The effect of intrathecal dexamethasone injection on plasma cortisol level.
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Adult↗
Biomedical subjects
G Loyau
Publications and source records attributed to G Loyau.
Comparative effects of interleukin-1 and tumor necrosis factor-alpha on collagen production and corresponding procollagen mRNA levels in human dermal fibroblasts.
The effects of recombinant human Interleukin-1 alpha (IL-1 alpha), Interleukin-1 beta (IL-1 beta), and Tumor Necrosis Factor-alpha (TNF-alpha) on collagen biosynthesis were studied in vitro using dermal fibroblast cultures. Both forms of IL-1 and TNF-alpha induced a dose-dependent inhibition of both types I and III collagen synthesis, as measured by radioimmunoassay, gel electrophoresis, or collagenase-sensitive material. This effect was accompanied by a significant release of prostaglandin E2 into the culture medium. However, indomethacin, a potent inhibitor of prostaglandin synthesis, could not prevent the inhibitory effect of the three cytokines on collagen synthesis. Measurement of type I and type III procollagen mRNA levels in IL-1 treated cells revealed that both IL-1 alpha and IL-1 beta were potent enhancers of procollagen gene expression at pretranslational level. On the other hand, TNF-alpha was found to reduce the steady-state levels of type I and III procollagen mRNA in a dose-dependent manner. Quantitation of IL-1 beta and TNF-alpha transcripts following TNF-alpha treatment of fibroblasts indicated that this cytokine can induce IL-1 beta gene expression in these cells. By contrast, TNF-alpha mRNA remained at a constant level after TNF-alpha exposure. These data suggest that IL-1 and TNF-alpha, two cytokines that share several biologic activities, modulate collagen deposition in dermal fibroblasts by mechanisms that are clearly different: TNF-alpha appears to act at a transcriptional level to inhibit collagen synthesis, whereas IL-1 inhibitory action involves important translational regulation, still unknown, that counterbalances its stimulatory effect on procollagen mRNA levels. Moreover, our data suggest the existence of local fibroblastic cytokine production that may be involved in the modulation of extracellular matrix deposition.
Adult↗
[Effect of unsaponifiable extracts of avocado and soybean (Piasclédine) on the collagenolytic action of cultures of human rheumatoid synoviocytes and rabbit articular chondrocytes treated with interleukin-1].
In this work, the authors have studied the effect of advocate/soya-bean extracts (Piasclédine) on the collagenolytic activity of cultured rabbit articular chondrocytes and human rheumatoid synovial cells. Incubation of these cells for 48 h with 10 micrograms/ml of Piasclédine show that this drug slightly increases collagenase production. As expected, incubation of these cells with interleukin-1 (100 pg/ml) induces an important release of collagenase. Piasclédine partially reverses the effect of interleukin-1 on synovial cells and totally abolishes its action on chondrocytes. Moreover, incubation of the two cell types for 5 days with Piasclédine prior to a 48 h-exposure to interleukin-1 prevents partially the effect of interleukin-1. These data suggest a potential role for Piasclédine to limit the deleterious effects of interleukin-1 in osteoarticular diseases by reducing the capacity of this cytokine to stimulate collagenase production by synoviocytes and chondrocytes.
Animals↗
Differential response of cultured rabbit articular chondrocytes (RAC) to transforming growth factor beta (TGF-beta)-evidence for a role of serum factors.
We show that addition of TGF-beta (0.01-10 ng/ml) to proliferating rabbit articular chondrocytes in presence of low level of fetal calf serum (FCS, 2%) results in a sustained decrease of cell number and DNA synthesis up to 72 h. In contrast, incubation with high serum concentration (10% FCS) induces a transient increase of cell number after 48 h without elevation of DNA synthesis. Moreover, when the factor is added in 10% FCS-containing medium, a differential effect is observed at 48 h (either increase or decrease of cell number) depending on the serum level (2 or 10%) present between 24 and 48 h. Recruitment of cells in late S-phase occurred under TGF-beta-treatment in both 2 and 10% FCS. These arrested cells may then be released by further exposure to 10% FCS-containing medium. The data show that factor(s) from the serum modulate(s) the action of TGF-beta on chondrocyte proliferation. Addition of epidermal growth factor (EGF) to the cultures in presence of 2% FCS mimicks the effects observed with 10% serum, suggesting that the serum component(s) involved in the mechanism could be of EGF type.
Animals↗
Role of cytokines in osteoarthritis: comparative effects of interleukin 1 and transforming growth factor-beta on cultured rabbit articular chondrocytes.
Monolayer culture of rabbit articular chondrocytes has been used to study the effects of transforming growth factor-beta (TGF-beta) and interleukin 1 (IL-1) on the production of matrix components, particularly collagens and proteoglycans. TGF-beta was shown to stimulate synthesis of collagen types II and XI as well as that of proteoglycans. The factor increases steady state level of procollagens I, II and III mRNA. Proteoglycans produced in the presence of TGF-beta had the same hydrodynamic sizes as those of controls, but a decrease of the ratio of chondroiting 6-sulfate: chondroitin 4-sulfate was observed. It was shown that TGF-beta may counteract the effect of IL-1 on synthesis of both collagen and proteoglycan and production of metalloproteases when it is introduced after IL-1, while it does not prevent the effect of the monokine when it is first added to the cultures.
Animals↗
[Epidemiology of osteoarthritis. Several remarks].
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Humans↗
[Definition of and diagnostic criteria for osteoarthritis. Application of anti-osteoarthritis agents to clinical experimentation].
The best definition of osteoarthritis is anatomical, but to be rigorous must include the biochemical characteristics of osteoarthritis cartilage. The most appropriate diagnostic criteria for clinical trials are those of Lequesne. However, radiological criteria assume that osteoarthritis had already developed and should be modified in order to permit the inclusion of early stages of osteoarthritis. The ACR classification criteria are less appropriate to the needs of clinical trials because of their lack of specificity. They are, nevertheless, of interest to the clinician in diagnosis and to the epidemiologist because of their simplicity. Diagnostic criteria of early-stage osteoarthritis proposed by Amor are of great interest to the clinician. However, their application to clinical trials still suggests certain difficulties. One can hope that such difficulties will be resolved with the development of M.R.I. and/or the discovery of novel biologic markers.
Humans↗
Differential effects of transforming growth factor-beta and epidermal growth factor on the cell cycle of cultured rabbit articular chondrocytes.
We examined the effect of transforming growth factor (TGF-beta) on the proliferative rate and cell cycle of cultured rabbit articular chondrocytes using cell counting, cytofluorometry, and [3H]-thymidine incorporation. In the presence of 2% or 10% FCS (fetal calf serum), TGF-beta at 0.01, 0.1, 1, and 10 ng/ml had an inhibitory effect on cell proliferation after 24 h exposure with a dose dependence only for 2% FCS. Flow cytometric analysis of cell DNA content at that time showed that a high proportion of cells were arrested in late S-phase (SQ or G2Q) in either 2% or 10% FCS-containing medium. In both cases, a disappearance of the cell blockage occurred between 24 and 48 h after TGF-beta addition. However, whereas a stimulation of cell proliferation rate was observed at that time in cultures containing 10% FCS, a dose-dependence inhibition of cell growth was detected, in contrast, for 2% FCS-treated cells. Presence of TGF-beta during the last 24 h was not necessary to release the arrested cells. Furthermore, platelet-poor plasma at 10% produced the same effects as FCS, suggesting that platelet-derived factors, such as platelet-derived growth factor (PDGF), could not be responsible for the release of blocked cells in this case. We compared the effect of TGF-beta to that of epidermal growth factor (EGF), used at an optimal concentration (10 ng/ml). In both slowly growing (2% FCS) and proliferating chondrocytes (10% FCS), EGF caused a significant increase of cell proliferation as early as 24 h. No arrest in late S-phase but an augmentation of the percentage of cells in S- and G2M-phases were observed. When combined, TGF-beta and EGF did not induce synergistic effect on the chondrocyte proliferation, as estimated by cell counting. [3H]-thymidine labeling showed that the factors induced identical maxima of incorporation but the peak occurred earlier for TGF-beta than for EGF (approximately 6 h versus 12 h, respectively). Although both factors induce similar cell-number increases at 48 h in 10% FCS-containing medium, these proliferative effects were due to different actions on the cell cycle. The present study indicates that TGF-beta induces first a recruitment of chondrocytes in noncycling SQ- or G2Q-blocked cells. The, the release of these cells may produce either apparent stimulation of cell proliferation if sufficient levels of an unknown serum factor are present (10% FCS) or an inhibition of growth rate when only reduced amounts of this factor are available (2% FCS).(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Modulation of extracellular matrix metabolism in rabbit articular chondrocytes and human rheumatoid synovial cells by the non-steroidal anti-inflammatory drug etodolac. I: Collagen synthesis.
Cultures of human rheumatoid synovial cells and rabbit articular chondrocytes were exposed to various concentrations of Etodolac (from 0.01 to 10 micrograms/ml) in presence or absence of 500 pg/ml (5 U/ml) human recombinant Interleukin-1 beta (IL-1 beta). Incubation of chondrocytes with Etodolac for 24 h did not alter collagen biosynthesis. In contrast, 1 micrograms/ml Etodolac caused a 20% increase of collagen production in synoviocytes. Addition of Etodolac in combination with IL-1 could partially suppress the inhibitory effect exerted by the cytokine on both cell types. Four-day exposure of chondrocytes to 0.1 and 1 micrograms/ml Etodolac led to an increased accumulation of collagen in the cell layer compartment. However, this treatment could not prevent the inhibitory effect of IL-1 on this collagen fraction. Treatment of synoviocytes for eight days with the same concentrations of Etodolac did not modify their collagen production but suppressed totally the inhibitory effect of IL-1. These data show that Etodolac is able to augment chondrocyte metabolism during a long term treatment. Moreover, under certain conditions, this drug can reduce or even suppress the IL-1-induced inhibition of collagen biosynthesis, a process that may take a part in the connective tissue alterations associated with osteoarticular diseases such as rheumatoid arthritis and osteoarthritis.
Animals↗
Modulation of extracellular matrix metabolism in rabbit articular chondrocytes and human rheumatoid synovial cells by the non-steroidal anti-inflammatory drug etodolac. II: Glycosaminoglycan synthesis.
The effect of Etodolac on glycosaminoglycan (GAG) synthesis by human synovial cells and rabbit articular chondrocytes in culture was studied at doses ranging from 0.01 to 10 micrograms/ml. In chondrocyte cultures, short-term exposure to Etodolac decreased the total amount of GAGs (mainly chondroitin sulfate) affecting essentially the cell layer-associated fraction. When cells were incubated with Interleukin-1 (IL-1), Etodolac still exerted its inhibiting effect on GAG synthesis. Long-term exposure of chondrocytes to Etodolac caused a diminution of the total GAG synthesis for the highest concentration studied (1 micrograms/ml). IL-1 alone or in combination with Etodolac decreased the synthesis of GAGs suggesting that pretreatment with Etodolac cannot prevent the action of IL-1. In synoviocyte cultures, the drug caused an inhibition of the GAG biosynthesis (mainly hyaluronic acid). In presence of IL-1, Etodolac at the highest concentration partially diminished the stimulatory effect of IL-1. A 8-day exposure of the cells to Etodolac led to a decrease of GAG synthesis. In the same experiment, IL-1 alone caused a slight increase of GAG production that was not abolished by Etodolac treatment.
Animals↗
The role of cytokines in the development of osteoarthritis.
A range of cytokines have been suggested as intermediaries which may have effects on cellular metabolism and proliferation. Interleukin 1 has been most intensively studied and has multiple biological activities, however other polypeptides may also have significant effects on cartilage. A greater understanding of the biochemical mechanisms involved in the development and progression of osteoarthritis (OA) may lead to a rational approach to therapeutic management.
Anti-Inflammatory Agents↗
[Systemic mastocytosis. Polymorphism of bone involvement. Report of 3 cases 2 of which with diffuse osteocondensation].
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Biopsy↗
Effects of associated cytokines (IL-1, TNF-alpha, IFN-gamma and TGF-beta) on collagen and glycosaminoglycan production by cultured human synovial cells.
The production of collagen and glycosaminoglycans (GAG) was studied in cultured human synovial cells exposed to four cytokines, alone or in dual combination, namely interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta). Among these cytokines, only TGF-beta (0.1-10 ng/ml) induced a significant and dose-dependent increase of collagen synthesis in a 24-h incubation. This effect was reversed when the factor was associated with either IL-1 beta (100-500 pg/ml), TNF-alpha (1-100 ng/ml) or IFN-gamma (100 U/ml). Except IFN-gamma which clearly inhibits the collagen production, the other cytokines IL-1 and TNF-alpha were not very effective when tested separately, although they generally induced a small reduction in collagen amount. IL-1 beta and TNF-alpha were found to be more efficient than TGF-beta in stimulating the production of GAG by the synovial cells. IFN-gamma exerted an antagonistic effect on the TGF-beta-induced stimulation of GAG synthesis. TNF-alpha and IL-1 beta were shown to have an additive effect on that production. The results indicate that interactions between cytokines present in the inflamed synovial tissue may modulate their respective actions and thus introduce differentials in their effect on collagen and GAG metabolism which are responsible for the alterations of synovial extracellular matrix in rheumatoid arthritis.
Biological Factors↗
[Postmenopausal osteoporosis: early detection of subjects at risk using spinal dual photon absorptiometry].
With quantification techniques of the spinal bone condition, especially with spinal biphotonic absorptiometry, early screening of patients risking subsequent development of osteoporosis complicated with vertebral compression is possible. An investigation was conducted in Lower Normandy, in 386 women who had undergone menopause or an ovariectomy, with ages ranging between 40 and 56 years; 274 were in a peri-menopausal state. We had previously established a curve of the bone mineral content according to age. From this curve, in semilogarhythmic representation, we assessed each patient's risk. This risk is considered as high in 30 p. cent of the patients, non existent in 52 p. cent and 18 p. cent are borderline. The percentage of high risk patients increases with the number of years since menopause. It is hoped that the incidence of osteoporosis will decrease with early screening and preventive therapeutic measures.
Absorptiometry, Photon↗
[Chronic lymphoid leukemia with iliac osteolysis].
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Humans↗
[Gonadal function in primary apparent male osteoporosis. 12 cases].
The testicular endocrine function was studied in 12 patients aged from 33 to 76 years (mean: 56.3 +/- 11.5 years) presenting with an apparently primary vertebral osteoporosis and in 14 age-matched controls (mean: 52.6 +/- 12.8 years). The mean bone mineral content, measured in the vertebral column by biphoton absorptiometry, was lower in patients than in control (P +/- 0.01). Plasma levels of testosterone, oestradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were the same in both groups. In two patients of each group, a rise of LH with normal testosteronaemia was suggestive of compensated Leydig's cell deficiency. There was no correlation between bone mineral content, plasma testosterone, LH, FSH level and the subjects' weight and height. However, a positive correlation was found between plasma oestradiol level and bone mineral contents in patients with osteoporosis (P +/- 0.01) ans in all subjects under study (P +/- 0.05). This study shows that primary osteoporosis is not due to testicular deficiency and suggests a possible action of oestradiol on male bone.
Adult↗
[Congestive outbreaks of osteo-arthrosis].
Osteo-arthritis is often interspersed with congestive episodes due to inflammation of the synovial membranes, the vascular component of which is more important than the cellular component. This explains why the clinical signs of inflammation are moderate and characterized mainly by a mechanical-type formula. The mechanism of these episodes involves several factors, and osteo-cartilaginous fragments, microcrystals and perhaps immune complexes have been blamed for their occurrence. The influence of inflammation on cartilage degradation has been proved experimentally, and this is supported by some clinical findings. Treatment consists of non-steroidal anti-inflammatory agents, intra-articular corticosteroid injections and relief of articular overload.
Humans↗
Knee arthroscopy after yttrium or osmic acid injection.
This study presents the macroscopic and histologic results of 35 knee arthroscopies performed on patients with rheumatoid arthritis, some months after an yttrium or osmic acid intraarticular injection. The procedure was most often performed after a failure of the injection or a relapse of synovitis. Arthroscopy provides an understanding of the cause of synoviorthesis failure--insufficient action of the product on the synovitis or its poor diffusion, fibri-nonecrotic deposits, or cartilaginous lesions--and may be used both diagnostically and therapeutically.
Adolescent↗