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Biomedical subjects

M Richard

Publications and source records attributed to M Richard.

At least 91 records · Page 5Linked to original sources

Calmodulin-dependent collagenase and proteoglycanase activities in chondrocytes from human osteoarthritic cartilage.

Chondrocyte metalloproteinases appear to play a major role in the development of osteoarthritis. The intracellular post-traductional mechanisms regulating collagenase and proteoglycanase are not known. Calmodulin antagonists including phenothiazine and sulfonamide derivatives significantly increased proteoglycanase activity and decreased collagenase activity. H-7, a specific inhibitor of protein kinase C, had no effect on the two metalloproteinase activities, and calmodulin was ineffective in in vitro assays upon metalloproteinase activities. We postulate that collagenase and proteoglycanase activities are controlled by calmodulin-dependent regulation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Serotonin-stimulated phospholipase A2 and collagenase activation in chondrocytes from human osteoarthritic articular cartilage.

We have previously described several receptors on the chondrocyte membrane. In an attempt to further characterize the coupling mechanisms of serotoninergic receptors, here we examined the involvement of serotonin in the phospholipase A2 activity. Serotonin dose-dependently stimulated phospholipase A2. This activation enhanced collagenase type II activity and had no effect on proteoglycanase activity.

Aged↗

In vitro effect of nonsteroidal antiinflammatory drugs on proteoglycanase and collagenase activity in human osteoarthritic cartilage.

The effects of several nonsteroidal antiinflammatory drugs, used at concentrations achievable in synovial fluid, on human osteoarthritic (OA) cartilage metallo-protease activity in vitro was studied. Acetaminophen and ketoprofen had no effect; sodium salicylate, indomethacin, and diclofenac slightly decreased proteoglycanase activity. Piroxicam and tenoxicam suppressed proteoglycanase activity by 48.2% and 68.3%, respectively, and suppressed collagenase activity by 19.1% and 36.8%, respectively. Use of these NSAIDs may help to decrease cartilage catabolism in patients with OA.

Acetaminophen↗

Plasma fibronectin and complement following infusion of colloidal solutions after spinal anaesthesia.

A randomized study of 30 patients undergoing uncomplicated surgery under spinal anesthesia was conducted to assess the influence of colloids on the kinetics of plasma fibronectin and complement. Both are opsonins of the reticuloendothelial system; moreover fibronectin is concerned with host resistance against septic complications following trauma and surgery. The patients were assigned to receive either Ringer's lactate (Group 1), gelatin (Group 2) or dextran 40 (Group 3). Blood samples were withdrawn before colloids or Ringer's infusion and during the 4 postoperative days. There was a reduction in plasma fibronectin throughout the study in groups 1 and 3, but an increase in group 2 by 24 h. The adhesion of plasma fibronectin to gelatin was maximal 1 h after infusion (44%) and remained significant up to day 2 in group 2. There was no relationship in groups 1 and 3. C3 and C4 components of complement exhibited a low value in the early post-operative period, due to hemodilution. This study shows an in vivo fibronectin-gelatin interaction, and suggests that gelatin infusion inhibits the increased shift of plasma fibronectin at the site of tissue injury after surgery.

Adult↗

The ability of suramin to block CD4-gp120 binding is reversed in the presence of albumin.

We have shown that suramin can directly inhibit the binding of the human immunodeficiency virus type 1 gp120 envelope protein to immobilized CD4, thus helping to explain the previously described antiviral properties of suramin. However, physiological concentrations of serum albumin significantly attenuated suramin's antiviral effects, suggesting that only free suramin has antiviral properties. Reported discrepancies between in vitro and clinical activities of suramin may be due to differences between free suramin levels in experimental assays and those achievable clinically.

Animals↗

[Serum hyaluronic acid and phospholipase A2 in an arthritic population].

Serum hyaluronic acid (HA) and A2 phospholipase (A2PL) activity were measured by radioimmunoassay (Pharmacia) and using a specific phospholipid substrate respectively, as potential markers of osteoarthritic synovitis. With neither age, treatment nor sample time taken into consideration, the concentration of HA (micrograms/ml) was 585 +/- 1,054 in rheumatoid arthritis, 379 +/- 409 in knee osteoarthrosis, 272 +/- 384 in hip osteoarthrosis, 131 +/- 144 in low back pain and 44 +/- 23 in osteoporosis, with no significant difference between the groups. HA was nevertheless found to be significantly higher in knee osteoarthrosis patients than in normal controls, when samples were drawn at the same time of day. Physical exercise (pedalling), as well as 20 hours lying flat and an intra-articular injection of corticosteroids did not cause any significant variation in serum HA levels in knee osteoarthrosis patients, in contrast to 20 hours of rest in the controls. A2PL activity was significantly higher in osteoarthrosis patients than in the controls, decreased with rest and corticosteroids and was not dependent upon sample time.

Aged↗

Study of an inhibitor of plasminogen activator (tranexamic acid) in the treatment of experimental osteoarthritis.

The effects of tranexamic acid, an inhibitor of plasminogen activator, were evaluated in a rabbit model of osteoarthritis induced by section of the knee joint anterior cruciate ligament. Prophylactic treatment administered intramuscularly thrice weekly for 12 or 24 weeks significantly reduced cartilage destructive lesions, increased cartilage hypertrophy but did not prevent changes in cartilage water and proteoglycan content. A suppression of synovial membrane stromelysin and collagenase activity was found while phospholipase A2 activity was unaffected.

Animals↗

[Effects of naproxen (naprosyne) on the metabolism of arthrotic cartilage in man in vivo].

Degradative enzyme (proteoglycanase and collagenase) as well as proteoglycan synthesis enzyme (glycosyl-transferase) activity was studied in osteoarthritic fibrillated cartilage. Proteoglycanase activity was significantly lower in 10 patients with hip osteoarthritis treated with Naproxen (1 g/daily for 4 weeks) than in 10 patients treated with acetaminophen. Synthesis enzyme activity was similar in both groups. The results which confirm in vitro studies suggest that naproxen has not toxic effect on human osteoarthritic cartilage and could rather be beneficial.

Acetaminophen↗

[Cytokines, prostaglandin E2, phospholipase A and metalloproteases in synovial fluid in osteoarthritis].

Concentrations of prostaglandin E2, interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha, phospholipase A2, collagenase and proteoglycanase activity were determined in synovial fluid from 26 patients with osteoarthrosis of the knee and 10 with rheumatoid arthritis. Osteoarthrosis synovial fluid was characterised by the absence of interleukin 1 beta while tumour necrosis factor alpha and interleukin 6 were present in relatively large amounts, by a very high phospholipase A2 activity contrasting with a very low concentration of prostaglandin E2, and by a collagenase/proteoglycanase activity only slightly less constant and high as in rheumatoid arthritis. In osteoarthrosis patients, the interleukin 6 concentration, but not that of tumor necrosis factor alpha, was correlated with the collagenase and proteoglycanase activity of synovial fluid.

Adult↗

Suramin blockade of insulinlike growth factor I-stimulated proliferation of human osteosarcoma cells.

The polyanionic compound suramin is currently being evaluated for antineoplastic activity. On the basis of previous in vitro studies, it has been suggested that the mechanism of action of suramin may be related to its ability to attenuate the mitogenic effects of peptide growth factors, such as platelet-derived growth factor and epidermal growth factor. We recently reported that MG-63 human osteosarcoma cells are mitogenically responsive to insulinlike growth factor I (IGF-I). We now demonstrate for the first time that suramin interferes with the interaction between IGF-I and its receptor and abolishes in vitro IGF-I-stimulated proliferation of these osteosarcoma cells. The fact that cell proliferation resumes when suramin is removed indicates that this is not a cytotoxic effect. We conclude that IGF-I should be added to the list of growth factors whose bioactivity can be attenuated by suramin and that clinical studies of suramin and its analogues are indicated in IGF-I-receptor-positive malignancies such as osteogenic sarcoma.

Affinity Labels↗

[Effects of non-steroidal anti-inflammatory drugs on the enzymatic degradation of osteoarthritic cartilage].

The proteoglycannasic and collagenolytic activity the fissured, osteoarthritic human cartilage has been studied in vitro, using proteoglycannases and collagen type II respectively as marked substrates. The effect of various NSAIDs, used at a concentration corresponding to that of the synovial fluid, on these enzymatic activities has been measured in vitro. Naproxen decreases in a significant and dose-dependent way the enzymatic degradation of the cartilage, but only an inhibition of the proteoglycannase can be hoped for in vivo. Not all NSAIDs seem to have inhibitory effects on the enzymatic degradation of the osteoarthritic cartilage.

Aged↗

Insulinlike growth factor I: a potent mitogen for human osteogenic sarcoma.

Insulinlike growth factor I (IGF-I) is among the peptide mitogens that play key roles in the regulation of normal skeletal growth. To investigate the possibility that certain skeletal neoplasms retain a sensitivity to mitogenic stimulation by IGF-I, we studied the effects of this growth factor on human osteosarcoma. Competitive-binding assays and affinity-labeling experiments on membranes prepared from MG-63 immortalized human osteosarcoma cells and primary human osteogenic sarcoma cells demonstrate the presence of specific IGF-I receptors. Furthermore, we show that IGF-I is a potent stimulator of proliferation of MG-63 cells in vitro and is active at concentrations as low as 10(-10) M. A blocking antibody against the IGF-I receptor (alpha-IR3) significantly reduces IGF-I-stimulated proliferation in a dose-dependent manner. These results are consistent with the hypothesis that at least a subset of human osteogenic sarcomas are responsive to IGF-I and indicate that it may be possible to exploit this responsiveness therapeutically.

Affinity Labels↗

French multicenter trial of anistreplase versus heparin in acute myocardial infarction.

Eighty-four patients aged less than 71 years with less than 4-hour duration acute myocardial infarction (AMI) were randomized in a multicenter study to 30 U anistreplase or heparin (single injection of 6500 IU followed by 1000 IU/hr). Early reperfusion was assessed from ECG changes (50% of sum ST decrease 2 hours postdosing) and the CK release profile (CK peak less than 16 hours after onset of symptoms, CK slope greater than 10%/hr). Reperfusion rates in patients meeting at least two criteria of reperfusion were 62.5% on anistreplase versus 27.5% on heparin. On delayed angiogram (13.7 +/- 3.4 days), patency rates were 66% with anistreplase versus 47% (NS) with heparin in 76 patients. Global LVF was similar in both groups. With anistreplase, the mean lowest fibrinogen level was 0.43 +/- 0.55 g/l, plasminogen was 20 +/- 9%, and the highest F.D.P. was 1447 +/- 548 micrograms/ml. All values recovered by hour 48. In-hospital and 1-year follow-up mortality was 7.2% (three patients) with anistreplase versus 10.2% (four patients) with heparin. Bleeding occurred in 9.7% and 5.1% of the patients (NS), respectively. No intracranial hemorrhage occurred. Thus, with combined clinical criteria or reperfusion, anistreplase is twice as efficient as heparin, has a good tolerance, and is easy to use as a single injection.

Anistreplase↗

Study of the effect of a glycosaminoglycan-peptide complex on the degradative enzyme activities in human osteoarthritic cartilage.

The in vitro collagenolytic and proteoglycanasic activity from human fibrillated osteoarthritic cartilage was determined using labelled proteoglycans and type II collagen as substrates. In vitro, a glycosaminoglycan-peptide complex (GP-C Rumalon) induced a dose-dependent inhibition of both collagenolytic and proteoglycanasic activities while sodium salicylate and indomethacin had only a weak suppressive effect on proteoglycanase. Phospholipase A2 activity was unmodified by GP-C suggesting that the effect of the drug on degradative enzymes was unrelated to prostaglandin formation.

Aged↗

Cartilage degradative enzymes in human osteoarthritis: effect of a nonsteroidal antiinflammatory drug administered orally.

The activity of stromelysin and collagenase was determined in fibrillated human OA cartilage using labeled proteoglycans and type II collagen as substrates. In vitro paracetamol had no effect on metalloprotease whereas TA induced a significant inhibition of stromelysin. In cartilage and synovium from nine patients treated with TA and nine patients treated with paracetamol during 8 weeks before surgery for hip OA, stromelysin activity was significantly lower in the TA than in the paracetamol group. The results suggest that TA has a potential chondroprotective effect in OA.

Acetaminophen↗

Endless-loop tachycardias: description and first clinical results of a new fully automatic protection algorithm.

Endless-loop tachycardia (ELT) is one of the most common pacemaker mediated tachycardia. An innovative ELT protection algorithm has proven to be clinically effective. A new improved version that will eliminate the need to program any parameter is now under clinical evaluation. Nine patients entered the study: six men and three women, aged 52 +/- 22 years. This automatic algorithm needs only 10 cycles to detect and confirm an ELT. Three hundred thirty-three ELTs lasting more than 9 cycles have been induced and analyzed. The total results are the following: mean duration: 6.7 sec +/- 3.1; mean ELT rate: 137 +/- 21.9 bpm, mean programmed upper rate limit (URL): 142.5 +/- 26.5 bpm (Only 70% of ELTs presented rates equal to programmed URL). (1) ELTs reduced by postventricular atrial refractory period (PVARP) extension on one cycle: 291 ELTs (87%). ELT rate: 128.5 +/- 18.2 bpm. (2) Retrograde block: algorithm operation may induce a retrograde block due to a short atrioventricular delay (AVD) applied during the confirmation phase to discriminate an ELT from a stable sinus rhythm. Thirty-two ELTs (10%) have been reduced and detected on a retrograde block occurrence. (3) Algorithm failure due to an unstable ventriculoatrial conduction time (VACT) even at fixed rate or to a retrograde Wenckebach behavior on AVD reduction during the confirmation phase. A total of 10 algorithms failed to detect or confirm an ELT have been recorded (3%). Mean duration: 8.2 +/- 4.2 sec, mean ELT rate: 148.9 +/- 14.3 bpm. This new fully automatic algorithm has reduced 97% of ELTs, including high rate episodes (100-175 bpm).(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗