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D Loeuille

Publications and source records attributed to D Loeuille.

At least 19 recordsLinked to original sources

[Is leptin the missing link between osteoarthritis and obesity?].

The contribution of leptin, as a possible link between osteoarthritis (OA) and obesity, was studied in cartilage and synovial fluid samples obtained from osteoarthritic patients. Its effect on cartilage was evaluated in rats after intraarticular injections of leptin. Leptin levels were measured in the synovial fluid samples by enzyme linked immunosorbent assay; leptin concentrations were correlated with the body mass index. Leptin was strongly expressed in osteophytes and OA cartilage, while, in normal cartilage, few chondrocytes produced leptin. The level of leptin expression was related to the grade of cartilage destruction and was in good relation with those of growth factors as IGF1 and TGFb. Studies in rats showed that intraarticular leptin injection stimulated anabolic functions of chondrocytes and induced the synthesis of leptin, IGF1 and TGFB in cartilage at both the chondrocytes and induced the synthesis of leptin, IGF1 and TGFB in cartilage at both the mRNA and protein levels. In conclusion, leptin may be a link between osteoarthritis and obesity, and may play a key role in cartilage metabolism. Leptin may contribute to the pathophysiology of OA.

Animals↗

[Not Available].

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Journal Article↗

Evaluation of cartilage repair tissue after biomaterial implantation in rat patella by using T2 mapping.

To evaluate the ability of MR T2 mapping (8.5 T) to characterize ex vivo longitudinally, morphologically and quantitatively, alginate-based tissue engineering in a rat model of patellar cartilage chondral focal defect. Calibrated rat patellar cartilage defects (1.3 mm) were created at day 0 (D0) and alginate sponge with (Sp/C+) or without (Sp/C-) autologous chondrocytes were implanted. Animals were sacrificed sequentially at D20, D40 and D60 after surgery and dissected patellae underwent MRI exploration (8.5 T). T2 values were calculated from eight SE images by using nonlinear least-squares curve fitting on a pixel-by-pixel basis (constant repetition time of 1.5 s, eight different echo times: 5.5, 7.5, 10.5, 12.5, 15.0, 20.0, 25.0 and 30.0 ms). On the T2 map, acquired in a transversal plane through the repair zone, global T2 values and zonal variation of T2 values of repair tissue were evaluated versus control group and compared with macroscopic score and histological studies (toluidine blue, sirius red and hematoxylin-eosin). "Partial", "total" and "hypertrophic" repair patterns were identified. At D40 and D60, Sp/C+ group was characterized by a higher proportion of "total" repair in comparison to Sp/C- group. At D60, the proportion of "hypertrophic" repair was two fold in Sp/C- group versus Sp/C+ group. As confirmed morphologically and histologically, the T2 map also permitted the distinction of three types of repair tissue: "total", "partial" and "hypertrophic". "Total" repair tissue was characterized by high T2 values versus normal cartilage (p<0.05). Zonal variation, reflecting the collagen network organization, appeared only at D60 for Sp/C+ group (p<0.05). "Hypertrophic" tissue, mainly observed at D60, presented high T2 global values without zonal variation with cartilage depth. These results confirm the potency of the MR T2 map (8.5 T) to characterize macroscopically and microscopically the patterns of the scaffold guided-tissue repair of a focal chondral lesion in the rat patella ("total", "partial" and "hypertrophic"). On T2 map, three parameters (i.e. MRI macroscopic pattern, T2 global values and zonal variation of T2 values) permit to characterize chondral repair tissue, as a virtual biopsy.

Animals↗

T2 mapping: an efficient MR quantitative technique to evaluate spontaneous cartilage repair in rat patella.

OBJECTIVE: To evaluate the ability of T2 mapping on an 8.5 T imager to characterize morphologically and quantitatively spontaneous repair of rat patellar cartilage following full thickness defect. METHODS: Patellar cartilage defects were created in 24 rats knees on D0. Eight rats per time-point were killed on D20, D40 and D60 after surgery. T2 maps of repair tissue in patellar defects were obtained from eight different axial spin echo images on an 8.5 T imager. Global, superficial and deep T2 values were evaluated in spontaneous repair tissues (3x8 right patellae) vs the opposite patellae (3x8 left patellae) of the same animals. MR data were compared with macroscopic and histological studies. RESULTS: T2 map was able to identify morphologically three types of repair tissue observed macroscopically and histologically: 'total', 'partial' and 'hypertrophic' repair tissue. 'Total' and 'partial' repair tissues were characterized by global T2 values almost similar to controls, whereas 'hypertrophic' repair tissues were characterized by T2 global values higher than controls. Zonal variation between superficial and deep T2 values observed in controls was not depicted in repair tissue before D60. CONCLUSION: T2 map is able to characterize quantitatively and qualitatively rat patellar cartilage repair, and thus can be promoted, as a non invasive technique, in clinical longitudinal studies of articular cartilage repair.

Animals↗

[MR-arthrography: general principles and applications].

The recent approval by the French Ministry of Health of the use of intra-articular Gadolinium could promote the increasing use of MR-arthrography in France. Although useful in specific pathologies, it should not be overly prescribed and should be considered only if it provides a more accurate diagnosis than other less invasive techniques. The technical aspects and medico-legal implications of MR-arthrography as well as its various indications are reviewed in this article. There are three possible techniques: indirect MR-arthrography with IV Gadolinium injection, direct MR-arthrography with intra-articular Gadolinium injection and lastly, direct MR-arthrography with intra-articular injection of iodinated contrast media (or saline solution). Indirect MR-arthrography cannot be recommended because of insufficient contrast enhancement and the absence of joint filling. Conversely, direct MR-arthrography allows joint expansion which smooths out capsule and ligaments, better delineates articular surfaces and yields a homogeneous high intensity signal of the entire joint. Direct MR-arthrography with iodinated contrast media combines standard arthrography with conventional MRI. Direct MR-arthrography with intra-articular injection of dilute Gadolinium is associated with T1WI, usually of higher quality than T2WI, even though the latter remains part of the protocol. Although, the last two techniques yield higher image quality and are often performed for various articular pathologies, they should not be randomly carried out in the evaluation of joint pathology. However, they should be recommended as the first step in the diagnosis of painful shoulders or hips in young adults and athletes.

Arthrography↗

Effect of articular cartilage proteoglycan depletion on high frequency ultrasound backscatter.

OBJECTIVE: To study the effect of variations of articular cartilage proteoglycans (PG) on high-frequency ultrasound backscatter. DESIGN: The study was performed on patellar cartilages of immature and mature rats (N=36). The variation of PG content was induced by enzyme digestion. Control and treated cartilages were explored in vitro using a 55MHz scanning acoustic microscopy, then assessed by histology for the fibrillar collagen organization analysis. The variations of proteoglycan and collagen content were evaluated. Thickness measurements performed on both B-scan images and histologic sections were compared. Ultrasonic radio-frequency signals reflected by the cartilage surface and backscattered from its internal matrix were processed to estimate the integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB). RESULTS: Although hyaluronidase treatment of immature and mature cartilages removed approximately 50% of the proteoglycans, the echogenicity level of ultrasound images of degraded cartilages was similar to that of controls. IRC and AIB parameters did not significantly vary. Histologic sections of degraded cartilage displayed no change in collagen fiber organization. The thickness mean values measured by ultrasound in PG-depleted groups were significantly higher than in controls, whereas no significant difference in thickness was detected by histological measurement. The increase in cartilage thickness may potentially be explained by a decrease of speed of sound in PG-depleted cartilages that is more likely subsequent to an increase of water content. CONCLUSION: Current results indicate that PG depletion has no significant effect on high frequency ultrasound backscattered from rat patellar cartilage. Ultrasound may provide information about variations of PG content via speed of sound measurement.

Acoustics↗

Structural evaluation of articular cartilage: potential contribution of magnetic resonance techniques used in clinical practice.

OBJECTIVE: To determine whether routine magnetic resonance imaging (MRI) techniques can detect age-related structural modifications of bovine articular cartilage. METHODS: The cartilage of 3-month-old, 3-year-old, and 13-year-old animals was studied. T1- and T2-weighted MR sequences were performed using a 1.5T clinical imager and a 3-inch surface coil. Histologic slices (5 microm) of cartilage specimens were stained with picrosirius red (for collagen) and toluidine blue (for glycosaminoglycans [GAGs]). A polarized light study was performed to determine the collagen network organization. Except for the 13-year-old animal cartilage, the biochemical content was studied on slices cut parallel to the surface to determine GAG and hydroxyproline (collagen) content. Cartilage profiles were performed to determine the MR pixel intensity and the histologic color intensity. RESULTS: On T1-weighted images, the cartilage was homogeneous, with pixel intensity profiles presenting low variations. On T2-weighted images, the cartilage was laminar in the 3-month-old animals and became homogeneous thereafter. The pixel intensity varied through the cartilage depth with a profile that depended on the age of the animal. The collagen and GAG staining showed abrupt transitions in the 3-month-old animal, while in older animals the cartilage became more homogeneous with a mild gradient of matrix constituents with depth. These results were confirmed by findings of a biochemical study. In addition to these matrix content variations, the bovine cartilage presented modifications of its collagen network organization with aging. CONCLUSION: The MR T2-weighted sequences depicted signal variations with age in bovine cartilage concomitant with modifications in its structure. If confirmed in clinics, these observations will reinforce the place of MRI in characterizing cartilage with aging and pathologic processes.

Aging↗

Assessment of rat articular cartilage maturation using 50-MHz quantitative ultrasonography.

OBJECTIVE: The objective was to assess the relationship between maturation-related structural changes of articular cartilage and variations of acoustic parameters estimated using high frequency ultrasonography. DESIGN: Patellae taken from 48 immature Wistar male rats and divided into six age groups (from five to 11 weeks old) were explored in vitro using 50-MHz scanning acoustic microscopy, then assessed by histology for the analysis of the cartilage cell distribution and fibrillar collagen organization. The variation of cartilage proteoglycan and collagen content with age was evaluated. Thickness measurements performed on both B-scan images and histologic sections were compared. Ultrasonic radiofrequency signals reflected by the cartilage surface and backscattered from its internal matrix were processed to estimate the integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB). RESULTS: One-way ANOVA indicated that acoustic parameters and thickness change significantly (P < 0.05) as the animal matures because of age-related changes in cartilage composition and morphology. A moderate correlation was found between IRC and the animal age. The parameter decreased slightly but significantly over time. However, a good correlation was observed between the rat age and the AIB, which decreased significantly over time. The parameter variation was mostly related to the changes in collagen fiber orientation, and/or to a change in cell size, density and organization. CONCLUSIONS: Current results indicate that acoustic properties of cartilage are affected by maturation-related cartilage changes. This suggests that high frequency ultrasonography may serve as a useful means for the investigation of cartilage matrix structural changes occurring under various clinical circumstances, like those observed during osteoarthritis, and for the evaluation of the efficacy of specific therapeutics.

Aging↗

[Familial articular chondrocalcinosis: study of an Alsatian family].

Familial articular chondrocalcinosis is a chronic articular disease characterized by acute intermittent attacks of arthritis, presence of calcium pyrophosphate dihydrate crystal in synovial fluid, cartilage and periarticular soft tissue and by x rays calcium deposition in articular cartilage. A family originating from Alsace, with an autosomal dominant transmission has been studied. As in English and Argentinean families, a linkage to the short arm of chromosome 5p has been found. These results suggest that a defective gene at this location may be related to the chondrocalcinosis in these families.

Adult↗

[Evaluation of tolerance to endovesical BCG treatment in France: analysis of severe adverse effects notified in 3 years].

OBJECTIVES: Intravesical BCG therapy remains the first-line prophylactic treatment for recurrences of superficial bladder tumours. However, necessary the safety of this medicinal product, for which a potential risk of complications was demonstrated during development, needs to be evaluated. MATERIAL AND METHODS: Based on spontaneous notifications of adverse events reported according to good pharmacovigilance practice and in the context of a survey conducted jointly with Health Authorities, the authors present an analysis of adverse event notifications received by the manufacturer over a three-year period. A summary of serious adverse events (SAE) was established and hypotheses concerning factors predisposing to these adverse events were discussed. Finally, practice guidelines were formulated. RESULTS: During this period, 97 SAEs were reported spontaneously, including 12 local SAEs, 12 regional SAEs and 73 systemic SAEs. 46 of the 73 systemic SAEs were suspected to be due to BCG infection, 18 were related to immune disorders and the cause of 9 SAEs could not be determined. Several hypotheses are formulated concerning the circumstances leading to the onset of these SAEs and practice guidelines are proposed. CONCLUSION: Pharmacovigilance has allowed a better understanding of the qualitative and quantitative safety of BCG-IT in France. Hypotheses concerning factors predisposing to adverse effects were formulated and practice guidelines were proposed. It is essential to continue this collaboration between practitioners, Health Authorities and the manufacturer to ensure optimal use of this medicinal product.

Adjuvants, Immunologic↗

Articular diffusion of meloxicam after a single oral dose: relationship to cyclo-oxygenase inhibition in synovial cells.

OBJECTIVE: To investigate the distribution of meloxicam in the human knee joint and to compare it with the inhibition of cyclo-oxygenase (COX) activity in synovial cells. DESIGN: Prospective pharmacokinetic study and in vitro laboratory investigation. PATIENTS AND PARTICIPANTS: 42 male and female patients aged 26 to 85 years hospitalised for rheumatic disease and requiring a diagnostic and/or therapeutic knee puncture. METHODS: After a single oral dose of meloxicam 15mg, synovial fluid and blood samples were collected once per patient at various intervals after administration. Meloxicam concentrations were determined by a validated high performance liquid chromatography assay, protein binding by equilibrium dialysis, and pharmacokinetic parameters were calculated by noncompartmental analysis from the mean drug concentration-time profiles. The inhibitory effect of meloxicam on COX activity was investigated separately in unstimulated or interleukin-1beta-stimulated human synovial cells from osteoarthritic patients. RESULTS: Meloxicam was found in synovial fluid at the earliest sampling time (1 hour). Peak concentrations were reached approximately 6 hours postdose in both plasma (842 microg/L) and synovial fluid (320 microg/L). A plateau was observed after the distribution phase (6 hours), corresponding to a constant ratio of drug concentration between synovial fluid and plasma of about 0.47. This ratio was higher in patients with acute inflammation (0.58) than in those with no inflammation (0.38). Meloxicam was extensively bound to protein, mainly to serum albumin. The area under the drug concentration-time curve (AUC) in plasma was more than 2.5 times that in synovial fluid. The AUC for free meloxicam was similar in plasma and synovial fluid. The 50% inhibitory concentrations (IC50) for basal and stimulated COX activity in human synovial cells were 33.7 nmol/L (11.8 microg/L) and 2.0 nmol/L (0.70 microg/L), respectively. The free concentration of meloxicam in synovial fluid was higher than the IC50 for stimulated COX activity from 6 to 36 hours postdose. CONCLUSION: On the basis of free synovial concentrations and the IC50 for stimulated COX activity, meloxicam is expected to have a long duration of action. Inhibition of COX activity is expected to be more marked in inflamed synovium compared with non-inflamed synovium.

Administration, Oral↗

Refinement of the chromosome 5p locus for familial calcium pyrophosphate dihydrate deposition disease.

Familial calcium pyrophosphate dihydrate deposition disease (CPPDD) is a disease of articular cartilage that is radiographically characterized by chondrocalcinosis due to the deposition of calcium-containing crystals in affected joints. We have documented the disease in an Argentinean kindred of northern Italian ancestry and in a French kindred from the Alsace region. Both families presented with a common phenotype including early age at onset and deposition of crystals of calcium pyrophosphate dihydrate in a similar pattern of affected joints. Affected family members were karyotypically normal. Linkage to the short arm of chromosome 5 was observed, consistent with a previous report of linkage of the CPPDD phenotype in a large British kindred to the 5p15 region. However, recombinants in the Argentinean kindred have enabled us to designate a region<1 cM in length between the markers D5S416 and D5S2114 as the CPPDD locus.

Calcium Pyrophosphate↗