scholarly journals The combination of microfracture with induction of Wnt / β- Catenin pathway, leads to enhanced cartilage regeneration

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Nikitas P. Schizas ◽  
Olga Savvidou ◽  
Kalliopi Diamantopoulou ◽  
Stamatios Papadakis ◽  
Panayiotis J. Papagelopoulos ◽  
...  

Abstract Introduction Microfracture does not lead to complete healing of full-thickness cartilage defects. The aim of this study was to evaluate the effect of modifying Wnt/β-catenin signaling following microfracture, on the restoration of a full-thickness cartilage defect in a rabbit model. The modification of the canonical Wnt pathway was achieved through per os administration of lithium carbonate, which is an intracellular inhibitor of glycogen synthase kinase 3-β (Gsk3-β) and therefore induces Wnt/β-catenin signaling. Materials and methods Full-thickness cartilage defects of 4 mm in diameter were created in the patellar groove of the right femurs of 18 male New Zealand white rabbits. The rabbits were divided into three groups of six (n = 6) based on post-surgery treatment differences, as follows: microfracture only (group 1), microfracture plus lithium carbonate 7 mM in the drinking water for 1 week (group 2), microfracture plus lithium carbonate 7 mM in the drinking water for 4 weeks (group 3). All animals were sacrificed 9 weeks after surgery. The outcome was assessed histologically, by using the International Cartilage Repair Society (ICRS) visual histological scale. Immunohistochemistry for type II collagen was also conducted. Results Statistical analysis of the histological ICRS scores showed that group 3 was significantly superior to group 1 in four out of six ICRS categories, while group 2 was superior to 1 in only two out of six. Conclusion The combination of microfracture and systematic administration of lithium carbonate 7 mM for 4 weeks shows statistically significant superiority in four out of six ICRS categories compared with microfracture only for the treatment of full-thickness cartilage defects in a rabbit experimental model.

2021 ◽  
Vol 9 (12) ◽  
pp. 232596712110607
Author(s):  
Yang-Soo Kim ◽  
Yun-Gyoung Lee ◽  
Min-Tae Kim ◽  
Hyo-Jin Lee

Background: Apoptosis and autophagy are known to be correlated with the extent of damage in torn rotator cuffs, and there is no biological evidence for self-recovery or healing of the rotator cuff tear. Purpose: To establish in a rat model of partial- and full-thickness rotator cuff tears how a glycogen synthase kinase 3β (GSK-3β) inhibitor affects the expression of apoptotic and autophagic markers. Study Design: Controlled laboratory study. Methods: Twelve-week-old Sprague Dawley rats were divided into 3 groups (n = 16 per group). Group 1 acted as the control, with no treatment; group 2 received partial-thickness (right side) and full-thickness (left side) rotator cuff tears only; and group 3 received the same rotator cuff injuries, with GSK-3β inhibitor injected afterward. The tendons from each group were harvested 42 days after surgery. Evaluation of gene expression, immunohistochemistry, and TUNEL staining (terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling) were performed for the following markers: caspases 3, 8, and 9 as well as Bcl-2 (B-cell lymphoma 2); BAX (Bcl-2-associated X protein); beclin 1; p53; and GSK-3β; which represented apoptotic and autophagic reactions. Statistical analysis was performed using 1-way analysis of variance. Results: In the group 2 rats with partial- and full-thickness tears, there were significant increases in the mRNA levels (fold changes) of all 8 markers as compared with group 1 (control). All these increased markers showed significant downregulation by the GSK-3β inhibitor in partial-thickness tears. However, the response to the GSK-3β inhibitor in full-thickness tears was not as prominent as in partial-thickness tears. The number of TUNEL-positive cells in group 2 (partial, 35.08% ± 1.625% [mean ± SE]; full, 46.92% ± 1.319%) was significantly higher than in group 1 (18.02% ± 1.036%; P < .01) and group 3 (partial, 28.04% ± 2.607% [ P < .01]; full, 38.97% ± 2.772% [ P < .01]), and immunohistochemistry revealed increased expression of all the markers in group 2 as compared with control. Conclusion: The apoptotic and autophagic activity induced in a rat model of an acute rotator cuff tear was downregulated after treatment with a GSK-3β inhibitor, particularly with partial-thickness rotator cuff tears. Clinical Relevance: A GSK-3β inhibitor may be able to modulate deterioration in a torn rotator cuff.


Pituitary ◽  
2021 ◽  
Author(s):  
Muhammad Fahad Arshad ◽  
Oluwafunto Ogunleye ◽  
Richard Ross ◽  
Miguel Debono

Abstract Purpose There is no consensus on quality of life (QOL) in patients with acromegaly requiring medical treatment after surgery compared with those achieving remission by surgery alone. Methods QuaLAT is a cross-sectional study comparing QOL in surgery-only treated acromegaly patients versus those requiring medical treatment post-surgery. Patients attending clinics were identified and divided into—Group 1: patients who had surgery only and were in biochemical remission, Group 2: all patients on medical treatment post-surgery, Group 3: patients from Group 2 with biochemical control. Participants were asked to fill three questionnaires; Acromegaly Quality of Life Questionnaire (ACROQOL), 36-Item Short Form Survey (SF36), and Fatigue Severity Scale (FSS). Results There were 32 patients in Group 1 and 25 in Group 2. There was no difference in QOL scores between groups 1 and 2, as measured by ACROQOL (mean difference [MD] = − 2.5, 95% CI − 16.6 to 11.6; p = 0.72), SF36v2 [Physical component score (PCS) MD = − 4.9, 95% CI − 10.9 to 1.2; p = 0.12; mental component score MD = − 3.0, 95% CI − 10.5 to 4.4; p = 0.44], or FSS (MD = − 0.004, 95% CI − 1.14 to 1.33; p = 0.1). Comparison between groups 1 and 3 however showed that PCS (and 3 subdomains) was significantly better in group 3 (MD = − 8.3, 95% CI − 14.8 to -1.8; p = 0.01). All three QOL scores were lower when compared with healthy controls. Conclusions Medical treatment not only achieves a QOL comparable to surgery, it may also be associated with better QOL in physical subdomains. When compared with healthy controls, QOL remains worse in treated acromegaly patients compared to controls.


2009 ◽  
Vol 2009 ◽  
pp. 1-5
Author(s):  
Stefano Luisi ◽  
Valentina Ciani ◽  
Massimo Gabbanini ◽  
Sofia Sollazzi ◽  
Michela Torricelli ◽  
...  

Following myomectomy the rate of fertility is restored and pregnancy may be attempted with a good outcome. In the present study a 3 month treatment with OCs in a group of women after a myomectomy was evaluated. The drug compliance and side effects, the benefits of OC in order to reduce symptoms, to increase post-surgical hemoglobin levels and to avoid an early pregnancy after myomectomy were analyzed. A group of women () each with myoma 5 cm was recruited: they presented menorrhagia, pelvic pain, dyspareunia and dysmenorrhae. After laparotomic myomectomy the women were divided into 3 groups. Group 1: women () treated with pill A (15 mcg of ethynilestradiol + 60 mcg of gestodene); group 2: women () treated with pill B (20 mcg of ethynilestradiol + 100 mcg of levonorgestrel); group 3: women () treated with a placebo (oral calcium). After three months from myomectomy and treatment patients in each group reported a reduced menorrhagia, dismenorrhea and pelvic pain. Serum haemoglobin levels increased in all women (). No pregnancy occurred in any group and the compliance was good. A post surgery treatment by using oral contraceptives guarentees pregnancy prevention, associated with reduction of pain, and improvement of haematologic conditions.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3387-3387
Author(s):  
Maurizio Zangari ◽  
Donghoon Yoon ◽  
Hanna Yoo ◽  
Young Sik Kim

Abstract The 5TGM1 transplanted C57BL6/KaLwRij mouse is widely used to study murine multiple myeloma development. It recapitulates many features of human multiple myeloma including monoclonal paraprotein as well as bone lesions. Using this mouse model we demonstrated the crucial role of the parathyroid hormone 1 receptor (PTH1R) on the survival of mice exposed to proteasome inhibitor drugs such as bortezomib and carfilzomib; specifically the blockage of the PTH1R function by parathyroid hormone antagonist (PTH 7-34) resulted in significant abrogation of the beneficial survival effect of proteasome inhibitor drugs. To further investigate the effect of the parathyroid hormone (PTH) axis on murine myeloma development we performed thyroparathyroidectomy on the C57BL6/KaLwRij mouse before or after 5TGM1 transplantation. Thyroparathyroidectomy was performed by trained personnel in general anesthesia with isoflurane; all surgical/postsurgical procedures and animal welfare followed an IACUC approved protocol at the University of Arkansas. To prevent hypocalcaemia at postsurgery, 1M CaCl2 solution in the drinking bottle was supplemented for a week. All tested mice received 0.5X106 5TGM1 cell infusion by intravenous injection; mice were divided into three groups; Group 1 control mice (n=10) received 5TGM1 infusion at day 0; Group 2 included 15 mice which on day 10 post 5TGM1 cell infusion underwent thyroparathyroidectomy; Group 3 included 15 mice which at 20 days post-surgery received infusion of 5TGM1 cells. 30% of animals experienced post-surgical complications and died in the first 7 days from procedure; those animals were not included in this survival analysis which is based on 10 animals for each cohort. Blood samples were collected at weekly intervals for IgG2 measurements. The survival curves of mice recovered after surgery are shown in the figure. Figure 1 Figure 1. All control mice (group 1) developed myeloma progression and died within 3 weeks post-transplant; 2 mice from group 2 and 5 mice of the third cohort manifested disease. All 7 animal deaths were pathologically and serologically attributed to myeloma progression. Compared to controls thyroparathyroidectomized mice (Group 2 and Group 3) showed significantly longer survival p<0.001 and p=0.003, respectively. The 13 surviving mice are still alive 6 months post-procedure and have not shown any serological or clinical evidence of disease progression. Two mice from previous experiment set are still alive and healthy after more than 2 years follow-up. In conclusion thyroparathyroidectomy achieves durable control and possibly cure of the 5TGM1 murine myeloma model suggesting an endocrinological control of myeloma progression. Currently the mechanism of action is under investigation. Disclosures Zangari: Norvartis: Membership on an entity's Board of Directors or advisory committees; Onyx: Research Funding; Millennium: Research Funding.


2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Jae Yeon Lee ◽  
Jeong Hun Park ◽  
Soo Jin Son ◽  
Mina Han ◽  
Gonhyung Kim ◽  
...  

The objective of this study was to evaluate the use of immunosuppressive therapy with high-dose cyclosporine, high-dose azathioprine, and a combination of low-dose cyclosporine and azathioprine after tracheal reconstruction by using a trachea-mimetic graft of polycaprolactone (PCL) bellows-type scaffold in a rabbit model. Twenty-four healthy New Zealand white rabbits were used in the study. All underwent circumferential tracheal replacement using tissue-engineered tracheal graft, prepared from PCL bellows scaffold reinforced with silicone ring, collagen hydrogel, and human turbinate mesenchymal stromal cell (hTMSC) sheets. The control group (Group 1) received no medication. The three experimental groups were given daily cyclosporine intramuscular doses of 10 mg/kg (Group 2), azathioprine oral doses of 5 mg/kg (Group 3), and azathioprine oral doses of 2.5 mg/kg plus cyclosporine intramuscular doses of 5 mg/kg (Group 4) for 4 weeks or until death. Group 1 had longer survival times compared to Group 2 or Group 3. Each group except for Group 1 experienced decreases in amount of nutrition and weight loss. In addition, compared with the other groups, Group 2 had significantly increased serum interleukin-2 and interferon-γ levels 7 days after transplantation. The results of this study showed that the administration of cyclosporine and/or azathioprine after tracheal transplantation had no beneficial effects. Furthermore, the administration of cyclosporine had side effects, including extreme weight loss, respiratory distress, and diarrhea. Therefore, cyclosporine and azathioprine avoidance may be recommended for tracheal reconstruction using a native trachea-mimetic graft of PCL bellows-type scaffold in a rabbit model.


1989 ◽  
Vol 70 (4) ◽  
pp. 599-604 ◽  
Author(s):  
Dennis G. Vollmer ◽  
Kazuhiro Hongo ◽  
Neal F. Kassell ◽  
Hisayuki Ogawa ◽  
Tetsuya Tsukahara ◽  
...  

✓ The ability of antithrombin III, an endogenous plasma glycoprotein, to reverse the arterial narrowing in a rabbit model of cerebral vasospasm was evaluated. The vasodilator activity of antithrombin III on rabbit arteries was first assessed in vitro using a myograph-arterial ring preparation. Antithrombin III (10 IU/ml) induced a 55.4% ± 2.66% (mean ± standard error of the mean) relaxation in basilar artery precontracted with serotonin (5-HT) in five specimens as compared with a 9.8% ± 1.6% relaxation of common carotid artery in six specimens. For in vivo analysis, 21 New Zealand White male rabbits were separated into three groups: Group 1 served as normal controls; Group 2 received a subarachnoid blood injection (SAH) and were sacrificed on Day 3 thereafter; and Group 3 animals were subjected to SAH, then received a 2-hour intracisternal infusion of antithrombin III (100 IU) in saline prior to sacrifice on Day 3. Basilar artery caliber was determined using a morphometric method to analyze perfusion-fixed arterial segments. Control basilar artery diameter in Group 1 was 0.64 ± 0.02 mm. In Group 2 a 27% reduction in arterial caliber to 0.47 ± 0.03 mm was observed by Day 3 post SAH (p < 0.0001). Group 3 animals had a mean basilar artery diameter of 0.68 ± 0.02 mm. This was significantly larger than the untreated SAH rabbits in Group 2 (p < 0.0001), but not different from control artery diameters in Group 1. The findings demonstrate that antithrombin III in saline has a significant ability to reverse delayed narrowing of the rabbit basilar artery after SAH.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Wanwisa Suwannaloet ◽  
Wiroon Laupattarakasem ◽  
Peerapol Sukon ◽  
Siriwan Ong-Chai ◽  
Pisamai Laupattarakasem

The osteochondral healing potential of hyaluronic acid (HA) plus diacerein was evaluated in subchondral-drilling- (SCD-) induced fibrocartilage generation in rabbits. A full-thickness chondral defect was created along the patellar groove of both knees and then SCD was subsequently performed only in the left knee. A week later, the rabbits were allocated into 3 groups to receive weekly intra-articular (IA) injection for 5 weeks with normal saline solution (NSS) (group 1) or with HA (group 2 and group 3). Starting at the first IA injection, rabbits were also gavaged daily for 9 weeks with NSS (group 1 and group 2) or with diacerein (group 3). The animals were then sacrificed for evaluation. The newly formed tissue in SCD lesions showed significantly better histological grading scale and had higher content of type II collagen in HA-treated group compared to NSS control. In addition, adding oral diacerein to HA injection enhanced healing potential of HA.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lina Stangvaltaite-Mouhat ◽  
Alina Puriene ◽  
Indre Stankeviciene ◽  
Jolanta Aleksejuniene

Abstract Background Dental caries is the most prevalent non-communicable health condition globally. The surface-based susceptibility hierarchy indicates that surfaces in the same group have similar susceptibility to caries, where the most susceptible group consists of occlusal surfaces of first molars and buccal surfaces of lower first molars, and the least susceptible surfaces are smooth and proximal surfaces of first premolars, canines and incisors. Therefore, fluoride in the drinking water could impact one group more than the other group. The present study examined the association between fluoride levels in the drinking water and dental caries experience in adults in the context of varying tooth surface susceptibility. Methods Data from the cross-sectional National Lithuanian Oral Health Survey conducted in 2017–2019 included a stratified random sample of 1398 35–74-year-olds (52% response rate). Dental caries experience in dentine was measured at a surface level. The surfaces were grouped according to their caries susceptibility (group 1 being the most and group 4 the least susceptible), and dental caries experience was calculated separately for each susceptibility group, creating four outcomes. Information about explanatory variable, fluoride levels in the drinking water, was provided by the water suppliers. The questionnaire inquired about potential determinants: sociodemographic characteristics and oral health-related behaviors. Chi-square, Mann–Whitney U and Kruskal Wallis tests were used for descriptive statistics, and linear regression analyses to examine the association between fluoride levels and four outcomes. Results The proportions of median decayed, missing, filled surfaces decreased following the surface-based susceptibility hierarchy (group 1–33%, group 2–28%, group 3–24%, group 4–15%). When adjusted for potential determinants, higher-level fluoride (≥ 0.7 ppm vs < 0.7 ppm) in the drinking water associated with lower dental caries experience in all surface-based susceptibility hierarchy groups; Group 1: β = − 0.23 (95 %CI − 0.44; − 0.001), Group 2: β = − 0.44 (95 %CI − 0.82; − 0.07), Group 3: β = − 1.14 (95 %CI − 1.88; − 0.41) and Group 4: β = − 6.28 (95 %CI − 9.29; − 3.30). Conclusions The higher-level fluoride in the drinking water associated with lower dental caries experience in adults and this was observed in all surface-based susceptibility groups. However, there is a need to validate the surface-based susceptibility hierarchy in longitudinal adult studies.


2017 ◽  
Vol 89 (2) ◽  
pp. 134
Author(s):  
Murat Tuken ◽  
Mustafa Zafer Temiz ◽  
Emrah Yuruk ◽  
Asuman Orcun Kaptanagasi ◽  
Kayhan Basak ◽  
...  

Objectives: The aim of this study is to evaluate the effects of the herbal agent in the prevention and treatment of bacterial cystitis in a rat model. Material and Methods: A total of twenty-eight male Sprague- Dawley rats were divided into four groups. Group-1 constituted the control group (operated and normal saline injected into the bladder, received only drinking water for 7 days); Group-2 constituted the no-treatment group (operated, E.coli J96 strain injected into the bladder, received only drinking water for 7 days); Group-3 constituted the short-term treatment (operated, E.coli J96 strain injected into the bladder, received the herbal agent added into drinking water for 7 days) and Group-4 constituted the long-term treatment (operated, E. coli J96 strain injected into the bladder, received herbal agent added into drinking water for 14 days). At the end of the pre-defined treatment periods of duration, the rats were sacrificed, urine samples collected from the bladder for culture and bladders were harvested for histopathological evaluation. Urine culture results and histopathological findings were comparatively evaluated between the groups. Results: Urine cultures were positive for implanted E. coli strains in 0%, 85.7%, 42.8% and 0% of rats in Group 1, Group 2, Group 3 and Group 4, respectively (p = 0.001). Although histopathological evaluation revealed increased vascular dilation in the bladder specimens obtained from Group 2 and Group 3 (p = 0.028) no significant difference was noticed in level of inflammation (p = 0.610), edema (p = 0.754) and thickness of uroepithelium (p = 0.138). Conclusion: While long term (14 days) treatment with an herbal agent added into the drinking water resulted in complete clearance of urine from E. coli; shorter application of the agent revealed partial clearance. Further clinical studies are needed to support our results.


2020 ◽  
Vol 17 (5) ◽  
pp. 717-727
Author(s):  
Lin Zhao ◽  
Junli Zhao ◽  
Jia-Jia Yu ◽  
Cangyu Zhang

Abstract Background: In previous studies, we succeeded in repairing a long bone defect with tissue-engineered periosteum (TEP), fabricated by incorporating rabbit mesenchymal stem cells with small intestinal submucosa. In this study, we investigated the feasibility of allogeneic irregular bone defect repair using TEP. Methods: We performed a subtotal resection of the scapula in 36 rabbits to establish a large irregular bone defect model. The rabbits were then randomly divided into three groups (n = 12 per group) and the defects were treated with TEP (Group 1), allogeneic deproteinized bone (DPB) (Group 2) or a hybrid of TEP and DPB (Group 3). At 4, 8, and 12 weeks after surgery, the rabbits were sacrificed, and the implants were harvested. X-ray radiographic and histological examinations were performed to detect bone healing. Ink-formaldehyde perfusion was introduced to qualitatively analyze vascularization in TEP engineered new bone. Results: The repair of scapular defects was diverse in all groups, shown by radiographic and histological tests. The radiographic scores in Group 1 and Group 3 were significantly higher than Group 2 at 8 and 12 weeks (p < 0.05). Histological scores further proved that Group 1 had significantly greater new bone formation compared to Group 3 (p < 0.05), while Group 2 had the lowest osteogenesis at all time-points (p < 0.001). Ink-formaldehyde perfusion revealed aboundant microvessels in TEP engineered new bone. Conclusion: We conclude that TEP is promising for the repair of large irregular bone defects. As a 3D scaffold, DPB could provide mechanical support and a shaping guide when combined with TEP. TEP engineered new bone has aboundant microvessels.


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