scholarly journals Preventing Friction-induced Chondrocyte Apoptosis: Comparison of Human Synovial Fluid and Hylan G-F 20

2012 ◽  
Vol 39 (7) ◽  
pp. 1473-1480 ◽  
Author(s):  
KIMBERLY A. WALLER ◽  
LING X. ZHANG ◽  
BRADEN C. FLEMING ◽  
GREGORY D. JAY
Keyword(s):  
Synovial Fluid ◽  
Caspase 3 ◽  
Treatment Options ◽  
Chondrocyte Apoptosis ◽  
Friction Testing ◽  
Joint Lubrication ◽  
Number Of Patients ◽  
Phosphate Buffered Saline ◽  
Human Synovial Fluid

Objective.Symptomatic osteoarthritis (OA) is a common painful disease with limited treatment options. A rising number of patients with OA have been treated with intraarticular injections of hyaluronic acid, including the high-molecular-weight hylan G-F 20, which is injected following arthrocentesis. We investigated the effectiveness of hylan G-F 20 to lower coefficient of friction (COF) and prevent chondrocyte apoptosis in vitro.Methods.A disc-on-disc bovine cartilage bearing was used to measure the static and kinetic COF when lubricated with hylan G-F 20, human synovial fluid (HSF), and phosphate buffered saline (PBS). Following friction testing, we stained paraffin-embedded sections of these cartilage bearings for activated caspase-3, a marker of apoptosis.Results.Bearings lubricated with hylan G-F 20 had kinetic COF values that were similar to bearings lubricated with PBS, but significantly higher than those lubricated with HSF. There were no significant differences in static COF values in bearings lubricated with hylan G-F 20 as compared to PBS or HSF. However, bearings lubricated with HSF had significantly lower static COF values compared to bearings lubricated with PBS. The mean percentage of caspase-3-positive chondrocytes in the superficial and upper intermediate zones of bearings lubricated with hylan G-F 20 was significantly higher compared to that of bearings lubricated with HSF or unloaded controls, but significantly lower than in those lubricated with PBS.Conclusion.These findings indicate that joint lubrication may prevent chondrocyte apoptosis by lowering the COF. Further, removal of synovial fluid prior to hylan G-F 20 injection may be detrimental to cartilage health.

scholarly journals miR-146a-5p Promotes Chondrocyte Apoptosis and Inhibits Autophagy of Osteoarthritis by Targeting NUMB

Cartilage ◽  
2021 ◽  
pp. 194760352110235
Author(s):  
Hongjun Zhang ◽  
Wendi Zheng ◽  
Du Li ◽  
Jia Zheng
Keyword(s):  
Caspase 3 ◽  
Cartilage Tissue ◽  
Luciferase Reporter ◽  
Chondrocyte Apoptosis ◽  
Knee Cartilage ◽  
Before And After ◽  
Related Proteins ◽  
Human And Mouse

Objective miR-146a-5p was found to be significantly upregulated in cartilage tissue of patients with osteoarthritis (OA). NUMB was shown to be involved in the autophagy regulation process of cells. We aimed to learn whether NUMB was involved in the apoptosis or autophagy process of chondrocytes in OA and related with miR-146a-5p. Methods QRT-PCR was used to detect miR-146a-5p level in 22 OA cartilage tissues and 22 controls. The targets of miR-146a-5p were analyzed using software and the luciferase reporter experiment. The apoptosis and autophagy, and related proteins were detected in chondrocytes treated with miR-146a-5p mimic/inhibitor or pcDNA3.1-NUMB/si-NUMB and IL-1β, respectively. In vivo experiment, intra-articular injection of miR-146a-5p antagomir/NC was administered at the knee of OA male mice before and after model construction. Chondrocyte apoptosis and the expression of apoptosis and autophagy-related proteins were also detected. Results miR-146a-5p was highly expressed in knee cartilage tissue of patients with OA, while NUMB was lowly expressed and negatively regulated by miR-146a-5p. Upregulation of miR-146a-5p can promote cell apoptosis and reduce autophagy of human and mouse chondrocytes by modulating the levels of cleaved caspase-3, cleaved PARP, Bax, Beclin 1, ATG5, p62, LC3-I, and LC3-II. Increasing the low level of NUMB reversed the effects of miR-146a-5p on chondrocyte apoptosis and autophagy. Intra-articular injection of miR-146a-5p antagomir can also reverse the effects of miR-146a-5p on the apoptosis and autophagy of knee joint chondrocytes in OA mice. Conclusion Downregulation of miR-146a-5p suppresses the apoptosis and promotes autophagy of chondrocytes by targeting NUMB in vivo and in vitro.

scholarly journals Dermal delivery of amitriptyline for topical analgesia

2021 ◽  
Author(s):  
Chin-Ping Kung ◽  
Bruno C. Sil ◽  
Yanling Zhang ◽  
Jonathan Hadgraft ◽  
Majella E. Lane ◽  
...  
Keyword(s):  
Treatment Options ◽  
Isopropyl Myristate ◽  
Promising Candidate ◽  
In Vitro Permeation ◽  
Base Form ◽  
Dermal Delivery ◽  
Phosphate Buffered Saline ◽  
Topical Analgesia ◽  
Topical Analgesic

Abstract Amitriptyline, administered orally, is currently one of the treatment options for the management of neuropathic pain and migraine. Because of the physicochemical properties of the molecule, amitriptyline is also a promising candidate for delivery as a topical analgesic. Here we report the dermal delivery of amitriptyline from a range of simple formulations. The first stage of the work required the conversion of amitriptyline hydrochloride to the free base form as confirmed by nuclear magnetic resonance (NMR). Distribution coefficient values were measured at pH 6, 6.5, 7, and 7.4. Solubility and stability of amitriptyline were assessed prior to conducting in vitro permeation and mass balance studies. The compound demonstrated instability in phosphate-buffered saline (PBS) dependent on pH. Volatile formulations comprising of isopropyl alcohol (IPA) and isopropyl myristate (IPM) or propylene glycol (PG) were evaluated in porcine skin under finite dose conditions. Compared with neat IPM, the IPM:IPA vehicles promoted 8-fold and 5-fold increases in the amount of amitriptyline that permeated at 24 h. Formulations containing PG also appear to be promising vehicles for dermal delivery of amitriptyline, typically delivering higher amounts of amitriptyline than the IPM:IPA vehicles. The results reported here suggest that further optimization of topical amitriptyline formulations should be pursued towards development of a product for clinical investigational studies. Graphical abstract

scholarly journals Effect of human synovial fluid in models of in vitro chondrogenic re-differentiation of human primary chondrocytes

2016 ◽  
Vol 24 ◽  
pp. S166
Author(s):  
C. Galeano-Garces ◽  
S.M. Riester ◽  
E.T. Camilleri ◽  
H.S. Ryan ◽  
J. Smith ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Primary Chondrocytes ◽  
Human Primary Chondrocytes ◽  
Human Synovial Fluid

scholarly journals Autophagy and salivary gland cancer: A putative target for salivary gland tumors

Tumor Biology ◽  
2020 ◽  
Vol 42 (12) ◽  
pp. 101042832098056
Author(s):  
Evangelos Koustas ◽  
Panagiotis Sarantis ◽  
Margarita Theodorakidou ◽  
Michalis V Karamouzis ◽  
Stamatios Theocharis
Keyword(s):  
Salivary Gland ◽  
Current Knowledge ◽  
Treatment Options ◽  
Treatment Strategies ◽  
In Vivo Studies ◽  
Salivary Gland Cancer ◽  
Number Of Patients ◽  
Salivary Gland Carcinomas

Salivary gland carcinomas are a group of heterogeneous tumors of different histological subtypes, presenting relatively low incidence but the entire variable of types. Although novel treatment options for salivary gland carcinomas patients’ outcomes have improved, the treatment of this type of cancer is still not standardized. In addition, a significant number of patients, with a lack of optimal treatment strategies, have reduced survival. In the last two decades, a plethora of evidence pointed to the importance of autophagy, an essential catabolic process of cytoplasmatic component digestion, in cancer. In vitro and in vivo studies highlight the importance of autophagy in salivary gland carcinomas development as a tumor suppressor or promoter mechanism. Despite the potential of autophagy in salivary gland carcinomas development, no therapies are currently available that specifically focus on autophagy modulation in salivary gland carcinomas. In this review, we summarize current knowledge and clinical trials in regard to the interplay between autophagy and the development of salivary gland carcinomas. Autophagy manipulation may be a putative therapeutic strategy for salivary gland carcinomas patients.

scholarly journals Chondrocyte apoptosis induced in vitro is caspase-3-mediated, but is not demonstrated in cartilage from patients with rheumatoid arthritis or osteoarthritis

2003 ◽  
Vol 111 (2) ◽  
pp. S321
Author(s):  
J.F. Van Offel ◽  
I.C. Koster ◽  
G.J. Van Elsen ◽  
A.J. Schuerwegh ◽  
C.H. Bridts ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Caspase 3 ◽  
Chondrocyte Apoptosis

scholarly journals Upregulation of P2Y12 Inhibits Chondrocyte Apoptosis in Lumbar Osteoarthritis Through PI3K/AKT Signaling Pathway

2021 ◽  
Author(s):  
Guanyin Wu ◽  
Pengfei Xue ◽  
Mo Zhang ◽  
Chao Gui ◽  
Guofeng Bao ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Gene Knockout ◽  
Cartilage Degeneration ◽  
Underlying Mechanism ◽  
Chondrocyte Apoptosis ◽  
Low Back ◽  
Role Changes ◽  
Apoptotic Effect ◽  
Lumbar Facet

Abstract Lumbar facet osteoarthritis (FJOA) is one of the major causes of severe low back pain and disability worldwide. However, the underlying mechanism of cartilage degeneration in FJOA remains unclear. The purpose of this study was to investigate the expression of P2Y12 in FJOA and its possible role. Changes of chondrocytes in rat facet joints with degenerative changes were observed by HE and ferro red solid green staining. The expression changes of P2Y12, MMP13 and COL2 in FJOA were observed by immunohistochemistry. In vitro, human SW1353 chondrosarcoma cells were stimulated with IL-β to establish chondrocyte apoptosis model. Western blot analysis showed that P2Y12 and cleaved caspase-3 were significantly expressed in SW1353 cells. Co-localization of P2Y12-cleaved Caspase-3 in apoptosis model was detected by double-standard immunofluorescence staining. We demonstrated that P2Y12 may have an anti-apoptotic effect in FJOA chondrocytes apoptosis by inhibiting the expression of P2Y12 by siRNA. In addition, flow cytometry showed that P2Y12 gene knockout enhanced apoptosis induced by P2Y12. Our data suggest that P2Y12 has a chondroprotective effect on FJOA.

Opening New Horizons in the Treatment of Childhood Onset Leukodystrophies

2019 ◽  
Vol 50 (04) ◽  
pp. 211-218 ◽  
Author(s):  
Stina Schiller ◽  
Marco Henneke ◽  
Jutta Gärtner
Keyword(s):  
Early Stage ◽  
Treatment Options ◽  
Clinical Signs ◽  
Disease Genes ◽  
Lysosomal Storage ◽  
Peroxisomal Disorders ◽  
Enzyme Replacement ◽  
Number Of Patients

AbstractLeukodystrophies (LDs) predominantly affect the white matter of the central nervous system and its main component, the myelin. The majority of LDs manifests in infancy with progressive neurodegeneration. Main clinical signs are intellectual and motor function losses of already attained developmental skills. Classical LDs include lysosomal storage disorders like metachromatic leukodystrophy (MLD), peroxisomal disorders like X-linked adrenoleukodystrophy (X-ALD), disorders of mitochondrial dysfunction, and myelin protein defects like Pelizaeus-Merzbacher disease. So far, there are only single LD disorders with effective treatment options in an early stage of disease. The increasing number of patients diagnosed with LDs emphasizes the need for novel therapeutic options. Impressive advances in biotechnology have not only led to the continuous identification of new disease genes for so far unknown LDs but also led to new effective neuroprotective and disease-modifying therapeutic approaches. This review summarizes ongoing and novel innovative treatment options for LD patients and their challenges. It includes in vitro and in vivo approaches with focus on stem cell and gene therapies, intrathecal substrate or enzyme replacement, and genome editing.

scholarly journals Influence of Nutrient Media Compared to Human Synovial Fluid on the Antibiotic Susceptibility and Biofilm Gene Expression of Coagulase-Negative Staphylococci In Vitro

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 790
Author(s):  
Stephan Josef Maria Steixner ◽  
Christopher Spiegel ◽  
Dietmar Dammerer ◽  
Alexander Wurm ◽  
Michael Nogler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Synovial Fluid ◽  
Antibiotic Susceptibility ◽  
Coagulase Negative Staphylococci ◽  
Nutrient Media ◽  
Rich Media ◽  
Significant Difference ◽  
Susceptibility Tests ◽  
Human Synovial Fluid

Bacterial antibiotic resistance and biofilm formation are mechanisms usually involved in the pathogeny of implant-related infections. Worldwide, antibiotic susceptibility tests are usually carried out using nutrient-rich media. Clinical routine laboratories and even research centers use for example EUCAST or CLSI for guidelines. In this study, we investigated the effect of different nutrient media on the antibiotic susceptibility and icaADBC gene expression of bacteria in biofilm. As media, Müller-Hinton Bouillon (MHB), Tryptic Soy Broth (TSB) and human synovial fluid (SF) diluted 1:4 in phosphate buffered saline (PBS), each also supplemented with 1% glucose, were used. The influence of different nutrient media on the antibiotic susceptibility of coagulase-negative staphylococci (CoNS) was evaluated by counting of colony-forming units (CFU) and by checking the metabolic activity of the bacteria. We used reverse transcriptase and real-time qPCR to investigate the influence of nutrient media on the biofilm gene expression. We used two-way analysis of variance (ANOVA). p < 0.05 was considered to be statistically significant. Significant differences in growth and antibiotic susceptibility were detected in all strains tested among the different media used. The nutrient media showed influence on the cell viability of all bacteria after antibiotic treatment. IcaADBC gene expression was significantly influenced by glucose and all nutrient media. The results highlight the influence of glucose on the antibiotic susceptibility, growth and gene expression of all strains tested. For all strains, a significant difference in bacterial recovery, viability and gene expression were found when compared to biofilm grown in SF.

Rhenium-188 Labeled Hydroxyapatite and Rhenium-188 Sulfur Colloid

1997 ◽  
Vol 36 (02) ◽  
pp. 71-75 ◽  
Author(s):  
S. Glatz ◽  
S. N. Reske ◽  
K. G. Grillenberger
Keyword(s):  
Synovial Fluid ◽  
Ph Value ◽  
Surgical Removal ◽  
Radiation Synovectomy ◽  
Sulfur Colloid ◽  
Target Organs ◽  
Aseptic Conditions ◽  
In Vitro Stability ◽  
Potential Use

Summary Aim: One therapeutic approach to rheumatoid arthritis and other inflammatory arthropathies besides surgical removal of inflamed synovium is radiation synovectomy using beta-emitting radionuclides to destroy the affected synovial tissue. Up to now the major problem associated with the use of labeled particles or colloids has been considerable leakage of radionuclides from the injected joint coupled with high radiation doses to liver and other non target organs. In this study we compared 188Re labeled hydroxyapatite particles and 188Re rhenium sulfur colloid for their potential use in radiation synovectomy. Methods: To this end we varied the labeling conditions (concentrations, pH-value, heating procedure) and analyzed the labeling yield, radiochemical purity, and in vitro stability of the resulting radiopharmaceutical. Results: After optimizing labeling conditions we achieved a labeling yield of more than 80% for 188Re hydroxyapatite and more than 90% for the rhenium sulfur colloid. Both of the radiopharmaceuticals can be prepared under aseptic conditions using an autoclav for heating without loss of activity. In vitro stability studies using various challenge solutions (water, normal saline, diluted synovial fluid) showed that 188Re labeled hydroxyapatite particles lost about 80% of their activity within 5 d in synovial fluid. Rhenium sulfur colloid on the other hand proved to be very stable with a remaining activity of more than 93% after 5 d in diluted synovial fluid. Conclusion: These in vitro results suggest that 188Re labeled rhenium sulfur colloid expects to be more suitable for therapeutic use in radiation synovectomy than the labeled hydroxyapatite particles.

Treatment Options in COVID-19: The Role of Bioavailable Antiviral Ribonucleoside Analog on NHC in vitro

2020 ◽  
Author(s):  
Lara Bittmann
Keyword(s):  
World Health Organization ◽  
Clinical Picture ◽  
Treatment Options ◽  
World Health ◽  
Wuhan City ◽  
The World ◽  
Novel Coronavirus ◽  
Health Organization

On December 31, 2019, WHO was informed of cases of pneumonia of unknown cause in Wuhan City, China. A novel coronavirus was identified as the cause by Chinese authorities on January 7, 2020 and was provisionally named "2019-nCoV". This new Coronavirus causes a clinical picture which has received now the name COVID-19. The virus has spread subsequently worldwide and was explained on the 11th of March, 2020 by the World Health Organization to the pandemic.

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