group at 2 weeks. Additionally, the treatment group presented significantly higher percentages of new trabecular bone, vessels/mm2, osteoclast number/mm2, and lower values for callus diameter, as well as total callus area ( p < 0.05 ), than the control group at 4 weeks. At 4 weeks, in the treatment group, force applied ( p = 0.003 ), energy at failure ( p = 0.004 ), and load at failure ( p = 0.003 ) were all significantly higher in the forearm specimens with the osteotomized ulnae compared to those without. Radiological bone union was demonstrated for animals receiving StR at 4 weeks compared with controls ( p = 0.045 ). Conclusion. StR appears to enhance fracture healing but further studies are warranted in order to better elucidate the mechanisms and benefits of StR treatment.


2003 ◽  
Vol 112 (8) ◽  
pp. 734-739 ◽  
Author(s):  
Miguel Caballero ◽  
Manuel Bernal-Sprekelsen ◽  
Carlos Calvo ◽  
Xavier Farré ◽  
Llucia Alós

A wide range of materials have been used to achieve medialization of the paralyzed vocal fold. Recently, medialization techniques using autologous cartilage have been described, but little information is available on cartilage integration and viability in this situation. In this prospective, experimental, controlled study, right vocal fold paralysis was surgically induced in 30 New Zealand rabbits. An autologous auricular cartilage transplant was inserted in the vocal fold in 15 animals. In the control group, only the laryngeal nerve was sectioned. Each group was divided into two groups with follow-ups of 6 weeks and 6 months, respectively. Histologic studies revealed no inflammatory reaction against the cartilage transplants. There were no differences in the transplant surfaces in the 6-week and 6-month groups. The results show tissue integration and a low level of initial transplant resorption that stabilizes with time. Autologous auricular cartilage appears to be an appropriate material for type I thyroplasty procedures because of the low absorption rate.


2007 ◽  
Vol 330-332 ◽  
pp. 1197-1200
Author(s):  
Zhong Li Shi ◽  
Wei Qi Yan ◽  
Jie Feng ◽  
Bing Gang Guan ◽  
Yang Bo Liu ◽  
...  

To evaluate the effectiveness of the cell-material in situ on joint resurfacing, a woven fabric polyglycolic acid (PGA) treated with fresh chondrocytes was used for repairing cartilage defects. Full-thickness defects were created in the weight-bearing surfaces of the femoral intercondylar fossa in a rabbit model. The defect was filled with and without PGA under surgical condition. Before implantation, chondrocytes were co-cultured with PGA for one day. The animals were sacrificed at eight weeks after implantation and evaluated grossly and histological score. Morphological examination showed that for PGA/chondrocytes group, the repaired tissue appeared similar in color and texture to the surrounding articular surface. While for the untreated control, no cartilage-like tissue was observed at all defects, but connective fibrous tissue. Histological analysis revealed neochondrogenesis and clusters of cartilage matrix with specific safranin-O staining for the PGA/cell group. The Gross and histological evaluation indicated a significantly higher score for PGA/cell group than for PGA and control group. These results suggest that the woven fabric PGA may facilitate the formation of cartilage tissues by providing a biodegradable and good-handle vehicle for the delivery to and retention of organized cell matrix constructs in vivo site. It might therefore enhance neochondrogenesis because of the superior biodegradable and biocompatible of PGA scaffold sheet, while the more suitable biological environment might sustain cell growth and in situ cell function, suggesting a promising candidate for functional tissue engineering of clinical environment.


2020 ◽  
Vol 31 (8) ◽  
pp. 1781-1795 ◽  
Author(s):  
Chuanqi Cai ◽  
Sreenivasulu Kilari ◽  
Chenglei Zhao ◽  
Michael L. Simeon ◽  
Avanish Misra ◽  
...  

BackgroundPercutaneous transluminal angioplasty (PTA) is the first line of treatment for stenosis in the arteriovenous fistula (AVF) created to provide access for hemodialysis, but resenosis still occurs. Transplants of adipose-derived mesenchymal stem cells (AMSCs) labeled with green fluorescent protein (GFP) to the adventitia could reduce pro-inflammatory gene expression, possibly restoring patency in a murine model of PTA for venous stenosis.MethodsPartial nephrectomy of male C57BL/6J mice induced CKD. Placement of the AVF was 28 days later and, 14 days after that, PTA of the stenotic outflow vein was performed with delivery of either vehicle control or AMSCs (5×105) to the adventitia of the vein. Mice were euthanized 3 days later and gene expression for interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha TNF-α) analyzed, and histopathologic analysis performed on day 14 and 28. GFP (+) AMSCs were tracked after transplantation for up to 28 days and Doppler ultrasound performed weekly after AVF creation.ResultsGene and protein expression of IL-1β and TNF-α, fibrosis, proliferation, apoptosis and smooth muscle actin decreased, and the proportions of macrophage types (M2/M1) shifted in a manner consistent with less inflammation in AMSC-transplanted vessels compared to controls. After PTA, AMSC-treated vessels had significantly higher wall shear stress, average peak, and mean velocity, with increased lumen vessel area and decreased neointima/media area ratio compared to the control group. At 28 days after delivery, GFP (+) AMSC were present in the adventitia of the outflow vein.ConclusionsAMSC-treated vessels had improved vascular remodeling with decreased proinflammatory gene expression, inflammation, and fibrotic staining compared to untreated vessels.


2010 ◽  
Vol 5 ◽  
pp. BMI.S6094 ◽  
Author(s):  
Marc A. Williams

Commercially available platforms to stabilize messenger RNA (mRNA) and microRNA are critically designed to optimize and ensure the quality and integrity of those nucleic acids. This is not only essential for gene expression analyses, but would provide technical utility in providing concordant standard operating procedures in preserving the structural integrity of RNA species in multicenter clinical research programs and biobanking of cells or tissues for subsequent isolation of intact RNA. The major challenge is that the presence of degraded samples may adversely influence the interpretation of expression levels on isolated mRNA or microRNA samples and that in the absence of a concordant operating procedure between multiple collaborating research centers would confound data analysis and interpretation. However, in this issue of Biomarker Insights, Weber et al provide a detailed and critical analysis of two common RNA preservation systems, PAXgene and RNAlater. Such studies are lacking in the literature. However, the authors provide compelling evidence that not all conservation platforms are created equal and only one system proves its worth.


2011 ◽  
Vol 23 (6) ◽  
pp. 759 ◽  
Author(s):  
R. M. García-García ◽  
P. G. Rebollar ◽  
M. Arias-Álvarez ◽  
O. G. Sakr ◽  
P. Bermejo-Álvarez ◽  
...  

Food deprivation affects female reproduction. The goal of the present study was to elucidate in the rabbit model the effects of acute energy restriction on ovarian function (follicle development, atresia rate and in vitro oocyte maturation) and embryonic development and gene expression of some candidate genes. Serum metabolic parameters (non-esterified fatty acids (NEFA), triglycerides, glucose, insulin and leptin concentrations) and endocrine markers (oestradiol-17β and progesterone concentrations) were also studied. A control group of nulliparous does fed ad libitum and a 72-h fasted group were used. At the end of the nutritional treatment, the ovaries of half of the animals were retrieved while the other animals were re-fed and artificially inseminated to recover embryos at 84 h after insemination, during the luteal phase. At the end of fasting, increased serum NEFA and decreased leptin concentrations were observed in the fasted group, but no differences appeared in serum steroid concentrations, follicle population and atresia rate or nuclear and cytoplasmic oocyte maturation. In the luteal phase, insulin concentrations increased notably in the fasted group. The number of recovered embryos per female and the speed of embryo development were reduced in the food-deprived group. Acute fasting altered both metabolic and endocrine markers and embryo development, but follicle and oocyte development and embryo gene expression were not affected.


2021 ◽  
Vol 11 (16) ◽  
pp. 7613
Author(s):  
Andrea Marchesini ◽  
Francesco De Francesco ◽  
Pier Paolo Pangrazi ◽  
Letizia Senesi ◽  
Andrea Campodonico ◽  
...  

Peritendinous adhesions are a frequent occurrence following tenolysis and present a major clinical challenge regarding prevention and management, with no recovery assured from conservative or surgical approaches. Herein, we investigated the effectiveness of Hyaloglide®, a hyaluronan gel-based product with a novel autocross-linked technology, in a rabbit model affected by tenolysis on the flexor digitorum communis tendon (FDC). A 1.5-cm-long scrubbing of the tendon surface was performed bilaterally to induce peritendinous adhesion on FDC of 30 animals with subsequent application of Hyaloglide® on the surrounding injured area, in one randomly chosen tendon. The contralateral tendon was treated with saline solution as the control. We sacrificed the rabbit models after 45 days of surgery and quantitatively assessed the generation of peritendinous adherence and regeneration of the tendon sheaths using histological (hematossyline-eosine, masson’s trichromic), histomorphometrical (Tang score, Soslowsky Svesson, and Cook score), light electron microscopic, and gene expression investigations. Four rabbits were devoted to biomechanical analysis. Peritendinous adhesions were limited in Hyaloglide®-treated tendons; moreover, well-regenerated tendon sheaths were observed conversely to untreated tendons presenting with extensive areas of adhesions on the tendon surface. Histomorphometrical analysis revealed an adhesion score (Tang score) significantly better in the treated group (p = 0.001 *) compared to the control group. Moreover, the Soslowsky, Svensson, and Cook score parameters revealed a significantly improved regeneration for fiber structure, cellularity, and vascularity in the treated group (p = 0.001 *). No differences were reported for cartilaginous formation (p = 0.08). Gene expression analysis showed a significant increase in collagen type I expression in the treated group compared to the control group, while metalloprotease 1 and 9 were significantly increased in the control group. Biomechanical analysis did not show significant differences in both groups. Hyaloglide® treatment was safe and well-tolerated, generating improved tissue status. Local application of Hyaloglide® prevents adhesion formation after tenolysis and promotes normal healing with regeneration of the synovial sheath in a rabbit model.


2020 ◽  
Vol 21 (1) ◽  
pp. 31-35
Author(s):  
Basma El-Desoky ◽  
Shaimaa El-Sayed ◽  
El-Said El-Said

Objective: Investigating the effect of green tea extract (GTE) on the testicular damage induced by cadmium chloride CdCl2 in male rats. Design: Randomized controlled study. Animals: 40 male Wistar rats. Procedures: Rats were randomly divided into four groups: A) control group (each rat daily received pellet diet); B) GTE group each rat daily received pellet diet as well as 3 ml of 1.5 % w/v GTE, C) CdCl2 group each rat was I/P injected a single dose of 1 mg/kg CdCl2, then daily received pellet diet, and D) CdCl2+GTE group each rat was I/P injected a single dose of 1 mg/kg CdCl2 then daily received pellet diet as well as 3 ml of 1.5 % w/v GTE. After 30 days, blood samples were collected for hormonal assays (testosterone, FSH, and LH). In addition, both testes were collected; one of them was used for quantification of 17-beta hydroxysteroid dehydrogenase III (17β-HSDIII) gene expression using a real-time PCR. The other testis was used for determination of catalase and reduced glutathione; GSH, Nitric oxide (NO) and malondialdehyde (MDA) levels. Results: CdCl2 decreased serum testosterone levels and its synthesis pathway (17β-HSDIII testicular gene expression). While antioxidants catalase and GSH were reduced, oxidants MDA were enriched in the testes of CdCl2-poisoned rats. This CdCl2-promoted testicular dysfunction was corrected via the administration of GTE to male rats. Conclusion and clinical relevance: GTE could be used as a remedy for protecting against CdCl2-induced testicular damage in male rats.


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