1. |
- Chen, Y-B, et al.
(author)
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GvHD after umbilical cord blood transplantation for acute leukemia : an analysis of risk factors and effect on outcomes
- 2017
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In: Bone Marrow Transplantation. - : NATURE PUBLISHING GROUP. - 0268-3369 .- 1476-5365. ; 52:3, s. 400-408
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Journal article (peer-reviewed)abstract
- Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (>= 18 years) = 810, double (< 18 years) = 594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.
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2. |
- Tay, J., et al.
(author)
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Pre-transplant marital status and hematopoietic cell transplantation outcomes
- 2020
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In: Current Oncology. - : MULTIMED INC. - 1198-0052 .- 1718-7729. ; 27:6, s. E596-E606
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Journal article (peer-reviewed)abstract
- Background Evidence about the impact of marital status before hematopoietic cell transplantation (HCT) on outcomes after HCT is conflicting. Methods We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent HCT between January 2008 and December 2015. Marital status before HCT was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after HCT. Results We identified 10,226 allogeneic and 5714 autologous HCT cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (GVHD), p < 0.001, and chronic GVHD, p = 0.04. The risk of grades 2-4 acute GVHD was increased in separated compared with married patients [hazard ratio (FIR): 1.13; 95% confidence interval (CI): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute GVHD (FIR: 0.87; 95% CI: 0.77 to 0.98). The risk of chronic GVHD was lower in widowed compared with married patients (FIR: 0.82; 95% CI: 0.67 to 0.99). Conclusions Overall survival after HCT is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic GVHD. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.
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4. |
- Giesers, B., et al.
(author)
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A stellar census in globular clusters with MUSE: Binaries in NGC 3201
- 2019
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In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 632
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Journal article (peer-reviewed)abstract
- We utilise multi-epoch MUSE spectroscopy to study binary stars in the core of the Galactic globular cluster NGC 3201. Our sample consists of 3553 stars with 54 883 spectra in total comprising 3200 main-sequence stars up to 4 magnitudes below the turn-off. Each star in our sample has between 3 and 63 (with a median of 14) reliable radial velocity measurements within five years of observations. We introduce a statistical method to determine the probability of a star showing radial velocity variations based on the whole inhomogeneous radial velocity sample. Using HST photometry and an advanced dynamical MOCCA simulation of this specific cluster we overcome observational biases that previous spectroscopic studies had to deal with. This allows us to infer a binary frequency in the MUSE field of view and enables us to deduce the underlying true binary frequency of (6.75 ± 0.72)% in NGC 3201. The comparison of the MUSE observations with the MOCCA simulation suggests a large portion of primordial binaries. We can also confirm a radial increase in the binary fraction towards the cluster centre due to mass segregation. We discovered that in the core of NGC 3201 at least (57.5 ± 7.9)% of blue straggler stars are in a binary system. For the first time in a study of globular clusters, we were able to fit Keplerian orbits to a significant sample of 95 binaries. We present the binary system properties of eleven blue straggler stars and the connection to SX Phoenicis-type stars. We show evidence that two blue straggler formation scenarios, the mass transfer in binary (or triple) star systems and the coalescence due to binary-binary interactions, are present in our data. We also describe the binary and spectroscopic properties of four sub-subgiant (or red straggler) stars. Furthermore, we discovered two new black hole candidates with minimum masses (M sin i) of (7.68 ± 0.50) M⊙, (4.4 ± 2.8) M⊙, and refine the minimum mass estimate on the already published black hole to (4.53 ± 0.21) M⊙. These black holes are consistent with an extensive black hole subsystem hosted by NGC 3201.
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6. |
- Sarajlić, M., et al.
(author)
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Germanium "hexa" detector : Production and testing
- 2017
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In: Journal of Instrumentation. - 1748-0221. ; 12:1
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Journal article (peer-reviewed)abstract
- Here we present new result on the testing of a Germanium sensor for X-ray radiation. The system is made of 3 × 2 Medipix3RX chips, bump-bonded to a monolithic sensor, and is called "hexa". Its dimensions are 45 × 30 mm2 and the sensor thickness was 1.5 mm. The total number of the pixels is 393216 in the matrix 768 × 512 with pixel pitch 55 μ m. Medipix3RX read-out chip provides photon counting read-out with single photon sensitivity. The sensor is cooled to -126°C and noise levels together with flat field response are measured. For -200 V polarization bias, leakage current was 4.4 mA (3.2 μ A/mm2). Due to higher leakage around 2.5% of all pixels stay non-responsive. More than 99% of all pixels are bump bonded correctly. In this paper we present the experimental set-up, threshold equalization procedure, image acquisition and the technique for bump bond quality estimate.
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7. |
- Belczynski, K., et al.
(author)
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Evolutionary roads leading to low effective spins, high black hole masses, and O1/O2 rates for LIGO/Virgo binary black holes
- 2020
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 636:A&A
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Journal article (peer-reviewed)abstract
- All ten LIGO/Virgo binary black hole (BH-BH) coalescences reported following the O1/O2 runs have near-zero effective spins. There are only three potential explanations for this. If the BH spin magnitudes are large, then: (i) either both BH spin vectors must be nearly in the orbital plane or (ii) the spin angular momenta of the BHs must be oppositely directed and similar in magnitude. Then there is also the possibility that (iii) the BH spin magnitudes are small. We consider the third hypothesis within the framework of the classical isolated binary evolution scenario of the BH-BH merger formation. We test three models of angular momentum transport in massive stars: A mildly efficient transport by meridional currents (as employed in the Geneva code), an efficient transport by the Tayler-Spruit magnetic dynamo (as implemented in the MESA code), and a very-efficient transport (as proposed by Fuller et al.) to calculate natal BH spins. We allow for binary evolution to increase the BH spins through accretion and account for the potential spin-up of stars through tidal interactions. Additionally, we update the calculations of the stellar-origin BH masses, including revisions to the history of star formation and to the chemical evolution across cosmic time. We find that we can simultaneously match the observed BH-BH merger rate density and BH masses and BH-BH effective spins. Models with efficient angular momentum transport are favored. The updated stellar-mass weighted gas-phase metallicity evolution now used in our models appears to be key for obtaining an improved reproduction of the LIGO/Virgo merger rate estimate. Mass losses during the pair-instability pulsation supernova phase are likely to be overestimated if the merger GW170729 hosts a BH more massive than 50âMâŠ. We also estimate rates of black hole-neutron star (BH-NS) mergers from recent LIGO/Virgo observations. If, in fact. angular momentum transport in massive stars is efficient, then any (electromagnetic or gravitational wave) observation of a rapidly spinning BH would indicate either a very effective tidal spin up of the progenitor star (homogeneous evolution, high-mass X-ray binary formation through case A mass transfer, or a spin-up of a Wolf-Rayet star in a close binary by a close companion), significant mass accretion by the hole, or a BH formation through the merger of two or more BHs (in a dense stellar cluster).
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8. |
- Barack, Leor, et al.
(author)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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In: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Research review (peer-reviewed)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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9. |
- Leveque, A., et al.
(author)
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MOCCA-survey data base: extra galactic globular clusters – II. Milky Way and Andromeda
- 2022
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 1365-2966 .- 0035-8711. ; 514:4, s. 5751-5766
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Journal article (peer-reviewed)abstract
- A comprehensive study of the co-evolution of globular cluster systems (GCS) in galaxies requires the ability to model both the large-scale dynamics (0.01–10 kpc) regulating their orbital evolution, and the small-scale dynamics (sub-pc – au) regulating the internal dynamics of each globular cluster (GC). In this work, we present a novel method that combine semi-analytic models of GCS with fully self-consistent Monte Carlo models to simultaneously evolve large GCSs. We use the population synthesis code MASinGa and the MOCCA-Survey Database I to create synthetic GC populations aimed at representing the observed features of GCs in the Milky Way (MW) and Andromeda (M31). Our procedure enables us to recover the spatial and mass distribution of GCs in such galaxies, and to constrain the amount of mass that GCs left either in the halo as dispersed debris, or in the galactic centre, where they can contribute to the formation of a nuclear star cluster (NSC) and can bring stellar and possibly intermediate mass black holes there. The final masses reported by our simulations are of a few order of magnitudes smaller than the observed values. These differences show that mass build-up of an NSC and central BHs in galaxies like MW and M31 cannot be solely explained by the infalling GC scenario. This build-up is likely to depend on the interplay between interactions and mergers of infalling GCs and gas. The latter can contribute to both in situ star formation in the NSC and growth of the central BH.
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10. |
- Leveque, A., et al.
(author)
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MOCCA-Survey Database: extra galactic globular clusters – III. The population of black holes in Milky Way and Andromeda-like galaxies
- 2023
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 1365-2966 .- 0035-8711. ; 520:2, s. 2593-2610
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Journal article (peer-reviewed)abstract
- This work investigates the black hole (BH) population of globular clusters (GCs) in Milky Way- and Andromeda-like galaxies. We combine the population synthesis code MASinGa and the MOCCA-Survey Database I to infer the properties of GCs harbouring a stellar-mass BH subsystem (BHS), an intermediate-mass BH (IMBH), or neither of those. We find that the typical number of GCs with a BHS, an IMBH, or none become comparable in the galactic outskirts, whilst the inner galactic regions are dominated by GCs without a significant dark component. We retrieve the properties of binary BHs (BBHs) that have either merged in the last 3 Gyr or survived in their parent cluster until present-day. We find that around 80 per cent of the merging BBHs form due to dynamical interactions while the remaining originate from evolution of primordial binaries. The inferred merger rate for both in-cluster and ejected mergers is 1.0−23yr−1Gpc−3 in the local Universe, depending on the adopted assumptions. We find around 100–240 BBHs survive in GCs until present-day and are mostly concentrated in the inner few kpc of the galaxy. When compared with the field, GCs are at least two times more efficient in the formation of BHs and binaries containing at least one BH. Around 1000–3000 single BHs and 100–200 BBHs are transported into the galactic nucleus from infalling clusters over a time span of 12 Gyr. We estimate that the number of BHs and BBHs lurking in the star cluster to be about 1.4–2.2 × 104 and 700–1100, respectively.
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11. |
- Mehta, Rohtesh S., et al.
(author)
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GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia
- 2019
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 3:9, s. 1441-1449
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Journal article (peer-reviewed)abstract
- We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P < .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P < .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.
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14. |
- Im, Annie, et al.
(author)
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Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
- 2020
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In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 26:8, s. 1459-1468
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Journal article (peer-reviewed)abstract
- Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.
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15. |
- Mehta, Rohtesh S., et al.
(author)
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Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT
- 2020
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In: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 38:18, s. 2062-2076
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Journal article (peer-reviewed)abstract
- PURPOSE There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor.METHODS We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant.RESULTS In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group.CONCLUSION Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.
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16. |
- Morawski, Jakub, et al.
(author)
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MOCCA-SURVEY Database I: Assessing GW kick retention fractions for BH-BH mergers in globular clusters
- 2018
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 1365-2966 .- 0035-8711. ; 481:2, s. 2168-2179
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Journal article (peer-reviewed)abstract
- Anisotropy of gravitational wave (GW) emission results in a net momentum gained by the black hole (BH) merger product, leading to a recoil velocity up to ∼103 km s−1, which may kick it out of a globular cluster (GC). We estimate GW kick retention fractions of merger products assuming different models for BH spin magnitude and orientation. We check how they depend on BH–BH merger time and properties of the cluster. We analyse the implications of GW kick retention fractions on intermediate massive BH formation by repeated mergers in a GC. We also calculate final spin of the merger product, and investigate how it correlates with other parameters: effective spin of the binary and gravitational kick velocity. We used data from MOCCA (MOnte Carlo Cluster simulAtor) GC simulations to get a realistic sample of BH–BH mergers, assigned each BH spin value according to a studied model, and calculated recoil velocity and final spin based on most recent theoretical formulas. We discovered that for physically motivated models, GW kick retention fractions are about 30 per cent 30 per cent and display small dependence on assumptions about spin, but are much more prone to cluster properties. In particular, we discovered a strong dependence of GW kick retention fractions on cluster density. We also show that GW kick retention fractions are high in final life stages of the cluster, but low at the beginning. Finally, we derive formulas connecting final spin with effective spin for primordial binaries, and with maximal effective spin for dynamical binaries.
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17. |
- Narayan, Rupa, et al.
(author)
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HLA Class I Genotype Is Associated with Relapse Risk after Allogeneic Stem Cell Transplantation for NPM1-Mutated Acute Myeloid Leukemia
- 2023
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In: Transplantation and cellular therapy. - : Elsevier BV. - 2666-6367. ; 29:7, s. 1-452
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Journal article (peer-reviewed)abstract
- Mutation-bearing peptide ligands from mutated nucleophosmin-1 (NPM1) protein have been empirically found to be presented by HLA class I in acute myeloid leukemia (AML). We hypothesized that HLA genotype may impact allogeneic hematopoietic stem cell transplantation (allo-HCT) outcomes in NPM1-mutated AML owing to differences in antigen presentation. We evaluated the effect of the variable of predicted strong binding to mutated NPM1 peptides using HLA class I genotypes from matched donor-recipient pairs on transplant recipients’ overall survival (OS) and disease-free survival (DFS) as part of the primary objectives and cumulative incidence of relapse and nonrelapse mortality (NRM) as part of secondary objectives. Baseline and outcome data reported to the Center for International Blood and Marrow Transplant Research from a study cohort of adult patients (n = 1020) with NPM1-mutated de novo AML in first (71%) or second (29%) complete remission undergoing 8/8 matched related (18%) or matched unrelated (82%) allo-HCT were analyzed retrospectively. Class I alleles from donor-recipient pairs were analyzed for predicted strong HLA binding to mutated NPM1 using netMHCpan 4.0. A total of 429 (42%) donor-recipient pairs were classified as having predicted strong-binding HLA alleles (SBHAs) to mutated NPM1. In multivariable analyses adjusting for clinical covariates, the presence of predicted SBHAs was associated with a lower risk of relapse (hazard ratio [HR],.72; 95% confidence interval [CI],.55 to.94; P =.015). OS (HR,.81; 95% CI,.67 to.98; P =.028) and DFS (HR,.84; 95% CI,.69 to 1.01; P =.070) showed a suggestion of better outcomes if predicted SBHAs were present but did not meet the prespecified P value of <.025. NRM did not differ (HR, 1.04; P =.740). These hypothesis-generating data support further exploration of HLA genotype-neoantigen interactions in the allo-HCT context.
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18. |
- Wustenhagen, Sofia, et al.
(author)
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PAIN IN OSTEOARTHRITIS MICE: OVARIAN HORMONES REGULATE THE RESPONSE OF A2B ADENOSINE RECEPTORS
- 2024
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In: Osteoarthritis and Cartilage. - 1522-9653 .- 1063-4584. ; 32:Supplement 1, s. S513-S513
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Conference paper (other academic/artistic)abstract
- Pain in osteoarthritis (OA) is a complex phenomenon, attributable to alteration of the subchondral bone, local inflammation of the articular tissues, and increased responsiveness of the peripheral nerve to non-noxious stimuli. The decline of ovarian hormones after menopause might be responsible for the alteration of the joint tissues, predisposing women to an increased risk of developing more painful knee OA compared to men. This could be a direct consequence of the well-known effect of estrogens on bone metabolism, on the regulation of the inflammatory mechanisms, and/or the mutual regulation of endogenous molecules. Indeed, it has been previously shown that estrogen receptors regulate adenosine synthesis and the expression of adenosine receptors. Adenosine, by activating its receptors, has an important role in the regulation of pain, inflammation, bone, and cartilage metabolism. The purpose of this study was to evaluate the effect of the pharmacological inhibition of the A2B adenosine receptors (A2BAR) in ovariectomized and control mice in the early and late stages of OA.
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