Intra-articular Adenosine, Lidocaine and Magnesium (ALM) solution decreases postoperative joint fibrosis in an experimental knee implant model

Abstract Background There is currently no drug therapy to prevent arthrofibrosis following knee surgery. We aimed to determine if the anti-ischemic and anti-inflammatory drug adenosine, lidocaine and Mg2+ (ALM), reduces surgery-related arthrofibrosis in a rat model of knee implant surgery. Methods Male Sprague-Dawley rats (n = 24) were randomly divided into ALM or saline groups. The right knee of each animal was implanted with custom titanium (femur) and polyethylene (tibia) implants, and the left knee served as a non-operated control. An intra-articular ALM or saline bolus (0.1 ml) was administered at the end of surgery, and animals monitored for 4 weeks. Fibrotic changes were assessed by macroscopic examination, histopathology, and expression of key inflammatory and fibrotic markers in the joint capsule and infrapatellar fat pad (IFP). Results Knee swelling was evident in both groups at 4 weeks. However, range of motion was 2-fold higher in the ALM-treated knees, and differences in macroscopic pathology indicated improved healing, compared to the control group. Histologically, ALM treatment also led to significantly decreased synovitis and fibrotic pathology in the joint capsule and IFP compared to saline controls. RNA and protein expression profiles of pro-fibrotic mediators (α-SMA, TGF-β1, FGF1, PDGFA) were also significantly lower in knees from ALM-treated animals. In addition, the expression of inflammatory mediators was lower in plasma (IL-1β, IL-10) and joint tissue (NFκB, IL-1β, IL-12), 4 weeks after surgery. Conclusion We show that intra-articular administration of a single ALM bolus significantly decreased fibrotic pathology and synovitis in an experimental model of knee implant surgery, by blunting inflammation and modulating essential genes of fibrosis. ALM has the therapeutic potential for translation into humans undergoing knee replacement surgery.

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How does intraarticular dexmedetomidine injection effect articular cartilage and synovium? An animal study

BMC Anesthesiology ◽

10.1186/s12871-020-01148-x ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Başak Akça ◽

Aysun Ankay Yılbaş ◽

Filiz Üzümcügil ◽

Berkem Büyükakkuş ◽

Elham Bahador Zırh ◽

...

Keyword(s):

Pain Relief ◽

Knee Joint ◽

Animal Study ◽

Left Knee ◽

Control Group ◽

Sprague Dawley ◽

Adult Rats ◽

Arthroscopic Knee ◽

The Right

Abstract Background Intraarticular injections are widely used to provide pain relief after arthroscopic procedures and minimize the use of opioids. Dexmedetomidine has been proven to potentiate pain relief and postpone the demand for the first analgesic drug when it is used intraarticularly following arthroscopic knee procedures. However, the effects of dexmedetomidine on articular structures have not yet been evaluated. Our aim was to determine the effects of intraarticular dexmedetomidine injection on articular structures such as cartilage and synovium. Design Animal study. Methods Twenty adult rats (Sprague-Dawley) were enrolled in the study. Following appropriate aseptic and anesthetic conditions, dexmedetomidine (100 mcg/ml) (0.25 ml) was injected into the right knee joint (the study group) and normal saline solution (0.25 ml) into the left knee joint (the control group) of the rats. Four rats were sacrificed from each group on days 1, 2, 7, 14, and 21, and knee joint samples were obtained. Histologists evaluated the articular and periarticular regions and the synovium using histological sections, and a five-point scale was used to grade the inflammatory changes in a blinded manner. Results The groups were found to be similar in terms of median congestion scores, edema and inflammation scores, subintimal fibrosis, neutrophil activation and cartilage structure at each of the time intervals. Conclusion In our placebo-controlled, in vivo trial, the intraarticular use of dexmedetomidine seemed to be safe with respect to the studied histopathological parameters. However, complementary studies investigating the histopathological effects, analgesic dosage and adverse effects of dexmedetomidine on damaged articular structure models are needed.

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Dose-dependent effect of betamethasone on the articular cartilage (experimental study)

Genij Ortopedii ◽

10.18019/1028-4427-2021-27-1-80-86 ◽

2021 ◽

Vol 27 (1) ◽

pp. 80-86

Author(s):

A.N. Nuriakhmetov ◽

◽

I.F. Akhtiamov ◽

D.E. Tsyplakov ◽

A.M. Abdullah ◽

...

Keyword(s):

Subchondral Bone ◽

Inflammatory Cell ◽

Left Knee ◽

Knee Joints ◽

Control Group ◽

Rabbit Knee ◽

Frequency Of Use ◽

The Right ◽

Dose Dependent ◽

Dose Dependent Effect

Introduction Glucocorticosteroid injections have been widely used in clinical practice. Betamethasone is one of the agents of this group of drugs. Its efficacy and therapeutic effect with intra-articular administration are undeniable. There are special instructions on the dosage and frequency of use of the drug but unfortunately there are cases of its wrong administration. There is also an evidence of an adverse effect on cartilage both of the drug itself and its combination with local anesthetics. Aim Evaluation of the results of different weekly intra-articular protocols of betamethasone administration on histological preparations of rabbit knee joints. Methods Histological preparations of the right knee joints of three groups of rabbits were studied: after one, three, and six administrations of betamethason per week and the control intact left knee joints. Results Histological preparations of the control group and the group with a single weekly administration of the drug did not have any changes in the structure of diarthrosis. Dystrophic and necrotic changes affecting all morphological components were observed in the joints of animals that received intra-articular injections of betamethason three times a week (compared to a single injection, the area of dystrophy and necrosis of the cartilage was greater by 10.05 ± 0.75 % (p < 0.05), of subchondral bone by 8.11 ± 0.5 % (p < 0.001), and of synovium by 6.25 ± 0.32 % (p < 0.05). The group with six injections of the drug per week had the most pronounced changes. The area of necrotic changes of the cartilage was greater by 6.39 ± 0.75 % than in the group with three injections per week (p < 0.001), of subchondral bone by 11.18 ± 0.5 % (p < 0.001), of synovium by 6.12 ± 0.32 % (p < 0.001). Discussion Inflammatory cell infiltration of joint structures was absent in all cases. It indicates an aseptic nature of tissue necrosis. Evidence has been obtained between the increase in the frequency of intra-articular injections of betamethasone and the severity of dystrophic and necrotic changes in all morphological components of the joint.

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Contralateral spreading of substances following intratympanic nanoparticle-conjugated gentamicin injection in a rat model

Scientific Reports ◽

10.1038/s41598-020-75725-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Sang-Yeon Lee ◽

Jeonghyo Kim ◽

Sangjin Oh ◽

Gaon Jung ◽

Ki-Jae Jeong ◽

...

Keyword(s):

Eustachian Tube ◽

Rat Model ◽

Control Group ◽

Fluorescent Nanoparticles ◽

Sprague Dawley ◽

Surface Charges ◽

Cochlear Hair Cells ◽

Intratympanic Injection ◽

Group 2 ◽

The Right

Abstract This study was performed to investigate the Eustachian tube as a potential route for contralateral spreading following intratympanic nanoparticle (NP)-conjugated gentamicin injection in a rat model. Sprague–Dawley rats were divided into three groups and substances were injected in the right ear: group 1 (fluorescent magnetic nanoparticles [F-MNPs], n = 4), group 2 (F-MNP-conjugated gentamicin [F-MNP@GM], n = 2), and control group (no injections, n = 2). T2-weighted sequences corresponding to the regions of interest at 1, 2, and 3 h after intratympanic injection were evaluated, along with immunostaining fluorescence of both side cochlea. The heterogeneous signal intensity of F-MNPs and F-MNP@GM on T2-weighted images, observed in the ipsilateral tympanum, was also detected in the contralateral tympanum in 4 out of 6 rats, recapitulating fluorescent nanoparticles in the contralateral cochlear hair cells. Computational simulations demonstrate the contralateral spreading of particles by gravity force following intratympanic injection in a rat model. The diffusion rate of the contralateral spreading relies on the sizes and surface charges of particles. Collectively, the Eustachian tube could be a route for contralateral spreading following intratympanic injection. Caution should be taken when using the contralateral ear as a control study investigating inner-ear drug delivery through the transtympanic approach.

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Dexmedetomidine elevates the lethal dose threshold of bupivacaine in rats: A dosing study

Human & Experimental Toxicology ◽

10.1177/0960327119889658 ◽

2019 ◽

Vol 39 (3) ◽

pp. 365-373

Author(s):

L Pan ◽

Y Zhang ◽

Y He ◽

Z Chen ◽

S Wang ◽

...

Keyword(s):

Femoral Vein ◽

Lethal Dose ◽

Control Group ◽

Sprague Dawley ◽

Dose Threshold ◽

Sd Rats ◽

Group 12 ◽

Group 3 ◽

The Right ◽

Group 1

Dexmedetomidine (DMED), an alpha-2 adrenoreceptor agonist, has been widely used in regional anesthesia procedures. However, the effect of DMED on local anesthetic cardiotoxicity has not been well delineated. This study consisted of two experiments. In experiment A, 42 Sprague–Dawley (SD) rats were randomly divided into 6 groups ( n = 7), each group was pretreated with DMED 0 μg kg−1 (D0 group), 1 μg kg−1 (D1 group), 3 μg kg−1 (D3 group), 6 μg kg−1 (D6 group), 12 μg kg−1 (D12 group), and 24 μg kg−1 (D24 group), administered through the right femoral vein. In experiment B, 20 SD rats were randomly divided into 4 groups ( n = 5), such as control group, DMED group, yohimbine (YOH) group, and DMED + YOH group. Each subgroup in experiment B was also pretreated similarly as in experiment A. After pretreatment of rats as described above (in experiments A and B), bupivacaine 2.5 mg kg−1 min−1 was infused to induce cardiac arrest. In experiment A, the lethal dose threshold of bupivacaine and plasma bupivacaine concentration in D3 and D6 group were higher than the other groups. In experiment B, there was no interaction between DMED and YOH in lethal dose threshold, arrhythmia time, plasma concentration of bupivacaine, and myocardial content of bupivacaine. DMED doses of 3–6 μg kg−1 elevated the lethal dose threshold of bupivacaine without involvement of the alpha-2 adrenoceptors.

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The Effects of α-Viniferin on Adjuvant-Induced Arthritis in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x04002168 ◽

2004 ◽

Vol 32 (04) ◽

pp. 521-530 ◽

Cited By ~ 10

Author(s):

Jae Yeong Lee ◽

Joong-Hyun Kim ◽

Seong Soo Kang ◽

Chun Sik Bae ◽

Seok Hwa Choi

Keyword(s):

Initial Point ◽

Bone Destruction ◽

Physiological Saline ◽

Control Group ◽

Sprague Dawley ◽

Mineral Density ◽

Entire Study ◽

Adjuvant Induced Arthritis ◽

Radiological Changes ◽

The Right

This study was performed to assess the efficacy of α-viniferin (Carex humilis Leyss) on adjuvant-induced arthritis in rats. Adjuvant arthritis was induced by a single subcutaneous injection of 0.1 ml complete Freund's adjuvant (CFA) containing 7.5 mg Mycobacterium butyricum suspended in 1 ml sterile paraffin oil into the right hind paw. Forty female Sprague-Dawley rats were injected. Righting reflex was uniformly lost and considered to be the initial point of arthritis development on day 7 after CFA injection. Rats were divided into four groups, and upon development of arthritis, tested groups were orally administered 3 or 10 mg/kg α-viniferin or 10 mg/kg ketoprofen every day for 14 days. The control group was orally administered 2 ml of physiological saline solution. Bone mineral density (BMD), radiological changes and edematous volumes were measured for 35 days. α-viniferin suppressed the development of inflammatory edema, and inhibited the bone destruction, noted with a decrease in BMD ( p <0.05). Hind paw edema volume, BMD and radiological changes did not differ significantly in the ketoprofen and α-viniferin groups during the entire study period. In conclusion, α-viniferin suppressed arthritic inflammation and bony change in rats.

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Effect of Qingxin Kaiqiao Fang on Hippocampus mRNA Expression of the Inflammation-Related Genes IL-1β, GFAP, and Aβin an Alzheimer’s Disease Rat Model

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/9267653 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Dan-Dan Mao ◽

Wen-Yu Yang ◽

Yan Li ◽

Jian-Wei Lin ◽

Shi-Yu Gao ◽

...

Keyword(s):

Rat Model ◽

Particle Deposition ◽

Therapeutic Potential ◽

Interleukin 1 ◽

Control Group ◽

Model Group ◽

Sprague Dawley ◽

Amyloid A ◽

Sprague Dawley Rats ◽

High Doses

Objective. To investigate the effects of QKF on expression of amyloid-beta (Aβ), interleukin-1 beta (IL-1β), and glial fibrillary acidic protein (GFAP) using a rat model of AD.Materials and Methods. Fifty-six male Sprague-Dawley rats were randomly divided into seven groups (eight rats each): control group, sham-operated group, AD model group, groups of AD rats administered with low, medium, and high doses of QKF, and the donepezil group. AD was established by bilateral injection ofβ-amyloid (Aβ) 1–40 into the hippocampus. Two days after AD was established, drugs were administered by gavage. After 14 days of treatment, we used RT-PCR, Western blotting, and immunohistochemistry to measure the transcript expression and protein abundance of Aβ, IL-1β, and GFAP, and methenamine silver staining was used to detect amyloid protein particle deposition.Results. Compared to the control group, the rats from the AD model group showed significantly greater expression levels of Aβ, IL-1β, and GFAP. However, these differences in expression were abolished by treatment with QKF or donepezil.Conclusion. QKF possesses therapeutic potential against AD because it downregulated Aβ, IL-1β, and GFAP in the hippocampus of AD rats. Future studies should further examine the mechanisms through which QKF produces its effects and the consequences of long-term QKF administration.

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Comprehensive Analysis of the Profiles of Differentially Expressed mRNAs, lncRNAs, and circRNAs in Phosgene-Induced Acute Lung Injury

BioMed Research International ◽

10.1155/2021/6278526 ◽

2021 ◽

Vol 2021 ◽

pp. 1-22

Author(s):

Yiru Shao ◽

Zhifeng Jiang ◽

Daikun He ◽

Jie Shen

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Therapeutic Potential ◽

Expression Profiles ◽

Mirna Gene ◽

Differentially Expressed ◽

Control Group ◽

Group A ◽

Group B ◽

Air Control

Phosgene exposure can cause acute lung injury (ALI), for which there is no currently available effective treatment. Mesenchymal stem cells (MSCs) which have been proven to have therapeutic potential and be helpful in the treatment of various diseases, but the mechanisms underlying the function of MSCs against phosgene-induced ALI are still poorly explored. In this study, we compared the expression profiles of mRNAs, lncRNAs, and circRNAs in the lung tissues from rats of three groups—air control (group A), phosgene-exposed (group B), and phosgene + MSCs (group C). The results showed that 389 mRNAs, 198 lncRNAs, and 56 circRNAs were differently expressed between groups A and B; 130 mRNAs, 107 lncRNAs, and 35 circRNAs between groups A and C; and 41 mRNAs, 88 lncRNAs, and 18 circRNAs between groups B and C. GO and KEGG analyses indicated that the differentially expressed RNAs were mainly involved in signal transduction, immune system processes, and cancers. In addition, we used a database to predict target microRNAs (miRNAs) interacting with circRNAs and the R network software package to construct a circRNA-targeted miRNA gene network map. Our study showed new insights into changes in the RNA expression in ALI, contributing to explore the mechanisms underlying the therapeutic potential of MSCs in phosgene-induced ALI.

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The Effect of Hydro-Alcoholic Extract of Ocimum basilicum on CaCl2-Induced Cardiac Arrhythmias in Rats

Jentashapir Journal of Cellular and Molecular Biology ◽

10.5812/jjcmb.110309 ◽

2020 ◽

Vol In Press (In Press) ◽

Author(s):

Mohammad Kheradmandpour ◽

Seyed Abolfazl Aminifar ◽

Mahin Dianat

Keyword(s):

Cardiac Arrhythmias ◽

Therapeutic Potential ◽

Heart Rhythm ◽

Ocimum Basilicum ◽

Lifestyle Changes ◽

Male Rats ◽

Control Group ◽

Alcoholic Extract ◽

Sprague Dawley ◽

Tissue Samples

: Ocimum basilicum (OB) contains more than 30 plant species that are found in different regions, especially in Africa. OB contains various substances, especially Chavikol, Methyl Ether or Strangol, Linalool, and Agenol, which have antioxidant, antihypertensive, antidiabetic, and anti-lipid properties. On the other hand, along with lifestyle changes, the prevalence of cardiovascular diseases, such as arrhythmias, which cause high mortality, is increasing. Moreover, the modern drugs used for arrhythmia can also induce another type of abnormal heart rhythm. Regarding the effectiveness and fewer side effects of herbal medicine, we decided to study the preventive effects of hydro-alcoholic extract of OB on CaCl2-induced arrhythmias in rats. Male rats (Sprague-Dawley) were divided into the control group (2 weeks, normal saline, gavage) and three groups receiving different concentrations of hydro-alcoholic extract of OB (100, 200, and 400 mg/kg, gavage for 2 weeks). The arrhythmia model was established using CaCl2 (IV, 140 mg/kg). The number of ventricular fibrillation (VF), ventricular premature (PVC), and ventricular tachycardia (VT) were studied. Also, the oxidative stress parameters, such as malondialdehyde (MDA) and superoxide dismutase (SOD), were measured in heart tissue samples. Statistical analysis was done using Fisher's exact test and ANOVA, and also, P < 0.05 was considered as a significant level. The obtained results showed that administration of OB caused a decrease in MDA and an increase in SOD levels, which were associated with improved electrocardiogram parameters and reduced cardiac arrhythmias, which suggests the therapeutic potential of the plant in cardiovascular disorders.

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Abstract 2713: Functional Recovery Associated with Connectivity Changes in Contralesional Hemisphere after Severe Transient Stroke.

Stroke ◽

10.1161/str.43.suppl_1.a2713 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

WOO HYUN SHIM ◽

Bruce Rosen ◽

Jaeseung Jeong ◽

Young Kim

Keyword(s):

Functional Connectivity ◽

Functional Recovery ◽

Brain Connectivity ◽

Control Group ◽

Sprague Dawley ◽

Sensorimotor Deficit ◽

Stroke Models ◽

Time Courses ◽

The Right ◽

The Brain

Stroke impairs connections in the brain system, commonly resulting in significant sensorimotor deficits. Some degree of functional recovery typically occurs even after a severe stroke, yet changes in the brain connectivity that underlie such recovery are poorly understood. In this study, using rat stroke models, we monitored functional connectivity when the sensorimotor deficit recovered after a severe ischemic stroke (defined DWI by more than 15% of the entire brain volume). We used seven Sprague-Dawley rats (∼350g), which showed nearly full recovery of both motor and sensory functions approximately 180 days after 90 min occlusion of the right middle cerebral artery. Six healthy age controlled rats were used for the control group. BOLD MRI time courses during rest (10min, TR=1s, 9 slices) were collected. Both the seed-voxel analysis and the ROI-based analysis were performed, in which seed voxels were selected in the left S1FL, and multiple ROIs were placed over the somatosensory regions. Stroke rats showed the markedly decreased functional connectivity in the ipsilesional side (right) for both voxelwise and ROI-based methods. Interestingly, in contralesional (non-stroke) side (left), the voxelwise connectivity spatially expanded into the entire cortical area. The cross-correlation coefficient values between ROI’s slightly increased in the contralesional hemisphere compared to the control rats. In conclusion, we demonstrated that the restoration of sensorimotor function is associated more with the increase and spatial expansion of functional connectivity within the contralesional than the ipsilesional hemisphere.

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Adipose tissue-derived mesenchymal stem cells ameliorate experimental acute colitis in rats

10.21203/rs.3.rs-1036129/v1 ◽

2021 ◽

Author(s):

Seyed Jalil Masoumi ◽

Negar Hassanshahi ◽

Seyed-Mohammad Kazem Hosseini-Asl ◽

Davood Mehrabani ◽

Seyedeh-Sara Hashemi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Therapeutic Potential ◽

Adipogenic Differentiation ◽

Control Group ◽

Sprague Dawley ◽

Acute Colitis ◽

Complete Treatment ◽

Anti Inflammatory

Abstract Complete treatment of ulcerative colitis (UC) is still difficult, while conventional therapies have various adverse effects. Mesenchymal stem cells (MSCs) have anti-inflammatory and immunomodulatory properties to be a therapeutic candidate for UC. We evaluated therapeutic potential of adipose tissue-derived mesenchymal stem cells (AdSCs) in treatment of an acute colitis rat model using histological and molecular assessments. Thirty male Sprague Dawley acetic acid-induced (2 mL of 3%) acute colitis rat models were randomly divided into three equal groups of control receiving 0.5 mL/kg of normal saline, sulfasalazine group receiving 500 mg/kg sulfasalazine and AdSCs group transplanted transrectally with 2×106 MSCs. They were evaluated histologically and by real time PCR for expression of apoptotic genes until 21 days. MSCs were spindle shape and positive for osteogenic and adipogenic differentiation. They displayed mesenchymal and lacked hematopoietic markers. In control group, severe inflammation, edema, ulcer, necrosis and infiltration of leukocytes were noticed. In sulfasalazine group, a moderate inflammation, edema, ulcer, necrosis and infiltration of leukocytes were visible; and in AdSCs group, mild inflammation, congestion, and infiltration of leukocytes were observed with a mild edema, but necrosis was absent in colonic tissue. A stronger decrease in expression of Bax, together with a higher increase in Bcl-2 was noted in AdSCs group. Based on histological and molecular findings, AdSCs were effective to ameliorate colitis lesions through their anti-inflammatory and anti-apoptotic activities showing that transplantation of AdSCS can be a potentially useful strategy in treatment of colitis.

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