Local Administration of Simvastatin Stimulates Healing of an Avascular Meniscus in a Rabbit Model of a Meniscal Defect

2016 ◽  
Vol 44 (7) ◽  
pp. 1735-1743 ◽  
Author(s):  
Shurong Zhang ◽  
Takehiko Matsushita ◽  
Ryosuke Kuroda ◽  
Kyohei Nishida ◽  
Tokio Matsuzaki ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Immunohistochemical Analysis ◽  
Biomechanical Analysis ◽  
Bone Morphogenetic Protein 2 ◽  
Local Administration ◽  
Control Group ◽  
Type I ◽  
Gelatin Hydrogel ◽  
Simvastatin Group ◽  
Meniscal Cells

Background: Repair of an avascular meniscus is challenging because of its low capacity for healing. Several reports have shown that simvastatin stimulates the anabolic activity of intervertebral fibrochondrocytes, suggesting that simvastatin may be used for the treatment of meniscal defects. Purpose: To test whether the local administration of simvastatin stimulates healing of an avascular meniscus in rabbits. Study Design: Controlled laboratory study. Methods: In 30 Japanese White rabbits, a cylindrical defect (1.5-mm diameter) was introduced into the avascular zone of the anterior part of the medial meniscus in bilateral knees. Either a gelatin hydrogel (control group) or simvastatin-conjugated gelatin hydrogel (simvastatin group) was implanted into the defect. Histological assessments were performed using qualitative scoring systems, and immunohistochemical analysis was performed at 12 weeks after surgery. The occupation ratio (OR) and safranin O staining occupation ratio (SOR) were evaluated quantitatively at each time point. Stiffness of the regenerated tissue was analyzed biomechanically at 12 weeks after surgery. Rabbit meniscal cells were cultured in the presence or absence of 0.5 μM simvastatin, and then real-time polymerase chain reaction was performed to evaluate gene expression. Results: The qualitative score was significantly higher in the simvastatin group after 8 and 12 weeks ( P = .031 and .035, respectively). The mean OR and SOR were also significantly higher in the simvastatin group (OR at 8 weeks: 0.396 ± 0.019 [control] vs 0.564 ± 0.123 [simvastatin], P = .008; OR at 12 weeks: 0.451 ± 0.864 [control] vs 0.864 ± 0.035 [simvastatin], P = .001; SOR at 8 weeks: 0.071 ± 0.211 [control] vs 0.487 ± 0.430 [simvastatin], P = .009; SOR at 12 weeks: 0.093 ± 0.088 [control] vs 0.821 ± 0.051 [simvastatin], P = .006). Immunohistochemical analysis showed that at 12 weeks, the reparative tissue was more strongly positive for type I collagen (COL1), type II collagen (COL2), bone morphogenetic protein 2 (BMP-2), and BMP-7 in the simvastatin group than in the control group. Biomechanical analysis showed significantly higher stiffness in the simvastatin group (2.417 ± 1.593 N/ms [control] vs 5.172 ± 1.078 N/ms [simvastatin]; P = .005). In rabbit meniscal cells, BMP-2 and BMP-7 were upregulated after 4 and 8 hours and after 7 and 14 days, whereas COL1A1 and COL2A1 were significantly upregulated by simvastatin after 7 and 14 days. Conclusion: The local administration of simvastatin promotes the regeneration of an avascular meniscus in the rabbit model of a meniscal defect. The mechanism may involve the upregulation of BMPs and the subsequent upregulation of COL1 and COL2. Clinical Relevance: This study suggests that simvastatin stimulated intrinsic healing of an avascular meniscus. The local administration of simvastatin is safe and inexpensive and seems to be a promising treatment of meniscal injuries.

scholarly journals Effectiveness of Hyaluronan Autocross-Linked-Based Gel in the Prevention of Peritendinous Adherence Following Tenolysis

2021 ◽  
Vol 11 (16) ◽  
pp. 7613
Author(s):  
Andrea Marchesini ◽  
Francesco De Francesco ◽  
Pier Paolo Pangrazi ◽  
Letizia Senesi ◽  
Andrea Campodonico ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adhesion Formation ◽  
Rabbit Model ◽  
Treated Group ◽  
Collagen Type I ◽  
Biomechanical Analysis ◽  
Surgical Approaches ◽  
Control Group ◽  
Type I ◽  
Electron Microscopic

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.

Autologous Elastic Cartilage for Laryngoplasty: Histologic Evaluation in a Rabbit Model

2003 ◽  
Vol 112 (8) ◽  
pp. 734-739 ◽  
Author(s):  
Miguel Caballero ◽  
Manuel Bernal-Sprekelsen ◽  
Carlos Calvo ◽  
Xavier Farré ◽  
Llucia Alós
Keyword(s):  
Vocal Fold ◽  
Rabbit Model ◽  
Controlled Study ◽  
Control Group ◽  
Type I ◽  
Auricular Cartilage ◽  
Tissue Integration ◽  
Wide Range ◽  
Histologic Evaluation ◽  
Surgically Induced

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.

scholarly journals Effects of rhBMP-2 gene transfection to periodontal ligament cells on osteogenesis

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Cong-Xiang Jian ◽  
Quan-Shui Fan ◽  
Yong-He Hu ◽  
Yong He ◽  
Ming-Zhe Li ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Expression Vector ◽  
Gene Transfection ◽  
Bone Morphogenetic Protein 2 ◽  
Periodontal Ligament Cells ◽  
Control Group ◽  
Type I ◽  
Alp Activity ◽  
Pdl Cells ◽  
And Control

The present study aims to investigate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the osteogenesis of periodontal ligament (PDL) cells. The expression vector of rhBMP-2 (pcDNA3.1-rhBMP-2) was established. PDL cells were obtained through the enzymatic digestion and tissue explant methods and verified by immunohistochemistry. Cells were classified into experimental (cells transfected with pcDNA3.1/rhBMP-2-EGFP), blank (cells with no transfection) and control group (cells transfected with empty plasmid). rhBMP-2 expression was assessed via Western blotting analysis. The mineralization ability, alkaline phosphatase (ALP) activity and level of related osteogenic biomarkers were detected to evaluate the osteogenic characteristics of PDL cells. The rhBMP-2 expression vector (pcDNA3.1-rhBMP-2) was successfully established. Primary PDL cells displayed a star or long, spindle shape. The cultured cells were long, spindle-shaped, had a plump cell body and homogeneous cytoplasm and the ellipse nucleus contained two or three nucleoli. Cells displayed a radial, sheaf-like or eddy-like arrangement after adherence growth. Immunohistochemical staining confirmed that cells originated from mesenchymal opposed to epithelium. The experimental group exhibited an enhanced mineralization ability, higher ALP activity and increased expression of rhBMP-2 and osteogenic biomarkers (Runx2, collagen type I and osteocalcin) than the blank and control group. The present study demonstrated that rhBMP-2 transfection enhances the osteogenesis of PDL cells and provides a possibility for the application of rhBMP-2 expression products in dental disease treatment.

scholarly journals Ghrelin attenuates avascular necrosis of the femoral head induced by steroids in rabbits

2020 ◽  
Vol 19 (10) ◽  
pp. 2097-2101
Author(s):  
Laigang Huang ◽  
Fanshuo Zeng ◽  
Baojuan Cui ◽  
Daoqing Wang ◽  
Min Sun ◽  
...  
Keyword(s):  
Femoral Head ◽  
Avascular Necrosis ◽  
Rabbit Model ◽  
Underlying Mechanism ◽  
Bone Morphogenetic Protein 2 ◽  
Vehicle Group ◽  
Control Group ◽  
Mrna Levels ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue

Purpose: Ghrelin is an endogenous ligand for growth hormone secretagogue receptor. The current study was aimed at examining the effect of ghrelin on avascular necrosis of the femoral head (ANFH) induced by steroids in a rabbit model and also exploring the underlying mechanism. Methods: Experimental rabbits were separated into three groups: Control, Vehicle and Ghrelin. We established a steroid-induced ANFH model in rabbits. Then, MRI scanning and hematoxylin-eosin staining (HE) were conducted to see ANFH. The mRNA levels of Vascular Endothelial Growth Factor (VEGF) and Bone Morphogenetic Protein 2 (BMP-2) were evaluated using real-time qRT-PCR. Results: Rabbits in the Vehicle group showed increased empty bone lacunae, reduced bone trabecula in femoral head; the number of hematopoietic cells in the bone marrow was reduced, whereas number of adipocytes increased with evident fusion phenomenon in comparison with the Control group. All of the changes induced in Vehicle group were attenuated in Ghrelin group. MRI scanning showed obvious necrosis of femoral head in the Vehicle group and less in the Ghrelin group. The mRNA levels of VEGF and BMP-2 were raised in Vehicle group and further enhanced in Ghrelin group. Conclusion: Ghrelin attenuates steroid-induced avascular necrosis in femoral head in rabbit model. A possible mechanism may be through VEGF/BMP-2 axis. Keywords: ANFH, BMP-2, Ghrelin, VEGF

Therapeutic Mechanism of Chinese Medicine on the Healing of Early and Middle Fractures in Rabbits Under the Expression Level of Bone Morphogenetic Protein-2 (BMP-2) in Bone Tissue

2022 ◽  
Vol 12 (1) ◽  
pp. 45-51
Author(s):  
Hegui Xu ◽  
Yang Liu ◽  
Yuxiong Li ◽  
Wenbing Luo ◽  
Zhenyang Liu ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Bone Morphogenetic Protein ◽  
Expression Level ◽  
Bone Morphogenetic Protein 2 ◽  
Bone Collagen ◽  
Control Group ◽  
Type I ◽  
Type Ii ◽  
Morphogenetic Protein ◽  
Therapeutic Mechanism

In order to explore the therapeutic mechanism of Chinese medicine on the healing of rabbits early and middle fractures, a rabbit fracture model was established in this study. The study was divided into several groups, i.e., treatment group (TG) (fed with Chinese medicine Capsule) and control group (CG) (fed with normal saline (NS)). The materials were collected at 1, 3, and 5 weeks after the start of the experiment for analysis. The experiment content included: callus Hematoxylin-Eosin staining (HE staining); Bone Morphogenetic protein-2 (BMP-2) protein level detection; Type I and type II bone collagen (BC) detection; and serum biochemical factors detection. The experimental results showed that the formation of callus in the TG was better than in the CG; the BMP-2 protein expression level in the TG was higher than in the CG, and there were statistically significant differences (SSDs); the type I and type II BC levels in the TG were higher than the CG, there were SSDs; the levels of serum calcium (SC), phosphorus ion (PI), and alkaline phosphatase (ALP) in the TG were also higher than in the CG, and there were SSDs.

scholarly journals Effects of amlodipine on bone metabolism in male albino Wistar rats

2011 ◽  
Vol 80 (4) ◽  
pp. 391-396 ◽  
Author(s):  
Iveta Gradošová ◽  
Helena Živná ◽  
Klára Švejkovská ◽  
Vladimír Palička ◽  
Aleš Tichý ◽  
...  
Keyword(s):  
Body Weight ◽  
Bone Metabolism ◽  
Wistar Rats ◽  
Type I Collagen ◽  
Bone Alkaline Phosphatase ◽  
Bone Morphogenetic Protein 2 ◽  
Control Group ◽  
Type I ◽  
Mineral Density ◽  
Procollagen Type

Amlodipine (dihydropyridine-type calcium channel blocker) is a widely used agent for the treatment of hypertension in human and veterinary medicine but detailed information about its effects on bone metabolism are missing. Therefore, the aim of our study was to investigate the effect of amlodipine on bone metabolism in male albino Wistar rats. Amlodipine (0.3 mg/100 g body weight; gavage) was administered to 8 rats for 8 weeks. Control group (n = 8) received aqua pro inj. (0.2 ml/100 g body weight; gavage). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I) and aminoterminal propeptide of procollagen type I in serum, and of bone alkaline phosphatase (BALP) in both serum and bone homogenate were measured by enzyme immunoassay. We investigated the expression of bone morphogenetic protein 2 (BMP-2) in proximal tibia using Western blotting, and bone mineral density was measured by Dual-energy X-ray Absorptiometry in lumbar and caudal vertebrae and in femoral areas. Mechanical properties of the femurs were measured by three-point bending of the shaft and compression testing of the femoral neck. After 8 weeks of amlodipine administration there was a significant decrease in serum concentrations of BALP (p = 0.0009) and CTX-I (p = 0.003), and the content of BALP in bone homogenate (p = 0.026) compared to the control. In addition, Western blot analysis indicated increased BMP-2 protein concentration after amlodipine administration. Our findings suggest that amlodipine has a retarding influence on bone metabolism in rats by decreasing bone turnover, which probably in consequence increases expression of BMP-2.

scholarly journals In vivo Evaluation of Fibrous Collagen Dura Substitutes

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenbo Liu ◽  
Xin Wang ◽  
Jinlei Su ◽  
Qingsong Jiang ◽  
Jing Wang ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Rabbit Model ◽  
Surrounding Tissue ◽  
Control Group ◽  
Regeneration Ability ◽  
Type I ◽  
Blank Control Group ◽  
In Vivo Evaluation ◽  
And Performance

Dura substitutes are applied in duraplasty to repair lost or damaged dura. Collagen-based dura substitutes are mainstream products in both the US and Chinese markets. In this study, dura substitute devices with potential dura regeneration ability are evaluated. The dura substitutes are composed of fibrous type I collagen that were purified from bovine tendon. Physical and chemical characterization demonstrated that the tested dura substitute has desirable porous scaffolding structures and is composed of highly purified type I collagen. The collagen dura substitutes were further investigated in vivo with a rabbit model for 6 months to evaluate their safety and performance to repair and regenerate dura. No inflammation or infection was observed during the course of in vivo study. The integration of the collagen dura substitutes with surrounding tissue was normal as compared to native tissue. The macroscopic and microscopic histological assessments of the sampled animal tissue showed that the damaged dura were regenerated. The collagen dura substitutes were resorbed between 3 and 6 months along with newly regenerated dura. Both tissue adhesion and dura repair was the worst in blank control group as compared to those in the collagen dura substitutes. Taken together, regenerative collagen dura substitutes demonstrated with suitable physicochemical properties. The in vivo evaluation in a rabbit model further demonstrated the safety and performance of such substitutes for dura repair and regeneration.

scholarly journals Dynamics of brain CD68+ and stabilin-1+ macrophage infiltration in patients with myocardial infarction

Kardiologiia ◽  
2019 ◽  
Vol 59 (4S) ◽  
pp. 44-50
Author(s):  
M. S. Rebenkova ◽  
A. E. Gombozhapova ◽  
Yu. V. Rogovskaya ◽  
V. V. Ryabov ◽  
Yu. G. Kzhyshkowska ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Temporal Dynamics ◽  
Immunohistochemical Analysis ◽  
Control Group ◽  
Type I ◽  
Positive Correlation ◽  
History Of ◽  
Group 2 ◽  
The Brain ◽  
Group 1

Te aim of the study was to evaluate the temporal dynamics of brain CD68+ and stabilin-1+ macrophage infltration in patients with fatal myocardial infarction (MI) type 1.Materials and Methods. Te study included 31 patients with fatal MI type I. Te control group comprised 10 patients of 18–40 age group who died from injuries incompatible with life. Patients with MI were divided into two groups. Group 1 comprised patients who died during the frst 72 hours of MI, group 2 comprised patients who died on days 4‒28. Macrophage infltration in the brain was assessed by immunohistochemical analysis. We used CD68 as a marker for the cells of the macrophage lineage and stabilin-1 as an M2-like macrophage biomarker.Results. In group 1 the number of brain CD68+ macrophages was signifcantly higher than in the control group. In group 2 the intensity of brain CD68+ cells infltration was lower than in group 1 and higher than in the control group. Tere was a small amount of stabilin-1+ macrophages in the brain of healthy people, as well as of patients who died from MI. Tere were no signifcant differences in the number of stabilin-1+ cells between group 1 and group 2. Correlation analysis revealed the presence of positive correlation between the number of CD68 + macrophages in the infarct, peri-infarct, and non-infarct areas of the myocardium and the number of CD68+ macrophages in the brain in patients with MI. Tere were not correlations between the number of CD68 + and stabilin-1+ cells and the presence of diabetes mellitus, history of stroke, history of MI, and pre-infarction angina.Conclusion. Te number of brain CD68+ macrophages signifcantly increased during the frst three days of MI. Te number of brain stabilin-1+ macrophages did not increase and did not differ from the control values. We observed a positive correlation between the number of CD68+ macrophages in the brain and myocardium.

CARDIOVASCULAR RISK FACTORS PECULIARITIES IN MEN UNDER 60 YEARS OLD WITH MYOCARDIAL INFARCTION AND CHRONIC INFLAMMATORY LUNG DISEASES

2020 ◽  
pp. 21-25
Author(s):  
Tupitsyn V.V. ◽  
Bataev Kh.M. ◽  
Men’shikova A.N. ◽  
Godina Z.N.
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Heart Disease ◽  
Cardiovascular Risk ◽  
Digestive System ◽  
Control Group ◽  
Study Group ◽  
Type I ◽  
Internal Organs ◽  
History Of

Relevance. Information about the cardiovascular diseases risk factors (CVD RF) for in men with chronic lung inflam-matory pathology (CLID) is contradictory and requires clarification. Aim. To evaluate the peculiarities of CVD RF in men under 60 years of age with CLID in myocardial infarction (MI) to improve prevention. Material and methods. The study included men aged 19-60 years old with type I myocardial infarction. Patients are divided into two age-comparable groups: I - the study group, with CLID - 142 patients; II - control, without it - 424 patients. A comparative analysis of the frequency of observation of the main and additional cardiovascular risk fac-tors in groups was performed. Results. In patients of the study group, more often than in the control group we observed: hereditary burden of is-chemic heart disease (40.8 and 31.6%, respectively; p = 0.0461) and arterial hypertension (54.2 and 44.6%; p = 0.0461), frequent colds (24.6 and 12.0%; p = 0.0003), a history of extrasystoles (19.7 and 12.7%; p = 0.04); chronic foci of infections of internal organs (75.4 and 29.5%; p˂0.0001), non-ulcer lesions of the digestive system (26.1 and 14.6%; p = 0.007), smoking (95.1 and 66.3%; p˂0.0001), MI in winter (40.8 and 25.9%; p = 0.006). Less commonly were observed: oral cavity infections (9.2 and 23.6%; p˂0.0001); hypodynamia (74.5 and 82.5%; p = 0.0358), over-weight (44.4 and 55.2%; p = 0.0136), a subjective relationship between the worsening of the course of coronary heart disease and the season of the year (43.7 and 55.2%; p = 0.0173) and MI - in the autumn (14.1 and 21.9%; p = 0.006) period. Conclusions. The structure of CVD RF in men under 60 years of age with CLID with MI is characterized by the pre-dominance of smoking, non-ulcer pathology of the digestive system, frequent pro-student diseases, meteorological dependence, a history of cardiac arrhythmias and foci of internal organ infections. It is advisable to use the listed factors when planning preventive measures in such patients.

PENGARUH PEMBERIAN KOMBINASI EKSTRAK BUAH MENGKUDU (Morinda citrifolia L.) DAN KUNYIT (Curcuma longa) TERHADAP HISTOPATOLOGI GINJAL TIKUS WISTAR YANG DIINDUKSI ALLOXAN

2020 ◽  
Vol 5 (2) ◽  
pp. 319-327
Author(s):  
Pelastri Rahayu ◽  
◽  
Retno Hestiningsih ◽  
Martini Martini ◽  
Dwi Sutiningsih ◽  
...  
Keyword(s):  
Body Weight ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Curcuma Longa ◽  
Morinda Citrifolia ◽  
Control Group ◽  
Type I ◽  
Turmeric Extract ◽  
Measurement Results ◽  
Diabetes Nephropathy

The prevalence of DM in Riskesdas in 2018 according to the Perkeni consensus in 2015 is higher than according to the Perkeni consensus in 2011, the prevalence was10.9%. The disease can develop into diabetes nephropathy, Increased prevalence of diabetic nephropathy directly proportional with an increase in diabetes prevalence. Diabetic nephropathy is a microvascular complication in diabetics that develops around 30% in patients with type I DM and about 40% in patients with type II DM. Turmeric extract has antioxidant and anti-inflammatory effects to prevent the bad development of diabetes nephropathy. This study looked at the effect of giving a combination of noni and turmeric extract on histopathology of alloxan-induced renal rats. A total of 25 mice were divided into 5 treatment groups, namely the PI group (250 mg / kgBB extract dose), PII group (500 mg / kgBB extract dose), PIII group (750 mg / kgBB extract dose), positive control group (glibenklamid) and negative control group (without extract and glibenklamid). The study used Post Test Only Group. The highest percentage decrease in blood glucose in the PI group was 56.11% and the lowest decrease in the PIII group was 24.12% with p = 0.012. The results of the study were not based on the number of extract doses. The measurement results of rat body weight and glomerular diameter were not affected by blood glucose level with p = 0.700 for body weight and p = 0.187 for glomerular measurement results.

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