scholarly journals Differences between infected and noninfected synovial fluid

2021 ◽  
Vol 10 (1) ◽  
pp. 85-95
Author(s):  
Pouya Akhbari ◽  
Matthew K. Jaggard ◽  
Claire L. Boulangé ◽  
Uddhav Vaghela ◽  
Gonçalo Graça ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Synovial Fluid ◽  
Small Molecule ◽  
Principal Component ◽  
Joint Infections ◽  
Prosthetic Joints ◽  
Markers Of Inflammation ◽  
Nucleoside Metabolism ◽  
Diseased State ◽  
End Stage

Aims The diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF. Methods In all, 16 SF samples (eight infected native and prosthetic joints plus eight noninfected joints requiring arthroplasty for end-stage osteoarthritis) were collected from patients. NMR spectroscopy was used to analyze the metabolites present in each sample. Principal component analysis and univariate statistical analysis were undertaken to investigate metabolic differences between the two groups. Results A total of 16 metabolites were found in significantly different concentrations between the groups. Three were in higher relative concentrations (lipids, cholesterol, and N-acetylated molecules) and 13 in lower relative concentrations in the infected group (citrate, glycine, glycosaminoglycans, creatinine, histidine, lysine, formate, glucose, proline, valine, dimethylsulfone, mannose, and glutamine). Conclusion Metabolites found in significantly greater concentrations in the infected cohort are markers of inflammation and infection. They play a role in lipid metabolism and the inflammatory response. Those found in significantly reduced concentrations were involved in carbohydrate metabolism, nucleoside metabolism, the glutamate metabolic pathway, increased oxidative stress in the diseased state, and reduced articular cartilage breakdown. This is the first study to demonstrate differences in the metabolic profile of infected and noninfected human SF, using a noninfected matched cohort, and may represent putative biomarkers that form the basis of new diagnostic tests for infected SF. Cite this article: Bone Joint Res 2021;10(1):85–95.

Implementing one-shot multiple-FID acquisition into homonuclear and heteronuclear NMR experiments

2018 ◽  
Vol 54 (96) ◽  
pp. 13507-13510 ◽  
Author(s):  
Kumar Motiram-Corral ◽  
Míriam Pérez-Trujillo ◽  
Pau Nolis ◽  
Teodor Parella
Keyword(s):  
Nmr Spectroscopy ◽  
Small Molecule ◽  
Efficient Solution ◽  
Heteronuclear Nmr ◽  
Pulse Sequences

The concept of multiple-FID acquisition (MFA) within the same scan is applied to acquire simultaneously multiple 2D spectra from a single NMR experiment. A discussion on the incorporation of the MFA strategy in homonuclear and heteronuclear pulse sequences is presented. Several novel COSY- and HMBC-type experiments are reported as a time-efficient solution in small-molecule NMR spectroscopy.

scholarly journals Bone and Joint Tissue Penetration of the Staphylococcus-Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery

2018 ◽  
Vol 63 (3) ◽  
Author(s):  
Annick Menetrey ◽  
Annick Janin ◽  
John Pullman ◽  
J. Scott Overcash ◽  
Amina Haouala ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Soft Tissue ◽  
Synovial Fluid ◽  
Hip Replacement ◽  
Clinical Development ◽  
Efficacy Data ◽  
Content Type ◽  
Replacement Surgery ◽  
Hip Replacement Surgery ◽  
Joint Infections

ABSTRACT Afabicin (formerly Debio 1450, AFN-1720) is a prodrug of afabicin desphosphono (Debio 1452, AFN-1252), a novel antibiotic in development which targets the staphylococcal enoyl-acyl carrier protein reductase (FabI) and exhibits selective potent antibacterial activity against staphylococcal species, including methicillin-resistant Staphylococcus aureus. As part of clinical development in bone and joint infections, a distribution study in bone was performed in 17 patients who underwent elective hip replacement surgery. Patients received 3 doses of 240 mg afabicin orally (every 12 h) at various time points before surgery. Afabicin desphosphono concentrations were measured by liquid chromatography-tandem mass spectrometry in plasma, cortical bone, cancellous bone, bone marrow, soft tissue, and synovial fluid collected during surgery at 2, 4, 6, or 12 h after the third afabicin dose. The study showed good penetration of afabicin desphosphono into bone tissues, with mean area under the curve ratios for cortical bone-, cancellous bone-, bone marrow-, soft tissue-, and synovial fluid-to-total plasma concentrations of 0.21, 0.40, 0.32, 0.35, and 0.61, respectively. When accounting for the free fraction in plasma (2%) and synovial fluid (9.4%), the mean ratio was 2.88, which is indicative of excellent penetration and which showed that the afabicin desphosphono concentration was beyond the MIC90 of S. aureus over the complete dosing interval. These findings, along with preclinical efficacy data, clinical efficacy data for skin and soft tissue staphylococcal infection, the availability of both intravenous and oral formulations, and potential advantages over broad-spectrum antibiotics for the treatment of staphylococcal bone or joint infections, support the clinical development of afabicin for bone and joint infections. (This study has been registered at ClinicalTrials.gov under identifier NCT02726438.)

scholarly journals Applicability of Small-Molecule Inhibitors in the Study of Peptidyl Arginine Deiminase 2 (PAD2) and PAD4

2021 ◽  
Vol 12 ◽  
Author(s):  
María Teresa Martín Monreal ◽  
Alexandra Stripp Rebak ◽  
Laura Massarenti ◽  
Santanu Mondal ◽  
Ladislav Šenolt ◽  
...  
Keyword(s):  
T Cells ◽  
Synovial Fluid ◽  
Small Molecule ◽  
Therapeutic Potential ◽  
Specific Inhibitor ◽  
Arginine Deiminase ◽  
Self Tolerance ◽  
Inhibition Of Pad ◽  
Pad Inhibitor ◽  
Dying Cells

Citrullination, the conversion of peptidyl-arginine into peptidyl-citrulline, is involved in the breakage of self-tolerance in anti-CCP-positive rheumatoid arthritis. This reaction is catalyzed by peptidyl arginine deiminases (PADs), of which PAD2 and PAD4 are thought to play key pathogenic roles. Small-molecule PAD inhibitors such as the pan-PAD inhibitor BB-Cl-amidine, the PAD2-specific inhibitor AFM-30a, and the PAD4-specific inhibitor GSK199 hold therapeutic potential and are useful tools in studies of citrullination. Using an ELISA based on the citrullination of fibrinogen, we found that AFM-30a inhibited the catalytic activity of PADs derived from live PMNs or lysed PBMCs and PMNs and of PADs in cell-free synovial fluid samples from RA patients, while GSK199 had minor effects. In combination, AFM-30a and GSK199 inhibited total intracellular citrullination and citrullination of histone H3 in PBMCs, as determined by Western blotting. They were essentially nontoxic to CD4+ T cells, CD8+ T cells, B cells, NK cells, and monocytes at concentrations ranging from 1 to 20 μM, while BB-Cl-amidine was cytotoxic at concentrations above 1 μM, as assessed by flow cytometric viability staining and by measurement of lactate dehydrogenase released from dying cells. In conclusion, AFM-30a is an efficient inhibitor of PAD2 derived from PBMCs, PMNs, or synovial fluid. AFM-30a and GSK199 can be used in combination for inhibition of PAD activity associated with PBMCs but without the cytotoxic effect of BB-Cl-amidine. This suggests that AFM-30a and GSK199 may have fewer off-target effects than BB-Cl-amidine and therefore hold greater therapeutic potential.

scholarly journals Prosthetic joint infection by Bordetella holmesii: Case report and a review of the literature

2020 ◽  
Vol 43 (11) ◽  
pp. 748-750
Author(s):  
Mariana Fernandez-Pittol ◽  
Jordi Bosch ◽  
Laura Morata ◽  
Luis Lozano ◽  
Juan Carlos Martínez Pastor ◽  
...  
Keyword(s):  
Case Report ◽  
Synovial Fluid ◽  
Antibiotic Treatment ◽  
Knee Prosthesis ◽  
Case Reports ◽  
Joint Effusion ◽  
Rrna Gene ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

Introduction: Bordetella holmesii is a Gram-negative coccobacillus involved in different infections mostly described in case reports. Prosthetic joint infections in relation to this pathogen are rare. Here, we present the third case of B. holmesii in a patient without anatomical or functional spleen dysfunction. Case report: The patient was a 62-year-old female with a total knee prosthesis implanted in 1997 that required multiple replacements of the femoral component due to aseptic loosening in the past years. The patient was admitted to our hospital for an elective replacement surgery due to new radiological signs of loosening. B. holmesii was isolated from synovial fluid obtained during surgery. The identification was performed by matrix-assisted laser desorption ionization–time of flight mass spectrometry and confirmed by 16S rRNA gene amplification and sequencing. Antibiotic treatment was started but 14 days after surgery the patient presented pain and joint effusion. An arthrocentesis was performed and synovial fluid culture was positive again for B. holmesii. Surgical debridement including polyethylene replacement was performed and antibiotic treatment was continued for 3 months. After a 2-year follow-up period, the patient remained asymptomatic and physical examination showed normal function of the prosthesis. Conclusion: B. holmesii is an uncommon cause of bone and joint infections. This case indicates that this microorganism is a potential pathogen of prosthetic or native arthritis, and it should be considered when cultures are negative and in cases presenting torpid evolution.

scholarly journals A Preliminary Study of Combined Detection of COMP, TIMP-1, and MMP-3 in Synovial Fluid: Potential Indicators of Osteoarthritis Progression

Cartilage ◽  
2020 ◽  
pp. 194760352094638
Author(s):  
Jana Plsikova Matejova ◽  
Timea Spakova ◽  
Denisa Harvanova ◽  
Marek Lacko ◽  
Vladimir Filip ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Matrix Protein ◽  
Weight Bearing ◽  
Knee Oa ◽  
Significant Linear Correlation ◽  
Starting Point ◽  
Osteoarthritis Progression ◽  
Grading Scale ◽  
Severity Of The Disease ◽  
End Stage

Objective Osteoarthritis (OA) commonly affects weight-bearing joints and is characterized by articular cartilage breakdown combined with osteophyte formation at the joint margins and chronic nonspecific inflammation of synovium. Understanding the profile of inflammation in a patient population is an essential starting point to predict or prevent OA progression. The aim of this study was to identify the profile of selected biomolecules in synovial fluid (SF) and investigate the correlation according to gender, age, and severity of the disease within patients from among the general knee OA population. Design In our study SF samples were aspirated from the knees of 65 OA patients (46 patients with early knee OA and 19 patients with end-stage knee OA according to the Kellgren-Lawrence grading scale). The concentration of interleukins (IL-6, IL-8), matrix metalloproteinases (MMP-1, MMP-3, MMP-13), MMPs inhibitors (TIMP-1, TIMP-2), cartilage oligomeric matrix protein (COMP), and adiponectin was analyzed using a multiplex ELISA-based approach. Conclusions Our results indicate significant linear correlation of MMP-13 and COMP concentration with age ( P < 0.05), but not with OA severity. In fact, 3 of the examined biomolecules, MMP-3 ( P < 0.01), TIMP-1 ( P < 0.01), and COMP ( P < 0.05) significantly correlate with the grade of knee OA and might be associated with OA severity.

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