Ultrasound detection of calcium pyrophosphate dihydrate crystal deposits in menisci: a pilot in vivo and ex vivo study: Table 1

Pure monoclinic calcium pyrophosphate dihydrate (m-CPPD) has been synthesized and characterized by synchrotron powder X-ray diffraction and neutron diffraction. Rietveld refinement of complementary diffraction data has, for the first time, allowed the crystal structure of m-CPPD to be solved. The monoclinic systemP21/nwas confirmed and unit-cell parameters determined:a= 12.60842 (4),b= 9.24278 (4),c= 6.74885 (2) Å and β = 104.9916 (3)°. Neutron diffraction data especially have allowed the precise determination of the position of H atoms in the structure. The relationship between the m-CPPD crystal structure and that of the triclinic calcium pyrophosphate dihydrate (t-CPPD) phase as well as other pyrophosphate phases involving other divalent cations are discussed by considering the inflammatory potential of these phases and/or their involvement in different diseases. These original structural data represent a key step in the understanding of the mechanisms of crystal formation involved in different types of arthritis and to improve early detection of calcium pyrophosphate (CPP) phasesin vivo.

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Calcium pyrophosphate dihydrate crystal deposition disease

Archives of Internal Medicine ◽

10.1001/archinte.123.6.636 ◽

1969 ◽

Vol 123 (6) ◽

pp. 636-644 ◽

Cited By ~ 7

Author(s):

M. Skinner

Keyword(s):

Calcium Pyrophosphate ◽

Calcium Pyrophosphate Dihydrate ◽

Crystal Deposition ◽

Crystal Deposition Disease ◽

Deposition Disease ◽

Pyrophosphate Dihydrate

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Tumoral calcium pyrophosphate dihydrate deposition disease with bone destruction in the shoulder

Acta Radiologica ◽

10.3109/02841859809172192 ◽

1998 ◽

Vol 39 (3) ◽

pp. 269-272

Author(s):

H. Mizutani ◽

S. Ohba ◽

M. Mizutani ◽

S. Sasaki ◽

K. Ando ◽

...

Keyword(s):

Bone Destruction ◽

Calcium Pyrophosphate ◽

Calcium Pyrophosphate Dihydrate ◽

Deposition Disease ◽

Pyrophosphate Dihydrate

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64Cu-ATSM/64Cu-Cl2 and their relationship to hypoxia in glioblastoma: a preclinical study

EJNMMI Research ◽

10.1186/s13550-019-0586-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Elodie A. Pérès ◽

Jérôme Toutain ◽

Louis-Paul Paty ◽

Didier Divoux ◽

Méziane Ibazizène ◽

...

Keyword(s):

Ex Vivo ◽

In Vitro Study ◽

Tumor Location ◽

Preclinical Study ◽

Significant Rise ◽

Lower Oxygen ◽

Cu Complexes ◽

Ex Vivo Study

Abstract Background Diacetyl-bis(N4-methylthiosemicarbazone), labeled with 64Cu (64Cu-ATSM) has been suggested as a promising tracer for imaging hypoxia. However, various controversial studies highlighted potential pitfalls that may disable its use as a selective hypoxic marker. They also highlighted that the results may be tumor location dependent. Here, we first analyzed uptake of Cu-ATSM and its less lipophilic counterpart Cu-Cl2 in the tumor over time in an orthotopic glioblastoma model. An in vitro study was also conducted to investigate the hypoxia-dependent copper uptake in tumor cells. We then further performed a comprehensive ex vivo study to compare 64Cu uptake to hypoxic markers, specific cellular reactions, and also transporter expression. Methods μPET was performed 14 days (18F-FMISO), 15 days (64Cu-ATSM and 64Cu-Cl2), and 16 days (64Cu-ATSM and 64Cu-Cl2) after C6 cell inoculation. Thereafter, the brains were withdrawn for further autoradiography and immunohistochemistry. C6 cells were also grown in hypoxic workstation to analyze cellular uptake of Cu complexes in different oxygen levels. Results In vivo results showed that Cu-ASTM and Cu-Cl2 accumulated in hypoxic areas of the tumors. Cu-ATSM also stained, to a lesser extent, non-hypoxic regions, such as regions of astrogliosis, with high expression of copper transporters and in particular DMT-1 and CTR1, and also characterized by the expression of elevated astrogliosis. In vitro results show that 64Cu-ATSM showed an increase in the uptake only in severe hypoxia at 0.5 and 0.2% of oxygen while for 64Cu-Cl2, the cell retention was significantly increased at 5% and 1% of oxygen with no significant rise at lower oxygen percentages. Conclusion In the present study, we show that Cu-complexes undoubtedly accumulate in hypoxic areas of the tumors. This uptake may be the reflection of a direct dependency to a redox metabolism and also a reflection of hypoxic-induced overexpression of transporters. We also show that Cu-ATSM also stained non-hypoxic regions such as astrogliosis.

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Newly developed pseudogout arthritis after therapy with MAGE-A4 directed TCR T cells responded to treatment with tocilizumab

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002716 ◽

2021 ◽

Vol 9 (7) ◽

pp. e002716

Author(s):

Sang T. Kim ◽

Jean Tayar ◽

Siqing Fu ◽

Danxia Ke ◽

Elliot Norry ◽

...

Keyword(s):

T Cells ◽

Synovial Fluid ◽

Th17 Cells ◽

Effector Cell ◽

Calcium Pyrophosphate ◽

Calcium Pyrophosphate Dihydrate ◽

Immune Effector Cell ◽

Cell Therapies ◽

Immune Effector ◽

Pyrophosphate Dihydrate

With durable cancer responses, genetically modified cell therapies are being implemented in various cancers. However, these immune effector cell therapies can cause toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Pseudogout arthritis is an inflammatory arthritis induced by deposition of calcium pyrophosphate dihydrate crystals. Here, we report a case of pseudogout arthritis in a patient treated with MAGE-A4 directed T cell receptor T cells, for fallopian tube cancer. The patient developed CRS and ICANS 7 days after infusion of the T cells. Concurrently, the patient newly developed sudden onset of left knee arthritis. Synovial fluid analyses revealed the presence of calcium pyrophosphate dihydrate crystal. Notably, the pseudogout arthritis was resolved with tocilizumab, which was administered for the treatment of CRS and ICANS. Immunoprofiling of the synovial fluid showed that the proportion of inflammatory interleukin 17 (IL-17)-producing CD4+ T (Th17) cells and amount of IL-6 were notably increased, suggesting a potential role of Th17 cells in pseudogout arthritis after T-cell therapy. To the best of our knowledge, this is the first reported case of pseudogout arthritis after cell therapy. Clinicians, especially hematologists, oncologists and rheumatologists, should be aware that pseudogout arthritis can be associated with CRS/ICANS.

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Optical Biomarkers for the Diagnosis of Osteoarthritis through Raman Spectroscopy: Radiological and Biochemical Validation Using Ex Vivo Human Cartilage Samples

Diagnostics ◽

10.3390/diagnostics11030546 ◽

2021 ◽

Vol 11 (3) ◽

pp. 546

Author(s):

Paula Casal-Beiroa ◽

Vanesa Balboa-Barreiro ◽

Natividad Oreiro ◽

Sonia Pértega-Díaz ◽

Francisco J. Blanco ◽

...

Keyword(s):

Raman Spectroscopy ◽

Articular Cartilage ◽

Ex Vivo ◽

Cartilage Degradation ◽

Calcium Pyrophosphate ◽

Calcium Pyrophosphate Dihydrate ◽

Label Free ◽

Molecular Fingerprint ◽

Human Cartilage ◽

Biochemical Validation

Osteoarthritis (OA) is the most common rheumatic disease, characterized by progressive articular cartilage degradation. Raman spectroscopy (RS) has been recently proposed as a label-free tool to detect molecular changes in musculoskeletal tissues. We used cartilage samples derived from human femoral heads to perform an ex vivo study of different Raman signals and ratios, related to major and minor molecular components of articular cartilage, hereby proposed as candidate optical biomarkers for OA. Validation was performed against the radiological Kellgren–Lawrence (K-L) grading system, as a gold standard, and cross-validated against sulfated glycosaminoglycans (sGAGs) and total collagens (Hyp) biochemical contents. Our results showed a significant decrease in sGAGs (SGAGs, A1063 cm−1/A1004 cm−1) and proteoglycans (PGs, A1375 cm−1/A1004 cm−1) and a significant increase in collagen disorganization (ColD/F, A1245 cm−1/A1270 cm−1), with OA severity. These were correlated with sGAGs or Hyp contents, respectively. Moreover, the SGAGs/HA ratio (A1063 cm−1/A960 cm−1), representing a functional matrix, rich in proteoglycans, to a mineralized matrix-hydroxyapatite (HA), was significantly lower in OA cartilage (K-L I vs. III–IV, p < 0.05), whilst the mineralized to collagenous matrix ratio (HA/Col, A960 cm−1/A920 cm−1) increased, being correlated with K-L. OA samples showed signs of tissue mineralization, supported by the presence of calcium crystals-related signals, such as phosphate, carbonate, and calcium pyrophosphate dihydrate (MGP, A960 cm−1/A1004 cm−1, MGC, A1070 cm−1/A1004 cm−1 and A1050 cm−1/A1004 cm−1). Finally, we observed an increase in lipids ratio (IL, A1450 cm−1/A1670 cm−1) with OA severity. As a conclusion, we have described the molecular fingerprint of hip cartilage, validating a panel of optical biomarkers and the potential of RS as a complementary diagnostic tool for OA.

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Calcium Pyrophosphate Dihydrate Crystals Increase the Granulocyte/Monocyte Progenitor (GMP) and Enhance Granulocyte and Monocyte Differentiation In Vivo

International Journal of Molecular Sciences ◽

10.3390/ijms22010262 ◽

2020 ◽

Vol 22 (1) ◽

pp. 262

Author(s):

Nobuyuki Onai ◽

Chie Ogasawara

Keyword(s):

Cell Differentiation ◽

Peripheral Blood ◽

Calcium Pyrophosphate ◽

Hematopoietic Progenitor Cell ◽

Calcium Pyrophosphate Dihydrate ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Hematopoietic Stem ◽

Cppd Crystal ◽

Pyrophosphate Dihydrate

Calcium pyrophosphate dihydrate (CPPD) crystals are formed locally within the joints, leading to pseudogout. Although the mobilization of local granulocytes can be observed in joints where pseudogout has manifested, the mechanism of this activity remains poorly understood. In this study, CPPD crystals were administered to mice, and the dynamics of splenic and peripheral blood myeloid cells were analyzed. As a result, levels of both granulocytes and monocytes were found to increase following CPPD crystal administration in a concentration-dependent manner, with a concomitant decrease in lymphocytes in the peripheral blood. In contrast, the levels of other cells, such as dendritic cell subsets, T-cells, and B-cells, remained unchanged in the spleen, following CPPD crystal administration. Furthermore, an increase in granulocytes/monocyte progenitors (GMPs) and a decrease in megakaryocyte/erythrocyte progenitors (MEPs) were also observed in the bone marrow. In addition, CPPD administration induced production of IL-1β, which acts on hematopoietic stem cells and hematopoietic progenitors and promotes myeloid cell differentiation and expansion. These results suggest that CPPD crystals act as a “danger signal” to induce IL-1β production, resulting in changes in course of hematopoietic progenitor cell differentiation and in increased granulocyte/monocyte levels, and contributing to the development of gout.

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